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Sample records for adrenal androgen levels

  1. Control of adrenal androgen production.

    PubMed

    Odell, W D; Parker, L N

    The major adrenal androgens are dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEAS) and androstenedione (delta 4). Studies by Cutler et al in 1978 demonstrated that these androgens are detectable in blood of all domestic and laboratory animals studied, but that only 4 species show increase in one or more with sexual maturation: rabbit, dog, chimpanzee and man. Studies by Grover and Odell in 1975 show these androgens do not bind to the androgen receptor obtained from rat prostate and thus probably are androgens only by conversion to an active androgen in vivo. Thomas and Oake in 1974 showed human skin converted DHEA to testosterone. The control of adrenal androgen secretion is in part modulated by ACTH. However, other factors or hormones must exist also, for a variety of clinical observations show dissociation in adrenal androgen versus cortisol secretion. Other substances that have been said to be controllers of adrenal androgen secretion include estrogens, prolactin, growth hormone, gonadotropins and lipotropin. None of these appear to be the usual physiological modulator, although under some circumstances each may increase androgen production. Studies from our laboratory using in vivo experiments in the castrate dog and published in 1979 indicated that crude extracts of bovine pituitary contained a substance that either modified ACTH stimulation of adrenal androgen secretion, or stimulated secretion itself - Cortisol Androgen Stimulating Hormone. Parker et al in 1983 showed a 60,000 MW glycoprotein was extractable from human pituitaries, which stimulated DHA secretion by dispersed canine adrenal cells in vitro, but did not stimulate cortisol secretion. This material contained no ACTH by radioimmunoassay. In 1982 Brubaker et al reported a substance was also present in human fetal pituitaries, which stimulated DHA secretion, but did not effect cortisol. PMID:6100259

  2. Ovarian and Adrenal Androgens and Their Link to High Human Chorionic Gonadotropin Levels: A Prospective Controlled Study

    PubMed Central

    Rodríguez-Gutiérrez, René; Villarreal-Pérez, Jesús Zacarías; Morales-Martinez, Felipe Arturo; Rodríguez-Guajardo, René; González-Saldivar, Gloria; Mancillas-Adame, Leonardo G.; Alvarez-Villalobos, Neri Alejandro; Lavalle-Gonzalez, Fernando Javier; González-González, José Gerardo

    2014-01-01

    Background. Although the association between human chorionic gonadotropin (hCG) and hyperandrogenism was identified more than 40 years ago, relevant questions remain unanswered. Design and Methods. We conducted a prospective, longitudinal, and controlled study in 23 women with a diagnosis of a complete hydatidiform mole (HM). Results. All participants completed the study. Before HM evacuation mean hCG was markedly higher in the cases than in the control group (P ≤ 0.001). Free testosterone (T) and dehydroepiandrosterone sulfate (DHEA-S) were found to be higher in the cases (2.78 ± 1.24 pg/mL and 231.50 ± 127.20 μ/dL) when compared to the control group (1.50 ± 0.75 pg/mL and 133.59 ± 60.69 μ/dL) (P = 0.0001 and 0.001), respectively. There was a strong correlation between hCG and free T/total T/DHEA-S concentrations (r = 0.78; P ≤ 0.001, r = 0.74;  P ≤ 0.001, and r = 0.71;  P ≤ 0.001), respectively. In the cases group 48 hours after HM evacuation, hCG levels were found to be significantly lower when compared to initial levels (P = 0.001) and free T and DHEA-S declined significantly (P = 0.0002 and 0.009). Conclusion. Before uterus evacuation, hCG, free T, and DHEA-S levels were significantly higher when compared with controls finding a strong correlation between hCG and free T/DHEA-S levels. Forty-eight hours after HM treatment hCG levels declined and the difference was lost. A novel finding of our study is that in cases, besides free T, DHEA-S was also found to be significantly higher and both the ovaries and adrenal glands appear to be the sites of this androgen overproduction. PMID:25505909

  3. Combined Adrenal and Ovarian Venous Sampling to Localize an Androgen Producing Tumor

    SciTech Connect

    Agarwal, Monica D.; Trerotola, Scott O.

    2010-12-15

    A postmenopausal woman presented with hirsutism and elevated serum testosterone levels. A 1-cm adrenal adenoma was noted on computed tomography. Combined adrenal and ovarian venous sampling was performed to localize an androgen producing tumor to the left ovary. The patient underwent a bilateral salpingo-oophrectomy and was spared an unnecessary adrenalectomy.

  4. A case of androgen-secreting adrenal carcinoma with non-classical congenital adrenal hyperplasia.

    PubMed

    Varma, Tarun; Panchani, Roopal; Goyal, Ashutosh; Maskey, Robin

    2013-10-01

    Androgen excess is one of the most common and disturbing endocrine disorder of reproductive-aged women, affecting approximately 7% of this population Androgen excess results in the development of androgenic features in the women affected, with the development of hirsutism, androgenic alopecia, ovulatory dysfunction, and, if extreme, even virilization and masculinization. Adrenocortical carcinoma (ACC) is a rare malignancy accounting for 0.02% of all annual cancers reported. About 60% are functional tumors secreting hormones, with its consequent clinical manifestations, the Cushing's syndrome due to cortisone, virilization due to androgens, feminization due to estrogens, or hypertension due to aldosterone. Adrenal tumors that secrete androgens exclusively are extremely rare. Here, we present a rare case of androgen-secreting adrenocortical carcinoma with non-classical congenital adrenal hyperplasia. PMID:24251173

  5. Adrenal hyperandrogenism is induced by fetal androgen excess in a rhesus monkey model of polycystic ovary syndrome

    PubMed Central

    Bird, Ian M.; Dumesic, Daniel A.; Abbott, David H.

    2005-01-01

    Context: Adrenal androgen excess is found in ∼25-60%% of women with polycystic ovary syndrome (PCOS), but the mechanisms underlying PCOS-related adrenal androgen excess are unclear. Objective: To determine whether adrenal androgen excess is manifest in a nonhuman primate model for PCOS, Participants: Six prenatally androgenized (PA) and 6 control female rhesus monkeys of similar age, body weight and BMI were studied during days 2-6 of two menstrual cycles or anovulatory 30-day periods. Interventions: Pre-dexamethasone adrenal steroid levels were assessed in the first cycle (cycle 1). In a subsequent cycle (cycle 2), occurring 1-3 cycles following cycle 1, adrenal steroids were determined 14.5-16.0h after an i.m. injection of 0.5mg/kg dexamethasone [post-dexamethasone levels] and following an i.v. injection of 50μg ACTH1-39. Results: Both before and after dexamethasone, serum levels of dehydroepiandrosterone (DHEA) in PA females exceeded those in controls. Following ACTH injection, PA females exhibited higher circulating levels of DHEA, androstenedione and corticosterone, but comparable levels of 17α-hydroxyprogesterone, cortisol, DHEAS, and testosterone, compared to controls. Conclusion: Enhanced basal and ACTH-stimulated adrenal androgen levels in PA female monkeys may reflect up-regulation of 17,20 lyase activity in the adrenal zona reticularis, causing adrenal androgen excess comparable to that found in PCOS women with adrenal androgen excess. These findings open the possibility that PCOS adrenal hyperandrogenism may have its origins in fetal androgen excess re-programming of adrenocortical function. PMID:16174719

  6. Increased adrenal androgen secretion with inhibition of 11beta-hydroxylase in HIV-infected women.

    PubMed

    Koutkia, Polyxeni; Berry, Jacqueline; Eaton, Kristina; Breu, Jeff; Grinspoon, Steven

    2006-05-01

    Adrenal androgen production is reduced in association with disease severity in HIV-infected women. This response may be maladaptive in terms of maintenance of lean body mass, functional status, and immune function. The aim of this study was to assess whether the use of an adrenal enzyme inhibitor of 11beta-hydroxylase might increase androgen production in this population. We conducted a randomized, double-blind, placebo-controlled study of metyrapone (500 mg p.o. qid) or placebo for 2 wk in 10 HIV-infected women with AIDS wasting [weight <90% ideal body weight (IBW) or weight loss >10%] and reduced androgen levels. Basal and ACTH-stimulated androgen, mineralocorticoid, and glucocorticoid levels were measured at baseline and after 14 days of treatment. Subjects were similar in age (40.9 +/- 0.9 yr), weight (91.7 +/- 3.5% IBW) and hormone concentrations at study entry. Total testosterone (84 +/- 54 vs. -0.4 +/- 2 ng/dl, P = 0.024), free testosterone (6.5 +/- 2.8 vs. 0.1 +/- 0.1 pg/ml, P = 0.024), DHEA (5.0 +/- 3.2 vs. -0.6 +/- 0.5 microg/l, P = 0.024), and 11-deoxycortisol (2,145 +/- 820 vs. -14 +/- 22 ng/dl, P = 0.024) levels increased in response to metyrapone compared with placebo treatment. In response to ACTH, significant increases in the DHEA/cortisol ratio (174 +/- 48 vs. 3 +/- 3, P = 0.008) were seen in the metyrapone group compared with placebo. Blood pressure and electrolytes did not change, and signs of adrenal insufficiency were not apparent. These data demonstrate that inhibition of 11beta-hydroxylase with metyrapone increases adrenal androgen secretion in HIV-infected women. Further studies are needed to assess the physiological effects of this strategy to increase anabolic hormone levels in severe stress, including detailed testing to rule out the potential risk of concomitant adrenal insufficiency. PMID:16303845

  7. Adrenal Androgen Production in Catarrhine Primates and the Evolution of Adrenarche

    PubMed Central

    Bernstein, Robin M.; Sterner, Kirstin N.; Wildman, Derek E.

    2015-01-01

    Adrenarche is a developmental event involving differentiation of the adrenal gland and production of adrenal androgens, and has been hypothesized to play a role in the extension of the preadolescent phase of human ontogeny. It remains unclear whether any nonhuman primate species shows a similar suite of endocrine, biochemical, and morphological changes as are encompassed by human adrenarche. Here, we report serum concentrations of the adrenal androgens dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) measured in 698 cross-sectional and mixed longitudinal serum samples from catarrhine primates ranging from 0.6 to 47 years of age. DHEAS in Pan is most similar to that of humans in both age-related pattern and absolute levels, and a transient early increase appears to be present in Gorilla. DHEA levels are highest in Cercocebus, Cercopithecus, and Macaca. We also tested for evidence of adaptive evolution in six genes that code for proteins involved in DHEA/S synthesis. Our genetic analyses demonstrate the protein-coding regions of these genes are highly conserved among sampled primates. We describe a tandem gene duplication event probably mediated by a retro-transposon that resulted in two 3-β-hydroxysteroid dehydrogenase/Delta 5-Delta 4 genes (HSD3B1 and HSD3B2) with tissue specific functions in catarrhines. In humans, HSD3B2 is expressed primarily in the adrenals, ovary, and testis, while HSD3B1 is expressed in the placenta. Taken together, our findings suggest that while adrenarche has been suggested to be unique to hominoids, the evolutionary roots for this developmental stage are more ancient. PMID:22271526

  8. Adrenal androgens and androgen precursors: definition, synthesis, regulation and physiologic actions

    PubMed Central

    Turcu, Adina; Smith, Joshua M.; Auchus, Richard; Rainey, William E.

    2015-01-01

    The human adrenal produces more 19 carbon (C19) steroids, by mass, than either glucocorticoids or mineralocorticoids. However, the mechanisms regulating adrenal C19 steroid biosynthesis continue to represent one of the most intriguing mysteries of endocrine physiology. This review will discuss the C19 steroids produced in the human adrenal and the features within the adrenal that allow production of these steroids. Finally, we consider the effects of these steroids in normal physiology and disorders of adrenal C19 steroid excess. PMID:25428847

  9. Hyposecretion of the adrenal androgen dehydroepiandrosterone sulfate and its relation to clinical variables in inflammatory arthritis.

    PubMed

    Dessein, P H; Joffe, B I; Stanwix, A E; Moomal, Z

    2001-01-01

    Hypothalamic-pituitary-adrenal underactivity has been reported in rheumatoid arthritis (RA). This phenomenon has implications with regard to the pathogenesis and treatment of the disease. The present study was designed to evaluate the secretion of the adrenal androgen dehydroepiandrosterone sulfate (DHEAS) and its relation to clinical variables in RA, spondyloarthropathy (Spa), and undifferentiated inflammatory arthritis (UIA). Eighty-seven patients (38 with RA, 29 with Spa, and 20 with UIA) were studied, of whom 54 were women. Only 12 patients (14%) had taken glucocorticoids previously. Age-matched, healthy women (134) and men (149) served as controls. Fasting blood samples were taken for determination of the erythrocyte sedimentation rate (ESR), serum DHEAS and insulin, and plasma glucose. Insulin resistance was estimated by the homeostasis-model assessment (HOMAIR). DHEAS concentrations were significantly decreased in both women and men with inflammatory arthritis (IA) (P < 0.001). In 24 patients (28%), DHEAS levels were below the lower extreme ranges found for controls. Multiple intergroup comparisons revealed similarly decreased concentrations in each disease subset in both women and men. After the ESR, previous glucocorticoid usage, current treatment with nonsteroidal anti-inflammatory drugs, duration of disease and HOMAIR were controlled for, the differences in DHEAS levels between patients and controls were markedly attenuated in women (P = 0.050) and were no longer present in men (P = 0.133). We concluded that low DHEAS concentrations are commonly encountered in IA and, in women, this may not be fully explainable by disease-related parameters. The role of hypoadrenalism in the pathophysiology of IA deserves further elucidation. DHEA replacement may be indicated in many patients with IA, even in those not taking glucocorticoids. PMID:11299059

  10. Brief Communication: Adrenal Androgens and Aging: Female Chimpanzees (Pan troglodytes) Compared With Women

    PubMed Central

    Blevins, James K.; Coxworth, James E.; Herndon, James G.; Hawkes, Kristen

    2015-01-01

    Ovarian cycling continues to similar ages in women and chimpanzees yet our nearest living cousins become decrepit during their fertile years and rarely outlive them. Given the importance of estrogen in maintaining physiological systems aside from fertility, similar ovarian aging in humans and chimpanzees combined with somatic aging differences indicates an important role for nonovarian estrogen. Consistent with this framework, researchers have nominated the adrenal androgen dehydroepiandrosterone (DHEA) and its sulfate (DHEAS), which can be peripherally converted to estrogen, as a biomarker of aging in humans and other primates. Faster decline in production of this steroid with age in chimpanzees could help explain somatic aging differences. Here, we report circulating levels of DHEAS in captive female chimpanzees and compare them with published levels in women. Instead of faster, the decline is slower in chimpanzees, but from a much lower peak. Levels reported for other great apes are lower still. These results point away from slowed decline but toward increased DHEAS production as one of the mechanisms underlying the evolution of human longevity. PMID:23818143

  11. Increased expression of ACTH (MC2R) and androgen (AR) receptors in giant bilateral myelolipomas from patients with congenital adrenal hyperplasia

    PubMed Central

    2014-01-01

    Background Although chronic adrenocorticotropic hormone (ACTH) and androgen hyperstimulation are assumed to be involved in the pathogenesis of adrenal myelolipomas associated with poor-compliance patients with congenital adrenal hyperplasia (CAH), the expression of their receptors has not yet been demonstrated in these tumors so far. Methods We analyzed Melanocortin 2 receptor (MC2R), Androgen Receptor (AR), Leptin (LEP), and Steroidogenic factor 1 (SF1) expression using real-time qRT-PCR in two giant bilateral adrenal myelolipomas from two untreated simple virilizing CAH cases and in two sporadic adrenal myelolipomas. In addition, the X-chromosome inactivation pattern and CAG repeat numbers in AR exon 1 gene were evaluated in the 4 cases. Results The MC2R gene was overexpressed in myelolipomas from 3 out of 4 patients. AR overexpression was detected in 2 tumors: a giant bilateral myelolipoma in a CAH patient and a sporadic case. Simultaneous overexpression of AR and MC2R genes was found in two of the cases. Interestingly, the bilateral giant myelolipoma associated with CAH that had high androgen and ACTH levels but lacked MC2R and AR overexpression presented a significantly shorter AR allele compared with other tumors. In addition, X-chromosome inactivation pattern analysis showed a polyclonal origin in all tumors, suggesting a stimulatory effect as the trigger for tumor development. Conclusion These findings are the first evidence for MC2R or AR overexpression in giant bilateral myelolipomas from poor-compliance CAH patients. PMID:24884994

  12. Stimulation of androgen-dependent gene expression by the adrenal precursors dehydroepiandrosterone and androstenedione in the rat ventral prostate

    SciTech Connect

    Labrie, C.; Simard, J.; Zhao, H.F.; Belanger, A.; Pelletier, G.; Labrie, F. )

    1989-06-01

    Androgens play a major role in the development, growth, and function of accessory sexual organs, especially the prostate. However, the testis is not the sole source of circulating androgens in man, since the adrenal gland secretes dehydroepiandrosterone (DHEA), DHEA sulfate, and androstenedione (delta 4-dione) in large quantities. The aim of the present study was to investigate the effect of plasma concentrations of DHEA and delta 4-dione similar to those found in adult man on sensitive and specific markers of androgen action in the rat ventral prostate. In addition to ventral prostate weight, we have measured the steady state levels of the mRNAs encoding the C1 component of rat prostatic binding protein (PBP-C1) and spermine-binding protein (SBP) using 35S-labeled cDNA probes for in situ hybridization. One week after castration, ventral prostate weight fell 84%, while prostatic 5 alpha-dihydrotestosterone (DHT) and androgen-dependent mRNAs were undetectable. When administered via Silastic implants to castrated adult rats for 1 week, plasma concentrations of 1.37 +/- 0.06 ng/ml DHEA or 0.43 +/- 0.08 ng/ml delta 4-dione independently caused increases in ventral prostate weight to 33% and 65% of normal values, respectively. The same plasma levels of DHEA and delta 4-dione resulted in high intraprostatic levels of DHT to 1.19 +/- 0.34 and 3.66 +/- 0.89 ng/g tissue, respectively. Furthermore, DHEA caused an increase in the steady state levels of PBP-C1 and SBP mRNAs to 50% and 57% of the normal state, respectively, while delta 4-dione caused increases corresponding to 80% and 119% of control values, respectively. Castrated adult rats receiving testosterone at a concentration of 1.66 +/- 0.37 ng/ml plasma maintained normal ventral prostate weight and gene expression levels.

  13. Adrenal-derived 11-Oxygenated 19-Carbon Steroids are the Dominant Androgens in Classic 21-Hydroxylase Deficiency

    PubMed Central

    Turcu, Adina F.; Nanba, Aya T.; Chomic, Robert; Upadhyay, Sunil K.; Giordano, Thomas J.; Shields, James J.; Merke, Deborah P.; Rainey, William E.; Auchus, Richard J.

    2016-01-01

    Objective To comprehensively characterize androgens and androgen precursors in classic 21-hydroxylase deficiency (21OHD) and to gain insight to the mechanisms of their formation. Design Serum samples were obtained from 38 patients (19 men) with classic 21OHD, age 3-59, and 38 sex- and age-matched controls; 3 patients with 11β-hydroxylase deficiency; 4 patients with adrenal insufficiency; and 16 patients (8 men) undergoing adrenal vein sampling. Paraffin-embedded normal (n=5) and 21OHD adrenal tissue (n=3) was used for immunohistochemical studies. Methods We measured 11 steroids in all sera using liquid chromatography-tandem mass spectrometry. Immunofluroescence localized 3β-hydroxysteroid dehydrogenase type 2 (HSD3B2) and cytochrome b5 (CYB5A) within the normal and 21OHD adrenals. Results Four 11-oxygenated 19-carbon (11oxC19) steroids were significantly higher in male and female 21OHD patients than in controls: 11β-hydroxyandrostenedione, 11-ketoandrostenedione 11β-hydroxytestosterone, and 11-ketotestosterone (3-4-fold, p< 0.0001). For 21OHD patients, testosterone and 11-ketotestosterone were positively correlated in females, but inversely correlated in males. All 11oxC19 steroids were higher in adrenal vein than in inferior vena cava samples from men and women and rose with cosyntropin stimulation. Only trace amounts of 11oxC19 steroids were found in sera from patients with 11β-hydroxylase deficiency and adrenal insufficiency, confirming their adrenal origin. HSD3B2 and CYB5A immunoreactivities were sharply segregated in the normal adrenal glands, whereas areas of overlapping expression were identified in the 21OHD adrenals. Conclusions All four 11oxC19 steroids are elevated in both men and women with classic 21OHD. Our data suggest that 11oxC19 steroids are specific biomarkers of adrenal-derived androgen excess. PMID:26865584

  14. [Adrenalitis].

    PubMed

    Saeger, W

    2016-05-01

    Inflammation of the adrenal glands is caused by autoimmunopathies or infections and can induce adrenal insufficiency. Autoimmune lymphocytic adrenalitis is often combined with other autoimmune diseases and the most frequent cause of Addison's disease; however, it only becomes clinically apparent when more than 90 % of the adrenal cortex has been destroyed. Histological features are characterized by lymphoplasmacytic inflammation leading to an increased destruction of adrenocortical tissue but less severe courses can also occur. The second most frequent form of adrenalitis is adrenal tuberculosis, showing typical granulomatous findings that are nearly always caused by spreading from a tuberculous pulmonary focus. Other bacterial as well as viral infections, such as Epstein-Barr virus (EBV), cytomegalovirus (CMV) and others, generally affect the adrenal glands only in patients with immunodeficiency disorders. In these infections, the adrenal cortex and medulla are frequently involved to roughly the same extent. Although surgical specimens from inflammatory adrenal lesions are extremely rare, the various forms of adrenalitis play an important role in the post-mortem examination of the adrenal glands for clarification of unclear causes of death (e.g. death during an Addisonian crisis). PMID:27099224

  15. Linking Prenatal Androgens to Gender-Related Attitudes, Identity, and Activities: Evidence From Girls With Congenital Adrenal Hyperplasia.

    PubMed

    Endendijk, Joyce J; Beltz, Adriene M; McHale, Susan M; Bryk, Kristina; Berenbaum, Sheri A

    2016-10-01

    Key questions for developmentalists concern the origins of gender attitudes and their implications for behavior. We examined whether prenatal androgen exposure was related to gender attitudes, and whether and how the links between attitudes and gendered activity interest and participation were mediated by gender identity and moderated by hormones. Gender attitudes (i.e., gender-role attitudes and attitudes about being a girl), gender identity, and gender-typed activities were reported by 54 girls aged 10-13 years varying in degree of prenatal androgen exposure, including 40 girls with classical congenital adrenal hyperplasia (C-CAH) exposed to high prenatal androgens and 14 girls with non-classical (NC) CAH exposed to low, female-typical, prenatal androgens. Both girls with C-CAH and NC-CAH reported positive attitudes about being a girl and egalitarian gender attitudes, consistent with their female-typical gender identity. In contrast, girls with C-CAH had more male-typed activity interest and participation than girls with NC-CAH. Gender attitudes were linked to activities in both groups, with gender identity mediating the links. Specifically, gender-role attitudes and positive attitudes about being a girl were associated with feminine gender identity, which in turn was associated with decreased male-typed activity interests and participation, and increased female-typed activity interests. Our results are consistent with schema theories, with attitudes more closely associated with gender identity than with prenatal androgens. PMID:26940967

  16. High 17-hydroxyprogesterone level in newborn screening test for congenital adrenal hyperplasia.

    PubMed

    Levy-Shraga, Yael; Pinhas-Hamiel, Orit

    2016-01-01

    We report a case of a female infant with an elevated 17-hydroxyprogesterone level detected in the newborn screening for 21-hydroxylase deficiency, the most common cause of congenital adrenal hyperplasia. The physical examination was unremarkable including no dysmorphism and no signs of virilisation. In the absence of clinical evidence of androgen excess, as would be expected in a female infant with 21-hydroxylase deficiency, further evaluation was performed and led to the diagnosis of the extremely rare disorder, 3β-hydroxysteroid dehydrogenase deficiency. This case highlights the differential diagnosis of elevated 17-hydroxyprogesterone levels in newborn screening and the importance of correct diagnosis for improving patient care. PMID:26912766

  17. Social modulation of androgen levels in male teleost fish.

    PubMed

    Oliveira, Rui F; Hirschenhauser, Katharina; Carneiro, Luis A; Canario, Adelino V M

    2002-05-01

    Androgens are classically thought of as the sex steroids controlling male reproduction. However, in recent years evidence has accumulated showing that androgens can also be affected by the interactions between conspecifics, suggesting reciprocal interactions between androgens and behaviour. These results have been interpreted as an adaptation for individuals to adjust their agonistic motivation and to cope with changes in their social environment. Thus, male-male interactions would stimulate the production of androgens, and the levels of androgens would be a function of the stability of its social environment ['challenge hypothesis', Gen. Comp. Endocrinol. 56 (1984) 417]. Here the available data on social modulation of androgen levels in male teleosts are reviewed and some predictions of the challenge hypothesis are addressed using teleosts as a study model. We investigate the causal link between social status, territoriality and elevated androgen levels and the available evidence suggests that the social environment indeed modulates the endocrine axis of teleosts. The association between higher androgen levels and social rank emerges mainly in periods of social instability. As reported in the avian literature, in teleosts the trade-off between androgens and parental care is indicated by the fact that during the parental phase breeding males decreased their androgen levels. A comparison of androgen responsiveness between teleost species with different mating and parenting systems also reveals that parenting explains the variation observed in androgen responsiveness to a higher degree than the mating strategy. Finally, the adaptive value of social modulation of androgens and some of its evolutionary consequences are discussed. PMID:11997222

  18. Androgen levels and female social dominance in Lemur catta.

    PubMed

    von Engelhardt, N; Kappeler, P M; Heistermann, M

    2000-08-01

    Morphological and behavioural traits which improve agonistic power are subject to intrasexual selection and, at the proximate level, are influenced by circulating androgens. Because intrasexual selection in mammals is more intense among males, they typically dominate females. Female social dominance is therefore unexpected and, indeed, rare. Ring-tailed lemurs (Lemur catta) are sexually monomorphic primates in which all adult females dominate all males. The goal of our study was to test the prediction that female dominance in this species is associated with high androgen levels. Using two captive groups, we collected data on agonistic behaviour and non-invasively assessed their androgen concentrations in faeces and saliva by enzyme immunoassay. We found that adult female L. catta do not have higher androgen levels than males. However, during the mating season there was a twofold increase in both the androgen levels and conflict rates among females. This seasonal increase in their androgen levels was probably not due to a general increase in ovarian hormone production because those females showing the strongest signs of follicular development tended to have low androgen concentrations. At the individual level neither the individual aggression rates nor the proportion of same-sexed individuals dominated were correlated with their androgen levels. We conclude that female dominance in ring-tailed lemurs is neither based on physical superiority nor on high androgen levels and that it is equally important to study male subordination and prenatal brain priming effects for a complete understanding of this phenomenon. PMID:11007329

  19. Perturbations of hypothalamic-pituitary-gonadal (HPG) axis and adrenal androgen (AA) functions in rheumatoid arthritis.

    PubMed

    Masi, A T; Da Silva, J A; Cutolo, M

    1996-05-01

    The available evidence reviewed does not allow definitive response to the question of a primary versus secondary role of sex hormone perturbations in RA. However, this conclusion should not be discouraging in view of the relatively recent focus upon this facet of the physiopathogenesis of RA and the enormous complexities of sex hormone biology and this disease. Specifically, data on the incidence of RA as well as life cycle changes in serum androgenic-anabolic (A-A) and sex hormone levels suggest important risk correlations. Furthermore, HLA-susceptibility markers for RA, gender, menopause and older age are all factors which significantly relate to the risk of developing RA and each has been shown to associate with sex hormone status. Whether or not HPG-AA hormonal status may modulate RA risk (or its course) primarily and independently or merely be predictive markers of other biological mechanisms was critically considered and requires further study. Sex hormone influences on cellular and humoral immunological reactivity and vascular pathogenetic mechanisms in RA were summarized. Androgens generally suppress immunoreactivity and cartilage responses to inflammation-mediated injury processes and may enhance synovial macrophage-like lining cell apoptosis. Oestrogens generally enhance immunoreactivity, offer some protection to inflammation-mediated cartilage damage (but less than androgens) and may inhibit apoptosis in certain in vitro cell models. Scant information is available on the balance of sex hormones (and glucocorticoids) in RA or its presumed pathogenetic mechanisms. Data were reviewed which support the concept of a spectrum of androgenicity in the normal population, particularly among women. A simplified schema of trophic and tropic steroidogenic mechanisms was proposed which could influence androgenic-anabolic (A-A) status and might relate to RA. Serum concentrations of DHAS (mumol/l), T (nmol/l) and O2 (pmol/l) span several orders of magnitude in normal

  20. Early Hormonal Influences on Cognitive Functioning in Congenital Adrenal Hyperplasia.

    ERIC Educational Resources Information Center

    Resnick, Susan M.; And Others

    1986-01-01

    Reports the results of cognitive test performance and early childhood activities in individuals with congenital adrenal hyperplasia, an autosomal recessive disorder associated with elevated prenatal adrenal androgen levels, demonstrating the effects of early exposure to excess androgenizing hormones on sexually dimorphic cognitive functioning.…

  1. Concentrations of the adrenocorticotropic hormone, corticosterone and sex steroid hormones and the expression of the androgen receptor in the pituitary and adrenal glands of male turkeys (Meleagris gallopavo) during growth and development.

    PubMed

    Kiezun, J; Kaminska, B; Jankowski, J; Dusza, L

    2015-01-01

    Androgens take part in the regulation of puberty and promote growth and development. They play their biological role by binding to a specific androgen receptor (AR). The aim of this study was to evaluate the expression of AR mRNA and protein in the pituitary and adrenal glands, to localize AR protein in luteinizing hormone (LH)-producing pituitary and adrenocortical cells, to determine plasma concentrations of adrenocorticotropic hormone (ACTH) and corticosterone and the concentrations of corticosterone, testosterone (T), androstenedione (A4) and oestradiol (E2) in the adrenal glands of male turkeys at the age of 4, 8, 12, 16, 20, 24 and 28weeks. The concentrations of hormones and the expression of AR varied during development. The expression of AR mRNA and protein in pituitary increased during the growth. The increase of AR mRNA levels in pituitary occurred earlier than increase of AR protein. The percentage of pituitary cells expressing ARs in the population of LH-secreting cells increased in week 20. It suggests that AR expression in LH-producing pituitary cells is determined by the phase of development. The drop in adrenal AR mRNA and protein expression was accompanied by an increase in the concentrations of adrenal androgens. Those results could point to the presence of a compensatory mechanism that enables turkeys to avoid the potentially detrimental effects of high androgen concentrations. Our results will expand our knowledge of the role of steroids in the development of the reproductive system of turkeys from the first month of age until maturity. PMID:25776460

  2. Serum estrogen and androgen levels following treatment for cervical cancer.

    PubMed

    Inskip, P D; Eby, N L; Cookfair, D; Freedman, R S; Richardson, G S; Wactawski-Wende, J; Hoover, R N; Boice, J D

    1994-01-01

    Endogenous sex hormones seem to influence the risk of several common and debilitating diseases. With a view toward better understanding the effects of surgical removal of the ovaries and high-dose pelvic radiotherapy on plasma sex hormone levels, we measured estrogen and androgen concentrations cross-sectionally among 147 women who had been treated for cervical cancer 0.3-18.5 years previously. Pelvic radiotherapy (mean dose to ovaries, 50 Gy) and bilateral ovariectomy were associated with similarly reduced hormone concentrations relative to levels among nonirradiated women with intact ovaries, most of whom had had early-stage disease and were treated by hysterectomy. There was little evidence that radiotherapy in addition to ovariectomy further lowered concentrations below levels associated with ovariectomy alone, such as might be expected if radiation was suppressing adrenal endocrine function. Among women age 50 years or older at the time of blood drawing, the removal or irradiation of the ovaries was associated with approximately 45% lower concentrations of estradiol (mean ratio [MR], 0.55; 95% confidence interval [CI], 0.32-0.95) and testosterone (MR, 0.57; 95% CI, 0.32-0.99), and 25-30% lower concentrations of estrone (MR, 0.69; 95% CI, 0.44-1.09) and androstenedione (MR, 0.76; 95% CI, 0.47-1.23), relative to the hysterectomy-only group. Among women younger than 50, ovariectomy and radiotherapy, alone or in combination, were associated with 83% lower estradiol concentrations (MR, 0.17; 95% CI, 0.09-0.31), 46% lower estrone concentrations (MR, 0.54; 95% CI, 0.37-0.81), 23% lower androstenedione concentrations (MR, 0.77; 95% CI, 0.57-1.04), and 14% lower testosterone levels (MR, 0.86; 95% CI, 0.64-1.15).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8118384

  3. Is androgen production in association with immune system activation potential evidence for existence of a functional adrenal/ovarian autoimmune system in women?

    PubMed Central

    2013-01-01

    Background Low functional ovarian reserve (FOR) is at all ages associated with low testosterone (T) levels. Causes are, however, unknown. We, therefore, investigate whether androgens with low FOR are associated with non-specific immune system activation. Methods 322 infertile women with low and normal FOR (controls) were assessed with a broadly based immune profile, which in previous studies has proven effective in differentiating infertile patients with and without immune system activation. Patients were either immune-positive (greater than or equal to one positive tested parameter) or immune negative (no positive test). 135 suffered from prematurely diminished FOR (POA/OPOI; < age 38), 155 from physiologic diminished FOR due to age (DOR; > age 40), and 32 were controls (< age 38 with normal age-specific FOR). Prevalence of immune-positive vs. negative was assessed in all 3 patient groups. Results Women with immune abnormalities, overall, demonstrated higher total T (TT, P = 0.004) and free T (FT, P < 0.001) levels than those without. The three clinical and two immunologic-defined patient groups demonstrated significant statistical interaction in mean TT (P = 0.008), with mean TT and FT in women with positive immune findings being significantly higher in control than in POA/OPOI and physiologic DOR patients (all 4 differences P < 0.001). No such differences between the three groups were seen in women without immune abnormalities. Conclusions In this study we used a definition of immune-positivity, which favors sensitivity over specificity, resulting in significant numbers of false-positives but likely only few false-negatives. The study allows suggesting the possibility of an immune system-derived androgen-production factor (APF), which maintains normal androgen levels but is deficient in women with low FOR and immune system inactivity. Existence of such an APF would suggest the presence of a still unknown functional adrenal autoimmune system

  4. Vocal cues to male androgen levels in giant pandas.

    PubMed

    Charlton, Benjamin D; Keating, Jennifer L; Kersey, David; Rengui, Li; Huang, Yan; Swaisgood, Ronald R

    2011-02-23

    Little is known about the potential of non-human mammal vocalizations to signal information on the hormonal status of the caller. In the current study, we used endocrine data and acoustic analyses to determine whether male giant panda bleats provide reliable information about the caller's current androgen levels. Our results revealed significant relationships between acoustic features of male giant panda bleats and the caller's faecal androgen metabolite concentrations. To our knowledge, this constitutes the first demonstration that the acoustic structure of a non-human mammal call has the potential to yield information about the caller's current androgen levels. We go on to discuss the anatomical basis for our findings and the potential functional relevance of signalling information on male androgen levels in giant panda sexual communication. PMID:20810426

  5. Blood androgen levels in male baboons throughout the year

    SciTech Connect

    Taranov, A.G.; Goncharov, N.P.

    1986-04-01

    This paper describes a study of possible dependence of the androgen level in male baboons on the time of year. Plasma was obtained by centrifugation of the blood at 3000 rpm and the following androgens were determined by radioimmunoassay, using chromatographic separation of the steroids on columns with celite: testosterone, 5s-dihydrotestosterone, and dehydroepiandrosterone. Plasma steriod concentrations were calculated and the results were subjected to statistical analysis by Students test. Seasonal change in the concentration of steroids in the animals' blood plasma were discovered. The results of androgen assay throughout the year and determination of their mean annual concentrations are shown.

  6. Androgens.

    PubMed

    Iyer, Rakesh; Handelsman, David J

    2016-01-01

    Androgen abuse is the most potent and prevalent form of sports doping detected. It originated from the early years of the Cold War as an epidemic confined to drug cheating within elite power sports. In the decades following the end of the Cold War, it has become disseminated into an endemic based within the illicit drug subcultures serving recreational abusers seeking cosmetic body sculpting effects. Within sports, both direct androgen abuse (administration of androgens), as well as indirect androgen abuse (administration of nonandrogenic drugs to increase endogenous testosterone), is mostly readily detectable with mass spectrometry-based anti-doping urine tests. The ongoing temptation of fame and fortune and the effectiveness of androgen abuse in power sports continue to entice cheating via renewed approaches aiming to exploit androgens. These require ongoing vigilance, inventiveness in anti-doping science, and targeting coaches as well as athletes in order to build resilience against doping and maintain fairness in elite sport. The challenge of androgen abuse in the community among recreational abusers has barely been recognized and effective approaches remain to be developed. PMID:27347677

  7. Spatial function in adolescents and young adults with congenital adrenal hyperplasia: clinical phenotype and implications for the androgen hypothesis.

    PubMed

    Hampson, Elizabeth; Rovet, Joanne F

    2015-04-01

    Females with the classic form of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency are said to perform better than unaffected female controls on tests of mental rotation or other visuospatial abilities, but findings are conflicting. We studied 31 adolescents and young adults with CAH and 19 unaffected sibling controls, who were given standardized spatial tests and tests of other sexually differentiated cognitive functions (verbal fluency, perceptual speed). The possible role of CAH subtype (salt-wasting or simple-virilizing) was evaluated. Only females with the more severe, salt-wasting form of CAH, but not females with the simple-virilizing form, performed significantly better than sex-matched sibling controls on measures of mental rotation. Subtype differences were not significant for verbal fluency or perceptual speed. Severity of prenatal genital virilization, but not postnatal age when medication was started, predicted accuracy on the Mental Rotations Test. Results are consistent with the possibility of an organizational effect of androgens in the central nervous system that impacts the development of spatial abilities. Implications for the timing of the hypothetical critical period are discussed. PMID:25686803

  8. Effects on gender identity of prenatal androgens and genital appearance: evidence from girls with congenital adrenal hyperplasia.

    PubMed

    Berenbaum, Sheri A; Bailey, J Michael

    2003-03-01

    To address questions about sex assignment in children with ambiguous genitalia, we studied gender identity in girls with congenital adrenal hyperplasia (CAH) in relation to characteristics of the disease and treatment, particularly genital appearance and surgery. A 9-item gender identity interview was administered to 43 girls with classical CAH ranging in age from 3-18 yr, 7 tomboys, and 29 sister control girls. Groups were compared on total score and on individual items. Results showed that, on the total gender identity score, 88% of girls with CAH had scores overlapping those of control girls, but the average score was intermediate between control girls and tomboys. On individual items of gender identity (discomfort as a girl, wish to be a boy), girls with CAH were similar to control girls. Gender identity in girls with CAH was not related to degree of genital virilization or age at which genital reconstructive surgery was done. Thus, moderate androgen excess early in development appears to produce a small increase in the risk of atypical gender identity, but this risk cannot be predicted from genital virilization. PMID:12629091

  9. Ovarian overproduction of androgens

    MedlinePlus

    ... syndrome (PCOS) can both cause too much androgen production. Cushing's disease is a problem with the pituitary ... the adrenal glands can also cause too much production of androgens and can lead to male body ...

  10. Leptin and androgens in male obesity: evidence for leptin contribution to reduced androgen levels.

    PubMed

    Isidori, A M; Caprio, M; Strollo, F; Moretti, C; Frajese, G; Isidori, A; Fabbri, A

    1999-10-01

    Leptin circulates in plasma at concentrations that parallel the amount of fat reserves. In obese males, androgen levels decline in proportion to the degree of obesity. Recently, we have shown that in rodent Leydig cells leptin inhibits hCG-stimulated testosterone (T) production via a functional leptin receptor isoform; others have found that leptin inhibits basal and hCG-induced T secretion by testis from adult rats. In this study, we further investigated the relationship linking leptin and androgens in men. Basal and hCG-stimulated leptin and sex hormone levels were studied in a large group of men ranging from normal weight to very obese (body mass index, 21.8-55.7). Initial cross-sectional studies showed that circulating leptin and fat mass (FM) were inversely related with total and free T (r = -0.51 and r = -0.38, P < 0.01 and P < 0.05, respectively). Multiple regression analysis indicated that the correlation between leptin or FM and T was not lost after controlling for SHBG and/or LH and/or estradiol (E2) levels and that leptin was the best hormonal predictor of the lower androgen levels in obesity. Dynamic studies showed that in obese men the area under the curve of T and free T to LH/hCG stimulation (5000 IU i.m.) was 30-40% lower than in controls and inversely correlated with leptin levels (r = -0.45 and r = -0.40, P < 0.01 and P < 0.05, respectively). Also, LH/hCG-stimulation caused higher increases in 17-OH-progesterone to T ratio in obese men than in controls, whereas no differences were observed between groups either in stimulated E2 levels or in the E2/T ratio. In all subjects, the percentage increases from baseline in the 17-OH-progesterone to T ratio were directly correlated with leptin levels or FM (r = 0.40 and r = 0.45, P < 0.01), but not with E2 or other hormonal variables. In conclusion, our studies, together with previous in vitro findings, indicate that excess of circulating leptin may be an important contributor to the development of reduced

  11. Cortisol levels in central adrenal insufficiency: light and shade.

    PubMed

    De Sanctis, Vincenzo; Soliman, Ashraf; Yassin, Mohamed; Garofalo, Piernicola

    2015-03-01

    Evaluating children or adolescents with central adrenal insufficiency (CAI) is a difficult task in clinical practice, especially in subjects with hypothalamic-pituitary diseases and partial ACTH deficiency, or in those with recent pituitary surgery or brain irradiation when the adrenal cortex may still be responsive to stress. In 2008, a meta-analysis reported a three-step approach for evaluating patients at risk for CAI with no acute illness. In particular, the authors recommended the evaluation of morning cortisol, a low dose ACTH test (LDST) and the "gold standard" insulin tolerance test or metyrapone test if the low LDCT was not diagnostic. Cortisol and ACTH secretion exhibit significant fluctuation throughout the day. The reference ranges supplied by labs are so wide that they only flag up extremely low cortisol levels. Interpreting the results correctly can be difficult for a physician without an experience in adrenal dysfunctions. The lack of uniformity in these cut-off levels could in part be attributed to differences in study populations, variability of dynainic tests, the use of different serum cortisol assays and dissimilar cut-off peak serum cortisol response indicative of a normal axis response and the difference in the clinical context in which the studies were done. Therefore, Laboratories have to advertise the need to establish reference values for given populations, both for basal or stimulated hormone levels. Failure to apply this rule may elicit false-positive and more critically, false-negative results. LDST (1 pg synthetic ACTH as iv bolus with measurement of serum cortisol) has been proposed as a sensitive test for the diagnosis of CAl. However, the advantage of LDST compared with the high dose test may be offset by the technical difficulties inherent to dilution of 250 pg ampoules. Clinical judgment remains imperative especially regarding the use of glucocorticoid supplementation during extreme stress. PMID:25962205

  12. CT mapping of the vertebral level of right adrenal vein

    PubMed Central

    Degenhart, Christoph; Strube, Hanna; Betz, Matthias J.; Pallauf, Anna; Bidlingmaier, Martin; Fischer, Evelyn; Reincke, Martin; Reiser, Maximilian F.; Wirth, Stefan

    2015-01-01

    PURPOSE We aimed to evaluate the accuracy of multidetector computed tomography (MDCT) venous mapping for the localization of the right adrenal veins (RAV) in patients suffering from primary aldosteronism. METHODS MDCT scans of 75 patients with primary aldosteronism between March 2008 and November 2011 were evaluated by two readers (a junior [R1] and a senior [R2] radiologist) according to the following criteria: quality of RAV depiction (scale, 1–5), localization of the RAV confluence with regard to the inferior vena cava, and depiction of anatomical variants. Results were compared with RAV venograms obtained during adrenal vein sampling and corroborated by laboratory testing of cortisol in selective RAV blood samples. Kappa statistics were calculated for interobserver agreement and for concordance of MDCT mapping with the gold standard. RESULTS Successful RAV sampling was achieved in 69 of 75 patients (92%). Using MDCT mapping, adrenal veins could be visualized in 78% (R1, 54/69) and 77% (R2, 53/69) of patients. MDCT mapping led to correct identification of RAV in 70% (R1, 48/69) and 88% (R2, 61/69) of patients. Venograms revealed five cases of anatomical variants, which were correctly identified in 60% (R1, R2). MDCT-based localizations were false or misleading in 16% (R1, 11/69) and 7% (R2, 5/69) of cases. CONCLUSION Preinterventional MDCT mapping may facilitate successful catheterization in adrenal vein sampling. PMID:25430527

  13. Adrenal steroidogenesis and congenital adrenal hyperplasia.

    PubMed

    Turcu, Adina F; Auchus, Richard J

    2015-06-01

    Adrenal steroidogenesis is a dynamic process, reliant on de novo synthesis from cholesterol, under the stimulation of ACTH and other regulators. The syntheses of mineralocorticoids (primarily aldosterone), glucocorticoids (primarily cortisol), and adrenal androgens (primarily dehydroepiandrosterone and its sulfate) occur in separate adrenal cortical zones, each expressing specific enzymes. Congenital adrenal hyperplasia (CAH) encompasses a group of autosomal-recessive enzymatic defects in cortisol biosynthesis. 21-Hydroxylase (21OHD) deficiency accounts for more than 90% of CAH cases and, when milder or nonclassic forms are included, 21OHD is one of the most common genetic diseases. PMID:26038201

  14. Adrenal Steroidogenesis and Congenital Adrenal Hyperplasia

    PubMed Central

    Turcu, Adina F.; Auchus, Richard J.

    2015-01-01

    Synopsis Adrenal steroidogenesis is a dynamic process, reliant on de novo synthesis from cholesterol, under the stimulation of ACTH and other regulators. The syntheses of mineralocorticoids, glucocorticoids and adrenal androgens occur in separate adrenal cortical zones, each expressing specific enzymes. Congenital adrenal hyperplasia (CAH) encompasses a group of autosomal recessive enzymatic defects in cortisol biosynthesis. 21-hydroxylase (21OHD) deficiency accounts for over 90% of CAH cases and when milder or nonclassic forms are included, 21OHD is one of the most common genetic diseases. This review discusses in detail the epidemiology, genetics, diagnostic, clinical aspects and management of 21OHD. PMID:26038201

  15. Androgen and the Development of Human Sex-Typical Behavior: Rough-and-Tumble Play and Sex of Preferred Playmates in Children with Congenital Adrenal Hyperplasia (CAH).

    ERIC Educational Resources Information Center

    Hines, Melissa; Kaufman, Francine R.

    1994-01-01

    Examined the rough-and-tumble play and gender of preferred playmates in three- to eight-year olds with congenital adrenal hyperplasia (CAH)--hypothesized to masculinize behaviors that show sex differences--and in unaffected three- to eight-year-old relatives. Found that CAH girls did not exhibit increased levels of masculine behavior when compared…

  16. Prenatal Androgens and Gender-Typed Behavior: A Study of Girls with Mild and Severe Forms of Congenital Adrenal Hyperplasia.

    ERIC Educational Resources Information Center

    Servin, Anna; Nordenstrom, Anna; Larsson, Agne; Bohlin, Gunilla

    2003-01-01

    Examined gender-typed behavior and interests in 2- to 10-year-old girls with congenital adrenal hyperplasia (CAH) and in unaffected girls matched for age. Found that, compared with unaffected girls, girls with CAH were more interested in masculine toys and less interested in feminine toys and were more likely to report having male playmates and…

  17. Penguin Chicks Benefit from Elevated Yolk Androgen Levels under Sibling Competition

    PubMed Central

    Poisbleau, Maud; Müller, Wendt; Carslake, David; Demongin, Laurent; Groothuis, Ton G. G.; Van Camp, Jeff; Eens, Marcel

    2012-01-01

    Crested penguins (genus Eudyptes) have a peculiar hatching pattern, with the first-laid egg (A-egg) hatching after the second-laid egg (B-egg) and chicks from A-eggs typically having a much lower survival probability. Maternal yolk androgens have been suggested to contribute to the competitive superiority of the B-chick in southern rockhopper penguins Eudyptes chrysocome, given their important role in mediating sibling competition in other species. We therefore increased the yolk androgen levels in freshly-laid eggs and examined the consequences for sibling competition - via effects on embryonic developmental times, chick growth and early survival. We placed one androgen-treated egg and one control egg into each foster nest, matching them for mass, laying date and laying order. The androgen treatment did not significantly affect embryonic developmental times or chick measurements at hatching. However, elevated yolk androgen levels benefitted chick growth in interaction with the number of siblings in a brood. Chicks from androgen-treated eggs had faster growth in the presence of a sibling than chicks from control eggs. Under these circumstances they also had a higher survival probability. Thus maternal androgens appear to reinforce the observed hatching pattern, facilitating brood reduction. This contrasts to most previous studies in other species where yolk androgens have been shown to compensate for the negative consequences of delayed hatching within the brood hierarchy. PMID:22860073

  18. A role for the androgen metabolite, 5alpha androstane 3beta, 17beta diol (3β-diol) in the regulation of the hypothalamo-pituitary-adrenal axis.

    PubMed

    Handa, Robert J; Sharma, Dharmendra; Uht, Rosalie

    2011-01-01

    Activation of the hypothalamo-pituitary-adrenal (HPA) axis is a basic reaction of animals to environmental perturbations that threaten homeostasis. These responses are ultimately regulated by neurons residing within the paraventricular nucleus (PVN) of the hypothalamus. Within the PVN, corticotrophin-releasing hormone (CRH), vasopressin (AVP), and oxytocin (OT) expressing neurons are critical as they can regulate both neuroendocrine and autonomic responses. Estradiol (E2) and testosterone (T) are well known reproductive hormones; however, they have also been shown to modulate stress reactivity. In rodent models, evidence shows that under some conditions E2 enhances stress activated adrenocorticotropic hormone (ACTH) and corticosterone secretion. In contrast, T decreases the gain of the HPA axis. The modulatory role of testosterone was originally thought to be via 5 alpha reduction to the potent androgen dihydrotestosterone (DHT) and its subsequent binding to the androgen receptor, whereas E2 effects were thought to be mediated by estrogen receptors alpha (ERalpha) and beta (ERbeta). However, DHT has been shown to be metabolized to the ERbeta agonist, 5α- androstane 3β, 17β Diol (3β-Diol). The actions of 3β-Diol on the HPA axis are mediated by ERbeta which inhibits the PVN response to stressors. In gonadectomized rats, ERbeta agonists reduce CORT and ACTH responses to restraint stress, an effect that is also present in wild-type but not ERbeta-knockout mice. The neurobiological mechanisms underlying the ability of ERbeta to alter HPA reactivity are not currently known. CRH, AVP, and OT have all been shown to be regulated by estradiol and recent studies indicate an important role of ERbeta in these regulatory processes. Moreover, activation of the CRH and AVP promoters has been shown to occur by 3β-Diol binding to ERbeta and this is thought to occur through alternate pathways of gene regulation. Based on available data, a novel and important role of 3β-Diol in

  19. A Role for the Androgen Metabolite, 5alpha Androstane 3beta, 17beta Diol (3β-Diol) in the Regulation of the Hypothalamo-Pituitary–Adrenal Axis

    PubMed Central

    Handa, Robert J.; Sharma, Dharmendra; Uht, Rosalie

    2011-01-01

    Activation of the hypothalamo-pituitary–adrenal (HPA) axis is a basic reaction of animals to environmental perturbations that threaten homeostasis. These responses are ultimately regulated by neurons residing within the paraventricular nucleus (PVN) of the hypothalamus. Within the PVN, corticotrophin-releasing hormone (CRH), vasopressin (AVP), and oxytocin (OT) expressing neurons are critical as they can regulate both neuroendocrine and autonomic responses. Estradiol (E2) and testosterone (T) are well known reproductive hormones; however, they have also been shown to modulate stress reactivity. In rodent models, evidence shows that under some conditions E2 enhances stress activated adrenocorticotropic hormone (ACTH) and corticosterone secretion. In contrast, T decreases the gain of the HPA axis. The modulatory role of testosterone was originally thought to be via 5 alpha reduction to the potent androgen dihydrotestosterone (DHT) and its subsequent binding to the androgen receptor, whereas E2 effects were thought to be mediated by estrogen receptors alpha (ERalpha) and beta (ERbeta). However, DHT has been shown to be metabolized to the ERbeta agonist, 5α- androstane 3β, 17β Diol (3β-Diol). The actions of 3β-Diol on the HPA axis are mediated by ERbeta which inhibits the PVN response to stressors. In gonadectomized rats, ERbeta agonists reduce CORT and ACTH responses to restraint stress, an effect that is also present in wild-type but not ERbeta-knockout mice. The neurobiological mechanisms underlying the ability of ERbeta to alter HPA reactivity are not currently known. CRH, AVP, and OT have all been shown to be regulated by estradiol and recent studies indicate an important role of ERbeta in these regulatory processes. Moreover, activation of the CRH and AVP promoters has been shown to occur by 3β-Diol binding to ERbeta and this is thought to occur through alternate pathways of gene regulation. Based on available data, a novel and important role of 3

  20. Steroidogenic enzyme profile in an androgen-secreting adrenocortical oncocytoma associated with hirsustism

    PubMed Central

    Tetsi Nomigni, Milène; Ouzounian, Sophie; Benoit, Alice; Vadrot, Jacqueline; Tissier, Frédérique; Renouf, Sylvie; Lefebvre, Hervé; Christin-Maitre, Sophie; Louiset, Estelle

    2015-01-01

    Hirsutism induced by hyperandrogenism can be associated with polycystic ovary syndrome, 21-hydroxylase (OH) deficiency or androgen-secreting tumors, including ovarian and adrenal tumors. Adrenal androgen-secreting tumors are frequently malignant. Adrenal oncocytomas represent rare causes of hyperandrogenism. The aim of the study was to investigate steroidogenic enzyme expression and steroid secretion in an androgen-secreting adrenal oncocytoma in a young woman presenting with hirsutism. Hyperandrogenism was diagnosed on the basis of elevated plasma Δ4-androstenedione and testosterone levels. Pelvic ultrasound was normal, CT scanning revealed a right adrenal mass. Androgens were assessed in adrenal and ovarian vein samples and proved a right adrenal origin. Adrenalectomy normalized androgen levels and the adrenal tumor was diagnosed as an oncocytoma. Real time-PCR, immunohistochemistry and cell culture studies were performed on tumor explants to investigate the steroid secretion profile. Among enzymes required for cortisol synthesis, 17α-OH and 3β-hydroxysteroid dehydrogenase 2 (3β-HSD2) were highly expressed whereas 21-OH and 11β-OH were weakly produced at the mRNA and/or protein levels. Enzymes involved in testosterone production, 17β-HSD5 and 17β-HSD3, were also detected. ACTH receptor was present in the tissue. Cortisol, Δ4-androstenedione and testosterone secretions by cultured cells were increased by ACTH. These results provide the first demonstration, to our knowledge, of abnormal expression profile of steroidogenic enzymes in an adrenocortical oncocytoma. Our results also indicate that Δ4-androstenedione hypersecretion resulted from high 17α-OH and 3β-HSD2 expression in combination with low expression of 21-OH and 11β-OH. Testosterone production was ascribed to occurrence of 17β-HSD5 and 17β-HSD3. Finally, our results indicate that androgen secretion was stimulated by ACTH. PMID:26034121

  1. Androgen action.

    PubMed

    Werner, Ralf; Holterhus, Paul-Martin

    2014-01-01

    Androgens are important for male sex development and physiology. Their actions are mediated by the androgen receptor (AR), a ligand-dependent nuclear transcription factor. The activity of the AR is controlled at multiple stages due to ligand binding and induced structural changes assisted by the foldosome, compartmentalization, recruitment of coregulators, posttranslational modifications and chromatin remodeling, leading to subsequent transcription of androgen-responsive target genes. Beside these short-term androgen actions, there is phenomenological and experimental evidence of long-term androgen programming in mammals and in the human during sensitive programming time windows, both pre- and postnatally. At the molecular level, research into androgen insensitivity syndrome has unmasked androgen programming at the transcriptome level, in genital fibroblasts and peripheral blood mononuclear cells, and at the epigenome level. Androgens are crucial for male sex development and physiology during embryogenesis, at puberty and in adult life. Testosterone and its more potent metabolite, dihydrotestosterone, which is converted from testosterone within the target cell by 5α-reductase II, are the main androgens involved in male sex differentiation. Androgen action is mediated by a single AR. The AR belongs to the nuclear receptor 3 group C, composed of the glucocorticoid receptor (NR3C1), mineralocorticoid receptor (NR3C2), progesterone receptor (NR3C3) and AR (NR3C4), and acts as a ligand-dependent transcription factor. PMID:25247642

  2. Estrogen Regulation of Fetal Adrenal Cortical Zone-Specific Development in the Nonhuman Primate Impacts Adrenal Production of Androgen and Cortisol and Response to ACTH in Females in Adulthood.

    PubMed

    Pepe, Gerald J; Maniu, Adina; Aberdeen, Graham; Lynch, Terrie J; Albrecht, Eugene D

    2016-05-01

    We showed that the volume of the fetal zone of the fetal adrenal gland and serum dehydroepiandrosterone sulfate (DHAS) levels at term were increased in baboons in which estradiol levels were suppressed by treatment with aromatase inhibitor 4,4-[1,2,3-triazol-1yl-methylene] bis-benzonitrite (letrozole). The fetal zone remodels postnatally into the reticular zone and DHAS production, and serum levels decline with age. Therefore, we determined whether the trajectory of reticular zone DHAS secretion and response to ACTH were altered in offspring deprived of estrogen in utero. Female offspring were delivered to baboons untreated or treated daily throughout the second half of gestation with letrozole (estradiol reduced >95%) or letrozole plus estradiol and cortisol and DHAS determined in blood samples obtained bimonthly between 4 and 125 months and after iv bolus of ACTH. The slope/rate of decline in serum DHAS with advancing age was greater (P < .01) in letrozole-treated (-0.54 ± 0.005) than untreated (-0.32 ± 0.003) baboons and partially restored by letrozole-estradiol (-0.43 ± 0.004). Serum cortisol was similar and relatively constant in all offspring. Moreover, in letrozole-treated offspring, serum DHAS at 61-66, 67-95, and 96-125 months were lower (P < .05), and cortisol to DHAS ratio was greater (P < .05) than in untreated offspring. ACTH at high level increased cortisol and DHAS in untreated baboons and cortisol but not DHAS in letrozole-treated offspring. We propose that postnatal development of the primate adrenal cortex, including the decline in reticular zone DHAS production, response to ACTH and maintenance of cortisol to DHAS ratio with advancing age is modulated by exposure of the fetal adrenal to estradiol. PMID:26990066

  3. Androgen Receptors in a Cichlid Fish, Astatotilapia burtoni: Structure, Localization, and Expression Levels

    PubMed Central

    HARBOTT, LENE K.; BURMEISTER, SABRINA S.; WHITE, RICHARD B.; VAGELL, MIKE; FERNALD, RUSSELL D.

    2009-01-01

    Androgens are an important output of the hypothalamic-pituitary-gonadal (HPG) axis that controls reproduction in all vertebrates. In male teleosts two androgens, testosterone and 11-ketotestosterone, control sexual differentiation and development in juveniles and reproductive behavior in adults. Androgenic signals provide feedback at many levels of the HPG axis, including the hypothalamic neurons that synthesize and release gonadotropin-releasing hormone 1 (GnRH1), but the precise cellular site of androgen action in the brain is not known. Here we describe two androgen receptor subtypes, ARα and ARβ, in the cichlid Astatotilapia burtoni and show that these subtypes are differentially located throughout the adult brain in nuclei known to function in the control of reproduction. ARα was expressed in the ventral part of the ventral telencephalon, the preoptic area (POA) of the hypothalamus and the ventral hypothalamus, whereas ARβ was more widely expressed in the dorsal and ventral telencephalon, the POA, and the ventral and dorsal hypothalamus. We provide the first evidence in any vertebrate that the GnRH1-releasing neurons, which serve as the central control point of the HPG axis, express both subtypes of AR. Using quantitative real-time PCR, we show that A. burtoni AR subtypes have different expression levels in adult tissue, with ARα showing significantly higher expression than ARβ in the pituitary, and ARβ expressed at a higher level than ARα in the anterior and middle brain. These data provide important insight into the role of androgens in regulating the vertebrate reproductive axis. PMID:17614300

  4. The androgen 5alpha-dihydrotestosterone and its metabolite 5alpha-androstan-3beta, 17beta-diol inhibit the hypothalamo-pituitary-adrenal response to stress by acting through estrogen receptor beta-expressing neurons in the hypothalamus.

    PubMed

    Lund, Trent D; Hinds, Laura R; Handa, Robert J

    2006-02-01

    Estrogen receptor beta (ERbeta) and androgen receptor (AR) are found in high levels within populations of neurons in the hypothalamus. To determine whether AR or ERbeta plays a role in regulating hypothalamo-pituitary-adrenal (HPA) axis function by direct action on these neurons, we examined the effects of central implants of 17beta-estradiol (E2), 5alpha-dihydrotestosterone (DHT), the DHT metabolite 5alpha-androstan-3beta, 17beta-diol (3beta-diol), and several ER subtype-selective agonists on the corticosterone and adrenocorticotropin (ACTH) response to immobilization stress. In addition, activation of neurons in the paraventricular nucleus (PVN) was monitored by examining c-fos mRNA expression. Pellets containing these compounds were stereotaxically implanted near the PVN of gonadectomized male rats. Seven days later, animals were killed directly from their home cage (nonstressed) or were restrained for 30 min (stressed) before they were killed. Compared with controls, E2 and the ERalpha-selective agonists moxestrol and propyl-pyrazole-triol significantly increased the stress induced release of corticosterone and ACTH. In contrast, central administration of DHT, 3beta-diol, and the ERbeta-selective compound diarylpropionitrile significantly decreased the corticosterone and ACTH response to immobilization. Cotreatment with the ER antagonist tamoxifen completely blocked the effects of 3beta-diol and partially blocked the effect of DHT, whereas the AR antagonist flutamide had no effect. Moreover, DHT, 3beta-diol, and diarylpropionitrile treatment significantly decreased restraint-induced c-fos mRNA expression in the PVN. Together, these studies indicate that the inhibitory effects of DHT on HPA axis activity may be in part mediated via its conversion to 3beta-diol and subsequent binding to ERbeta. PMID:16452668

  5. Developmental changes in serum androgen levels of Eastern Screech-Owls (Megascops asio)

    USGS Publications Warehouse

    Kozlowski, Corinne P.; Hahn, D. Caldwell

    2010-01-01

    We studied androgen production during development in nestling Eastern Screech-Owls (Megascops asio) and hypothesized that gender and hatch order might influence serum levels of testosterone and androstenedione. Testosterone levels were highest immediately after hatching and declined significantly in the 4 weeks leading to fledging. The average level of testosterone for 1-7 day-old owls was 3.99 - 0.68 ng/ml. At 22-28 days of age, the average testosterone level for nestling owls was 0.83 - 0.18 ng/ml. Testosterone levels did not differ between males or females. The average testosterone level for male nestlings was 2.23 - 0.29 ng/ml and 2.39 - 0.56 ng/ml for female nestlings. The average level of androstenedione for nestling owls was 1.92 - 0.11 ng/ml and levels remained constant throughout development. Levels were significantly higher in males than females. The average androstenedione level was 1.77 - 0.16 ng/ml for male nestlings and 1.05 - 0.24 ng/ml for female nestlings. Hatching order did not affect levels of either androgen. Our results provide a foundation for future studies of androgen production by nestling owls.

  6. TBT-induced imposex in marine neogastropods is mediated by an increasing androgen level

    NASA Astrophysics Data System (ADS)

    Bettin, C.; Oehlmann, J.; Stroben, E.

    1996-09-01

    Tributyltin (TBT) exposure at different concentrations (5, 60, and 100 ng TBT as Sn/l) induces a concentration- and time-dependent imposex (=pseudohermaphroditism) development in female Nucella lapillus and Hinia reticulata. In both species the average imposex stage, termed as vas deferens sequence (VDS) index, and the average female penis length increases with increasing TBT concentration and duration of TBT exposure. Testosterone added at a concentration of 500 ng/l induces a faster and more intensive imposex development compared to that induced by the TBT concentrations used in the present experiments. Radioimmunological determination of endogenous steroid content reveals increasing testosterone titres in female gastropods exposed to TBT which correlate with the TBT concentration used and the duration of the experiment. The most marked and highest increase of the endogenous testosterone level is exhibited by females, of both species exposed to testosterone. Simulataneous exposure to TBT and to the antiandrogen cyproterone acetate which suppresses imposex development completely in N. lapillus and reduces imposex development strongly in H. reticulata proves that the imposex-inducing effects of TBT are mediated by an increasing androgen level and are not caused directly by the organotin compound itself. Further-more, TBT-induced imposex development can be suppressed in both snails by adding estrogens to the aqueous medium. These observations suggest that TBT causes an inhibition of the cytochrome P-450 dependent aromatase system which catalyses the aromatization of androgens to estrogens. The increase of the androgen content or the shift of the androgen-estrogen balance in favour of androgens induces the development of pseudohermaphroditism in marine prosobranchs. Artificial inhibition of the cytochrome P-450 dependent aromatase system using SH 489 (1-methyl-1,4-androstadiene-3,17-dione) as a steroidal aromatase inhibitor and flavone as a nonsteroidal aromatase

  7. Adrenal Insufficiency

    MedlinePlus

    ... What is adrenal insufficiency? Did you know? The adrenal glands, located on top of the kidneys, make hormones ... body functions. The outer layer (cortex) of the adrenal glands makes three types of steroid hormones. In adrenal ...

  8. Increased DHT levels in androgenic alopecia have been selected for to protect men from prostate cancer.

    PubMed

    Bhargava, Shiva

    2014-04-01

    Androgenic alopecia, a condition characterized by increased levels of DHT could have been selected for due to the benefits that prostaglandin D2 (PGD(2)) has on the prostate. A DHT metabolite can increase the transcription of prostaglandin D2 synthase through estrogen receptor beta. The increase of PGD(2) can decrease the risk of prostate cancer and proliferation of prostate cancer cells. Therefore, the mechanisms behind male pattern baldness may also curtail the advancement of prostate cancer. PMID:24548754

  9. Androgen receptor functions in castration-resistant prostate cancer and mechanisms of resistance to new agents targeting the androgen axis

    PubMed Central

    Yuan, X; Cai, C; Chen, S; Chen, S; Yu, Z; Balk, SP

    2016-01-01

    The metabolic functions of androgen receptor (AR) in normal prostate are circumvented in prostate cancer (PCa) to drive tumor growth, and the AR also can acquire new growth-promoting functions during PCa development and progression through genetic and epigenetic mechanisms. Androgen deprivation therapy (ADT, surgical or medical castration) is the standard treatment for metastatic PCa, but patients invariably relapse despite castrate androgen levels (castration-resistant PCa, CRPC). Early studies from many groups had shown that AR was highly expressed and transcriptionally active in CRPC, and indicated that steroids from the adrenal glands were contributing to this AR activity. More recent studies showed that CRPC cells had increased expression of enzymes mediating androgen synthesis from adrenal steroids, and could synthesize androgens de novo from cholesterol. Phase III clinical trials showing a survival advantage in CRPC for treatment with abiraterone (inhibitor of the enzyme CYP17A1 required for androgen synthesis that markedly reduces androgens and precursor steroids) and for enzalutamide (new AR antagonist) have now confirmed that AR activity driven by residual androgens makes a major contribution to CRPC, and led to the recent Food and Drug Administration approval of both agents. Unfortunately, patients treated with these agents for advanced CRPC generally relapse within a year and AR appears to be active in the relapsed tumors, but the molecular mechanisms mediating intrinsic or acquired resistance to these AR-targeted therapies remain to be defined. This review outlines AR functions that contribute to PCa development and progression, the roles of intratumoral androgen synthesis and AR structural alterations in driving AR activity in CRPC, mechanisms of action for abiraterone and enzalutamide, and possible mechanisms of resistance to these agents. PMID:23752196

  10. Serum cortisol level and adrenal reserve as a predictor of patients’ outcome after successful cardiopulmonary resuscitation

    PubMed Central

    Mosaddegh, Reza; Kianmehr, Nahid; Mahshidfar, Babak; Rahmani, Zahra; Aghdam, Hamed; Mofidi, Mani

    2016-01-01

    Introduction: It is thought that pituitary-adrenal axis has a fundamental role in outcome of cardiopulmonary arrest (CPA). This study designed to evaluate the correlation between adrenal reserve and post-resuscitation outcome. Methods: In this clinical trial study, 52 consecutive patients with CPA were enrolled in two emergency departments (EDs) over a 3-month period. Plasma cortisol level was measured at the beginning of CPR. Intravenous adrenocorticotropic hormone (ACTH) stimulation test was carried out after successful CPR, and blood samples were taken at 30 and 60 minutes, and 24 hours thereafter. Patients were divided into two groups: in-hospital death or hospital discharge. Results: In patients who died, baseline and post-ACTH serum cortisol after 30 and 60 minutes and 24 hours were higher than patients who discharged from the hospital, but it was not statistically significant except to that of minute 60 (P=0.49). A model of multivariate logistic regression analysis showed that age and need for vasopressor infusion correlated with mortality. Conclusion: Current study could not show the statistically significant difference in initial and post-ACTH serum cortisol levels between survivor and non-survivor patients with cardiac arrest who had initial successful CPR, except to that of minute 60. PMID:27489598

  11. Association of androgen with gender difference in serum adipocyte fatty acid binding protein levels

    PubMed Central

    Hu, Xiang; Ma, Xiaojing; Pan, Xiaoping; Luo, Yuqi; Xu, Yiting; Xiong, Qin; Bao, Yuqian; Jia, Weiping

    2016-01-01

    Clinical investigations have indicated women have higher levels of adipocyte fatty acid binding protein (A-FABP) than men. The present study aimed to identify factors related to gender difference in serum A-FABP levels. A total of 507 participants (194 men, 132 premenopausal women, and 181 postmenopausal women) were enrolled in the present study. Serum A-FABP levels increased in the order from men to premenopausal women to postmenopausal women in both body mass index categories (<25.0 and ≥25.0 kg/m2; all P < 0.05). Multiple stepwise regression analyses showed that after adjustment for factors related to serum A-FABP levels, the trunk fat mass was an independent and positive factor of serum A-FABP levels. For men, total testosterone was associated independently and inversely with serum A-FABP levels. For pre- and postmenopausal women, bioavailable testosterone and total testosterone were independent and positive factors associated with serum A-FABP levels, respectively. The present study demonstrated that the androgen was correlated with the serum A-FABP levels negatively in men, but positively in women. With these effects on the fat content, especially trunk fat, androgen might contribute to the gender difference in serum A-FABP levels. PMID:27270834

  12. Association of androgen with gender difference in serum adipocyte fatty acid binding protein levels.

    PubMed

    Hu, Xiang; Ma, Xiaojing; Pan, Xiaoping; Luo, Yuqi; Xu, Yiting; Xiong, Qin; Bao, Yuqian; Jia, Weiping

    2016-01-01

    Clinical investigations have indicated women have higher levels of adipocyte fatty acid binding protein (A-FABP) than men. The present study aimed to identify factors related to gender difference in serum A-FABP levels. A total of 507 participants (194 men, 132 premenopausal women, and 181 postmenopausal women) were enrolled in the present study. Serum A-FABP levels increased in the order from men to premenopausal women to postmenopausal women in both body mass index categories (<25.0 and ≥25.0 kg/m(2); all P < 0.05). Multiple stepwise regression analyses showed that after adjustment for factors related to serum A-FABP levels, the trunk fat mass was an independent and positive factor of serum A-FABP levels. For men, total testosterone was associated independently and inversely with serum A-FABP levels. For pre- and postmenopausal women, bioavailable testosterone and total testosterone were independent and positive factors associated with serum A-FABP levels, respectively. The present study demonstrated that the androgen was correlated with the serum A-FABP levels negatively in men, but positively in women. With these effects on the fat content, especially trunk fat, androgen might contribute to the gender difference in serum A-FABP levels. PMID:27270834

  13. Nonclassic Congenital Adrenal Hyperplasia

    PubMed Central

    Witchel, Selma Feldman; Azziz, Ricardo

    2010-01-01

    Nonclassic congenital adrenal hyperplasia (NCAH) due to P450c21 (21-hydroxylase deficiency) is a common autosomal recessive disorder. This disorder is due to mutations in the CYP21A2 gene which is located at chromosome 6p21. The clinical features predominantly reflect androgen excess rather than adrenal insufficiency leading to an ascertainment bias favoring diagnosis in females. Treatment goals include normal linear growth velocity and “on-time” puberty in affected children. For adolescent and adult women, treatment goals include regularization of menses, prevention of progression of hirsutism, and fertility. This paper will review key aspects regarding pathophysiology, diagnosis, and treatment of NCAH. PMID:20671993

  14. The Association between Androgenic Hormone Levels and the Risk of Developing Coronary Artery Disease (CAD)

    PubMed Central

    ALLAMEH, Farzad; POURMAND, Gholamreza; BOZORGI, Ali; NEKUIE, Sepideh; NAMDARI, Farshad

    2016-01-01

    Background: The aim of the study was to evaluate the relationship between the serum levels of androgens and Coronary Artery Disease (CAD) in an Iranian population. Methods: Male individuals admitted to Tehran Heart Center and Sina Hospital, Tehran, Iran from 2011–2012 were categorized into CAD and control groups based on selective coronary angiography. Baseline demographic data, including age, BMI, diabetes, and a history of hypertension were recorded. Patients were also assessed for their serum levels of total testosterone, free testosterone, estradiol, dehydroepi and rosterone sulfate (DHEA-S), and Sex Hormone Binding Globulin (SHBG). Data analysis was carried out chi-square and ANOVA tests as well as logistic regression analysis. Results: Two hundred patients were in the CAD group and 135 individuals in control group. In the CAD group, 69 had single-vessel disease, 49 had two-vessel diseases, and 82 had three-vessel diseases. Statistically significant differences were observed between the individuals in the two groups with respect to age (P<0.0001), diabetes (P<0.0001), and a history of hypertension (P=0.018). The serum levels of free testosterone (P=0.048) and DHEA-S (P<0.0001) were significantly higher in the control group than in the CAD group; however, the serum level of SHBG was higher in the CAD group than in the control group (P=0.007). Results of the logistic regression analysis indicated that only age (P=0.042) and diabetes (P=0.003) had significant relationships with CAD. Conclusion: Although the serum levels of some of the androgens were significantly different between the two groups, no association was found between androgenic hormone levels and the risk of CAD, due mainly to the effect of age and diabetes. PMID:27057516

  15. Dietary copper can regulate the level of mRNA for dopamine B-hydroxylase in rat adrenal gland

    SciTech Connect

    Sabban, E.L.; Failla, M.L.; McMahon, A.; Seidel, K.E. Dept. of Agriculture, Beltsville, MD )

    1991-03-15

    Recent studies have shown that Cu deficiency markedly alters the levels of dopamine (DA) and norepinephrine (NE) in several peripheral tissues of rodents. Conversion of DA to NE is mediated by dopamine B-hydroxylase (DBM). Here the authors examined the effect of dietary Cu deficiency on the levels of DA, NE and DBM mRNA in rat adrenal gland. Severe Cu deficiency was induced by feeding low Cu diet to dams beginning at 17d gestation and weaning pups to the same diet. At 7 wks of age rats fed {minus}Cu diet were characterized by depressed growth, low tissue Cu, enlarged hearts and moderate anemia. Concentrations of DA were higher in adrenals and hearts of {minus}Cu rats compared to +Cu controls. While cardiac level of NE in {minus}Cu rats were reduced to 17% that of controls, adrenal NE was unchanged by Cu deficiency. To investigate possible mechanisms responsible for the response of adrenal gland to Cu deficiency, RNA was isolated and the levels of DBH mRNA and tyrosine hydroxylase (TH) mRNA were analyzed by Northern blots. Steady state levels of adrenal DBH mRNA was increased 2-3 fold in {minus}Cu rats, whereas TH mRNA were unchanged by dietary Cu status. Upon feeding the {minus}Cu rats the Cu adequate diet overnight, there was a further increase in DBH mRNA and a slight elevation of TH mRNA levels. The results indicate that dietary copper can markedly affect the level of DBH mRNA in rat adrenal gland.

  16. Plasma pregnenolone levels in cynomolgus monkeys following pharmacological challenges of the hypothalamic-pituitary-adrenal axis.

    PubMed

    Porcu, Patrizia; Rogers, Laura S M; Morrow, A Leslie; Grant, Kathleen A

    2006-08-01

    Pregnenolone (PREG) is an endogenous neuroactive steroid that is increased in rodent brain and plasma after hypothalamic-pituitary-adrenal (HPA) activation by acute stress or ethanol administration. Plasma levels of PREG metabolites are altered by pharmacological challenges of the HPA axis, however little is known about HPA regulation of PREG levels in monkeys. PREG concentrations were determined by radioimmunoassay in plasma samples from cynomolgus monkeys, following challenge with naloxone (125 and 375 microg/kg), corticotropin-releasing factor (CRF; 1 microg/kg), dexamethasone (130 microg/kg), adrenocorticotropic hormone (ACTH; 10 ng/kg; 4-6 h after 0.5 mg/kg dexamethasone) and ethanol (1.0 and 1.5 g/kg). Naloxone increased PREG levels, while CRF appeared to increase metabolism of PREG to deoxycorticosterone (DOC). ACTH, administered after dexamethasone, reduced PREG levels, despite an increase in plasma cortisol. Ethanol did not alter PREG levels. Changes in PREG levels were correlated with changes in DOC levels after naloxone 125 microg/kg, CRF, ethanol 1.5 g/kg, and dexamethasone challenges. Furthermore, dexamethasone-induced changes in PREG levels were correlated with subsequent alcohol intake. These data suggest that PREG responses to dexamethasone challenge may represent a trait marker of alcohol drinking. The lack of effect of ethanol on PREG levels suggests differential regulation in non-human primates vs. rodents. PMID:16790266

  17. A Comparison of Salivary Steroid Levels during Diagnostic Tests for Adrenal Insufficiency.

    PubMed

    Dušková, Michaela; Šimůnková, Kateřina; Vítků, Jana; Sosvorová, Lucie; Jandíková, Hana; Pospíšilová, Hana; Šrámková, Monika; Kosák, Mikuláš; Kršek, Michal; Hána, Václav; Žánová, Magdaléna; Springer, Drahomíra; Stárka, Luboslav

    2016-01-01

    Numerous diagnostic tests are used to evaluate the hypothalamic-pituitary-adrenal axis (HPA axis). The gold standard is still considered the insulin tolerance test (ITT), but this test has many limitations. Current guidelines therefore recommend the Synacthen test first when an HPA axis insufficiency is suspected. However, the dose of Synacthen that is diagnostically most accurate and sensitive is still a matter of debate. We investigated 15 healthy men with mean/median age 27.4/26 (SD±4.8) years, and mean/median BMI (body mass index) 25.38/24.82 (SD±3.2) kg/m2. All subjects underwent 4 dynamic tests of the HPA axis, specifically 1 μg, 10 μg, and 250 μg Synacthen (ACTH) tests and an ITT. Salivary cortisol, cortisone, pregnenolone, and DHEA (dehydroepiandrosterone) were analysed using liquid chromatography-tandem mass spectrometry. During the ITT maximum salivary cortisol levels over 12.5 nmol/l were found at 60 minutes. Maximum cortisol levels in all of the Synacthen tests were higher than this; however, demonstrating that sufficient stimulation of the adrenal glands was achieved. Cortisone reacted similarly as cortisol, i.e. we did not find any change in the ratio of cortisol to cortisone. Pregnenolone and DHEA were higher during the ITT, and their peaks preceded the cortisol peak. There was no increase of pregnenolone or DHEA in any of the Synacthen tests. We demonstrate that the 10 μg Synacthen dose is sufficient stimulus for testing the HPA axis and is also a safe and cost-effective alternative. This dose also largely eliminates both false negative and false positive results. PMID:26995200

  18. Congenital adrenal hyperplasia: issues in diagnosis and treatment in children.

    PubMed

    Sharma, Rajni; Seth, Anju

    2014-02-01

    Congenital adrenal hyperplasia (CAH) is a common disorder of impaired adrenal cortisol biosynthesis with associated androgen excess. The clinical presentation of 21-hydroxylase deficiency, the commonest cause of CAH, forms a spectrum and can be divided into classic and non-classic types. The former consists of life threatening salt wasting and non-life threatening simple virilizing phenotypes. Patients with the non-classic form are asymptomatic or have mild features of androgen excess. Most developed countries have newborn screening facilities for CAH. In the absence of newborn screening, the diagnosis of CAH may be missed or delayed. This can result in neonatal mortality in salt wasting forms and incorrect sex of rearing in females with simple virilizing form. The diagnosis is reached by demonstrating high serum 17-hydroxyprogesterone (17OHP) levels. Preterm birth and neonatal illness can cause physiological elevation of 17OHP, thus complicating the diagnosis of CAH in the newborn period. Prenatal diagnosis and treatment with dexamethasone to prevent virilization of affected female fetuses is another area of controversy. The management of CAH is complicated by the need to use supraphysiologic doses of glucocorticoids to suppress adrenal androgen synthesis. In this review, the authors address pertinent issues related to the diagnosis and management of CAH in children. PMID:24254335

  19. The Environmental Pollutant Tributyltin Chloride Disrupts the Hypothalamic-Pituitary-Adrenal Axis at Different Levels in Female Rats.

    PubMed

    Merlo, Eduardo; Podratz, Priscila L; Sena, Gabriela C; de Araújo, Julia F P; Lima, Leandro C F; Alves, Izabela S S; Gama-de-Souza, Letícia N; Pelição, Renan; Rodrigues, Lívia C M; Brandão, Poliane A A; Carneiro, Maria T W D; Pires, Rita G W; Martins-Silva, Cristina; Alarcon, Tamara A; Miranda-Alves, Leandro; Silva, Ian V; Graceli, Jones B

    2016-08-01

    Tributyltin chloride (TBT) is an environmental contaminant that is used as a biocide in antifouling paints. TBT has been shown to induce endocrine-disrupting effects. However, studies evaluating the effects of TBT on the hypothalamus-pituitary-adrenal (HPA) axis are especially rare. The current study demonstrates that exposure to TBT is critically responsible for the improper function of the mammalian HPA axis as well as the development of abnormal morphophysiology in the pituitary and adrenal glands. Female rats were treated with TBT, and their HPA axis morphophysiology was assessed. High CRH and low ACTH expression and high plasma corticosterone levels were detected in TBT rats. In addition, TBT leads to an increased in the inducible nitric oxide synthase protein expression in the hypothalamus of TBT rats. Morphophysiological abnormalities, including increases in inflammation, a disrupted cellular redox balance, apoptosis, and collagen deposition in the pituitary and adrenal glands, were observed in TBT rats. Increases in adiposity and peroxisome proliferator-activated receptor-γ protein expression in the adrenal gland were observed in TBT rats. Together, these data provide in vivo evidence that TBT leads to functional dissociation between CRH, ACTH, and costicosterone, which could be associated an inflammation and increased of inducible nitric oxide synthase expression in hypothalamus. Thus, TBT exerts toxic effects at different levels on the HPA axis function. PMID:27267847

  20. Increased androgen levels in rats impair glucose-stimulated insulin secretion through disruption of pancreatic beta cell mitochondrial function.

    PubMed

    Wang, Hongdong; Wang, Xiaping; Zhu, Yunxia; Chen, Fang; Sun, Yujie; Han, Xiao

    2015-11-01

    Although insulin resistance is recognized to contribute to the reproductive and metabolic phenotypes of polycystic ovary syndrome (PCOS), pancreatic beta cell dysfunction plays an essential role in the progression from PCOS to the development of type 2 diabetes. However, the role of insulin secretory abnormalities in PCOS has received little attention. In addition, the precise changes in beta cells and the underlying mechanisms remain unclear. In this study, we therefore attempted to elucidate potential mechanisms involved in beta cell alterations in a rat model of PCOS. Glucose-induced insulin secretion was measured in islets isolated from DHT-treated and control rats. Oxygen consumption rate (OCR), ATP production, and mitochondrial copy number were assayed to evaluate mitochondrial function. Glucose-stimulated insulin secretion is significantly decreased in islets from DHT-treated rats. On the other hand, significant reductions are observed in the expression levels of several key genes involved in mitochondrial biogenesis and in mitochondrial OCR and ATP production in DHT-treated rat islets. Meanwhile, we found that androgens can directly impair beta cell function by inducing mitochondrial dysfunction in vitro in an androgen receptor dependent manner. For the first time, our study demonstrates that increased androgens in female rats can impair glucose-stimulated insulin secretion partly through disruption of pancreatic beta cell mitochondrial function. This work has significance for hyperandrogenic women with PCOS: excess activation of the androgen receptor by androgens may provoke beta cell dysfunction via mitochondrial dysfunction. PMID:26348137

  1. Intra- and interspecific social challenges modulate the levels of an androgen precursor in a seasonally territorial tropical damselfish.

    PubMed

    Damjanovic, Katarina; Glauser, Gaétan; Bshary, Redouan; Ros, Albert F H

    2015-05-01

    Studies on different vertebrate groups have provided evidence that androgen levels in males increase after competitive social interactions during the breeding season, as postulated by the Challenge Hypothesis. However, social modulation of androgen levels may vary with latitude and may differ between species holding seasonal versus year-round territories. Here, we tested the Challenge Hypothesis on a seasonal tropical damselfish, Abudefduf sexfasciatus, where males temporarily defend territory and eggs against both intra- and interspecific individuals. Carrying out simulated territorial intrusions (STIs) in the laboratory, we document for the first time a consistent increase in the plasma level of the androgen precursor 11-ketoandrostenedione (11KA) in fish confronted to either intra- or interspecific challenges. Collecting samples in the field also revealed higher 11KA levels in fish facing frequent territorial interactions than in non-territorial individuals. Levels of 11-ketotestosterone (11KT) were high in territorial males in the field, but were not incremented after simulated territorial intrusions in the laboratory. Plasma levels of cortisol and testosterone were not affected by challenges but were different in wild and captive specimens. Although the endocrine responses to STIs did not differ between intra- and interspecific challenges, agonistic displays expressed by resident fish were more intense towards intraspecific intruders. Taken together, our study emphasizes the need to incorporate androgen precursor concentrations to advance our understanding on the physiology of territorial interactions. PMID:25917864

  2. Management of adolescents with congenital adrenal hyperplasia

    PubMed Central

    Merke, Deborah P; Poppas, Dix P

    2014-01-01

    The management of congenital adrenal hyperplasia involves suppression of adrenal androgen production, in addition to treatment of adrenal insufficiency. Management of adolescents with congenital adrenal hyperplasia is especially challenging because changes in the hormonal milieu during puberty can lead to inadequate suppression of adrenal androgens, psychosocial issues often affect adherence to medical therapy, and sexual function plays a major part in adolescence and young adulthood. For these reasons, treatment regimen reassessment is indicated during adolescence. Patients with non-classic congenital adrenal hyperplasia require reassessment regarding the need for glucocorticoid drug treatment. No clinical trials have compared various regimens for classic congenital adrenal hyperplasia in adults, thus therapy is individualised and based on the prevention of adverse outcomes. Extensive patient education is key during transition from paediatric care to adult care and should include education of females with classic congenital adrenal hyperplasia regarding their genital anatomy and surgical history. Common issues for these patients include urinary incontinence, vaginal stenosis, clitoral pain, and cosmetic concerns; for males with classic congenital adrenal hyperplasia, common issues include testicular adrenal rest tumours. Transition from paediatric to adult care is most successful when phased over many years. Education of health-care providers on how to successfully transition patients is greatly needed. PMID:24622419

  3. Adrenal glands

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/002219.htm Adrenal glands To use the sharing features on this page, please enable JavaScript. The adrenal glands are two triangle-shaped glands. One gland is ...

  4. Antiandrogens Act as Selective Androgen Receptor Modulators at the Proteome Level in Prostate Cancer Cells*

    PubMed Central

    Brooke, Greg N.; Gamble, Simon C.; Hough, Michael A.; Begum, Shajna; Dart, D. Alwyn; Odontiadis, Michael; Powell, Sue M.; Fioretti, Flavia M.; Bryan, Rosie A.; Waxman, Jonathan; Wait, Robin; Bevan, Charlotte L.

    2015-01-01

    Current therapies for prostate cancer include antiandrogens, inhibitory ligands of the androgen receptor, which repress androgen-stimulated growth. These include the selective androgen receptor modulators cyproterone acetate and hydroxyflutamide and the complete antagonist bicalutamide. Their activity is partly dictated by the presence of androgen receptor mutations, which are commonly detected in patients who relapse while receiving antiandrogens, i.e. in castrate-resistant prostate cancer. To characterize the early proteomic response to these antiandrogens we used the LNCaP prostate cancer cell line, which harbors the androgen receptor mutation most commonly detected in castrate-resistant tumors (T877A), analyzing alterations in the proteome, and comparing these to the effect of these therapeutics upon androgen receptor activity and cell proliferation. The majority are regulated post-transcriptionally, possibly via nongenomic androgen receptor signaling. Differences detected between the exposure groups demonstrate subtle changes in the biological response to each specific ligand, suggesting a spectrum of agonistic and antagonistic effects dependent on the ligand used. Analysis of the crystal structures of the AR in the presence of cyproterone acetate, hydroxyflutamide, and DHT identified important differences in the orientation of key residues located in the AF-2 and BF-3 protein interaction surfaces. This further implies that although there is commonality in the growth responses between androgens and those antiandrogens that stimulate growth in the presence of a mutation, there may also be influential differences in the growth pathways stimulated by the different ligands. This therefore has implications for prostate cancer treatment because tumors may respond differently dependent upon which mutation is present and which ligand is activating growth, also for the design of selective androgen receptor modulators, which aim to elicit differential proteomic

  5. Sex-specific chronic stress response at the level of adrenal gland modifies sexual hormone and leptin receptors

    PubMed Central

    Balog, Marta; Miljanović, Milan; Blažetić, Senka; Labak, Irena; Ivić, Vedrana; Viljetić, Barbara; Borbely, Attila; Papp, Zoltán; Blažeković, Robert; Vari, Sandor G.; Fagyas, Miklós; Heffer, Marija

    2015-01-01

    Aim To compare cardiometabolic risk-related biochemical markers and sexual hormone and leptin receptors in the adrenal gland of rat males, non-ovariectomized females (NON-OVX), and ovariectomized females (OVX) under chronic stress. Methods Forty six 16-week-old Sprague-Dawley rats were divided into male, NON-OVX, and OVX group and exposed to chronic stress or kept as controls. Weight, glucose tolerance test (GTT), serum concentration of glucose, and cholesterol were measured. Adrenal glands were collected at the age of 28 weeks and immunohistochemical staining against estrogen beta (ERβ), progesterone (PR), testosterone (AR), and leptin (Ob-R) receptors was performed. Results Body weight, GTT, serum cholesterol, and glucose changed in response to stress as expected and validated the applied stress protocol. Stressed males had significantly higher number of ERβ receptors in comparison to control group (P = 0.028). Stressed NON-OVX group had significantly decreased AR in comparison to control group (P = 0.007). The levels of PR did not change in any consistent pattern. The levels of Ob-R increased upon stress in all groups, but the significant difference was reached only in the case of stressed OVX group compared to control (P = 0.033). Conclusion Chronic stress response was sex specific. OVX females had similar biochemical parameters as males. Changes upon chronic stress in adrenal gland were related to a decrease in testosterone receptor in females and increase in estrogen receptor in males. PMID:25891869

  6. Congenital adrenal hyperplasia

    PubMed Central

    Dessinioti, Cleo; Katsambas, Andreas

    2009-01-01

    Congenital adrenal hyperplasia consists of a heterogenous group of inherited disorders due to enzymatic defects in the biosynthetic pathway of cortisol and/or aldosterone. This results in glucocorticoid deficiency, mineralocorticoid deficiency, and androgen excess. 95% of CAH cases are due to 21-hydroxylase deficiency. Clinical forms range from the severe, classical CAH associated with complete loss of enzyme function, to milder, non-classical forms (NCAH). Androgen excess affects the pilosebaceous unit, causing cutaneous manifestations such as acne, androgenetic alopecia and hirsutism. Clinical differential diagnosis between NCAH and polycystic ovary syndrome may be difficult. In this review, the evaluation of patients with suspected CAH, the clinical presentation of CAH forms, with emphasis on the cutaneous manifestations of the disease, and available treatment options, will be discussed. PMID:22523607

  7. Temperature-induced variation in yolk androgen and thyroid hormone levels in avian eggs.

    PubMed

    Ruuskanen, Suvi; Groothuis, Ton G G; Schaper, Sonja V; Darras, Veerle M; de Vries, Bonnie; Visser, Marcel E

    2016-09-01

    Global warming has substantially changed the environment, but the mechanisms to cope with these changes in animals, including the role of maternal effects, are poorly understood. Maternal effects via hormones deposited in eggs, have important environment-dependent effects on offspring development and fitness: thus females are expected to adjust these hormones to the environment, such as the ambient temperature. Longer-term temperature variation could function as a cue, predicting chick rearing conditions to which yolk hormone levels are adjusted, while short-term temperature variation during egg formation may causally affect hormone transfer to eggs. We studied the effects of ambient temperature on yolk androgens (testosterone and androstenedione) and thyroid hormones (thyroxine and triiodothyronine) in great tits (Parus major) using data from unmanipulated clutches from a wild population and from aviary birds (ad libitum food) exposed to different experimental temperature treatments during five years. Both in the wild and in captivity, longer-term pre-laying ambient temperature was not associated with clutch mean yolk hormone levels, while the way androstenedione and thyroxine levels varied across the laying sequence did associate with pre-laying temperature in the wild. Yolk testosterone levels were positively correlated with short-term temperature (during yolk formation) changes within clutches in both wild and captivity. We also report, for the first time in a wild bird, that yolk thyroxine levels correlated with a key environmental factor: thyroxine levels were negatively correlated with ambient temperature during egg formation. Thus, yolk hormone levels, especially testosterone, seem to be causally affected by ambient temperature. These short-term effects might reflect physiological changes in females with changes in ambient temperature. The adaptive value of the variation with ambient temperatures pre-laying or during egg formation should be studied with

  8. Seasonal variations of androgens and of several sexual parameters in male Meriones shawi in southern Morocco.

    PubMed

    Zaime, A; Laraki, M; Gautier, J Y; Garnier, D H

    1992-05-01

    Seasonal changes of several parameters related to sexual activity were studied in the gerbil (Rodentia: Gerbillidae). The weight of the testes, seminal vesicles, and adrenals fluctuate throughout the year. Plasma androgen levels and histological aspect of the testes also vary throughout the year. Spermatogonial and steroid activities are synchronous and are maximal in winter and spring. The relationship between these activities and environmental climatic parameters is discussed: the beginning of sexual activity seems correlated with the first rains. PMID:1601278

  9. Gonadal steroid hormones and the hypothalamo-pituitary-adrenal axis.

    PubMed

    Handa, Robert J; Weiser, Michael J

    2014-04-01

    The hypothalamo-pituitary-adrenal (HPA) axis represents a complex neuroendocrine feedback loop controlling the secretion of adrenal glucocorticoid hormones. Central to its function is the paraventricular nucleus of the hypothalamus (PVN) where neurons expressing corticotropin releasing factor reside. These HPA motor neurons are a primary site of integration leading to graded endocrine responses to physical and psychological stressors. An important regulatory factor that must be considered, prior to generating an appropriate response is the animal's reproductive status. Thus, PVN neurons express androgen and estrogen receptors and receive input from sites that also express these receptors. Consequently, changes in reproduction and gonadal steroid levels modulate the stress response and this underlies sex differences in HPA axis function. This review examines the make up of the HPA axis and hypothalamo-pituitary-gonadal (HPG) axis and the interactions between the two that should be considered when exploring normal and pathological responses to environmental stressors. PMID:24246855

  10. Congenital Adrenal Hyperplasia

    MedlinePlus

    MENU Return to Web version Congenital Adrenal Hyperplasia Overview What is congenital adrenal hyperplasia? Congenital adrenal hyperplasia, or CAH, is a disorder that affects the adrenal glands. The adrenal ...

  11. [The ovarian origin of hiperandrogenism in the postmenopausal woman the adrenal adenoma--a case report].

    PubMed

    Mrozińska, Sandra; Kiałka, Marta; Doroszewska, Katarzyna; Milewicz, Tomasz; Jach, Robert

    2015-01-01

    Hyperandrogenism is a clinical condition characterized by excessive secretion of male sex hormones. An excess amount of androgens in women is manifested by symptoms of defeminization and masculinization. Hormonally active adrenal and ovarian tumors and non-tumor causes must be considered in the differential diagnosis. The authors describe the case of a 77-year-old patient who had hirsutism and reduction of the timbre of the voice. At the beginning she was suspected to have adrenal hyperandrogenism because of the tumor in the adrenal gland. Then adrenalectomy was conducted but it did not lead to alleviate symptoms. A MRI of the pelvis revealed a change of appendages projection and the patient underwent the total hysterectomy. The normalization of testosterone levels as well as reduction of the symptoms was observed after the operation. Finally, the ovary etiology of hyperandrogenism was confirmed. This case report is an example of difficulties in recognition the etiology of hyperandrogenism. PMID:26817354

  12. COMPARISON OF THE EFFECTS OF TWO AR ANTAGONISTS ON ANDROGEN DEPENDENT TISSUES WEIGHTS AND HORMONE LEVELS IN MALE RATS AND ON EXPRESSION OF THREE ANDROGEN DEPENDENT GENES IN THE VENTRAL PROSTATE

    EPA Science Inventory

    Comparison of the effects of two AR antagonists on tissue weights and hormone levels in male rats and on expression of three androgen dependent genes in the ventral prostate
    VS Wilson, CR Wood, GA Held, CS Lambright, JS Ostby, JR Furr, LE Gray Jr. US EPA, ORD, NHEERL, RTD, ...

  13. Androgens and estrogens modulate the immune and inflammatory responses in rheumatoid arthritis.

    PubMed

    Cutolo, Maurizio; Seriolo, Bruno; Villaggio, Barbara; Pizzorni, Carmen; Craviotto, Chiara; Sulli, Alberto

    2002-06-01

    Generally, androgens exert suppressive effects on both humoral and cellular immune responses and seem to represent natural anti-inflammatory hormones; in contrast, estrogens exert immunoenhancing activities, at least on humoral immune response. Low levels of gonadal androgens (testosterone/dihydrotestosterone) and adrenal androgens (dehydroepiandrosterone and its sulfate), as well as lower androgen/estrogen ratios, have been detected in body fluids (that is, blood, synovial fluid, smears, salivary) of both male and female rheumatoid arthritis patients, supporting the possibility of a pathogenic role for the decreased levels of the immune-suppressive androgens. Several physiological, pathological, and therapeutic conditions may change the sex hormone milieu and/or peripheral conversion, including the menstrual cycle, pregnancy, the postpartum period, menopause, chronic stress, and inflammatory cytokines, as well as use of corticosteroids, oral contraceptives, and steroid hormonal replacements, inducing altered androgen/estrogen ratios and related effects. Therefore, sex hormone balance is still a crucial factor in the regulation of immune and inflammatory responses, and the therapeutical modulation of this balance should represent part of advanced biological treatments for rheumatoid arthritis and other autoimmune rheumatic diseases. PMID:12114267

  14. Androgen deprivation therapy: progress in understanding mechanisms of resistance and optimizing androgen depletion

    PubMed Central

    Harris, William P; Mostaghel, Elahe A; Nelson, Peter S; Montgomery, Bruce

    2010-01-01

    SUMMARY Androgen deprivation therapy remains a critical component of treatment for men with advanced prostate cancer, and data supports its use in metastatic disease and in conjunction with surgery or radiation in specific settings. Alternatives to standard androgen deprivation therapy, such as intermittent androgen suppression and estrogen therapy, hold the potential to improve toxicity profiles while maintaining clinical benefit. Current androgen deprivation strategies seem to incompletely suppress androgen levels and androgen-receptor-mediated effects at the tissue level. Advances in the understanding of mechanisms that contribute to castration-resistant prostate cancer are leading to rationally designed therapies targeting androgen metabolism and the androgen receptor. The results of large trials investigating the optimization of primary androgen deprivation therapy, including evaluation of intermittent androgen suppression and estrogen patch assessment, as well as phase III studies of novel androgen synthesis inhibitors, such as abiraterone acetate, are eagerly awaited. PMID:19198621

  15. Stimulation of secretion from bovine adrenal chromaffin cells by microsecond bursts of therapeutic levels of ultrasound.

    PubMed Central

    Robinson, I M; Kinnick, R R; Greenleaf, J F; Fernandez, J M

    1996-01-01

    1. In this study the secretory response of individual bovine adrenal chromaffin cells was monitored using amperometric carbon-fibre microelectrodes. Cells were stimulated to secrete by exposure to 20-100 microseconds long tonebursts of ultrasound (2-4 x 10(5) Pa; peak pressure at 1 MHz). 2. Three types of secretory responses were observed: an almost instantaneous response, a delayed release of catecholamines, or a series of 'burst-like' secretory bouts. 3. Fura-2 measurements of intracellular Ca2+ concentrations showed that the release of catecholamines was accompanied by an increase in the intracellular Ca2+ concentration. In the absence of extracellular Ca2+, secretory responses were not evoked showing that Ca2+ entry was necessary to elicit catecholamine release. Images Figure 1 PMID:8730600

  16. Oral contraceptives as anti-androgenic treatment of acne.

    PubMed

    Lemay, André; Poulin, Yves

    2002-07-01

    Although acne is seldom associated with high serum levels of androgens, it has been shown that female acne patients have definite increases in ovarian and adrenal androgen levels when compared to appropriate controls. As shown in several pilot and in multiple open and comparative studies, oral contraceptives (OCs) are effective in causing a significant regression of mild to moderate acne. These results have been confirmed by multicentre randomized trials where low-dose OCs did not cause side effects different from those of the placebo-controlled group. The beneficial effect of OCs is related to a decrease in ovarian and adrenal androgen precursors; to an increase in sex hormone-binding globulin (SHBG), which limits free testosterone; and to a decrease in 3a-androstenediol glucuronide conjugate, the catabolite of dihydrotestosterone (DHT) formed in peripheral tissues. The estrogen-progestin combination containing cyproterone acetate (CPA) is particularly effective in treating acne, since this progestin also has a direct peripheral anti-androgenic action in blocking the androgen receptor. Only two open studies and one randomized study on small numbers of patients have reported some efficacy of spironolactone used alone or in combination with an OC in the treatment of acne. The new non-steroidal anti-androgens flutamide and finasteride are being evaluated for the treatment of hirsutism. Oral antibiotics are prescribed to patients with inflammatory lesions, where they are effective in decreasing the activity of microbes, the activity of microbial enzymes, and leukocyte chemotaxis. Concomitant intake of an OC and an antibiotic usually prescribed for acne does not impair the contraceptive efficacy of the OC. A second effective contraceptive method should be used whenever there would be decreased absorption or efficacy of the OC (digestive problems, breakthrough bleeding), lack of compliance and use of a type or dose of antibiotic different from that usually prescribed

  17. Adrenal myelolipoma.

    PubMed

    Cyran, K M; Kenney, P J; Memel, D S; Yacoub, I

    1996-02-01

    In 1905, Gierke [1] first described the occurrence of a tumor in the adrenal composed of mature fat and mixed myeloid and erythroid cells, subsequently termed "formations myelolipomatoses" by Oberling [2] in 1929. PMID:8553954

  18. Androgen insensitivity.

    PubMed

    Gottlieb, B; Pinsky, L; Beitel, L K; Trifiro, M

    1999-12-29

    The androgen receptor (AR) protein regulates transcription of certain genes. Usually, this activity depends upon a central DNA-binding domain that permits the binding of androgen-AR complexes to regulatory DNA sequences near or in a target gene. The AR also has a C-terminal androgen-binding domain (ABD) and an N-terminal modulatory domain. These domains interact among themselves and with coregulatory, nonreceptor proteins to determine vector control over a gene's transcription rate. The precise roles of these proteins are active research areas. Severe X-linked androgen receptor gene (AR) mutations cause complete androgen insensitivity, mild ones impair virilization with or without infertility, and moderate ones sometimes yield a wide phenotypic spectrum among sibs. Different expressivity may reflect variability of AR-interactive proteins. The family history must identify heterozygous XX females with sparse, delayed, or asymmetric pubic/axillary hair or delayed menarche and infertile XY maternal aunts or uncles. Mutation type and density vary along the length of the AR. N-terminal polyglutamine tract expansion limits AR transactivation, causing a form of mild androgen insensitivity. Analysis of ABD mutations that do not impair androgen binding or impair it selectively will illuminate its intradomain properties. For partial androgen insensitivity and mild androgen insensitivity, pharmacotherapy with certain androgens or other steroids may overcome some dysfunction of certain mutant ARs. Experience with this approach is limited; outcomes have been generally disappointing. PMID:10727996

  19. Growth inhibition of human prostate cells in vitro by novel inhibitors of androgen synthesis.

    PubMed

    Klus, G T; Nakamura, J; Li, J S; Ling, Y Z; Son, C; Kemppainen, J A; Wilson, E M; Brodie, A M

    1996-11-01

    The long-standing strategy for the treatment of metastatic prostate cancer has been to reduce androgenic stimulation of tumor growth by removal of the testes, the primary site of testosterone synthesis. However, a low level of androgenic stimulation may continue, even after castration, by the conversion of adrenal androgens to 5alpha-dihydrotestosterone (DHT) in the prostate tumor cells. Two important enzymes of the androgen biosynthetic pathway are 17alpha-hydroxylase/C17,20-lyase, which regulates an early step in the synthesis of testosterone and other androgens in both the testes and adrenal glands, and 5alpha-reductase, which converts testosterone to the more potent androgen, DHT, in the prostate. We have identified new inhibitors of these enzymes that may be of use in achieving a more complete ablation of androgens in the treatment of metastatic prostate cancer. Three derivatives of androstene were shown to inhibit 17alpha-hydroxylase/C17,20-lyase with potencies 2-20-fold greater than that of ketoconazole, a previously established inhibitor of this enzyme. Derivatives of pregnane and pregnene displayed activities against 5alpha-reductase that were comparable to that of N-(1,1-dimethyl-ethyl)-3-oxo-4-aza-5alpha-androst-1-ene-17beta-car boxamide. All of the 5alpha-reductase inhibitors were able to at least partially inhibit the mitogenic effect of testosterone in either histocultures of human benign prostatic hypertrophic tissue or in cultures of the LNCaP human prostatic tumor cell line. For these compounds, it appears that this inhibition can be attributed to a reduction of DHT synthesis in these cultures, because no inhibitory effect was observed in DHT-treated cultures, and none of the compounds had a cytotoxic effect. Surprisingly, one of the inhibitors of 17alpha-hydroxylase/C17,20-lyase, 17beta-(4-imidazolyl)-5-pregnen-3beta-ol, was also able to inhibit the mitogenic effect of testosterone in both the histoculture and cell culture assays and had an effect

  20. The Effect of Simvastatin on Plasma Steroid Hormone Levels in Metformin-Treated Women with Non-Classic Congenital Adrenal Hyperplasia.

    PubMed

    Krysiak, R; Kowalcze, K; Bednarska-Czerwińska, A; Okopień, B

    2016-04-01

    Non-classic congenital adrenal hyperplasia (NC-CAH), one of the most common genetic disorders, is often associated with the presence of hyperandrogenism. Recently both simvastatin and metformin were found to reduce plasma steroid hormone levels in this disorder. This study included 8 women with NC-CAH and diabetes or impaired glucose tolerance, as well as 12 matched women with similar glucose metabolism abnormalities but normal adrenal function. Both groups of women, receiving metformin for at least 6 months, were then treated with simvastatin (20 mg daily) for the following 12 weeks. Compared to patients with normal adrenal function, metformin-treated women with NC-CAH showed increased plasma levels of 17-hydroxyprogesterone, total testosterone, free testosterone, androstenedione and DHEA-S. Simvastatin reduced total and LDL cholesterol levels in both patients with NC-CAH and normal adrenal function. Moreover, in the former group of women, statin therapy decreased plasma levels of testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulphate and tended to reduce 17-hydroxyprogesterone. Our results suggest that metformin-statin combination therapy may be useful in the management of symptomatic women with NC-CAH. PMID:26824284

  1. Dexamethasone-suppression adrenal scintigraphy in hyperandrogenism: concise communication

    SciTech Connect

    Gross, M.D.; Freitas, J.E.; Swanson, D.P.; Woodbury, M.C.; Schteingart, D.E.; Beierwaltes, W.H.

    1981-01-01

    To assess the contribution of adrenal-derived androgens in women with hirsutism, adrenal scintigrams under dexamethasone suppression (DS) were performed on 35 women with increasing facial or body hair and irregular or absent menses. Based upon the DS regimen chosen (8 mg/d for 2 days or 4 md/d for 7 days before the injection of 6..beta..-(/sup 131/I)iodomethylnorcholesterol), three imaging patterns were identified. The first was the absence of uptake before 3 days (8-mg DS) or before 5 days (4-mg DS) after injection. This imaging pattern was seen in 17 of the 35 patients studied and was considered normal. The second pattern was bilateral uptake earlier than 3 days (8-mg DS regimen) or 5 days (4-mg DS) after injection. This was seen in 13 of the 35 patients and was interpreted as bilateral early visualization. Adrenal-vein catheterization performed on six patients with this pattern showed increased adrenal-vein testosterone. The third pattern, observed in five patients, was unilateral early visualization, which in four cases investigated to date was the result of an adrenocortical adenoma. This study confirms the adrenal cortex as a source of androgens in women with hirsutism and hyperandrogenism and demonstrates that DS adrenal scintigraphy can be utilized to identify those women in whom adrenal-derived androgens contribute to their hyperandrogenism.

  2. The validity of androgen assays

    PubMed Central

    Carruthers, Malcolm; Trinick, Tom R.; Wheeler, Michael J.

    2007-01-01

    Problems in the measurement of androgens and in interpreting results have been reviewed and classified as follows: Preanalytical factors The exact sampling conditions in relation to circadian and seasonal variations, diet, alcohol, physical activity and posture. Physiological and medical factors Androgen levels vary according to the patient's general health, stress, sexual activity and smoking habits. Analytical variables Sample preservation and storage variables are often unknown. The different androgen assays used have widely differing accuracy and precision and are subject to large inter-laboratory variation, which especially in women and children can render the results of routinely available direct immunoassays meaningless. Interpretation of results Laboratory reference ranges vary widely, largely independent of methodology, and fail to take into account the log-normal distribution of androgen values, causing errors in clinical diagnosis and treatment. Other unknowns are antagonists such as SHBG, estrogens, catecholamines, cortisol, and anti-androgens. As well as age, androgen receptor polymorphisms play a major role in regulating androgen levels and resistance to their action. Conclusions Though laboratory assays can support a diagnosis of androgen deficiency in men, they should not be used to exclude it. It is suggested that there needs to be greater reliance on the history and clinical features, together with careful evaluation of the symptomatology, and where necessary a therapeutic trial of androgen treatment given. PMID:17701661

  3. Therapy of adrenal insufficiency: an update.

    PubMed

    Falorni, Alberto; Minarelli, Viviana; Morelli, Silvia

    2013-06-01

    Adrenal insufficiency may be caused by the destruction or altered function of the adrenal gland with a primary deficit in cortisol secretion (primary adrenal insufficiency) or by hypothalamic-pituitary pathologies determining a deficit of ACTH (secondary adrenal insufficiency). The clinical picture is determined by the glucocorticoid deficit, which may in some conditions be accompanied by a deficit of mineralcorticoids and adrenal androgens. The substitutive treatment is aimed at reducing the signs and symptoms of the disease as well as at preventing the development of an addisonian crisis, a clinical emergency characterized by hypovolemic shock. The oral substitutive treatment should attempt at mimicking the normal circadian profile of cortisol secretion, by using the lower possible doses able to guarantee an adequate quality of life to patients. The currently available hydrocortisone or cortisone acetate preparations do not allow an accurate reproduction of the physiological secretion pattern of cortisol. A novel dual-release formulation of hydrocortisone, recently approved by EMEA, represents an advancement in the optimization of the clinical management of patients with adrenal insufficiency. Future clinical trials of immunomodulation or immunoprevention will test the possibility to delay (or prevent) the autoimmune destruction of the adrenal gland in autoimmune Addison's disease. PMID:23179775

  4. Physiological Basis for the Etiology, Diagnosis, and Treatment of Adrenal Disorders: Cushing’s Syndrome, Adrenal Insufficiency, and Congenital Adrenal Hyperplasia

    PubMed Central

    Raff, Hershel; Sharma, Susmeeta T.; Nieman, Lynnette K.

    2014-01-01

    The hypothalamic-pituitary-adrenal (HPA) axis is a classic neuroendocrine system. One of the best ways to understand the HPA axis is to appreciate its dynamics in the variety of diseases and syndromes that affect it. Excess glucocorticoid activity can be due to endogenous cortisol overproduction (spontaneous Cushing’s syndrome) or exogenous glucocorticoid therapy (iatrogenic Cushing’s syndrome). Endogenous Cushing’s syndrome can be subdivided into ACTH-dependent and ACTH-independent, the latter of which is usually due to autonomous adrenal overproduction. The former can be due to a pituitary corticotroph tumor (usually benign) or ectopic ACTH production from tumors outside the pituitary; both of these tumor types overexpress the proopiomelanocortin gene. The converse of Cushing’s syndrome is the lack of normal cortisol secretion and is usually due to adrenal destruction (primary adrenal insufficiency) or hypopituitarism (secondary adrenal insufficiency). Secondary adrenal insufficiency can also result from a rapid discontinuation of long-term, pharmacological glucocorticoid therapy because of HPA axis suppression and adrenal atrophy. Finally, mutations in the steroidogenic enzymes of the adrenal cortex can lead to congenital adrenal hyperplasia and an increase in precursor steroids, particularly androgens. When present in utero, this can lead to masculinization of a female fetus. An understanding of the dynamics of the HPA axis is necessary to master the diagnosis and differential diagnosis of pituitary-adrenal diseases. Furthermore, understanding the pathophysiology of the HPA axis gives great insight into its normal control. PMID:24715566

  5. Reflex splanchnic nerve stimulation increases levels of proenkephalin A mRNA and proenkephalin A-related peptides in the rat adrenal medulla.

    PubMed Central

    Kanamatsu, T; Unsworth, C D; Diliberto, E J; Viveros, O H; Hong, J S

    1986-01-01

    The effect of reflex splanchnic nerve stimulation on proenkephalin A biosynthesis was investigated in the rat adrenal medulla. Tissue levels of native [Met5]enkephalin-like immunoreactivity (IR) (measured by direct RIA of tissue extracts), cryptic [Met5]enkephalin-like IR (calculated as the increase in [Met5]enkephalin-like IR detected in tissue extracts after sequential digestion with trypsin and carboxypeptidase B), and proenkephalin A mRNA were determined in adrenal medulla from rats sacrificed at various times after a period of insulin-induced hypoglycemia. Two hours of insulin hypoglycemia, which produced intense reflex stimulation of the splanchnic nerves as evidenced by a 55% decrease in the adrenal medulla catecholamine levels, resulted in a 3-fold increase in proenkephalin A mRNA levels in this tissue. The proenkephalin A mRNA levels reached a maximum 15-fold increase over control values 24 hr after this period of hypoglycemic stress and then gradually declined with an approximate half-life of 4 days. Native and cryptic [Met5]enkephalin-like IR had increased 9-fold and 12-fold, respectively, 24 hr after this period of hypoglycemia, and both demonstrated maximum increases of 130-fold and 50-fold, respectively, after 96 hr. Combined pretreatment (i.p. administration) with the ganglionic and muscarinic blocking agents chlorisondamine (5 mg/kg of body weight) and atropine (1 mg/kg) blocked the increase in levels of proenkephalin A mRNA seen in the rat adrenal medulla following insulin hypoglycemia. These data indicate that reflex splanchnic nerve discharge stimulates proenkephalin biosynthesis, probably at the level of gene expression. Images PMID:3538020

  6. Ashwagandha root in the treatment of non-classical adrenal hyperplasia

    PubMed Central

    Kalani, Amir; Bahtiyar, Gul; Sacerdote, Alan

    2012-01-01

    Congenital adrenal hyperplasia (CAH) is a well-characterised family of disorders of the adrenal cortices, resulting in varying degrees of cortisol, aldosterone and androgen deficiency or androgen excess, depending on the enzyme(s) affected and the degree of quantitative or functional enzyme deficit. Withania somnifera (WS), commonly known as Ashwagandha, is a medicinal plant that has been employed for centuries in ayurvedic medicine. Preclinical studies have shown that WS increases circulating cortisol levels and improves insulin sensitivity. We report the case of a 57-year-old woman with non-classical adrenal hyperplasia due to both 3-β-ol dehydrogenase deficiency and aldosterone synthase deficiency who was self-treated with WS for 6 months. After 6 months of treatment her serum 18-OH-hydroxycorticoserone, 17-OH-pregnenolone, corticosterone and 11-deoxycortisol decreased by 31%, 66%, 69% and 55%, respectively. The biochemical improvement was accompanied by a noticeable reduction in scalp hair loss. PMID:22987912

  7. Intra- and interspecific challenges modulate cortisol but not androgen levels in a year-round territorial damselfish.

    PubMed

    Ros, Albert F H; Vullioud, Philippe; Bruintjes, Rick; Vallat, Armelle; Bshary, Redouan

    2014-05-15

    Interactions between individuals of different species are commonplace in animal communities. Some behaviors displayed during these interspecific social interactions may be very similar to those displayed during intraspecific social interactions. However, whether functional analogies between intra- and interspecific behaviors translate at the proximate level into an overlap in their underlying endocrine mechanisms remains largely unknown. Because steroids both mediate social behaviors and respond to them, we approached this question by comparing the behavioral and steroid response of free-living dusky gregories (Stegastes nigricans) to standardized territorial intrusions (sTI) of either conspecific or heterospecific food competitors. Stegastes nigricans is a year-round territorial fish that 'cultivates' the algae on which it feeds and is highly aggressive to both intra- and interspecific intruders. Behavioral differences between intra- and interspecific aggressive responses to sTI were marginal, and sTI tests caused an increase in cortisol levels that was positively related with the levels of aggression. In contrast, androgen levels did not increase in response to sTI, yet they showed a positive relationship with agonistic behavior. These results parallel a pattern that was first described for year-round territorial bird species. Furthermore, they suggest that changes in endocrine-hormone levels during territoriality might be independent of the species that induces the territorial response. PMID:24577440

  8. Dopamine receptor expression and function in human normal adrenal gland and adrenal tumors.

    PubMed

    Pivonello, Rosario; Ferone, Diego; de Herder, Wouter W; de Krijger, Ronald R; Waaijers, Marlijn; Mooij, Diana M; van Koetsveld, Peter M; Barreca, Antonina; De Caro, Maria Laura del Basso; Lombardi, Gaetano; Colao, Annamaria; Lamberts, Steven W J; Hofland, Leo J

    2004-09-01

    Dopamine is known to play a role in the modulation of aldosterone and catecholamine secretion from the adrenal gland, where dopamine receptors (DR), in particular the DR type 2 (D(2)), have been found to be expressed. DR expression has also been demonstrated in some types of benign adrenal tumors. The aims of the current study were to evaluate DR expression and D(2) localization in the normal adrenal gland and in different types of benign and malignant adrenal tumors, as well as to evaluate the in vitro effects of the dopamine agonists bromocriptine and cabergoline on hormone secretion in nontumoral adrenal cells. Adrenal tissues from 25 patients, subjected to adrenal surgery for different diseases, were studied. These included three normal adrenals; five adrenal hyperplasias; four aldosterone-secreting, two cortisol-secreting, and two clinically nonfunctioning adrenal adenomas; two aldosterone-secreting, two cortisol-secreting, and two androgen-secreting adrenal carcinomas; and three pheochromocytomas. In all tissues, DR and D(2) isoform (D(2long) and D(2short)) expression was evaluated by RT-PCR. D(2) localization was also evaluated by immunohistochemistry using a specific polyclonal antibody, whereas D(2)-like receptor expression was evaluated by receptor-ligand binding study, using the radiolabeled D(2) analog (125)I-epidepride. The effects of bromocriptine and cabergoline on baseline and ACTH and/or angiotensin II-stimulated aldosterone, cortisol, and androstenedione secretion were evaluated in cell cultures derived from five different adrenal hyperplasia. At RT-PCR, both D(1)-like and D(2)-like receptors were expressed in all normal and hyperplastic adrenals. D(2) and D(4) were expressed in aldosterone- and cortisol-secreting adenomas, cortisol-secreting carcinomas, and clinically nonfunctioning adenomas, whereas no DR was expressed in aldosterone- and androgen-secreting carcinomas. D(2), D(4), and D(5) were expressed in pheochromocytomas. In all D(2

  9. Bilateral adrenal haemorrhage leading to adrenal crisis

    PubMed Central

    McGowan-Smyth, Sam

    2014-01-01

    A 77-year-old man presented with an acute worsening of chronic back pain. CT showed dense bilateral adrenal glands suggestive of adrenal haemorrhage which was confirmed by MRI. Despite appropriate glucocorticoid replacement for adrenal insufficiency, 7 days after admission this patient suffered an adrenal crisis. Owing to the timely diagnosis, appropriate treatment was given and the patient survived. Large bilateral adrenal haemorrhage however, can lead to cardiovascular collapse and death if not appropriately diagnosed and managed promptly. Despite its rarity, bilateral adrenal haemorrhage should always be considered as a differential for back pain in the setting of an acute illness due to its potentially fatal consequences. PMID:24969071

  10. Proliferation and phenotypic changes of stromal cells in response to varying estrogen/androgen levels in castrated rats

    PubMed Central

    Zhou, Ying; Xiao, Xiang-Qian; Chen, Lin-Feng; Yang, Rui; Shi, Jian-Dang; Du, Xiao-Ling; Klocker, Helmut; Park, Irwin; Lee, Chung; Zhang, Ju

    2009-01-01

    It is known that human benign prostatic hyperplasia might arise from an estrogen/androgen (E/T) imbalance. We studied the response of castrated rat prostate to different ratios of circulating E/T. The castrated male Wistar rats were randomly injected with E/T at different ratios for 4 weeks. The prostates of E/T (1:100) group showed a distinct prostatic hyperplasia response by prostatic index, hematoxylin and eosin staining, and quantitative immunohistochemical analysis of α-smooth muscle actin (SMA). In this group, cells positive for Vimentin, non-muscle myosin heavy chain (NMMHC) and proliferating cell nuclear antigen (PCNA) increased in the stroma and epithelium. Furthermore, the mRNA levels of smooth muscle myosin heavy chain (SMMHC) and NMMHC increased. So E/T at a ratio of 1:100 can induce a stromal hyperplastic response in the prostate of castrated rats. The main change observed was an increase of smooth muscle cells, whereas some epithelial changes were also seen in the rat prostates. PMID:19483715

  11. Adrenal Gland Tumor

    MedlinePlus

    ... here Home > Types of Cancer > Adrenal Gland Tumor Adrenal Gland Tumor This is Cancer.Net’s Guide to Adrenal Gland Tumor. Use the menu below to choose ... social workers, and patient advocates. Cancer.Net Guide Adrenal Gland Tumor Introduction Statistics Risk Factors Symptoms and ...

  12. Elevation of serum 25-hydroxycalciferol levels in androgen-treated and ultraviolet-irradiated rats.

    PubMed

    Ohata, M; Sakagami, Y; Fujita, T

    1977-10-01

    Administration of 4-8 mg testosterone propionate significantly raised 25-hydroxycalciferol levels in the ultraviolet irradiated rats compared to the ultraviolet irradiated controls, but failed to influence serum 25-hydroxycalciferol levels in the non-irradiated animals. Estradiol benzoate and progesterone did not influence serum 25-hydroxycalciferol levels regardless of the ultraviolet irradiation. These findings implicate that testosterone enhances vitamin D biosynthesis induced by ultraviolet irradiation in rats, in accordance with the clinical observation that males often show higher levels of serum 25-hydroxycalciferol than females. PMID:303993

  13. Loss of lean body and muscle mass correlates with androgen levels in hypogonadal men with acquired immunodeficiency syndrome and wasting.

    PubMed

    Grinspoon, S; Corcoran, C; Lee, K; Burrows, B; Hubbard, J; Katznelson, L; Walsh, M; Guccione, A; Cannan, J; Heller, H; Basgoz, N; Klibanski, A

    1996-11-01

    The acquired immunodeficiency syndrome (AIDS) wasting syndrome (AWS) is a devastating complication of human immunodeficiency virus infection characterized by a disproportionate decrease in lean body mass. The pathogenesis of the AWS is unknown, but recent data suggest that endogenous secretion of the potent anabolic hormone, testosterone; is decreased in 30-50% of men with AIDS. However, it is unknown whether decreased androgen levels are associated with decreased lean body mass and/or functional decreases in muscle strength and aerobic capacity in hypogonadal men with the AWS. In addition, testosterone is known to have stimulatory effects on GH secretion, and the loss of these effects on the GH-insulin-like growth factor I (IGF-I) axis may be an additional mechanism of decreased lean body mass in this population. Twenty hypogonadal subjects (free-testosterone < 12 pg/mL) with weight loss > 10% of preillness weight or absolute weight < 90% ideal body weight (IBW) were enrolled in the study. None of the subjects were receiving Megace. Lean body mass and fat-free mass were determined by potassium-40 isotope analysis (40K) and dual-energy x-ray absorptiometry, respectively, and analyzed with respect to gonadal function by linear regression analysis. Muscle mass was determined by urinary creatinine excretion, and exercise functional capacity was assessed by a 6-min walk test, a sit-to-stand test, and a timed get-up-and-go test. Results also were compared with gonadal function by regression analysis. IGF-I and mean overnight GH levels, determined from frequent sampling (q20 min from 2000-0800 h), were compared with results obtained from age- and sex-matched normal controls. Subjects were 26-58 yr of age (39 +/- 7 yr, mean +/- SD) with a CD4 cell count of 150 +/- 186 cells/mm3. Serum levels of FSH were elevated in 30% of the subjects. Muscle mass was significantly reduced, compared with expected mass for height (23.3 +/- 5.5 vs. 29.3 +/- 1.7 kg, P = 0.0001) and was

  14. Perchlorate disrupts embryonic androgen synthesis and reproductive development in threespine stickleback without changing whole-body levels of thyroid hormone

    PubMed Central

    Petersen, Ann M.; Dillon, Danielle; Bernhardt, Richard A.; Torunsky, Roberta; Postlethwait, John H.; von Hippel, Frank A.; Buck, C. Loren; Cresko, William A.

    2014-01-01

    Perchlorate, an environmental contaminant, disrupts normal functioning of the thyroid. We previously showed that perchlorate disrupts behavior and gonad development, and induces external morphological changes in a vertebrate model organism, the threespine stickleback. Whether perchlorate alters these phenotypes via a thyroid-mediated mechanism, and the extent to which the effects depend on dose, are unknown. To address these questions, we chronically exposed stickleback to control conditions and to three concentrations of perchlorate (10, 30 and 100 ppm) at various developmental stages from fertilization to reproductive maturity. Adults chronically exposed to perchlorate had increased numbers of thyroid follicles and decreased numbers of thyrocytes. Surprisingly, T4 and T3 levels in larval, juvenile, and adult whole fish chronically exposed to perchlorate did not differ from controls, except at the lowest perchlorate dose, suggesting a non-monotonic dose response curve. We found no detectable abnormalities in external phenotype at any dose of perchlorate, indicating that the increased number of thyroid follicles compensated for the disruptive effects of these doses. In contrast to external morphology, gonadal development was altered substantially, with the highest dose of perchlorate causing the largest effects. Perchlorate increased the number both of early stage ovarian follicles in females and of advanced spermatogenic stages in males. Perchlorate also disrupted embryonic androgen levels. We conclude that chronic perchlorate exposure may not result in lasting adult gross morphological changes but can produce lasting modifications to gonads when compensation of T3 and T4 levels occurs by thyroid follicle hyperplasia. Perchlorate may therefore affect vertebrate development via both thyroidal and non-thyroidal mechanisms. PMID:25448260

  15. Cushing syndrome due to adrenal tumor

    MedlinePlus

    ... levels Dexamethasone suppression test Blood cortisol levels Blood DHEA level Saliva cortisol level Tests to determine cause ... not possible, such as in cases of adrenal cancer, medicines can be used to stop the release ...

  16. An update of congenital adrenal hyperplasia.

    PubMed

    New, Maria I

    2004-12-01

    Congenital adrenal hyperplasia (CAH) is a family of autosomal recessive disorders caused by mutations that encode for enzymes involved in one of the various steps of adrenal steroid synthesis. These defects result in the absence or the decreased synthesis of cortisol from its cholesterol precursor. The anterior pituitary secretes excess adrenocorticotrophic hormone (ACTH) via feedback regulation by cortisol, which results in overstimulation of the adrenals and causes hyperplasia. Symptoms due to CAH can vary from mild to severe depending on the degree of ensymatic defect. In the classical form of CAH, there is a severe enzymatic defect owing to mutations in the CYP21 gene. Classically affected female fetuses undergo virilization of the genitalia prenatally and present with genital ambiguity at birth; however, prenatal treatment of CAH with dexamethasone to prevent ambiguity has been successfully utilized for over a decade. In the less severe, late-onset form of CAH, prenatal virilization does not occur. The milder enzyme deficiency was termed nonclassical 21-hydroxylase deficiency (NC21OHD) in 1979 and was later found to be the most common autosomal recessive disorder in humans. Disease frequency of NC21OHD varies between ethnic groups with the highest ethnic-specific disease frequency in Ashkenazi Jews at 1/27. NC21OHD is diagnosed by serum elevations of 17-OHP that plot on a nomogram between the range for unaffected individuals and levels observed for classical CAH and is typically confirmed with molecular genetic analysis. Similar to classical CAH, nonclassical 21-hydroxylase deficiency may cause premature development of pubic hair, advanced bone age, accelerated linear growth velocity and diminished final height in both males and females. Severe cystic acne has also been attributed to nonclassical CAH. Women may present with symptoms of androgen excess, including hirsutism, temporal baldness, and infertility. Menarche in females may be normal or delayed and

  17. Breast cancer size in postmenopausal women is correlated with body mass index and androgen serum levels.

    PubMed

    Asseryanis, E; Ruecklinger, E; Hellan, M; Kubista, E; Singer, C F

    2004-01-01

    Our objective was to investigate the effects of age, weight, body mass index (BMI), sex steroid receptor status and serum parameters such as estradiol, testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS) and leptin on the size of a malignant breast tumor. A total of 62 premenopausal (median age 44.0 years) and 151 postmenopausal (median age 59.1 years) Caucasian women undergoing lumpectomy or mastectomy for invasive breast cancer were examined. Patient parameters (age, body weight, BMI), tumor parameters (tumor size, estrogen and progesterone receptor status) and serum parameters (estradiol, testosterone, androstenedione, DHEAS and leptin) were measured. An increase of BMI and DHEAS levels was associated with larger tumors by partial correlation (rp) analysis (rp = 0.418, p = 0.008; and rp = 0.329, p = 0.041, respectively), whereas higher androstenedione levels corresponded with smaller tumors. Furthermore, BMI, androstenedione and DHEAS levels were correlated: an increase in DHEAS was associated with higher androstenedione serum concentrations (rp = 0.603, p < 0.001), but was also associated with a lower BMI (rp = -0.378, p < 0.001). BMI and androstenedione serum concentrations were also associated (rp = 0.242, p = 0.009), thus closing a circle of mutual interactions. We conclude that, although breast cancer progression is characterized by autonomous growth that has become independent of growth regulatory mechanisms, tumor size at the time of detection is influenced by a complex system of counter-regulatory feedback mechanisms that might represent the body's physiological attempt to control the size of a malignant tumor. PMID:15106362

  18. Can we avoid high levels of dose escalation for high-risk prostate cancer in the setting of androgen deprivation?

    PubMed Central

    Shakespeare, Thomas P; Wilcox, Shea W; Aherne, Noel J

    2016-01-01

    Aim Both dose-escalated external beam radiotherapy (DE-EBRT) and androgen deprivation therapy (ADT) improve outcomes in patients with high-risk prostate cancer. However, there is little evidence specifically evaluating DE-EBRT for patients with high-risk prostate cancer receiving ADT, particularly for EBRT doses >74 Gy. We aimed to determine whether DE-EBRT >74 Gy improves outcomes for patients with high-risk prostate cancer receiving long-term ADT. Patients and methods Patients with high-risk prostate cancer were treated on an institutional protocol prescribing 3–6 months neoadjuvant ADT and DE-EBRT, followed by 2 years of adjuvant ADT. Between 2006 and 2012, EBRT doses were escalated from 74 Gy to 76 Gy and then to 78 Gy. We interrogated our electronic medical record to identify these patients and analyzed our results by comparing dose levels. Results In all, 479 patients were treated with a 68-month median follow-up. The 5-year biochemical disease-free survivals for the 74 Gy, 76 Gy, and 78 Gy groups were 87.8%, 86.9%, and 91.6%, respectively. The metastasis-free survivals were 95.5%, 94.5%, and 93.9%, respectively, and the prostate cancer-specific survivals were 100%, 94.4%, and 98.1%, respectively. Dose escalation had no impact on any outcome in either univariate or multivariate analysis. Conclusion There was no benefit of DE-EBRT >74 Gy in our cohort of high-risk prostate patients treated with long-term ADT. As dose escalation has higher risks of radiotherapy-induced toxicity, it may be feasible to omit dose escalation beyond 74 Gy in this group of patients. Randomized studies evaluating dose escalation for high-risk patients receiving ADT should be considered. PMID:27274277

  19. Seasonal changes in androgen levels in stream- and hatchery-reared Atlantic salmon parr and their relationship to smolting

    USGS Publications Warehouse

    Shrimpton, J.M.; McCormick, S.D.

    2002-01-01

    In stream-reared Atlantic salmon Salmo salar, plasma androgens were significantly greater in mature male parr than immature males and females in October, but had declined by January and did not differ significantly from immature fish throughout the spring. Immature fish in March were significantly larger and had greater gill Na+,K+-ATPase activity than their previously mature counterparts. Bimodal growth distribution was seen in hatchery-reared Atlantic salmon and a proportion of the male fish in the lower mode matured. Plasma testosterone (T) and 11-ketotestosterone (11-KT) were significantly elevated from September to December in mature male (1+ year) parr. In January, plasma androgens had declined in mature males and did not differ significantly from immature fish. By May all the hatchery fish were large enough to smolt and a proportion of the previously mature males had increased gill Na+,K+-ATPase activity. Therefore elevated androgens in the previous autumn do not prevent smolting. Parr with higher plasma T and 11-KT in April and May, that are presumably beginning to mature, had lower gill Na+,K+-ATPase activity, indicating that future maturation and associated increases in androgens may inhibit smolting. ?? 2002 The Fisheries Society of the British Isles. Published by Elsevier Science Ltd. All rights reserved.

  20. Natesto™ , a novel testosterone nasal gel, normalizes androgen levels in hypogonadal men.

    PubMed

    Rogol, A D; Tkachenko, N; Bryson, N

    2016-01-01

    Advantages of testosterone nasal gel include ease of administration, low dose, and no risk of secondary transference. The efficacy and safety of testosterone nasal gel was evaluated in hypogonadal males. The ninety-day, randomized, open-label, dose-ranging study, included potential dose titration and sequential safety extensions to 1 year. At 39 US outpatient sites, 306 men (mean age 54.4 years) with two fasting morning total serum testosterone levels <300 ng/dL were randomized (n = 228, b.i.d. dosing; n = 78, t.i.d. dosing). Natesto(™) Testosterone Nasal Gel was self-administered, using a multiple-dose dispenser, as two or three daily doses (5.5 mg per nostril, 11.0 mg single dose). Total daily doses were 22 mg or 33 mg. The primary endpoint was the Percentage of patients with Day-90 serum total testosterone average concentration (C(avg)) value within the eugonadal range (≥300 ng/dL, ≤1050 ng/dL). At Day 90, 200/273 subjects (73%; 95% CI 68, 79) in the intent-to-treat (ITT) population and 180/237 subjects (76%; 71, 81) in the per-protocol (PP) population were in the normal range. Also, in the normal range were 68% (61, 74) of ITT subjects and 70% (63, 77) of PP subjects in the titration arm, as well as, 90% (83, 97) of ITT subjects and 91% (84, 98) of PP subjects in the fixed-dose arm. Natesto(™) 11 mg b.i.d. or 11 mg t.i.d. restores normal serum total testosterone levels in most hypogonadal men. Erectile function, mood, body composition, and bone mineral density improved from baseline. Treatment was well tolerated; adverse event rates were low. Adverse event discontinuation rates were 2.1% (b.i.d.) and 3.7% (t.i.d.). This study lacked a placebo or an active comparator control which limited the ability to adequately assess some measures. PMID:26695758

  1. How Is Adrenal Surgery Performed?

    MedlinePlus

    HOME ADRENAL GLANDS Background Where are the adrenal glands? What do the adrenal glands do? Is this adrenal tumor a genetic problem? Primary hyperaldosteronism (aldosterone-producing tumor) What is primary hyperaldosteronism? Signs ...

  2. Transcriptional up-regulation of the human androgen receptor by androgen in bone cells.

    PubMed

    Wiren, K M; Zhang, X; Chang, C; Keenan, E; Orwoll, E S

    1997-06-01

    Androgen regulation of androgen receptor (AR) expression has been observed in a variety of tissues, generally as inhibition, and is thought to attenuate cellular responses to androgen. AR is expressed in osteoblasts, the bone-forming cell, suggesting direct actions of androgens on bone. Here we characterized the effect of androgen exposure on AR gene expression in human osteoblastic SaOS-2 and U-2 OS cells. Treatment of osteoblastic cells with the nonaromatizable androgen 5alpha-dihydrotestosterone increased AR steady state messenger RNA levels in a time- and dose-dependent fashion. Reporter assays with 2.3 kilobases of the proximal 5'-flanking region of the human AR promoter linked to the chloramphenicol acetyltransferase gene in transfected cultures showed that up-regulation of AR promoter activity by androgen was time and dose dependent. Treatment with other steroid hormones, including progesterone, 17beta-estradiol, and dexamethasone, was without effect. The antiandrogen hydroxyflutamide completely antagonized androgen up-regulation. Thus, in contrast to many other androgen target tissues, androgen exposure increases steady state AR messenger RNA levels in osteoblasts. This regulation occurs at least partially at the level of transcription, is mediated by the 5'-promoter region of the AR gene, and is dependent on functional AR. These results suggest that physiological concentrations of androgens have significant effects on AR expression in skeletal tissue. PMID:9165014

  3. Adrenal Lymphangioma Masquerading as a Catecholamine Producing Tumor

    PubMed Central

    Hodish, Israel; Schmidt, Lindsay; Moraitis, Andreas G.

    2015-01-01

    Objective. To report the unusual case of an adrenal lymphangioma presenting in a patient with an adrenal cystic lesion and biochemical testing concerning for pheochromocytoma. The pertinent diagnostic and imaging features of adrenal lymphangiomas are reviewed. Methods. We describe a 59-year-old patient who presented with hyperhidrosis and a 2.2 by 2.2 cm left adrenal nodule. Biochemical evaluation revealed elevated plasma-free normetanephrine, urine normetanephrine, urine vanillylmandelic acid, and urine norepinephrine levels. Elevated plasma norepinephrine levels were not suppressed appropriately with clonidine administration. Results. Given persistent concern for pheochromocytoma, the patient underwent adrenalectomy. The final pathology was consistent with adrenal lymphangioma. Conclusions. Lymphangiomas are benign vascular lesions that can very rarely occur in the adrenal gland. Imaging findings are generally consistent with a cyst but are nonspecific. Excluding malignancy in patients presenting with adrenal cysts can be difficult. Despite its benign nature, the diagnosis of adrenal lymphangioma may ultimately require pathology. PMID:26618011

  4. Adrenal cortex dysfunction: CT findings

    SciTech Connect

    Huebener, K.H.; Treugut, H.

    1984-01-01

    The computed tomographic appearance of the adrenal gland was studied in 302 patients with possible endocrinologic disease and 107 patients undergoing CT for nonendocrinologic reasons. Measurements of adrenal size were also made in 100 adults with no known adrenal pathology. CT proved to be a sensitive diagnostic tool in combination with clinical studies. When blood hormone levels are increased, CT can differentiate among homogeneous organic hyperplasia, nodular hyperplasia, benign adenoma, and malignant cortical adenoma. When blood hormone levels are decreased, CT can demonstrate hypoplasia or metastatic tumorous destruction. Calcifications can be demonstrated earlier than on plain radiographs. When hormone elimination is increased, the morphologic substrate can be identified; tumorous changes can be localized and infiltration of surrounding organs recognized.

  5. Adrenal Gland Disorders

    MedlinePlus

    The adrenal glands are small glands located on top of each kidney. They produce hormones that you can't live ... stress and has many other important functions. With adrenal gland disorders, your glands make too much or not ...

  6. Adrenal Gland Cancer

    MedlinePlus

    ... either benign or malignant. Benign tumors aren't cancer. Malignant ones are. Most adrenal gland tumors are ... and may not require treatment. Malignant adrenal gland cancers are uncommon. Types of tumors include Adrenocortical carcinoma - ...

  7. Laparoscopic Adrenal Gland Removal

    MedlinePlus

    ... adrenal tumors that appear malignant. What are the Advantages of Laparoscopic Adrenal Gland Removal? In the past, ... of procedure and the patients overall condition. Common advantages are: Less postoperative pain Shorter hospital stay Quicker ...

  8. Effects of androgen treatment on behavioral and physiological responses of heifers to fear-eliciting situations.

    PubMed

    Boissy, A; Bouissou, M F

    1994-03-01

    Sex steroids are known to influence dominance relationships in cattle. This effect seems due to a reduction of fear in response to conspecifics. In order to determine if gonadal steroid can also modulate fear reactions in nonsocial situations, testosterone-treated heifers were exposed to various events reported to elicit fear in cattle. The experimental subjects received daily im injections of testosterone propionate (0.60 mg/kg body wt) for 100 days while controls received the same volume of the vehicle. In a first experiment, the influence of testosterone treatment on behavioral reactions of animals was studied. Treated heifers were much less fearful than controls: they were less reactive to an unfamiliar environment or to a novel object, and they were also less disturbed by a surprising event. In a second experiment, the effects of androgen treatment on cardiac and adrenal responses were evaluated in another group of subjects placed in the same situations. Whereas heart rates after the fear-eliciting events never differed between groups, the increase in cortisol levels was always lower in treated heifers than that in controls in response to human approach, to a surprising event, and to fear conditioning. Furthermore, after stimulation of the adrenal cortex by ACTH administration, the increase in cortisol levels was twice as great in controls than in treated heifers. Thus, prolonged androgen treatment reduces fearfulness in cattle, at least in some situations. Possible mechanisms by which testosterone influences fear-related behaviors are proposed. PMID:8034283

  9. Adrenal imaging (Part 2): Medullary and secondary adrenal lesions

    PubMed Central

    Dhamija, Ekta; Panda, Ananya; Das, Chandan J.; Gupta, A. K.

    2015-01-01

    Adrenal malignancies can be either primary adrenal tumors or secondary metastases, with metastases representing the most common malignant adrenal lesion. While imaging cannot always clearly differentiate between various adrenal malignancies, presence of certain imaging features, in conjunction with appropriate clinical background and hormonal profile, can suggest the appropriate diagnosis. The second part of the article on adrenal imaging describes adrenal medullary tumors, secondary adrenal lesions, bilateral adrenal lesions, adrenal incidentalomas and provides an algorithmic approach to adrenal lesions based on current imaging recommendations. PMID:25593821

  10. Congenital Adrenal Hyperplasia: Unresolved Issues.

    PubMed

    Yau, Mabel; Khattab, Ahmed; Poppas, Dix; Ghizzoni, Lucia; New, Maria

    2016-01-01

    Congenital adrenal hyperplasia (CAH) describes a family of disorders that comes from enzymatic deficiencies in cortisol production, with 21-hydroxylase deficiency causing ∼90% of cases. Distinction is made between the severe classical form and milder nonclassical form of CAH. Molecular genetic analysis is used to confirm the hormonal diagnosis. A high rate of genotype-phenotype disconcordance has been found in 21-hydroxylase deficiency. The goal of treatment is to replace with synthetic glucocorticoids and mineralocorticoids and suppress adrenal androgen production. The treatment of patients affected with nonclassical CAH, particularly males, remains controversial. Variable synthetic glucocorticoids are used and new modes of glucocorticoid delivery are under investigation. To improve height, growth hormone and other adjuvant therapies are employed. Long-term outcomes of genital surgery using modern techniques in females affected with classical CAH continue to be investigated. Prenatal treatment with dexamethasone is available to avoid ambiguous genitalia in these females. Although studies have shown its safety to mother and fetus, prenatal treatment is still regarded as experimental. Currently, prenatal diagnosis of CAH can only be obtained through invasive methods. Recently, the detection of cell-free fetal DNA in maternal plasma has made it possible to make this diagnosis earlier and noninvasively. PMID:27211889

  11. Endogenous Levels of Circulating Androgens and Risk of Crohn's Disease and Ulcerative Colitis Among Women: A Nested Case–Control Study from the Nurses' Health Study Cohorts

    PubMed Central

    Ananthakrishnan, Ashwin N.; Konijeti, Gauree G.; Higuchi, Leslie M.; Fuchs, Charles S.; Richter, James M.; Tworoger, Shelley S.; Hankinson, Susan E.; Chan, Andrew T.

    2015-01-01

    Background: Androgens, which are known to be altered by exogenous hormone use, have recently been linked to alterations of the gut microbiome and mucosal immune function. No study has evaluated the association between circulating levels of androgens and risk of Crohn's disease (CD) and ulcerative colitis (UC). Methods: We conducted a nested case–control study of women enrolled in the Nurses' Health Study and Nurses' Health Study II who provided a blood specimen. Cases of CD and UC were each matched to 2 controls. Prediagnosis plasma levels of dehydroepiandrosterone sulfate, testosterone, and sex hormone–binding globulin were measured. We examined the association of each analyte with risk of CD or UC using conditional logistic regression models. Results: Compared with women in the lowest quintile of testosterone, the multivariable-adjusted odds ratios for CD were 0.86 (95% confidence interval, 0.39–1.90) for women in the second quintile, 0.49 (95% confidence interval, 0.21–1.15) for the third quartile, 0.22 (0.08–0.65) for the fourth quintile, and 0.39 (95% confidence interval, 0.16–0.99) for the highest quintile (Plinear trend = 0.004). In contrast, we did not observe a consistent association between prediagnostic testosterone and risk of UC (Plinear trend = 0.84). We also did not observe any association between plasma levels of sex hormone–binding globulin or dehydroepiandrosterone sulfate and risk of UC or CD (all Plinear trends > 0.10). Conclusions: Among women, prediagnostic circulating testosterone is associated with a lower risk of CD but not UC. Further studies to understand the biological mechanisms by which endogenous androgens may mediate the etiopathogenesis of CD are warranted. PMID:25844961

  12. Signaling in multiple modalities in male rhesus macaques: sex skin coloration and barks in relation to androgen levels, social status, and mating behavior

    PubMed Central

    Higham, James P.; Pfefferle, Dana; Heistermann, Michael; Maestripieri, Dario; Stevens, Martin

    2014-01-01

    The past decade has seen an increasing shift in animal communication towards more studies that incorporate aspects of signaling in multiple modalities. Although nonhuman primates are an excellent group for studying the extent to which different aspects of condition may be signaled in different modalities, and how such information may be integrated during mate choice, very few studies of primate species have incorporated such analyses. Here, we present data from free-ranging male rhesus macaques on sex skin coloration (modeled to receiver perception), bark vocal signals, androgen levels, morphometric variables, dominance status, and female mate choice. We show that, consistent with data on females, most intra- and interindividual variation in sex skin appearance occurs in luminance rather than color. Sex skin luminance was significantly correlated across different skin regions. Sex skin luminance did not correlate with the majority of bark parameters, suggesting the potential for the two signals to convey different information. Sex skin appearance was not related to androgen levels although we found some evidence for links between androgen levels and bark parameters, several of which were also related to morphometric variables. We found no evidence that either signal was related to male dominance rank or used in female mate choice, though more direct measures of female proceptive behavior are needed. Overall, the function of male sex skin coloration in this species remains unclear. Our study is among the first nonhuman primate studies to incorporate measurements of multiple signals in multiple modalities, and we encourage other authors to incorporate such analyses into their work. PMID:25013266

  13. A case of adrenal Cushing’s syndrome with bilateral adrenal masses

    PubMed Central

    Guo, Ya-Wun; Hwu, Chii-Min; Won, Justin Ging-Shing; Chu, Chia-Huei

    2016-01-01

    Summary A functional lesion in corticotrophin (ACTH)-independent Cushing’s syndrome is difficult to distinguish from lesions of bilateral adrenal masses. Methods for distinguishing these lesions include adrenal venous sampling and 131I-6β-iodomethyl-19-norcholesterol (131I-NP-59) scintigraphy. We present a case of a 29-year-old Han Chinese female patient with a history of hypercholesterolaemia and polycystic ovary syndrome. She presented with a 6month history of an 8kg body weight gain and gradual rounding of the face. Serial examinations revealed loss of circadian rhythm of cortisol, elevated urinary free-cortisol level and undetectable ACTH level (<5pg/mL). No suppression was observed in both the low- and high-dose dexamethasone suppression tests. Adrenal computed tomography revealed bilateral adrenal masses. Adrenal venous sampling was performed, and the right-to-left lateralisation ratio was 14.29. The finding from adrenal scintigraphy with NP-59 was consistent with right adrenal adenoma. The patient underwent laparoscopic right adrenalectomy, and the pathology report showed adrenocortical adenoma. Her postoperative cortisol level was 3.2μg/dL, and her Cushingoid appearance improved. In sum, both adrenal venous sampling and 131I-NP-59 scintigraphy are good diagnostic methods for Cushing’s syndrome presenting with bilateral adrenal masses. Learning points The clinical presentation of Cushing’ syndrome includes symptoms and signs of fat redistribution and protein-wasting features. The diagnosis of patients with ACTH-independent Cushing’s syndrome with bilateral adrenal masses is challenging for localisation of the lesion. Both adrenal venous sampling and 131I-NP-59 scintigraphy are good methods to use in these patients with Cushing’s syndrome presenting with bilateral adrenal masses. PMID:27252858

  14. Steroid 21 hydroxylase deficiency congenital adrenal hyperplasia.

    PubMed

    Nimkarn, Saroj; Lin-Su, Karen; New, Maria I

    2011-10-01

    Steroid 21 hydroxylase deficiency is the most common form of congenital adrenal hyperplasia (CAH). The severity of this disorder depends on the extent of impaired enzymatic activity, which is caused by various mutations of the 21 hydroxylase gene. This article reviews adrenal steroidogenesis and the pathophysiology of 21 hydroxylase deficiency. The three forms of CAH are then discussed in terms of clinical presentation, diagnosis and treatment, and genetic basis. Prenatal diagnosis and treatment are also reviewed. The goal of therapy is to correct the deficiency in cortisol secretion and suppress androgen overproduction. Glucocorticoid replacement has been the mainstay of treatment for CAH, but new treatment strategies continue to be developed and studied. PMID:21981961

  15. Adrenal Insufficiency and Addison's Disease

    MedlinePlus

    ... through hormonal blood and urine tests. A health care provider uses these tests first to determine whether cortisol levels are too ... if the diagnosis remains unclear. [ Top ] What other tests might a health care provider perform after diagnosis of adrenal insufficiency? After ...

  16. Ample Evidence: Dehydroepiandrosterone (DHEA) Conversion into Activated Steroid Hormones Occurs in Adrenal and Ovary in Female Rat

    PubMed Central

    Zhou, Yingqiao; Kang, Jian; Chen, Di; Han, Ningning; Ma, Haitian

    2015-01-01

    Dehydroepiandrosterone (DHEA) is important for human health, especially for women. All estrogens and practically half of androgens are synthesized from DHEA in peripheral tissues. However, the mechanism and exact target tissues of DHEA biotransformation in the female are not fully clear. The present study showed that maximal content of androstenedione (AD) and testosterone (T) were observed at 3h after DHEA administration in female rats, which was 264% and 8000% above the control, respectively. Estradiol (E2) content significantly increased at 6h after DHEA administration, which was 113% higher than that in control group. Gavage with DHEA could significantly reduce 3β-hydroxysteroid dehydrogenase (3β-HSD) mRNA level at 3-12h and 17β-hydroxysteroid dehydrogenase (17β-HSD) mRNA level at 12h in ovary, while increasing aromatase mRNA levels at 6, 24, and 48h. It is interesting that administration of DHEA caused a significant increase of 17β-HSD, 3β-HSD and aromatase mRNA levels in adrenal. The AD and T contents also markedly increased by 537% and 2737% after DHEA administration in ovariectomised rats, in company with a significant increase in 17β-HSD and 3β-HSD mRNA levels and decreased aromatase mRNA level in adrenal. However, DHEA administration did not restore the decreased E2, estrone (E1), and progesterone (P) caused by the removal of the ovaries in females. These results clearly illustrated that exogenous DHEA is preferentially converted into androgens in adrenal, while its conversion to estrogens mainly happens in the ovary through steroidogenic enzyme in female rats. PMID:25962158

  17. Androgens and erythropoiesis: past and present.

    PubMed

    Shahani, S; Braga-Basaria, M; Maggio, M; Basaria, S

    2009-09-01

    Association between androgens and erythropoiesis has been known for more than seven decades. Androgens stimulate hematopoietic system by various mechanisms. These include stimulation of erythropoietin release, increasing bone marrow activity and iron incorporation into the red cells. Before the discovery of recombinant erythropoietin (rhEpo), androgens were used in the treatment of anemia associated with renal disease, bone marrow suppression, and hypopituitarism. Anabolism is an additional advantage of androgen therapy. Furthermore, in light of recent reports regarding adverse effects of rhEpo, the role of androgen therapy in various types of anemias should be readdressed. Polycythemia remains a known side effect of androgen therapy. In this review, we will briefly discuss the initial animal and human studies which demonstrated the role of androgens in the treatment of anemia, their mechanism of action, a detailed account of the efficacy of androgens in the treatment of various anemias, the erythropoietic side effects of androgens and finally, the relationship between hematocrit levels and cardiovascular disease. PMID:19494706

  18. The next 150 years of congenital adrenal hyperplasia.

    PubMed

    Turcu, Adina F; Auchus, Richard J

    2015-09-01

    Congenital adrenal hyperplasias (CAH) are a group of autosomal recessive defects in cortisol biosynthesis. Substantial progress has been made since the description of the first report, 150 years ago. This article reviews some of the recent advances in the genetics, diagnosis and treatment of CAH. In addition, we underline the aspects where further progress is required, including, among others, better diagnostic modalities for the mild phenotype and for some of the rare forms of disease, elucidation of epigenetic factors that lead to different phenotypes in patients with identical genotype and expending on treatment options for controlling the adrenal androgen excess. PMID:26047556

  19. The Next 150 Years of Congenital Adrenal Hyperplasia

    PubMed Central

    Turcu, Adina F.; Auchus, Richard J.

    2015-01-01

    Congenital adrenal hyperplasias (CAH) are a group of autosomal recessive defects in cortisol biosynthesis. Substantial progress has been made since the description of the first report, 150 years ago. This article reviews some of the recent advances in the genetics, diagnosis and treatment of CAH. In addition, we underline the aspects where further progress is required, including, among others, better diagnostic modalities for the mild phenotype and for some of the rare forms of disease, elucidation of epigenetic factors that lead to different phenotypes in patients with identical genotype and expending on treatment options for controlling the adrenal androgen excess. PMID:26047556

  20. Neural control of adrenal medullary and cortical blood flow during hemorrhage

    SciTech Connect

    Breslow, M.J.; Jordan, D.A.; Thellman, S.T.; Traystman, R.J.

    1987-03-01

    Hemorrhagic hypotension produces an increase in adrenal medullary blood flow and a decrease in adrenal cortical blood flow. To determine whether changes in adrenal blood flow during hemorrhage are neurally mediated, the authors compared blood flow responses following adrenal denervation (splanchnic nerve section) with changes in the contralateral, neurally intact adrenal. Carbonized microspheres labeled with /sup 153/Gd, /sup 114/In, /sup 113/Sn, /sup 103/Ru, /sup 95/Nb or /sup 46/Se were used. Blood pressure was reduced and maintained at 60 mmHg for 25 min by hemorrhage into a pressurized bottle system. Adrenal cortical blood flow decreased to 50% of control with hemorrhage in both the intact and denervated adrenal. Adrenal medullary blood flow increased to four times control levels at 15 and 25 min posthemorrhage in the intact adrenal, but was reduced to 50% of control at 3, 5, and 10 min posthemorrhage in the denervated adrenal. In a separate group of dogs, the greater splanchnic nerve on one side was electrically stimulated at 2, 5, or 15 Hz for 40 min. Adrenal medullary blood flow increased 5- to 10-fold in the stimulated adrenal but was unchanged in the contralateral, nonstimulated adrenal. Adrenal cortical blood flow was not affected by nerve stimulation. They conclude that activity of the splanchnic nerve profoundly affects adrenal medullary vessels but not adrenal cortical vessels and mediates the observed increase in adrenal medullary blood flow during hemorrhagic hypotension.

  1. Exercise and Serum Androgens in Women.

    ERIC Educational Resources Information Center

    Westerlind, Kim C.; And Others

    1987-01-01

    This study examining the effect of a 10-week hydraulic resistance exercise program on serum androgen levels, strength, and lean body weight in 18 college women revealed that training did not result in significant increases in androgen hormones, although there were significant gains in strength. (Author/CB)

  2. A clinical update on female androgen insufficiency--testosterone testing and treatment in women presenting with low sexual desire.

    PubMed

    Burger, Henry G; Papalia, Mary-Anne

    2006-05-01

    The diagnosis of female androgen deficiency syndrome is suggested by complaints of a diminished sense of well being, persistent unexplained fatigue and decreased sexual desire, sexual receptivity and pleasure in a woman who is oestrogen-replete and in whom no other significant contributing factors can be identified. The diagnosis is supported by the finding of low circulating concentrations of free testosterone. Barriers to its recognition include the non-specificity of the symptoms and methodological problems due to insensitive testosterone assays. Barriers to its treatment include the unavailability of satisfactory forms of testosterone for administration to women and lack of data regarding long-term safety. Although several conditions lead to clear-cut androgen deficiency, such as hypopituitarism, adrenal and ovarian insufficiency, glucocorticoid therapy and use of oral contraceptives and oral oestrogens, it is important for clinicians to recognise that in normal women, androgen levels decline by 50% from the early 20s to the mid 40s, and hence age-related androgen insufficiency may occur in women in their late 30s and 40s, as well as postmenopausally. Satisfactory measurements of free testosterone requires a sensitive and reliable assay for total testosterone, and quantitation of sex hormone binding globulin, from which free testosterone is readily calculated. Adverse effects of testosterone treatment are few if replacement is monitored to achieve physiological circulating testosterone concentrations. Currently, available methods include testosterone implants and testosterone creams, and transdermal patches and sprays are in development. PMID:16800391

  3. REGULATION OF ADRENAL CHROMAFFIN CELL DEVELOPMENT BY THE CENTRAL MONOAMINERGIC SYSTEM: DIFFERENTIAL CONTROL OF NOREPINEPHRINE AND EPINEPHRINE LEVELS AND SECRETORY RESPONSES (JOURNAL VERSION)

    EPA Science Inventory

    In the mature rat, reflex sympathetic stimulation by insulin-induced hypoglycemia resulted in profound depletion of adrenal epinephrine, and to a lesser extent, Norepinephrine. In the developing rat, insulin evoked little or no secretory response from the adrenals prior to 1 week...

  4. Adrenal function testing.

    PubMed

    Dluhy, R G

    1978-12-01

    Glucocorticoid stimulation and suppression tests are essential to the definitive diagnosis of diseases of the hypothalamic-pituitary-adrenal axis, because they document abnormal physiologic control of hormonal secretion. Similarly, diseases of the renin-angiotensin-aldosterone axis are diagnosed by mineralocorticoid stimulation and suppression testing. [Ed. Note: See Moore TJ, Williams GH: Adrenal causes of hypertension, in this issue.] Unlike tests of glucocorticoid function, testing of the renin-angiotension-aldosterone system is more complicated, because knowledge of posture and dietary sodium are necessary to interpret the results. However, measurement of the tropic hormone renin and plasma levels of aldosterone can be accurately made, allowing precise definition of this system. Errors are most commonly encountered when dynamic tests of cortisol output are performed in patients taking medications that may interfere with the assays or with the metabolism of the administered compounds, such as dexamethasone or metyrapone. Abnormal, spurious values may also be obtained in some individuals who do not have adrenocortical hyperfunction if they are very obese or if testing is performed in a setting of clinical stress. Careful attention to these pitfalls will avoid errors and allow the clinician to arrive at the correct diagnosis. PMID:216524

  5. Increased Expression of Kindlin 2 in Luteinized Granulosa Cells Correlates With Androgen Receptor Level in Patients With Polycystic Ovary Syndrome Having Hyperandrogenemia

    PubMed Central

    Yang, Mei; Du, Juan; Lu, Danyu; Ren, Caixia; Shen, Huan; Qiao, Jie; Zhang, Hongquan

    2014-01-01

    Hyperandrogenemia is the leading defect in patients with polycystic ovary syndrome (PCOS) and considered to be involved in the ovulation dysfunction of PCOS. During the process of ovulation, granulosa cells (GCs) undergo epithelial–mesenchymal transition (EMT), and integrin-interacting protein kindlin 2 is a well-known regulator in EMT. Therefore, our objective here was to compare the expression levels of kindlin 2 in luteinized GCs between patients with PCOS and control women and the relationship between kindlin 2 and PCOS pathogenesis. In this study, kindlin 2 expression was significantly increased in luteinized GCs from patients with PCOS, and kindlin 2 could be induced by testosterone both in vitro and in vivo. Meanwhile, kindlin 2 was positively correlated with androgen receptor (AR) in PCOS GCs. Taken together, kindlin 2 may play a role in luteinized GCs, especially in the case of excess androgen. Further studies are required to assess the specific role of kindlin 2 in follicular development and PCOS pathogenesis. PMID:24336678

  6. Steroid disorders in children: Congenital adrenal hyperplasia and apparent mineralocorticoid excess

    PubMed Central

    New, Maria I.; Wilson, Robert C.

    1999-01-01

    Our research team and laboratories have concentrated on two inherited endocrine disorders, congenital adrenal hyperplasia (CAH) and apparent mineralocorticoid excess, in thier investigations of the pathophysiology of adrenal steroid hormone disorders in children. CAH refers to a family of inherited disorders in which defects occur in one of the enzymatic steps required to synthesize cortisol from cholesterol in the adrenal gland. Because of the impaired cortisol secretion, adrenocorticotropic hormone levels rise due to impairment of a negative feedback system, which results in hyperplasia of the adrenal cortex. The majority of cases is due to 21-hydroxylase deficiency (21-OHD). Owing to the blocked enzymatic step, cortisol precursors accumulate in excess and are converted to potent androgens, which are secreted and cause in utero virilization of the affected female fetus genitalia in the classical form of CAH. A mild form of the 21-OHD, termed nonclassical 21-OHD, is the most common autosomal recessive disorder in humans, and occurs in 1/27 Ashkenazic Jews. Mutations in the CYP21 gene have been identified that cause both classical and nonclassical CAH. Apparent mineralocorticoid excess is a potentially fatal genetic disorder causing severe juvenile hypertension, pre- and postnatal growth failure, and low to undetectable levels of potassium, renin, and aldosterone. It is caused by autosomal recessive mutations in the HSD11B2 gene, which result in a deficiency of 11β-hydroxysteroid dehydrogenase type 2. In 1998, we reported a mild form of this disease, which may represent an important cause of low-renin hypertension. PMID:10536001

  7. Evaluation of the glucocorticoid, mineralocorticoid, and adrenal androgen secretion dynamics in a large cohort of patients aged 6-18 years with transfusion-dependent β-thalassemia major, with an emphasis on the impact of cardiac iron load.

    PubMed

    Uçar, Ahmet; Öner, Nergiz; Özek, Gülcihan; Çetinçakmak, Mehmet Güli; Abuhandan, Mahmut; Yıldırım, Ali; Kaya, Cemil; Ünverdi, Sena; Emeksiz, Hamdi Cihan; Yılmaz, Yasin; Yetim, Aylin

    2016-07-01

    The variable presence of adrenal insufficiency (AI) due to hypocortisolemia (HC) in patients with thalassemia is well established; however, the prevalence of adrenocortical hypofunction (ACH) in the zona glomerulosa and zona reticularis of the adrenal cortex is unknown. To establish the prevalence of ACH, we examined the cortisol response to 1-µg and 250-µg ACTH tests, plasma aldosterone (A)/plasma renin activity (PRA) ratio, and serum dehydroepiandrosterone sulfate (DHEAS) levels in a large cohort of patients with thalassemia, and to investigate the impact of total body iron load (TBIL) on adrenocortical function. The setting used was University hospital and government-based tertiary care center. One hundred twenty-one (52 females) patients with β-thalassemia major (β-TM) and 72 healthy peers (38 females) were enrolled. The patients underwent a 250-µg cosyntropin test if their peak cortisol was <500 nmol/L in a 1-µg cosyntropin test. Magnetic resonance imaging (MRI) was performed to assess the MRI-based liver iron content and cardiac MRI T2* iron. The associations between ACH and TBIL were investigated. The patients with thalassemia had lower ACTH, cortisol, DHEAS, and A/PRA values compared with the controls (p < 0.001). Thirty-nine patients (32.2 %) had HC [primary (n = 1), central (n = 36), combined (n = 2)], and 47 (38.8 %) patients had reduced DHEAS levels; 29 (24.0 %) patients had reduced A/PRA ratios. Forty-six (38.0 %) patients had hypofunction in one of the adrenal zones, 26 (21.5 %) had hypofunction in two adrenal zones, and 9 (7.4 %) had hypofunction in all three zones. Patient age and TBIL surrogates were significant independent parameters associated with ACH. Cardiac MRI T2* iron was the only significant parameter that predicted the severity of ACH at a cut-off of 20.6 ms, with 81 % sensitivity and 78 % specificity. Patients with thalassemia have a high prevalence of AI due to HC and zona glomerulosa and zona reticularis

  8. Congenital Adrenal Hyperplasia

    PubMed Central

    Speiser, Phyllis W.

    2015-01-01

    Congenital adrenal hyperplasia associated with deficiency of steroid 21-hydroxylase is the most common inborn error in adrenal function and the most common cause of adrenal insufficiency in the pediatric age group. As patients now survive into adulthood, adult health-care providers must also be familiar with this condition. Over the past several years, F1000 has published numerous commentaries updating research and practical guidelines for this condition. The purposes of this review are to summarize basic information defining congenital adrenal hyperplasia and to highlight current knowledge and controversies in management. PMID:26339484

  9. Antiandrogens and androgen depleting therapies in prostate cancer: novel agents for an established target

    PubMed Central

    Chen, Yu; Clegg, Nicola J.; Scher, Howard I

    2010-01-01

    Summary Activation of the androgen receptor is critical for prostate cancer growth at all points in the illness. Currently therapies targeting the androgen receptor, including androgen depletion approaches and antiandrogens, do not completely inhibit androgen receptor activity. Prostate cancer cells develop resistance to castration by acquiring changes such as AR overexpression that result in reactivation of the receptor. Based on understanding of these resistance mechanisms and androgen synthesis pathways, novel antiandrogens and androgen depleting agents have been tested. Notably, MDV3100, a novel antiandrogen designed for activity in prostate cancer model systems with overexpressed AR and, abiraterone acetate, a 17-α-hydroxylase/17,20 lyase inhibitor that blocks steroid biosynthesis in the adrenal gland and in the tumor, have demonstrated significant activity in early phase trials and are being tested in the phase III setting. PMID:19796750

  10. Androgen-responsive gene database: integrated knowledge on androgen-responsive genes.

    PubMed

    Jiang, Mei; Ma, Yunsheng; Chen, Congcong; Fu, Xuping; Yang, Shu; Li, Xia; Yu, Guohua; Mao, Yumin; Xie, Yi; Li, Yao

    2009-11-01

    Androgen signaling plays an important role in many biological processes. Androgen Responsive Gene Database (ARGDB) is devoted to providing integrated knowledge on androgen-controlled genes. Gene records were collected on the basis of PubMed literature collections. More than 6000 abstracts and 950 original publications were manually screened, leading to 1785 human genes, 993 mouse genes, and 583 rat genes finally included in the database. All the collected genes were experimentally proved to be regulated by androgen at the expression level or to contain androgen-responsive regions. For each gene important details of the androgen regulation experiments were collected from references, such as expression change, androgen-responsive sequence, response time, tissue/cell type, experimental method, ligand identity, and androgen amount, which will facilitate further evaluation by researchers. Furthermore, the database was integrated with multiple annotation resources, including National Center for Biotechnology Information, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway, to reveal the biological characteristics and significance of androgen-regulated genes. The ARGDB web site is mainly composed of the Browse, Search, Element Scan, and Submission modules. It is user friendly and freely accessible at http://argdb.fudan.edu.cn. Preliminary analysis of the collected data was performed. Many disease pathways, such as prostate carcinogenesis, were found to be enriched in androgen-regulated genes. The discovered androgen-response motifs were similar to those in previous reports. The analysis results are displayed in the web site. In conclusion, ARGDB provides a unified gateway to storage, retrieval, and update of information on androgen-regulated genes. PMID:19762544

  11. Androgen regulation of adrenocorticotropin and corticosterone secretion in the male rat following novelty and foot shock stressors.

    PubMed

    Handa, R J; Nunley, K M; Lorens, S A; Louie, J P; McGivern, R F; Bollnow, M R

    1994-01-01

    To examine mechanisms responsible for sex differences in hypothalamo-pituitary-adrenal (HPA) axis responsiveness to stress, we studied the role of androgens in the regulation of the adrenocorticotropin (ACTH) and corticosterone (CORT) responses to foot shock and novelty stressors in gonadectomized (GDX) or intact male F344 rats. Foot shock or exposure to a novel open field increased plasma ACTH and CORT, which was significantly greater in GDX vs. intacts. Testosterone (T) or dihydrotestosterone propionate (DHT) treatment of GDX animals returned poststress levels of ACTH and CORT to intact levels. Estrogen treatment of GDX males further increased poststress CORT secretion above GDX levels. There was no difference in the ACTH response of anterior pituitaries from intact, GDX, and GDX+DHT animals to CRF using an in vitro perifusion system. There were no differences in beta max or binding affinity of type I or II CORT receptors in the hypothalamus or hippocampus of intact, GDX, or GDX+DHT groups. These data demonstrate an effect of GDX on hormonal indices of stress. The increased response in GDX rats appears to be due to the release from androgen receptor mediated inhibition of the HPA axis. This inhibition by androgen is not due to changes in anterior pituitary sensitivity to CRH, nor to changes in type I or type II corticosteroid receptor concentrations. PMID:8140154

  12. Androgen receptor-mediated regulation of adrenocortical activity in the sand rat, Psammomys obesus.

    PubMed

    Benmouloud, Abdelouafi; Amirat, Zaina; Khammar, Farida; Patchev, Alexandre V; Exbrayat, Jean M; Almeida, Osborne F X

    2014-12-01

    The wild sand rat, Psammomys obesus, displays seasonal variations in adrenocortical activity that parallel those of testicular activity, indicating functional cross-talk between the hypothalamo-pituitary-adrenal and hypothalamo-pituitary-gonadal axes. In the present study, we examined androgen receptor (AR)-mediated actions of testicular steroids in the regulation of adrenocortical function in the sand rat. Specifically, we examined the expression of AR in the adrenal cortex, as well as adrenal apoptosis in male sand rats that had been surgically castrated or castrated and supplemented with testosterone; biochemical indices of adrenocortical function and hormone profiles were also measured. Orchiectomy was followed by an increase in adrenocorticotropic hormone secretion from the anterior pituitary and subsequently, increased adrenocortical activity; the latter was evidenced by orchiectomy-induced increases in the adrenal content of cholesterol and lipids as well as adrenal hypertrophy (seen as an elevation of the RNA/DNA ratio). Further, androgen deprivation respectively up- and downregulated the incidence of apoptosis within the glucocorticoid-producing zona fasciculata and sex steroid-producing zona reticularis. Interestingly, orchiectomy resulted in increased expression of AR in the zona fasciculata. All of the orchiectomy-induced cellular and biochemical responses were reversible after testosterone substitution therapy. Together, these data suggest that adrenocortical activity in the sand rat is seasonally modulated by testicular androgens that act through AR located in the adrenal cortex itself. PMID:25179180

  13. A validated UHPLC-MS/MS method to quantify low levels of anabolic-androgenic steroids naturally present in urine of untreated horses.

    PubMed

    Decloedt, Anneleen; Bailly-Chouriberry, Ludovic; Vanden Bussche, Julie; Garcia, Patrice; Popot, Marie-Agnes; Bonnaire, Yves; Vanhaecke, Lynn

    2015-06-01

    Doping control is a main priority for regulatory bodies of both the horse racing industry and the equestrian sports. Urine and blood samples are screened for the presence of hundreds of forbidden substances including anabolic-androgenic steroids (AASs). Based on the suspected endogenous origin of some AASs, with β-boldenone as the most illicit candidate, this study aimed to improve the knowledge of the naturally present AAS in horse urine. To this extent, a novel ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated according to the Association of Official Racing Chemists (AORC) and European Commission (EC) guidelines, proving the power of this new method. Low limits of detection (0.2 ng/mL), good reproducibility (percentage of standard deviation (%RSD) < 10%), high recovery (94.6 to 117.1%), selectivity and specificity, and a linear response (confirmed with R(2) > 0.99 and lack-of-fit analysis) were obtained for all included AASs. With this method, urine samples of 105 guaranteed untreated horses (47 geldings, 53 mares, and 5 stallions serving as a control) were screened for β-boldenone and five related natural steroids: androstadienedione (ADD), androstenedione (AED), alpha-testosterone (αT), beta-testosterone (βT), and progesterone (P). Progesterone, β-testosterone, and α-testosterone were detected in more than half of the horses at low concentrations (<2 ng/mL). Occasionally, not only testosterone and progesterone but also low concentrations of AED, ADD, and boldenone (Bol) were found (0.5-5 ng/mL). Graphical Abstract A sensitive, new and fully validated UHPLC-MS/MS method has been developed that is able to quantify low levels of anabolic-androgenic steroids naturally present in urine of untreated horses (mares and geldings). PMID:25595834

  14. Sexual Differentiation of Circadian Clock Function in the Adrenal Gland.

    PubMed

    Kloehn, Ian; Pillai, Savin B; Officer, Laurel; Klement, Claire; Gasser, Paul J; Evans, Jennifer A

    2016-05-01

    Sex differences in glucocorticoid production are associated with increased responsiveness of the adrenal gland in females. However, the adrenal-intrinsic mechanisms that establish sexual dimorphic function remain ill defined. Glucocorticoid production is gated at the molecular level by the circadian clock, which may contribute to sexual dimorphic adrenal function. Here we examine sex differences in the adrenal gland using an optical reporter of circadian clock function. Adrenal glands were cultured from male and female Period2::Luciferase (PER2::LUC) mice to assess clock function in vitro in real time. We confirm that there is a pronounced sex difference in the intrinsic capacity to sustain PER2::LUC rhythms in vitro, with higher amplitude rhythms in adrenal glands collected from males than from females. Changes in adrenal PER2::LUC rhythms over the reproductive life span implicate T as an important factor in driving sex differences in adrenal clock function. By directly manipulating hormone levels in adult mice in vivo, we demonstrate that T increases the amplitude of PER2::LUC rhythms in adrenal glands of both male and female mice. In contrast, we find little evidence that ovarian hormones modify adrenal clock function. Lastly, we find that T in vitro can increase the amplitude of PER2::LUC rhythms in male adrenals but not female adrenals, which suggests the existence of sex differences in the mechanisms of T action in vivo. Collectively these results reveal that activational effects of T alter circadian timekeeping in the adrenal gland, which may have implications for sex differences in stress reactivity and stress-related disorders. PMID:27007073

  15. The effect of anabolic-androgenic steroids on aromatase activity and androgen receptor binding in the rat preoptic area.

    PubMed

    Roselli, C E

    1998-05-11

    The level of aromatase in the preoptic area of rats is transcriptionally regulated through a specific androgen-receptor mediated mechanism and can be used as a measure of central androgenic effect. Therefore, several commonly abused anabolic-androgenic steroids (AAS) were tested for their ability to induce aromatase activity in the preoptic area of castrated rats. In addition, we determined the relative binding affinities of these compounds for the androgen receptor, as well as their ability to bind androgen receptor in vivo following subcutaneous injections. All of the AAS compounds tested significantly stimulated POA aromatase activity above castrate levels. The compounds that produced the greatest stimulation of aromatase activity were those that bound most avidly to the androgen receptor in vitro (i.e., testosterone, dihydrotestosterone and nandrolone). In contrast, the 17alpha-alkylated compounds that were tested (stanozolol, danazol, methandrostenolone) modestly stimulated aromatase and were weak competitors for the androgen receptor. The subcutaneous injection of AAS compounds increased the concentrations of occupied nuclear androgen receptors in the brain, but the magnitude of effect was not related to their potency for inducing aromatase or their relative binding affinity for the androgen receptor suggesting that androgen receptor occupancy in POA is not correlated with the action of androgen on aromatase. The present results help explain the behavioral effects of AAS compounds in rats. PMID:9593936

  16. Steroid Sulfatase Deficiency and Androgen Activation Before and After Puberty

    PubMed Central

    Idkowiak, Jan; Taylor, Angela E.; Subtil, Sandra; O'Neil, Donna M.; Vijzelaar, Raymon; Dias, Renuka P.; Amin, Rakesh; Barrett, Timothy G.; Shackleton, Cedric H. L.; Kirk, Jeremy M. W.; Moss, Celia

    2016-01-01

    Context: Steroid sulfatase (STS) cleaves the sulfate moiety off steroid sulfates, including dehydroepiandrosterone (DHEA) sulfate (DHEAS), the inactive sulfate ester of the adrenal androgen precursor DHEA. Deficient DHEA sulfation, the opposite enzymatic reaction to that catalyzed by STS, results in androgen excess by increased conversion of DHEA to active androgens. STS deficiency (STSD) due to deletions or inactivating mutations in the X-linked STS gene manifests with ichthyosis, but androgen synthesis and metabolism in STSD have not been studied in detail yet. Patients and Methods: We carried out a cross-sectional study in 30 males with STSD (age 6–27 y; 13 prepubertal, 5 peripubertal, and 12 postpubertal) and 38 age-, sex-, and Tanner stage-matched healthy controls. Serum and 24-hour urine steroid metabolome analysis was performed by mass spectrometry and genetic analysis of the STS gene by multiplex ligation-dependent probe amplification and Sanger sequencing. Results: Genetic analysis showed STS mutations in all patients, comprising 27 complete gene deletions, 1 intragenic deletion and 2 missense mutations. STSD patients had apparently normal pubertal development. Serum and 24-hour urinary DHEAS were increased in STSD, whereas serum DHEA and testosterone were decreased. However, total 24-hour urinary androgen excretion was similar to controls, with evidence of increased 5α-reductase activity in STSD. Prepubertal healthy controls showed a marked increase in the serum DHEA to DHEAS ratio that was absent in postpubertal controls and in STSD patients of any pubertal stage. Conclusions: In STSD patients, an increased 5α-reductase activity appears to compensate for a reduced rate of androgen generation by enhancing peripheral androgen activation in affected patients. In healthy controls, we discovered a prepubertal surge in the serum DHEA to DHEAS ratio that was absent in STSD, indicative of physiologically up-regulated STS activity before puberty. This may

  17. Androgens and sexuality.

    PubMed

    Hutchinson, K A

    1995-01-16

    A review of the literature reveals that the endocrine determinants of female sexuality are complex and difficult to characterize. In adolescent males, free testosterone directly affects sexual motivation, with social factors exerting little or no effect. In adolescent girls, by contrast, societal and peer pressure play a pivotal role in the appearance of certain sexual behaviors. Throughout a woman's life, hormonal and psychosocial factors are critical influences. It is possible that cyclic patterns of testosterone are less important for female sexual behavior than the "tonic" effect of overall testosterone levels. Although the estrogen dependence of the vaginal epithelium--important for postmenopausal women--has been clearly established, the role of other hormonal factors and treatments, particularly those involving androgens, in human female sexual behavior remains enigmatic. The search for an understanding of these relationships is not merely an interesting academic exercise but is necessary to determine what role, if any, androgens may play in the treatment of sexual dysfunction during the female reproductive years. PMID:7825630

  18. Adolescents and Androgens, Receptors and Rewards

    PubMed Central

    Sato, Satoru M.; Schulz, Kalynn M.; Sisk, Cheryl L.; Wood, Ruth I.

    2008-01-01

    Adolescence is associated with increases in pleasure-seeking behaviors, which, in turn, are shaped by the pubertal activation of the hypothalamo-pituitary-gonadal axis. In animal models of naturally rewarding behaviors, such as sex, testicular androgens contribute to the development and expression of the behavior in males. To effect behavioral maturation, the brain undergoes significant remodeling during adolescence, and many of the changes are likewise sensitive to androgens, presumably acting through androgen receptors (AR). Given the delicate interaction of gonadal hormones and brain development, it is no surprise that disruption of hormone levels during this sensitive period significantly alters adolescent and adult behaviors. In male hamsters, exposure to testosterone during adolescence is required for normal expression of adult sexual behavior. Males deprived of androgens during puberty display sustained deficits in mating. Conversely, androgens alone are not sufficient to induce mating in prepubertal males, even though brain AR are present before puberty. In this context, wide-spread use of anabolic-androgenic steroids (AAS) during adolescence is a significant concern. AAS abuse has the potential to alter both the timing and the levels of androgens in adolescent males. In hamsters, adolescent AAS exposure increases aggression, and causes lasting changes in neurotransmitter systems. In addition, AAS are themselves reinforcing, as demonstrated by self-administration of testosterone and other AAS. However, recent evidence suggests that the reinforcing effects of androgens may not require classical AR. Therefore, further examination of interactions between androgens and rewarding behaviors in the adolescent brain is required for a better understanding of AAS abuse. PMID:18343381

  19. Androgen Receptors in the Posterior Bed Nucleus of the Stria Terminalis Increase Neuropeptide Expression and the Stress-Induced Activation of the Paraventricular Nucleus of the Hypothalamus

    PubMed Central

    Bingham, Brenda; Myung, Clara; Innala, Leyla; Gray, Megan; Anonuevo, Adam; Viau, Victor

    2011-01-01

    The posterior bed nuclei of the stria terminalis (BST) are important neural substrate for relaying limbic influences to the paraventricular nucleus (PVN) of the hypothalamus to inhibit hypothalamic-pituitary-adrenal (HPA) axis responses to emotional stress. Androgen receptor-expressing cells within the posterior BST have been identified as projecting to the PVN region. To test a role for androgen receptors in the posterior BST to inhibit PVN motor neurons, we compared the effects of the non-aromatizable androgen dihydrotestosterone (DHT), the androgen receptor antagonist hydroxyflutamide (HF), or a combination of both drugs implanted unilaterally within the posterior BST. Rats bearing unilateral implants were analyzed for PVN Fos induction in response to acute-restraint stress and relative levels of corticotrophin-releasing hormone and arginine vasopressin (AVP) mRNA. Glutamic acid decarboxylase (GAD) 65 and GAD 67 mRNA were analyzed in the posterior BST to test a local involvement of GABA. There were no changes in GAD expression to support a GABA-related mechanism in the BST. For PVN neuropeptide expression and Fos responses, basic effects were lateralized to the sides of the PVN ipsilateral to the implants. However, opposite to our expectations of an inhibitory influence of androgen receptors in the posterior BST, PVN AVP mRNA and stress-induced Fos were augmented in response to DHT and attenuated in response to HF. These results suggest that a subset of androgen receptor-expressing cells within the posterior BST region may be responsible for increasing the biosynthetic capacity and stress-induced drive of PVN motor neurons. PMID:21412226

  20. Adipose Tissue and Adrenal Glands: Novel Pathophysiological Mechanisms and Clinical Applications

    PubMed Central

    Kargi, Atil Y.; Iacobellis, Gianluca

    2014-01-01

    Hormones produced by the adrenal glands and adipose tissues have important roles in normal physiology and are altered in many disease states. Obesity is associated with changes in adrenal function, including increase in adrenal medullary catecholamine output, alterations of the hypothalamic-pituitary-adrenal (HPA) axis, elevations in circulating aldosterone together with changes in adipose tissue glucocorticoid metabolism, and enhanced adipocyte mineralocorticoid receptor activity. It is unknown whether these changes in adrenal endocrine function are in part responsible for the pathogenesis of obesity and related comorbidities or represent an adaptive response. In turn, adipose tissue hormones or “adipokines” have direct effects on the adrenal glands and interact with adrenal hormones at several levels. Here we review the emerging evidence supporting the existence of “cross talk” between the adrenal gland and adipose tissue, focusing on the relevance and roles of their respective hormones in health and disease states including obesity, metabolic syndrome, and primary disorders of the adrenals. PMID:25018768

  1. Acute adrenal crisis

    MedlinePlus

    ... cortisol and adrenaline are released in response to stress . Cortisol production is regulated by the pituitary gland. This ... adrenal crisis include: Dehydration Infection and other physical ... medicines such as prednisone or hydrocortisone Surgery Trauma

  2. Hemoglobin levels do not predict biochemical outcome for localized prostate cancer treated with neoadjuvant androgen-suppression therapy and external-beam radiotherapy

    SciTech Connect

    Pai, Howard Huaihan . E-mail: hpai@bccancer.bc.ca; Ludgate, Charles; Pickles, Tom; Paltiel, Chuck M.Sc.; Agranovich, Alex; Berthelet, Eric; Duncan, Graeme; Kim-Sing, Charmaine; Kwan, Winkle; Lim, Jan; Liu, Mitchell; Tyldesley, Scott

    2006-07-15

    Purpose: To investigate whether hemoglobin (Hb) levels affect outcome in men with localized prostate adenocarcinoma (LPA) treated with neoadjuvant androgen-suppression therapy (NAST) and external-beam radiotherapy (EBRT). Methods and Materials: A total of 563 men with LPA treated with NAST (median: 5.3 months) and EBRT who had Hb levels during treatment were retrospectively reviewed. Patient, tumor, and treatment variables, including the following Hb variables, were subjected to univariate and multivariable analyses to identify factors that predict biochemical control (bNED) and overall survival (OS): pre-EBRT Hb, Hb nadir during EBRT, and change in Hb from pre-EBRT to nadir during EBRT. Results: Median PSA follow-up was 4.25 years. Forty-nine percent of men were anemic during EBRT, with a median Hb of 13.4 g/dL, and 68% experienced a decline in Hb from pre-EBRT to during EBRT of median 0.6 g/dL. Five-year Nadir + 2 bNED and OS rates were similar for anemic and nonanemic patients during EBRT. High percent-positive biopsies, PSA and Gleason score, and use of AA monotherapy predicted worse bNED. High stage and age predicted worse OS. Hb variables were not predictive of bNED or OS. Conclusions: Anemia is a common side effect of NAST and is usually mild. Hb levels, however, do not predict biochemical control or survival.

  3. Breeding under unpredictable conditions: Annual variation in gonadal maturation, energetic reserves and plasma levels of androgens and corticosterone in anurans from the Brazilian semi-arid.

    PubMed

    Madelaire, Carla Bonetti; Gomes, Fernando Ribeiro

    2016-03-01

    Anurans living in arid and semi-arid habitats are subjected to unpredictable rain patterns. Consequently, they should be prepared to reproduce at the onset of rain events. We investigated the covariation between calling behavior, testicular maturation, abdominal fat body index (FBI), plasma levels of androgens (T-DHT) and corticosterone (CORT) of males from three species of anurans in the Brazilian semi-arid during the reproductive period and drought. One of these species aestivates during the drought, while the other two species remain foraging. Although the three species display different behavioral strategies during the dry period, they present the same general reproductive patterns. T-DHT levels on the plasma and germinative cyst diameters were higher during the reproductive and breeding period compared to the drought. Additionally, the germinative cysts had all cell stages including sperm bundles during the dry season, however, it was only during the breeding event that free spermatozoa were found in the cyst lumen. These results suggest that these species present the reproductive pattern typical of desert anurans, consisting of opportunistic breeders that reproduce when triggered by a rain stimulus. Rhinella jimi and Pleurodema diplolister had higher CORT when males were calling. Moreover, Rhinella granulosa and P. diplolister showed lower FBI during breeding event, when males were calling. The high levels of CORT and lower FBI during reproductive period are associated, indicating that CORT modulates the recruitment of energy stores to prepare and maintain reproduction, particularly the expensive calling effort. PMID:26808964

  4. Pilot Study on the Effect of Botanical Medicine (Tribulus terrestris) on Serum Testosterone Level and Erectile Function in Aging Males With Partial Androgen Deficiency (PADAM).

    PubMed

    Roaiah, Mohamed Farid; El Khayat, Yasser Ibrahim; GamalEl Din, Sameh Fayek; Abd El Salam, Mohamed Ahmed

    2016-05-18

    This study was conducted on 30 consecutive male patients presenting to Kasr-Al Ainy Andrology outpatient clinic complaining of manifestations of partial androgen deficiency in aging males (PADAM). In this study (750 mg/day) of Tribulus terrestris in 3 divided doses, each of 250 mg, as an endogenous testosterone enhancer had been tried for a duration of 3 months and the evaluation of its effect had been monitored for each patient concerning its effect on serum testosterone (total and free) and luteinizing hormone (LH), as well as its impact on erectile function, which was evaluated by the International Index of Erectile Function-5 (IIEF-5) questionnaire for those patients. Results showed a statistically significant difference in the level of testosterone (total and free) and IIEF-5, but no statistically significant difference in the level of LH before and after treatment. Also, the study showed statistically significant correlation between testosterone (total and free) and IIEF-5, but no statistically significant correlation between the level of LH and the IIEF-5 before and after treatment. PMID:25849625

  5. Multi-Level Risk Factors for Suicidal Ideation Among at-Risk Adolescent Females: The Role of Hypothalamic-Pituitary-Adrenal Axis Responses to Stress.

    PubMed

    Giletta, Matteo; Calhoun, Casey D; Hastings, Paul D; Rudolph, Karen D; Nock, Matthew K; Prinstein, Mitchell J

    2015-07-01

    Adopting a multi-level approach, this study examined risk factors for adolescent suicidal ideation, with specific attention to (a) hypothalamic-pituitary-adrenal (HPA) axis stress responses and (b) the interplay between HPA-axis and other risk factors from multiple domains (i.e., psychological, interpersonal and biological). Participants were 138 adolescent females (M(age) = 14.13 years, SD = 1.40) at risk for suicidal behaviors. At baseline, lifetime suicidal ideation and a number of risk factors were assessed (i.e., depressive symptoms, impulsiveness, pubertal status and peer stress). Participants were exposed to a psychosocial stress task and HPA-axis responses were assessed by measuring cortisol levels pre- and post-stressor. At 3 months post-baseline, suicidal ideation again was assessed. Using group-based trajectory modeling, three groups of cortisol stress-response patterns were identified (i.e., hyporesponsive, normative, and hyperresponsive). As compared to females in the normative and hyporesponsive group, females in the hyperresponsive group were more likely to report a lifetime history of suicidal ideation at baseline, above and beyond the effects of the other predictors. Moreover, as compared to females in the normative group, females in the hyperresponsive group were at increased risk for reporting suicidal ideation 3 months later, after controlling for prior ideation. No interactions between cortisol group and the other risk factors were significant, with the exception of a non-significant trend between impulsiveness and cortisol group on lifetime suicidal ideation. Findings highlight the importance of HPA-axis responses to acute stressors as a risk factor for suicidal ideation among adolescents. PMID:24958308

  6. Multi-Level Risk Factors for Suicidal Ideation Among at-Risk Adolescent Females: The Role of Hypothalamic-Pituitary-Adrenal Axis Responses to Stress

    PubMed Central

    Calhoun, Casey D.; Hastings, Paul D.; Rudolph, Karen D.; Nock, Matthew K.; Prinstein, Mitchell J.

    2014-01-01

    Adopting a multi-level approach, this study examined risk factors for adolescent suicidal ideation, with specific attention to (a) hypothalamic-pituitary-adrenal (HPA) axis stress responses and (b) the interplay between HPA-axis and other risk factors from multiple domains (i.e., psychological, interpersonal and biological). Participants were 138 adolescent females (Mage=14.13 years, SD=1.40) at risk for suicidal behaviors. At baseline, lifetime suicidal ideation and a number of risk factors were assessed (i.e., depressive symptoms, impulsiveness, pubertal status and peer stress). Participants were exposed to a psychosocial stress task and HPA-axis responses were assessed by measuring cortisol levels pre- and post-stressor. At 3 months post-baseline, suicidal ideation again was assessed. Using group-based trajectory modeling, three groups of cortisol stress-response patterns were identified (i.e., hyporesponsive, normative, and hyperresponsive). As compared to females in the normative and hyporesponsive group, females in the hyperresponsive group were more likely to report a lifetime history of suicidal ideation at baseline, above and beyond the effects of the other predictors. Moreover, as compared to females in the normative group, females in the hyperresponsive group were at increased risk for reporting suicidal ideation 3 months later, after controlling for prior ideation. No interactions between cortisol group and the other risk factors were significant, with the exception of a non-significant trend between impulsiveness and cortisol group on lifetime suicidal ideation. Findings highlight the importance of HPA-axis responses to acute stressors as a risk factor for suicidal ideation among adolescents. PMID:24958308

  7. Quality of life in patients with adrenal insufficiency correlates stronger with hydrocortisone dosage, than with long-term systemic cortisol levels.

    PubMed

    Andela, Cornelie D; Staufenbiel, Sabine M; Joustra, Sjoerd D; Pereira, Alberto M; van Rossum, Elisabeth F C; Biermasz, Nienke R

    2016-10-01

    In patients with adrenal insufficiency (AI) a higher hydrocortisone intake has been associated with more impairment in quality of life (QoL). Irrespective of age, sex and severity of AI the dosage of hydrocortisone is titrated around 20mg/D in all patients with AI based on physical and mental signs and symptoms. However, until now it is unknown whether these QoL impairments are related to increased systemic cortisol exposure. Measurement of hair cortisol levels (CORThair) can be used to assess chronic systemic cortisol exposure. This study aimed to explore whether QoL in patients with AI is associated with CORThair and daily hydrocortisone intake. We performed a cross-sectional study in 120 patients with AI on stable hydrocortisone replacement, in whom hair samples and QoL data were collected. CORThair were measured with ELISA, and QoL was assessed with validated questionnaires (SF-36, EQ-5D, HADS, MFI-20). Patients reported impairments in 14 of 15 QoL subscales (p<0.001). More impairments in physical aspects of QoL correlated with higher CORThair and higher daily hydrocortisone intake (p<0.05), an effect that was more pronounced in female patients. Regression analyses including both CORThair and hydrocortisone intake revealed a significant negative contribution of higher hydrocortisone intake on physical aspects of QoL (p≤0.046), whereas no significant contribution was found for CORThair. The present study showed that patients with AI report several impairments in QoL which are associated with hydrocortisone intake, and to a lesser extent reflected by chronic systemic cortisol exposure as measured by hair cortisol. This suggests that QoL impairments in patients with AI are not per se the effect of prolonged exposure to elevated systemic cortisol levels. PMID:27388687

  8. Androstenedione and testosterone biosynthesis by the adrenal cortex of the horse

    SciTech Connect

    Silberzahn, P.; Rashed, F.; Zwain, I.; Leymarie, P.

    1984-02-01

    An homogenate from cortical tissue of mare adrenals was incubated in the presence of tritiated pregnenolone. The (/sup 3/H) androstenedione and the (/sup 3/H) testosterone synthesized during the incubation were extracted, purified, and co-crystallized to constant specific activity in the presence of unlabeled carriers. The rate of conversion of pregnenolone to androstenedione and testosterone was of the order of 5 and 0.15 per cent respectively. The high ratio of (/sup 3/H) androstenedione to (/sup 3/H) testosterone observed in this study suggests that androstenedione is the main androgen produced by mare adrenals. It is concluded that adrenals could contribute to the production of blood androgens in normal as well as hyperandrogenic mares.

  9. Long-term androgen deprivation therapy improves survival in prostate cancer patients presenting with prostate-specific antigen levels >20 ng/mL

    SciTech Connect

    Berthelet, Eric . E-mail: eberthel@bccancer.bc.ca; Pickles, Tom; Lee, Kenny Won Jae; Liu, Mitchell; Truong, Pauline T.

    2005-11-01

    Purpose: To assess the benefit of androgen deprivation (AD) and its optimal duration in patients with prostate cancer treated with external beam radiotherapy, who present with prostate-specific antigen levels >20 ng/mL. Methods and Materials: A total of 307 patients treated with external beam radiotherapy, AD, and presenting with a PSA level >20 ng/mL were identified from the Prostate Cancer Outcomes Initiative database of the British Columbia Cancer Agency. Androgen deprivation was defined as short term (ST-AD, <12 months) or long term (LT-AD, {>=}12 months). The endpoints analyzed were biochemical control (no evidence of disease) (bNED), overall survival, and cause-specific survival. Statistical analysis was conducted with Kaplan-Meier estimates, log-rank tests, and multivariate analyses with logistic and Cox regression models. Results: There were 151 patients in the ST-AD group and 156 in the LT-AD group. The distributions of Gleason score and stage were comparable in the two cohorts. Median follow-up times were 48 months for patients treated with ST-AD and 45 months for patients treated with LT-AD. The median durations of AD were 6 and 25.6 months for the ST-AD and LT-AD groups, respectively. The bNED rate was 37% for the ST-AD group and 62.5% for the LT-AD group (p < 0.0001). The 5-year overall survival rate was 75% in the ST-AD group vs. 87.5% for the LT-AD group (p = 0.0091). The 5-year cause-specific survival rate was 82% for the ST-AD group vs. 94% for the LT-AD group (p = 0.0072). Conclusions: Several randomized trials have demonstrated the benefit of LT-AD in high-risk patients with prostate cancer. In some reports, the survival advantage seems to be restricted to patients with high Gleason score. The present analysis supports the hypothesis that LT-AD improves bNED and survival rates in patients presenting with a PSA level >20, irrespective of Gleason score or T stage.

  10. Recommendations for Treatment of Nonclassic Congenital Adrenal Hyperplasia (NCCAH): an Update

    PubMed Central

    Trapp, Christine M.; Oberfield, Sharon E.

    2013-01-01

    Congenital adrenal hyperplasia (CAH) is a family of autosomal recessive disorders. 21-hydroxylase deficiency, in which there are mutations in CYP21A2 (the gene encoding the adrenal 21-hydroxylase enzyme), is the most common form (90%) of CAH. In classic CAH there is impaired cortisol production with diagnostic increased levels of 17-OH progesterone. Excess androgen production results in virilization and in the newborn female may cause development of ambiguous external genitalia. Three-fourths of patients with classic CAH also have aldosterone insufficiency, which can result in salt-wasting; in infancy this manifests as shock, hyponatremia and hyperkalemia. CAH has a reported incidence of 1:10,000–1:20,000 births although there is an increased prevalence in certain ethnic groups. Nonclassic CAH (NCCAH) is a less severe form of the disorder, in which there is 20–50% of 21-hydroxylase enzyme activity (vs. 0–5% in classic CAH) and no salt wasting. The degree of symptoms related to androgen excess is variable and may be progressive with age, although some individuals are asymptomatic. NCCAH has an incidence of 1:1000–1:2000 births (0.1–0.2% prevalence) in the White population; an even higher prevalence is noted in certain ethnic groups such as Ashkenazi Jews (1–2%). As many as two-thirds of persons with NCCAH are compound heterozygotes and carry a severe and mild mutation on different alleles. This paper discusses the genetics of NCCAH, along with its variable phenotypic expression, and reviews the clinical course in untreated patients, which includes rapid early childhood growth, advanced skeletal age, premature adrenarche, acne, impaired reproductive function in both sexes and hirsutism as well as menstrual disorders in females. Finally, it addresses treatment with glucocorticoids vs. and other alternatives, particularly with respect to long term issues such as adult metabolic disease including insulin resistance, cardiovascular disease, metabolic syndrome

  11. [Addison's disease : Primary adrenal insufficiency].

    PubMed

    Pulzer, A; Burger-Stritt, S; Hahner, S

    2016-05-01

    Adrenal insufficiency, a rare disorder which is characterized by the inadequate production or absence of adrenal hormones, may be classified as primary adrenal insufficiency in case of direct affection of the adrenal glands or secondary adrenal insufficiency, which is mostly due to pituitary or hypothalamic disease. Primary adrenal insufficiency affects 11 of 100,000 individuals. Clinical symptoms are mainly nonspecific and include fatigue, weight loss, and hypotension. The diagnostic test of choice is dynamic testing with synthetic ACTH. Patients suffering from chronic adrenal insufficiency require lifelong hormone supplementation. Education in dose adaption during physical and mental stress or emergency situations is essential to prevent life-threatening adrenal crises. Patients with adrenal insufficiency should carry an emergency card and emergency kit with them. PMID:27129928

  12. Toxic Identification and Evaluation of Androgen Receptor Antagonistic Activities in Acid-Treated Liver Extracts of High-Trophic Level Wild Animals from Japan.

    PubMed

    Misaki, Kentaro; Suzuki, Go; Tue, Nguyen Minh; Takahashi, Shin; Someya, Masayuki; Takigami, Hidetaka; Tajima, Yuko; Yamada, Tadasu K; Amano, Masao; Isobe, Tomohiko; Tanabe, Shinsuke

    2015-10-01

    Sulfuric acid-treated liver extracts of representative high-trophic level Japanese animals were analyzed by toxic identification and evaluation (TIE) with chemically activated luciferase expression (CALUX) and chemical analysis to elucidate androgen receptor (AR) antagonistic activities and potential contributions of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs). The activities were detected in striped dolphins (n = 5), Stejneger's beaked whales (n = 6), golden eagle (n = 1), and Steller's sea eagle (n = 1) with CALUX-flutamide equivalents (FluEQs) as follow: 38 (20-52), 47 (21-96), 5.0, and 80 μg FluEQ/g-lipid, respectively. The AR antagonism was detected in limited number of specimens at lower levels for finless porpoise, raccoon dog, and common cormorant. Theoretical activities (Theo-FluEQs) were calculated using the concentration of OCPs and PCBs and their IC25-based relative potency (REP) values. These total contribution to CALUX-FluEQ was 126%, 84%, 53%, 55%, and 44% for striped dolphin, Steller's sea eagle, Stejneger's beaked whale, finless porpoise, and golden eagle, respectively, and the main contributor was p,p'-DDE. However, most of the activities for raccoon dog (7.6%) and common cormorant (17%) could not be explained by OCPs and PCBs. This suggests other unknown compounds could function as AR antagonists in these terrestrial species. PMID:26321157

  13. Contribution of allelic variability in prostate specific antigen (PSA) & androgen receptor (AR) genes to serum PSA levels in men with prostate cancer

    PubMed Central

    Chavan, Sushant V.; Maitra, Anurupa; Roy, Nobhojit; Chavan, Padma R.

    2014-01-01

    Background & objectives: Wide variability in serum prostate specific antigen (PSA) levels exists in malignant conditions of the prostate. PSA is expressed in normal range in 20 to 25 per cent of prostate cancer cases even in presence of high grade Gleason score. This study was aimed to assess the influence of genetic variants exhibited by PSA and androgen receptor (AR) genes towards the variable expression of PSA in prostate cancer. Methods: Pre-treatment serum PSA levels from 101 prostate cancer cases were retrieved from medical record. PSA genotype analysis in promoter region and AR gene microsatellite Cytosine/Adenine/Guanine (CAG) repeat analysis in exon 1 region was performed using DNA sequencing and fragment analysis techniques. Results: A total of seven single nucleotide polymorphisms (SNPs) in the PSA promoter region were noted. Only two SNPs viz., 158G/A (P<0.001) in the proximal promoter region and -3845G/A (P<0.001) in enhancer region showed significant association with serum PSA levels. The carriers of homozygous GG genotype (P<0.001) at both of these polymorphic sites showed higher expression of PSA whereas homozygous AA genotype (P<0.001) carriers demonstrated lower PSA levels. The combination effect of PSA genotypes along with stratified AR CAG repeats lengths (long, intermediate and short) was also studied. The homozygous GG genotype along with AR long CAG repeats and homozygous AA genotype along with AR short CAG repeats at position -3845 and -158 showed strong interaction and thus influenced serum PSA levels. Interpretation & conclusions: The genetic variants exhibited by PSA gene at positions -3845G/A and -158G/A may be accountable towards wide variability of serum PSA levels in prostate cancer. Also the preferential binding of G and A alleles at these polymorphic sites along with AR long and short CAG repeats may contribute towards PSA expression. PMID:24820830

  14. The interaction of serum testosterone levels and androgen receptor CAG repeat polymorphism on the risk of erectile dysfunction in aging Taiwanese men.

    PubMed

    Liu, C C; Lee, Y C; Tsai, V F S; Cheng, K H; Wu, W J; Bao, B Y; Huang, C N; Yeh, H C; Tsai, C C; Wang, C J; Huang, S P

    2015-09-01

    Testosterone has been found to play important roles in men's sexual function. However, the effects of testosterone can be modulated by androgen receptor (AR) CAG repeat polymorphism. It could also contribute to the risk of erectile dysfunction (ED). The aim of this study is to evaluate the interaction of serum testosterone levels and AR CAG repeat polymorphism on the risk of ED in aging Taiwanese men. This cross-sectional data of Taiwanese men older than 40 years were collected from a free health screening held between August 2010 and August 2011 in Kaohsiung city, Taiwan. All participants completed a health questionnaires included five-item version of the International Index of Erectile Function (IIEF-5) and the International Prostate Symptoms Score, received a detailed physical examination and provided 20 cm3 whole blood samples for biochemical and genetic evaluation. The IIEF-5 was used to evaluate ED. Serum albumin, total testosterone (TT), and sex hormone-binding globulin levels were measured. Free testosterone level was calculated. AR gene CAG repeat polymorphism was determined by direct sequencing. Finally, 478 men with the mean age of 55.7 ± 4.8 years were included. When TT levels were above 330 ng/dL, the effect of testosterone level on erectile function seemed to reach a plateau and a significantly negative correlation between AR CAG repeat length and the score of IIEF-5 was found (r = -0.119, p = 0.034). After adjusting for other covariates, the longer AR CAG repeat length was still an independent risk factor for ED in subjects with TT above 330 ng/dL (p = 0.006), but not in TT of 330 ng/dL or below. In conclusion, both serum testosterone levels and AR CAG repeat polymorphism can influence erectile function concomitantly. In subjects with normal TT concentration, those with longer AR CAG repeat lengths have a higher risk of developing ED. PMID:26216079

  15. Androgens in pregnancy: roles in parturition

    PubMed Central

    Makieva, Sofia; Saunders, Philippa T.K.; Norman, Jane E.

    2014-01-01

    potential roles for androgens in myometrial relaxation via non-genomic, AR-independent pathways critical for the pregnancy reaching term. Understanding of the molecular events leading to myometrial relaxation is an important step towards development of novel targeted tocolytic drugs. CONCLUSIONS The increase in androgen levels throughout gestation is likely to be important for establishment and maintenance of pregnancy and initiation of parturition. Further investigation of the underlying mechanisms of androgen action on cervical remodelling and myometrial contractility is needed. The insights gained may facilitate the development of new therapeutic approaches to manage pregnancy complications such as preterm birth. PMID:24643344

  16. Recovery of Adrenal Function in Patients with Glucocorticoids Induced Secondary Adrenal Insufficiency

    PubMed Central

    Baek, Jong Ha; Kim, Soo Kyoung; Jung, Jung Hwa; Hahm, Jong Ryeal

    2016-01-01

    Background The chronic use of glucocorticoids (GC) suppresses function of the hypothalamic-pituitary-adrenal axis and often results in secondary adrenal insufficiency (AI). The present study aimed to determine the recovery rate of adrenal function in patients with secondary AI within 1 to 2 years and to assess the factors predictive of adrenal function recovery. Methods This was a retrospective observational study that enrolled patients diagnosed with GC-induced secondary AI between 2007 and 2013. AI was defined by peak serum cortisol levels <18 µg/dL during a standard-dose short synacthen test (SST). A follow-up SST was performed after 1 to 2 years, and responders were defined as those with adrenocorticotropic hormone (ACTH)-stimulated peak serum cortisol levels ≥18 µg/dL. Results Of the total 34 patients diagnosed with GC-induced secondary AI at first, 20 patients (58.8%) recovered normal adrenal function by the time of the follow-up SST (median follow-up period, 16.5 months). Although the baseline serum ACTH and cortisol levels at the first SST did not differ between responders and non-responders, the incremental cortisol response during the first SST was higher in responders than that of non-responders (7.88 vs. 3.56, P<0.01). Additionally, higher cortisol increments during the first SST were an independent predictive factor of the adrenal function recovery (odds ratio, 1.58; 95% confidence interval, 1.02 to 2.46; P<0.05). Conclusion In the present study, adrenal function recovery was achieved frequently in patients with GC-induced secondary AI within 1 to 2 years. Additionally, an incremental cortisol response at the first SST may be an important predictive factor of adrenal function recovery. PMID:26676337

  17. In situ androgen and estrogen biosynthesis in endometrial cancer: focus on androgen actions and intratumoral production.

    PubMed

    Ito, Kiyoshi; Miki, Yasuhiro; Suzuki, Takashi; McNamara, Keely May; Sasano, Hironobu

    2016-07-01

    In situ estrogen biosynthesis is considered to play pivotal roles in the development and progression of human endometrial carcinoma. However, the biological roles of androgen have remained virtually unknown. Various epidemiological studies have revealed that elevated serum androgen levels are generally associated with an increased risk of developing endometrial carcinoma; however, studies directly examining androgens in carcinoma tissues are relatively rare and reviews summarizing this information are scarce. Therefore, we summarized recent studies on androgens in endometrial carcinoma, especially focusing androgen actions and in situ androgen biosynthesis. Among the enzymes required for local biosynthesis of androgen, 17β-hydroxysteroid dehydrogenase type 5 (conversion from androstenedione to testosterone) and 5α-reductase (reduction of testosterone to dihydrotestosterone (DHT)) are the principal enzymes involved in the formation of biologically most potent androgen, DHT. Both enzymes and androgen receptor were expressed in endometrial carcinoma tissues, and in situ production of DHT has been reported to exist in endometrial carcinoma tissues. However, testosterone is not only a precursor of DHT production, but also a precursor of estradiol synthesis, as a substrate of the aromatase enzyme. Therefore, aromatase could be another key enzyme serving as a negative regulator for in situ production of DHT by reducing amounts of the precursor. In an in vitro study, DHT was reported to exert antiproliferative effects on endometrial carcinoma cells. Intracrine mechanisms of androgens, the downstream signals of AR, which are directly related to anticancer progression, and the clinical significance of DHT-AR pathway in the patients with endometrial carcinoma have, however, not been fully elucidated. PMID:27287451

  18. Brain serotonin and pituitary-adrenal functions

    NASA Technical Reports Server (NTRS)

    Vernikos-Danellis, J.; Berger, P.; Barchas, J. D.

    1973-01-01

    It had been concluded by Scapagnini et al. (1971) that brain serotonin (5-HT) was involved in the regulation of the diurnal rhythm of the pituitary-adrenal system but not in the stress response. A study was conducted to investigate these findings further by evaluating the effects of altering brain 5-HT levels on the daily fluctuation of plasma corticosterone and on the response of the pituitary-adrenal system to a stressful or noxious stimulus in the rat. In a number of experiments brain 5-HT synthesis was inhibited with parachlorophenylalanine. In other tests it was tried to raise the level of brain 5-HT with precursors.

  19. Clinical outcomes of anti-androgen withdrawal and subsequent alternative anti-androgen therapy for advanced prostate cancer following failure of initial maximum androgen blockade

    PubMed Central

    MOMOZONO, HIROYUKI; MIYAKE, HIDEAKI; TEI, HIROMOTO; HARADA, KEN-ICHI; FUJISAWA, MASATO

    2016-01-01

    The present study aimed to investigate the significance of anti-androgen withdrawal and/or subsequent alternative anti-androgen therapy in patients with advanced prostate cancer (PC) who relapsed after initial maximum androgen blockade (MAB). The present study evaluated the clinical outcomes of 272 consecutive advanced PC patients undergoing anti-androgen withdrawal and/or subsequent alternative anti-androgen therapy with flutamide following the failure of initial MAB using bicalutamide. With the exception of 41 patients (15.1%) who did not undergo anti-androgen withdrawal due to the characteristics of PC suggesting aggressive diseases, prostate-specific antigen (PSA) declined from the baseline value in 83 patients (35.9%), including 18 (7.8%) with PSA decline >50%, but not in the remaining 148 (64.1%). No significant difference in the overall survival (OS) or cancer-specific survival (CSS) among the three groups was observed based on the response to anti-androgen withdrawal. Following the introduction of alternative anti-androgen therapy with flutamide, PSA decline was observed in 185 patients (68.0%), including 103 (37.9%) who achieved a PSA reduction of >50%; however, the PSA level continued to elevate in the remaining 87 (32.0%). Furthermore, of the numerous factors examined, only the duration of the initial MAB therapy was shown to be significantly correlated with the PSA decline following alternative anti-androgen therapy. Multivariate analysis of several factors identified revealed that only PSA decline following alternative anti-androgen therapy was an independent predictor of CSS and OS. If initial MAB is effective, the introduction of alternative anti-androgen therapy may be considered; however, anti-androgen withdrawal should be omitted, irrespective of the characteristics of advanced PC. PMID:27123292

  20. Combined steroidogenic characters of fetal adrenal and Leydig cells in childhood adrenocortical carcinoma.

    PubMed

    Fujisawa, Yasuko; Sakaguchi, Kimiyoshi; Ono, Hiroyuki; Yamaguchi, Rie; Kato, Fumiko; Kagami, Masayo; Fukami, Maki; Ogata, Tsutomu

    2016-05-01

    Although childhood adrenocortical carcinomas (c-ACCs) with a TP53 mutation are known to produce androgens, detailed steroidogenic characters have not been clarified. Here, we examined steroid metabolite profiles and expression patterns of steroidogenic genes in a c-ACC removed from the left adrenal position of a 2-year-old Brazilian boy with precocious puberty, using an atrophic left adrenal gland removed at the time of tumorectomy as a control. The c-ACC produced not only abundant dehydroepiandrosterone-sulfate but also a large amount of testosterone via the Δ5 pathway with Δ5-androstenediol rather than Δ4-androstenedione as the primary intermediate metabolite. Furthermore, the c-ACC was associated with elevated expressions of CYP11A1, CYP17A1, POR, HSD17B3, and SULT2A1, a low but similar expression of CYB5A, and reduced expressions of AKR1C3 (HSD17B5) and HSD3B2. Notably, a Leydig cell marker INSL3 was expressed at a low but detectable level in the c-ACC. Furthermore, molecular studies revealed a maternally inherited heterozygous germline TP53 mutation, and several post-zygotic genetic aberrations in the c-ACC including loss of paternally derived chromosome 17 with a wildtype TP53 and loss of maternally inherited chromosome 11 and resultant marked hyperexpression of paternally expressed growth promoting gene IGF2 and drastic hypoexpression of maternally expressed growth suppressing gene CDKN1C. These results imply the presence of combined steroidogenic properties of fetal adrenal and Leydig cells in this patient's c-ACC with a germline TP53 mutation and several postzygotic carcinogenic events. PMID:26940356

  1. What Is Adrenal Cortical Cancer?

    MedlinePlus

    ... include pheochromocytomas (which are most often benign) and neuroblastomas . This document is about tumors and cancers of ... does not discuss tumors of the adrenal medulla. Neuroblastoma s are covered in a separate document . Adrenal cortex ...

  2. Percutaneous Ablation of Adrenal Tumors

    PubMed Central

    Venkatesan, Aradhana M.; Locklin, Julia; Dupuy, Damian E.; Wood, Bradford J.

    2010-01-01

    Adrenal tumors comprise a broad spectrum of benign and malignant neoplasms, and include functional adrenal adenomas, pheochromocytomas, primary adrenocortical carcinoma and adrenal metastases. Percutaneous ablative approaches that have been described and used in the treatment of adrenal tumors include percutaneous radiofrequency ablation (RFA), cryoablation, microwave ablation and chemical ablation. Local tumor ablation in the adrenal gland presents unique challenges, secondary to the adrenal gland’s unique anatomic and physiologic features. The results of clinical series employing percutaneous ablative techniques in the treatment of adrenal tumors are reviewed in this article. Clinical and technical considerations unique to ablation in the adrenal gland are presented, including approaches commonly used in our practices, and risks and potential complications are discussed. PMID:20540918

  3. Incidence and Cause of Hypertension During Adrenal Radiofrequency Ablation

    SciTech Connect

    Yamakado, Koichiro Takaki, Haruyuki; Yamada, Tomomi; Yamanaka, Takashi; Uraki, Junji; Kashima, Masataka; Nakatsuka, Atsuhiro; Takeda, Kan

    2012-12-15

    Purpose: To evaluate the incidence and cause of hypertension prospectively during adrenal radiofrequency ablation (RFA). Methods: For this study, approved by our institutional review board, written informed consent was obtained from all patients. Patients who received RFA for adrenal tumors (adrenal ablation) and other abdominal tumors (nonadrenal ablation) were included in this prospective study. Blood pressure was monitored during RFA. Serum adrenal hormone levels including epinephrine, norepinephrine, dopamine, and cortisol levels were measured before and during RFA. The respective incidences of procedural hypertension (systolic blood pressure >200 mmHg) of the two patient groups were compared. Factors correlating with procedural systolic blood pressure were evaluated by regression analysis.ResultsNine patients underwent adrenal RFA and another 9 patients liver (n = 5) and renal (n = 4) RFA. Asymptomatic procedural hypertension that returned to the baseline by injecting calcium blocker was found in 7 (38.9%) of 18 patients. The incidence of procedural hypertension was significantly higher in the adrenal ablation group (66.7%, 6/9) than in the nonadrenal ablation group (11.1%, 1/9, P < 0.0498). Procedural systolic blood pressure was significantly correlated with serum epinephrine (R{sup 2} = 0.68, P < 0.0001) and norepinephrine (R{sup 2} = 0.72, P < 0.0001) levels during RFA. The other adrenal hormones did not show correlation with procedural systolic blood pressure. Conclusion: Hypertension occurs frequently during adrenal RFA because of the release of catecholamine.

  4. [Giant adrenal myelolipoma].

    PubMed

    El Mejjad, Amine; Fekak, Hamid; Dakir, Mohamed; Sarf, Ismail; Manni, Ahmed; Meziane, Fethi

    2004-02-01

    Adrenal myelolipoma is a rare, benign, non-secreting tumour composed of adipose and haematopoietic tissue. The authors report a rare case of giant adrenal myelolipoma in a 53-year-old patient presenting with low back pain and a palpable flank mass on examination. CT scan suggested the diagnosis and surgical resection was indicated in view of the size and symptomatic nature of this mass. Histological examination confirmed the diagnosis. The outcome was favourable without recurrence after a follow-up of one year. The diagnosis of adrenal myelolipoma is based on radiology. Conservative management is generally sufficient for small asymptomatic tumours, but resection is required for large (> 5 cm) and/or symptomatic tumours. PMID:15098761

  5. Amitosis in human adrenal cells.

    PubMed

    Magalhães, M C; Pignatelli, D; Magalhães, M M

    1991-04-01

    Adrenal pieces obtained from 3 female and 2 male patients showed morphological figures of amitosis in adrenal zona reticularis cells. Such aspects were observed in both normal and hyperactive adrenals. Nuclei appeared constricted, heavily stained, with coarse chromatin, sometimes scattered among cytoplasmic organelles, but never marginating in crescentic caps. Cleavage of the cells originated two halves with a nucleolus in each pole. Binucleated cells were also seen in zona reticularis. The meaning of amitosis in human adrenal is discussed. PMID:1802124

  6. Polycystic Ovaries Associated with Congenital Adrenal Hyperplasia

    PubMed Central

    Lucis, O. J.; Hobkirk, R.; Hollenberg, C. H.; MacDonald, S. A.; Blahey, P.

    1966-01-01

    Polycystic ovaries were found in a 16-year-old female with congenital absence of vagina, male-like external genitalia, and congenital adrenal hyperplasia. Masculinization was sufficiently severe to cause the patient to be reared as a male. Biochemical studies of ovarian tissue revealed hyperactivity and an imbalance of enzyme systems concerned with steroid-hormone biosynthesis, which led to production of large amounts of androgens. The pathway towards estrogens was preserved but less efficient than normal. Urinary steroid metabolites before and after hysterectomy and bilateral salpingo-oophorectomy revealed an absence of Porter-Silber chromogens and tetrahydrocortisone. Excretion of aldosterone was normal and that of corticosterone slightly higher than normal. The patterns of urinary 17-ketosteroids, pregnanediol, pregnanetriol and pregnanetriolone were similar to those commonly seen in congenital adrenal hyperplasia with steroid 21-hydroxylase deficiency. Urinary estrogens after panhysterectomy were low, being in the post-menopausal range. The pathogenesis of polycystic ovaries and their possible contribution to masculinization are discussed. ImagesFig. 1Fig. 2Fig. 3 PMID:5901591

  7. Social modulation of androgens in male birds.

    PubMed

    Goymann, Wolfgang

    2009-09-01

    Most seasonally reproducing vertebrates show pronounced changes in testosterone levels throughout the year. The Challenge Hypothesis [Wingfield, J.C., Hegner, R.E., Dufty, A.M., Ball, G. F., 1990. The "challenge hypothesis": theoretical implications for patterns of testosterone secretion, mating systems, and breeding strategies. Am. Nat. 136, 829-846] predicts that seasonal patterns in circulating androgen concentrations vary as a function of mating system, male-male aggression and paternal care. In most comparative studies, the predictions of the Challenge Hypothesis have been tested primarily by calculating the ratio between breeding peak and breeding baseline testosterone concentrations, using this ratio as a proxy for the effect that social interactions have on testosterone levels (androgen responsiveness R). Recently, we suggested that it is preferable to separate the seasonal testosterone response (R(season)) from the androgen responsiveness to male-male interactions (R(male-male)), as these two measures do not correlate and can differ both in magnitude and direction [Goymann, W., Landys, M.M., Wingfield, J.C., 2007. Distinguishing seasonal androgen responses from male-male androgen responsiveness-revisiting the Challenge Hypothesis. Horm. Behav. 51, 463-476]. Here, I discuss several methodological and ecological factors that may explain why R(season) and R(male-male) differ. Furthermore, I describe three other kinds of androgen responsiveness, namely the androgen responsiveness of males to receptive females (R(male-female)), to non-social environmental cues (R(environment)), and the potential androgen responsiveness (R(potential)). The latter is measured before and after an injection of gonadotropin releasing hormone (GnRH), which typically leads to a maximal release of testosterone from the testes. I argue that separation of different kinds of androgen responsiveness and putting them into context with the natural history and ecology of a study species may

  8. Adrenal venous sampling in a patient with adrenal Cushing syndrome

    PubMed Central

    Villa-Franco, Carlos Andrés; Román-Gonzalez, Alejandro; Velez-Hoyos, Alejandro; Echeverri-Isaza, Santiago

    2015-01-01

    The primary bilateral macronodular adrenal hyperplasia or the independent adrenocorticotropic hormone bilateral nodular adrenal hyperplasia is a rare cause hypercortisolism, its diagnosis is challenging and there is no clear way to decide the best therapeutic approach. Adrenal venous sampling is commonly used to distinguish the source of hormonal production in patients with primary hyperaldosteronism. It could be a useful tool in this context because it might provide information to guide the treatment. We report the case of a patient with ACTH independent Cushing syndrome in whom the use of adrenal venous sampling with some modifications radically modified the treatment and allowed the diagnosis of a macronodular adrenal hyperplasia. PMID:26309345

  9. Androgen mediated translational and postranslational regulation of IGFBP-2 in androgen-sensitive LNCaP human prostate cancer cells

    PubMed Central

    DeGraff, David J; Aguiar, Adam A; Chen, Qian; Adams, Lisa K; Williams, B. Jill; Sikes, Robert A

    2010-01-01

    The insulin-like growth factor (IGF) axis is associated intimately with prostate cancer (PCa) development, growth, survival and metastasis. In particular, increased levels of IGFBP-2 expression are associated with advanced PCa, bone metastasis, and the development of castrate resistant PCa. Previously, we reported that androgen treatment decreased intracellular and extracellular IGFBP-2 in the androgen sensitive (AS) PCa cell line, LNCaP. Nonetheless, the mechanism by which androgen treatment decreases expression of IGFBP-2 is not clear. Since elevated IGFBP-2 is associated with a variety of advanced cancers, including PCa, coupled with the fact that hormone ablation is the customary treatment modality for advanced PCa, a complete understanding of the influence of androgens on IGFBP-2 expression is essential. Androgen treatment initially increased steady state IGFBP-2 mRNA levels in LNCaP cells. Extended androgen treatment on LNCaP resulted in a time-dependent decrease in both steady state IGFBP-2 mRNA and protein. Polysomal mRNA analysis showed no difference in IGFBP-2 association with a given fraction; however, Q-PCR revealed less IGFBP-2 mRNA in each androgen-treated fraction. In addition, there was an overall decrease in polysome mRNA after androgen treatment. Extracellular proteolysis of IGFBP-2 was prevented in the presence of serine protease inhibitors. These data indicate that androgen acts via multiple levels to down-regulate IGFBP-2 in LNCaP PCa cells. PMID:20407609

  10. [Androgenic treatment of male hypogonadism].

    PubMed

    Kuhn, Jean-Marc; Prévost, Gaëtan

    2014-02-01

    The diagnosis of male hypogonadism should be clearly established on a clinical and biological basis before considering the initiation of a substitutive treatment with androgens. A careful evaluation of advantages, constraints and limitations of the treatment should be done previously. The potential advantages of an androgenic substitution include an improvement of the symptoms of hypogonadism and the prevention of its bone and metabolic consequences. Absolute (namely prostatic) or relative contraindications should be detected before starting any substitution. The modalities of treatment will be adapted to both the patient's age and the goals to reach. The different available formulations do not induce a similar pattern of plasma testosterone levels. Patches, gel applications and long-acting intramuscular formulations [injected every 3 months] result in stable plasma levels in the physiologic range. The main limitation to their use is linked to a financial aspect as they are not the object of any refund. A careful survey (on clinical, biological and radiological basis) should be established after starting the substitutive treatment with androgens. PMID:24268959

  11. Androgens and prostate disease

    PubMed Central

    Cooper, Lori A; Page, Stephanie T

    2014-01-01

    A growing body of literature has established the anabolic benefits of testosterone (T) therapy in hypogonadal men. However, there remains a paucity of data regarding the risks of exogenous androgen use in older men and the potential for adverse effects on the prostate gland. Whether T therapy in older, hypogonadal men might worsen lower urinary tract symptoms or exacerbate, unmask, or even incite prostate cancer development has tempered enthusiasm for T therapy, while known prostatic disease has served as a relative contraindication to T therapy. Androgens are necessary for the development and maintenance of the prostate gland. However, epidemiologic studies do not consistently find a positive relationship between endogenous serum androgen concentrations and the risk of prostate disease. Recent data demonstrate that 5α-reductase inhibitors decrease the risk of low-grade prostate cancer, suggesting that modifying androgen metabolism may have beneficial effects on prostate health, yet similar reductions in high-grade disease have not been observed, thereby questioning the true clinical benefits of these agents for chemoprevention. Knowing how to best investigate the relationship between androgens and the development of prostate disease given the lack of large, randomized trials is difficult. Accumulating data challenges the assumption that alterations in serum androgens have parallel effects within the prostate hormonal environment or change androgen-regulated processes within the gland. Long-term intervention studies are needed to truly ascertain the effects of androgen manipulation on prostate tissue and disease risk. However, available data do not support the notion that restoring serum androgens to normal physiologic ranges drives prostate disease. PMID:24407178

  12. Limited significance of asymmetric adrenal visualization on dexamethasone-suppression scintigraphy

    SciTech Connect

    Gross, M.D.; Shapiro, B.; Freitas, J.E.

    1985-01-01

    To access whether a single measurement of the adrenal uptake of 6..beta..-(/sup 131/I)-iodomethylnorocholesterol (NP-59) on constant dexamethasone suppression would allow discrimination of adenoma from normal and bilateral hyperplasia, the adrenal uptake of 6..beta..-(/sup 131/I)-iodomethylnorocholesterol (NP-59) was determined in 50 patients with primary aldosteronism (30 adenoma, 20 hyperplasia) and in 13 with hyperandrogenism (six adenoma, seven hyperplasia). Bilateral adrenal NP-59 activity at 5 days was seen in 14 of 36 patients with adenoma whereas marked asymmetric uptake of NP-59 was seen in six of 27 patients with hyperplasia. Thus the level of adrenal NP-59 uptake does not alone serve to distinguish either adenoma from the normal, contralateral adrenal or the adrenal glands in bilateral hyperplasia in all cases. It appears that the pattern of adrenal imaging best serves to separate adrenal adenoma from bilateral hyperplasia.

  13. Exposure to Paper Mill Effluent at a Site in North Central Florida Elicits Molecular-Level Changes in Gene Expression Indicative of Progesterone and Androgen Exposure

    PubMed Central

    Brockmeier, Erica K.; Jayasinghe, B. Sumith; Pine, William E.; Wilkinson, Krystan A.; Denslow, Nancy D.

    2014-01-01

    Endocrine disrupting compounds (EDCs) are chemicals that negatively impact endocrine system function, with effluent from paper mills one example of this class of chemicals. In Florida, female Eastern mosquitofish (Gambusia holbrooki) have been observed with male secondary sexual characteristics at three paper mill-impacted sites, indicative of EDC exposure, and are still found at one site on the Fenholloway River. The potential impacts that paper mill effluent exposure has on the G. holbrooki endocrine system and the stream ecosystem are unknown. The objective of this study was to use gene expression analysis to determine if exposure to an androgen receptor agonist was occurring and to couple this analysis with in vitro assays to evaluate the presence of androgen and progesterone receptor active chemicals in the Fenholloway River. Focused gene expression analyses of masculinized G. holbrooki from downstream of the Fenholloway River paper mill were indicative of androgen exposure, while genes related to reproduction indicated potential progesterone exposure. Hepatic microarray analysis revealed an increase in the expression of metabolic genes in Fenholloway River fish, with similarities in genes and biological processes compared to G. holbrooki exposed to androgens. Water samples collected downstream of the paper mill and at a reference site indicated that progesterone and androgen receptor active chemicals were present at both sites, which corroborates previous chemical analyses. Results indicate that G. holbrooki downstream of the Fenholloway River paper mill are impacted by a mixture of both androgens and progesterones. This research provides data on the mechanisms of how paper mill effluents in Florida are acting as endocrine disruptors. PMID:25198161

  14. Exposure to paper mill effluent at a site in North Central Florida elicits molecular-level changes in gene expression indicative of progesterone and androgen exposure.

    PubMed

    Brockmeier, Erica K; Jayasinghe, B Sumith; Pine, William E; Wilkinson, Krystan A; Denslow, Nancy D

    2014-01-01

    Endocrine disrupting compounds (EDCs) are chemicals that negatively impact endocrine system function, with effluent from paper mills one example of this class of chemicals. In Florida, female Eastern mosquitofish (Gambusia holbrooki) have been observed with male secondary sexual characteristics at three paper mill-impacted sites, indicative of EDC exposure, and are still found at one site on the Fenholloway River. The potential impacts that paper mill effluent exposure has on the G. holbrooki endocrine system and the stream ecosystem are unknown. The objective of this study was to use gene expression analysis to determine if exposure to an androgen receptor agonist was occurring and to couple this analysis with in vitro assays to evaluate the presence of androgen and progesterone receptor active chemicals in the Fenholloway River. Focused gene expression analyses of masculinized G. holbrooki from downstream of the Fenholloway River paper mill were indicative of androgen exposure, while genes related to reproduction indicated potential progesterone exposure. Hepatic microarray analysis revealed an increase in the expression of metabolic genes in Fenholloway River fish, with similarities in genes and biological processes compared to G. holbrooki exposed to androgens. Water samples collected downstream of the paper mill and at a reference site indicated that progesterone and androgen receptor active chemicals were present at both sites, which corroborates previous chemical analyses. Results indicate that G. holbrooki downstream of the Fenholloway River paper mill are impacted by a mixture of both androgens and progesterones. This research provides data on the mechanisms of how paper mill effluents in Florida are acting as endocrine disruptors. PMID:25198161

  15. Serum prolactin levels in castrated rams at various times of the year and during treatment with androgens or oestrogen.

    PubMed

    Parrott, R F; Hills, F

    1979-10-01

    Prolactin concentrations were measured in serum from wethers at various times of the year before and during treatment with testosterone proprionate, dihydrotestosterone propionate, 19-hydroxytestosterone dipropionate and oestradiol dipropionate. Levels of prolactin in serum were lower in untreated wethers during short (October) than during long (April-August) days. Seasonal differences persisted throughout the experiment but became less obvious during tretment with oestradiol dipropionate and 19-hydroxytestosterone dipropionate, both of which raised prolactin concentrations. Neither testosterone propionate nor dihydrotestosterone propionate altered the levels of prolactin. PMID:521705

  16. Distinguishing seasonal androgen responses from male-male androgen responsiveness-revisiting the Challenge Hypothesis.

    PubMed

    Goymann, Wolfgang; Landys, Meta M; Wingfield, John C

    2007-04-01

    Androgen levels show strong patterns throughout the year in male vertebrates and play an important role in the seasonal modulation of the frequency, intensity and persistence of aggression. The Challenge Hypothesis (Wingfield, J.C., Hegner, R.E., Dufty, A.M., Ball, G.F., 1990. The "Challenge Hypothesis": Theoretical implications for patterns of testosterone secretion, mating systems, and breeding strategies. Am. Nat. 136, 829-846) predicts that seasonal patterns in androgen levels vary as a function of mating system, male-male aggression and paternal care. Although many studies have addressed these predictions, investigators have often assumed that the ratio of the breeding season maximum and breeding baseline concentrations (termed "androgen responsiveness") reflects hormonal responses due to social stimulation. However, increasing evidence suggests that seasonal androgen elevations are not necessarily caused by social interactions between males. Here, we separate the seasonal androgen response (R(seasonal)) and the androgen responsiveness to male-male competition (R(male-male)) to begin to distinguish between different kinds of hormonal responses. We demonstrate that R(seasonal) and R(male-male) are fundamentally different and should be treated as separate variables. Differences are particularly evident in single-brooded male birds that show no increase in plasma androgen levels during simulated territorial intrusions (STIs), even though R(seasonal) is elevated. In multiple-brooded species, STIs typically elicit a rise in androgens. We relate these findings to the natural history of single- and multiple-brooded species and suggest a research approach that could be utilized to increase our understanding of the factors that determine different types of androgen responses. This approach does not only include R(seasonal) and R(male-male), but also the androgen responsiveness to receptive females (R(male-female)) and to non-social environmental cues (R

  17. Specificity of anti-prostate cancer CYP17A1 inhibitors on androgen biosynthesis.

    PubMed

    Udhane, Sameer S; Dick, Bernhard; Hu, Qingzhong; Hartmann, Rolf W; Pandey, Amit V

    2016-09-01

    The orteronel, abiraterone and galeterone, which were developed to treat castration resistant prostate cancer, inhibit 17,20 lyase activity but little is known about their effects on adrenal androgen biosynthesis. We studied the effect of several inhibitors and found that orteronel was selective towards 17,20 lyase activity than abiraterone and galeterone. Gene expression analysis showed that galeterone altered the expression of HSD3B2 but orteronel did not change the expression of HSD3B2, CYP17A1 and AKR1C3. The CYP19A1 activity was not inhibited except by compound IV which lowered activity by 23%. Surprisingly abiraterone caused complete blockade of CYP21A2 activity. Analysis of steroid metabolome by gas chromatography - mass spectrometry revealed changes in steroid levels caused by different inhibitors. We can conclude that orteronel is a highly specific inhibitor of 17,20 lyase activity. The discovery of these specific drug actions on steroidogenic enzyme activities would be valuable for understanding the regulation of androgens. PMID:27395338

  18. Sex Hormones in Allergic Conjunctivitis: Altered Levels of Circulating Androgens and Estrogens in Children and Adolescents with Vernal Keratoconjunctivitis

    PubMed Central

    Sacchetti, Marta; Lambiase, Alessandro; Moretti, Costanzo; Bonini, Stefano

    2015-01-01

    Purpose. Vernal keratoconjunctivitis (VKC) is a chronic allergic disease mainly affecting boys in prepubertal age and usually recovering after puberty. To evaluate a possible role of sex hormones in VKC, serum levels of sex hormones in children and adolescents with VKC were assessed. Methods. 12 prepubertal and 7 early pubertal boys with active VKC and 6 male patients with VKC in remission phase at late pubertal age and 48 healthy age and sex-matched subjects were included. Serum concentration of estrone, 17 beta-estradiol, dehydroepiandrosterone-sulfate, total testosterone and free testosterone, dihydrotestosterone (DHT), cortisol, delta-4-androstenedione, follicle-stimulating hormone, luteinizing hormone, and sex-hormones binding globuline (SHBG) were evaluated. Results. Serum levels of Estrone were significantly increased in all groups of patients with VKC when compared to healthy controls (P < 0.001). Prepubertal and early pubertal VKC showed a significant decrease in DHT (P = 0.007 and P = 0.028, resp.) and SHBG (P = 0.01 and P = 0.002, resp.) when compared to controls and serum levels of SHBG were increased in late pubertal VKC in remission phase (P = 0.007). Conclusions and Relevance. VKC patients have different circulating sex hormone levels in different phases of the disease and when compared to nonallergic subjects. These findings suggest a role played by sex hormones in the pathogenesis and/or activity of VKC. PMID:25756057

  19. Bilateral adrenal hemorrhage in polycythemia vera.

    PubMed

    Bhandari, Shruti; Agito, Katrina; Krug, Esther I

    2016-01-01

    Bilateral adrenal hemorrhage (BAH) is a rare complication typically seen in critically ill patients, which can lead to acute adrenal insufficiency and death unless it is recognized promptly and treated appropriately. We describe the case of a 64-year-old man with polycythemia vera found to be unresponsive with fever, hypotension, tachycardia, and hypoglycemia. Electrocardiogram showed ST-elevation with elevated troponin, hemoglobin, prothrombin time, and partial thromboplastin time. He required aggressive ventilator and vasopressor support. Despite primary coronary intervention, he remained hypotensive. Random cortisol level was low. He received stress dose hydrocortisone with immediate hemodynamic stability. BAH was highly suspected and was confirmed by non-contrast abdominal computed tomography. Prompt recognition and timely initiated treatment remain crucial to impact the mortality associated with acute adrenal insufficiency. PMID:27609733

  20. Congenital adrenal hyperplasia

    MedlinePlus

    ... or inappropriately). Congenital adrenal hyperplasia can affect both boys and girls. About 1 in 10,000 to 18,000 ... penis but normal testes Well-developed muscles Both boys and girls will be tall as children, but much shorter ...

  1. Diagnosis and management of classical congenital adrenal hyperplasia.

    PubMed

    Marumudi, Eunice; Khadgawat, Rajesh; Surana, Vineet; Shabir, Iram; Joseph, Angela; Ammini, Ariachery C

    2013-08-01

    Congenital adrenal hyperplasia (CAH) is among the most common genetic disorders. Deficiency of adrenal steroid 21-hydroxylase deficiency due to mutations in the CYP21A2 gene accounts for about 95% cases of CAH. This disorder manifests with androgen excess with or without salt wasting. It also is a potentially life threatening disorder; neonatal screening with 17-hydroxyprogesterone measurement can diagnose the condition in asymptomatic children. Carefully monitored therapy with glucocorticoid and mineralocorticoid supplementation will ensure optimal growth and development for children with CAH. Genital surgery may be required for girls with CAH. Continued care is required for individuals with CAH as adults to prevent long-term adverse consequences of the disease, including infertility, metabolic syndrome and osteoporosis. PMID:23624029

  2. PROCHLORAZ INHIBITS TESTOSTERONE PRODUCTION AT DOSAGE LEVELS BELOW THOSE THAT AFFECT ANDROGEN-DEPENDENT ORGAN WEIGHTS OR THE ONSET OF MALE RAT PUBERTY

    EPA Science Inventory

    Prochloraz (PCZ) is an imidazole fungicide that has several endocrine modes of action. In vitro, PCZ inhibits steroidogenesis and acts as an androgen receptor (AR) antagonist. We hypothesized that pubertal exposure to prochloraz would delay preputial separation and growth of an...

  3. Motor development in individuals with congenital adrenal hyperplasia: Strength, targeting, and fine motor skill

    PubMed Central

    Collaer, Marcia L.; Brook, Charles; Conway, Gerard S.; Hindmarsh, Peter C.; Hines, Melissa

    2009-01-01

    Summary This study investigated early androgen influence on the development of human motor and visuomotor characteristics. Participants, ages 12 to 45 years, were individuals with congenital adrenal hyperplasia (CAH), a disorder causing increased adrenal androgen production before birth (40 females, 29 males) and their unaffected relatives (29 females, 30 males). We investigated grip strength and visuomotor targeting tasks on which males generally outperform females, and fine motor pegboard tasks on which females generally outperform males. Physical characteristics (height and weight) were measured to explore whether body parameters could explain differences in motor skills. Females with CAH were stronger and showed better targeting than unaffected females and showed reduced fine visuomotor skill on one pegboard measure, with no difference on the other. Males with CAH were weaker than unaffected males in grip strength but did not differ on the targeting or pegboard measures. Correction for body size could not explain the findings for females, but suggests that the reduced strength of males with CAH may relate to their smaller stature. Further, the targeting advantage in females with CAH persisted following adjustment for their greater strength. Results in females support the hypothesis that androgen may masculinize, or promote, certain motor characteristics at which males excel, and contribute to defeminization of certain fine motor characteristics at which females excel. Thus, these data suggest that organizational effects of androgens on behavior during prenatal life may extend to motor characteristics and may contribute to general sex differences in motor-related behaviors; however, alternative explanations based on activational influences of androgen or altered experiential factors cannot be excluded without further study. KEYWORDS: congenital adrenal hyperplasia (CAH), androgen, sex, motor, strength, targeting PMID:18938041

  4. Former Abusers of Anabolic Androgenic Steroids Exhibit Decreased Testosterone Levels and Hypogonadal Symptoms Years after Cessation: A Case-Control Study

    PubMed Central

    Selmer, Christian; Østergren, Peter Busch; Pedersen, Karen Boje; Schou, Morten; Gustafsson, Finn; Faber, Jens; Juul, Anders; Kistorp, Caroline

    2016-01-01

    Aims Abuse of anabolic androgenic steroids (AAS) is highly prevalent among male recreational athletes. The objective of this study was to investigate the impact of AAS abuse on reproductive hormone levels and symptoms suggestive of hypogonadism in current and former AAS abusers. Methods This study had a cross-sectional case-control design and involved 37 current AAS abusers, 33 former AAS abusers (mean (95%CI) elapsed duration since AAS cessation: 2.5 (1.7; 3.7) years) and 30 healthy control participants. All participants were aged 18–50 years and were involved in recreational strength training. Reproductive hormones (FSH, LH, testosterone, inhibin B and anti-Müllerian hormone (AMH)) were measured using morning blood samples. Symptoms of hypogonadism (depressive symptoms, fatigue, decreased libido and erectile dysfunction) were recorded systematically. Results Former AAS abusers exhibited significantly lower median (25th –75th percentiles) total and free testosterone levels than control participants (total testosterone: 14.4 (11.9–17.7) nmol/l vs. 18.8 (16.6–22.0) nmol/l) (P < 0.01). Overall, 27.2% (13.3; 45.5) of former AAS abusers exhibited plasma total testosterone levels below the lower reference limit (12.1 nmol/l) whereas no control participants exhibited testosterone below this limit (P < 0.01). Gonadotropins were significantly suppressed, and inhibin B and AMH were significantly decreased in current AAS abusers compared with former AAS abusers and control participants (P < 0.01). The group of former AAS abusers had higher proportions of participants with depressive symptoms ((24.2%) (11.1; 42.2)), erectile dysfunction ((27.3%) (13.3; 45.6)) and decreased libido ((40.1%) (23.2; 57.0)) than the other two groups (trend analyses: P < 0.05). Conclusions Former AAS abusers exhibited significantly lower plasma testosterone levels and higher frequencies of symptoms suggestive of hypogonadism than healthy control participants years after AAS cessation

  5. CD44 expression in normal adrenal tissue and adrenal tumours.

    PubMed Central

    Barshack, I; Goldberg, I; Nass, D; Olchovsky, D; Kopolovic, J

    1998-01-01

    BACKGROUND: CD44 is a cell surface glycoprotein found on many normal cells, mainly lymphoid and epithelial. Normal cells usually express standard CD44 (CD44-S), whereas malignant tumours may express CD44 variant isoforms (CD44-V). CD44 expression has been described for neural crest derivatives. Characterisation of differences in CD44 expression may help in the diagnosis and differentiation of distinct adrenal tumours. AIMS: To examine CD44 expression in different layers of cortical cortex, in adrenal medulla, and in adrenal tumours. METHODS: CD44-S and CD44-V6 expression were studied in 12 cases of adrenal cortical adenoma, 3 of adrenal cortical carcinoma, 10 of pheochromocytoma, and 4 normal adrenal glands. RESULTS: CD44-V6 staining showed cytoplasmic expression in normal adrenal cortex and in cortical adenomas and carcinomas. Pheochromocytomas also showed CD44-V6 expression but in 5 of the 10 cases it was sparse, focal, and sometimes perinuclear. Strong membranous staining for CD44-S was observed in normal adrenal medulla. Analysis of CD44-S expression revealed differences between cortical adrenal tumours and pheochromocytomas. Ten of 12 cortical adenomas and 2 of 3 cortical carcinoma cells showed weak to moderate cytoplasmic staining, but all cases of pheochromocytoma had strong membranous staining. CONCLUSIONS: Membranous CD44-S staining may help to distinguish pheochromocytoma from adrenal cortical adenoma. Images PMID:9577373

  6. A case of postmenopausal androgen excess.

    PubMed

    Lambrinoudaki, Irene; Dafnios, Nikos; Kondi-Pafiti, Agathi; Triantafyllou, Nikos; Karopoulou, Evangelia; Papageorgiou, Anastasia; Augoulea, Areti; Armeni, Eleni; Creatsa, Maria; Vlahos, Nikolaos

    2015-10-01

    Ovarian steroid cell tumors are very rare but potentially life-threatening neoplasms. They represent less than 0.1% of all ovarian tumors, typically present in premenopausal women and frequently manifest with virilization. Signs of hyperandrogenism may appear in postmenopausal women due to tumorοus and non-tumorοus adrenal and ovarian causes as well due to the normal aging process. In any case, steroid cell tumor should be suspected in postmenopausal women who present with rapid progressive androgen excess symptoms. This report describes a case of a 67-year-old postmenopausal woman with signs of hyperandrogenism, where an ovarian steroid cell tumor was diagnosed and treated by laparoscopic bilateral salpingo-oophorectomy and synchronous hysterectomy. PMID:26287476

  7. Racial differences in the androgen/androgen receptor pathway in prostate cancer.

    PubMed Central

    Pettaway, C. A.

    1999-01-01

    Pathologic and epidemiologic data suggest that while little racial variation exists in prostate cancer prevalence ("autopsy cancer"), striking racial variation exists for the clinically diagnosed form of the disease. A review of the available literature was performed to define whether racial differences in serum androgen levels or qualitative or quantitative differences in the androgen receptor were correlated with prostate cancer incidence or severity. Black men were found to be exposed to higher circulating testosterone levels from birth to about age 35 years. Such differences were not consistently noted among older men. Significant differences also were found for dihydrotestosterone metabolites among black, white, and Asian men. Unique racial genetic polymorphisms were noted for the gene for 5 alpha-reductase type 2 among black and Asian men. Novel androgen receptor mutations recently have been described among Japanese, but not white, men with latent prostate cancer. Finally, androgen receptor gene polymorphisms leading to shorter or longer glutamine and glycine residues in the receptor protein are correlated with racial variation in the incidence and severity of prostate cancer. This same polymorphism also could explain racial variation in serum prostate-specific antigen levels. Collectively, these data strongly suggest racial differences within the androgen/androgen receptor pathway not only exist but could be one cause of clinically observed differences in the biology of prostate cancer among racial groups. Images Figure 1 PMID:10628124

  8. A Place to Hide in the Home-Cage Decreases Yolk Androgen Levels and Offspring Emotional Reactivity in Japanese Quail

    PubMed Central

    Guesdon, Vanessa; Bertin, Aline; Houdelier, Cécilia; Lumineau, Sophie; Formanek, Laureline; Kotrschal, Kurt; Möstl, Erich; Richard-Yris, Marie-Annick

    2011-01-01

    An animal's emotional responses are the result of its cognitive appraisal of a situation. This appraisal is notably influenced by the possibility of an individual to exert control over an aversive event. Although the fact that environment controllability decreases emotional responses in animals is well established, far less is known about its potential trans-generational effects. As the levels of avian yolk hormones can vary according to the mother's environment, we hypothesized that housing environment of mothers would modulate the quality of her eggs and in turn her offspring's behaviour. Two groups of female Japanese quail were constituted: a group that had access to a place to hide in their home-cage (Hd, n = 20) and a group that had nowhere to hide (NoHd, n = 20) when stressed. Both groups were submitted to daily human disturbances for a twenty-day-period. Hd females produced eggs with both less testosterone and androstenedione than did NoHd females. The emotional and social reactivity of Hd females' offspring were lower and their growth was slower than those of NoHd females' offspring. Our results show that a minor difference in housing environment had substantial effects on eggs and offspring. The presence of a shelter probably helped quail to cope with daily human disturbances, producing less reactive offspring. This transgenerational effect caused by an opportunity to hide could lead to applications in care of laboratory animals, conservation biology and animal welfare. PMID:21980338

  9. Sex bias in CNS autoimmune disease mediated by androgen control of autoimmune regulator.

    PubMed

    Zhu, Meng-Lei; Bakhru, Pearl; Conley, Bridget; Nelson, Jennifer S; Free, Meghan; Martin, Aaron; Starmer, Joshua; Wilson, Elizabeth M; Su, Maureen A

    2016-01-01

    Male gender is protective against multiple sclerosis and other T-cell-mediated autoimmune diseases. This protection may be due, in part, to higher androgen levels in males. Androgen binds to the androgen receptor (AR) to regulate gene expression, but how androgen protects against autoimmunity is not well understood. Autoimmune regulator (Aire) prevents autoimmunity by promoting self-antigen expression in medullary thymic epithelial cells, such that developing T cells that recognize these self-antigens within the thymus undergo clonal deletion. Here we show that androgen upregulates Aire-mediated thymic tolerance to protect against autoimmunity. Androgen recruits AR to Aire promoter regions, with consequent enhancement of Aire transcription. In mice and humans, thymic Aire expression is higher in males compared with females. Androgen administration and male gender protect against autoimmunity in a multiple sclerosis mouse model in an Aire-dependent manner. Thus, androgen control of an intrathymic Aire-mediated tolerance mechanism contributes to gender differences in autoimmunity. PMID:27072778

  10. CT demonstration of bilateral adrenal hemorrhage

    SciTech Connect

    Ling, D.; Korobkin, M.; Silverman, P.M.; Dunnick, N.R.

    1983-08-01

    Bilateral adrenal hemorrhage with subsequent adrenal insufficiency is a recognized complication of anticoagulant therapy. Because the clinical manifestations are often nonspecific, the antemortem diagnosis of adrenal hemorrhage has been a difficult clinical problem. Computed tomography (CT) provides detailed images of the adrenal glands that are not possible with conventional imaging methods. The CT findings of bilateral adrenal hemorrhage in an anticoagulated patient are reported.

  11. Primary Adrenal Failure due to Antiphospholipid Syndrome

    PubMed Central

    Sahin, Murat; Oguz, Ayten; Tuzun, Dilek; Boysan, Serife Nur; Mese, Bülent; Sahin, Hatice; Gul, Kamile

    2015-01-01

    Background. Antiphospholipid syndrome (APS) characterized by thrombosis and abortus may rarely cause primary adrenal failure. Case Presentations. A 34-year-old male presented with hypotension, hypoglycemia, hyperpigmentation on his skin and oral mucosa, scars on both legs, and loss of consciousness. In laboratory examinations, hyponatremia (135 mmol/L), hyperpotassemia (6 mmol/L), and thrombocytopenia (83 K/µL) were determined. Cortisol (1.91 µg/dL) and adrenocorticotropic (550 pg/mL) hormone levels were also evaluated. The patient was hospitalized with a diagnosis of acute adrenal crisis due to primary adrenal insufficiency. A Doppler ultrasound revealed venous thrombosis. The patient was diagnosed with antiphospholipid syndrome after the detection of venous thrombosis, thrombocytopenia, elevated aPTT, and anticardiolipin antibody levels. Anticoagulation treatment was started for antiphospholipid syndrome. The patient is now following up with hydrocortisone, fludrocortisone, and warfarin sodium. Conclusion. Antiphospholipid syndrome is a rare reason for adrenal failure. Antiphospholipid syndrome should be suspected if patients have morbidity secondary to venous-arterial thrombosis. PMID:26583075

  12. Stress and Androgen Activity During Fetal Development

    PubMed Central

    Swan, Shanna H.

    2015-01-01

    Prenatal stress is known to alter hypothalamic-pituitary-adrenal axis activity, and more recent evidence suggests that it may also affect androgen activity. In animal models, prenatal stress disrupts the normal surge of testosterone in the developing male, whereas in females, associations differ by species. In humans, studies show that (1) associations between prenatal stress and child outcomes are often sex-dependent, (2) prenatal stress predicts several disorders with notable sex differences in prevalence, and (3) prenatal exposure to stressful life events may be associated with masculinized reproductive tract development and play behavior in girls. In this minireview, we examine the existing literature on prenatal stress and androgenic activity and present new, preliminary data indicating that prenatal stress may also modify associations between prenatal exposure to diethylhexyl phthalate, (a synthetic, antiandrogenic chemical) and reproductive development in infant boys. Taken together, these data support the hypothesis that prenatal exposure to both chemical and nonchemical stressors may alter sex steroid pathways in the maternal-placental-fetal unit and ultimately alter hormone-dependent developmental endpoints. PMID:26241065

  13. Stress and Androgen Activity During Fetal Development.

    PubMed

    Barrett, Emily S; Swan, Shanna H

    2015-10-01

    Prenatal stress is known to alter hypothalamic-pituitary-adrenal axis activity, and more recent evidence suggests that it may also affect androgen activity. In animal models, prenatal stress disrupts the normal surge of testosterone in the developing male, whereas in females, associations differ by species. In humans, studies show that (1) associations between prenatal stress and child outcomes are often sex-dependent, (2) prenatal stress predicts several disorders with notable sex differences in prevalence, and (3) prenatal exposure to stressful life events may be associated with masculinized reproductive tract development and play behavior in girls. In this minireview, we examine the existing literature on prenatal stress and androgenic activity and present new, preliminary data indicating that prenatal stress may also modify associations between prenatal exposure to diethylhexyl phthalate, (a synthetic, antiandrogenic chemical) and reproductive development in infant boys. Taken together, these data support the hypothesis that prenatal exposure to both chemical and nonchemical stressors may alter sex steroid pathways in the maternal-placental-fetal unit and ultimately alter hormone-dependent developmental endpoints. PMID:26241065

  14. Radioguided Adrenal Surgery

    PubMed Central

    Deus, Javier; Millera, Alfonso; Andrés, Alejandro; Prats, Enrique; Gil, Ismael; Suarez, Manuel; Salcini, José L.; Lahoz, Manuel

    2015-01-01

    Abstract The laparoscopic adrenalectomy is considered as the procedure of choice for the treatment of adrenal hyperplasia and tumor lesions. However, some special situations may limit the use of this method due to the difficulty to locate the gland and perform the lesion excision. We analyze 2 patients of a left adrenal tumor, explaining how they have overcome the difficulties in both situations. The first case was a patient with a history of intra-abdominal surgery and the other patient suffered from severe obesity. We performed with the use of the gamma probe, and the 2 cases, was of great help to access and glandular localization. The help of gamma probe test was achieved in the surgical bed, that removal was complete. The use of the portable gamma probe facilitated the access to the left adrenal gland as well as conducting the glandular excision without delay, despite the difficulties due to the intra abdominal surgery caused by the previous surgery, and in the case of severe obesity. PMID:26426608

  15. Impact of nandrolone decanoate on gene expression in endocrine systems related to the adverse effects of anabolic androgenic steroids.

    PubMed

    Alsiö, Johan; Birgner, Carolina; Björkblom, Lars; Isaksson, Pernilla; Bergström, Lena; Schiöth, Helgi B; Lindblom, Jonas

    2009-11-01

    Elite athletes, body builders and adolescents misuse anabolic-androgenic steroids (AAS) in order to increase muscle mass or to enhance physical endurance and braveness. The high doses misused are associated with numerous adverse effects. The purpose of this study was to evaluate the impact of chronic supratherapeutic AAS treatment on circulating hormones and gene expression in peripheral tissues related to such adverse effects. Quantitative real-time PCR was used to measure expression levels of in total 37 genes (including peptide hormones, cell membrane receptors, nuclear receptors, steroid synthesising enzymes and other enzymes) in the pituitary, testes, adrenals, adipose tissue, kidneys and liver of male Sprague-Dawley rats after 14-day administration of the AAS nandrolone decanoate, 3 or 15 mg/kg. Plasma glucose and levels of adrenocorticotropic hormone (ACTH), adiponectin, corticosterone, ghrelin, insulin and leptin were also measured. We found several expected effects on the hypothalamic-pituitary-gonadal axis, while the treatment also caused a number of other not previously identified changes in circulating factors and gene transcription levels such as the dose-dependent reduction of the beta(3)-adrenergic receptor in adipose tissue, reduction of both circulating and mRNA levels of adiponectin, up-regulation of both hydroxymethylglutaryl-CoA-reductase, the rate-limiting enzyme in de novo synthesis of cholesterol, and the receptor for ACTH in the adrenals. The results provide evidence for wide ranging effects of AAS on the hypothalamic-pituitary-adrenal axis, adipose tissue and substrates of the renal control of blood pressure. PMID:19549128

  16. Rapid intra-adrenal feedback regulation of glucocorticoid synthesis.

    PubMed

    Walker, J J; Spiga, F; Gupta, R; Zhao, Z; Lightman, S L; Terry, J R

    2015-01-01

    The hypothalamic-pituitary-adrenal axis is a vital neuroendocrine system that regulates the secretion of glucocorticoid hormones from the adrenal glands. This system is characterized by a dynamic ultradian hormonal oscillation, and in addition is highly responsive to stressful stimuli. We have recently shown that a primary mechanism generating this ultradian rhythm is a systems-level interaction where adrenocorticotrophin hormone (ACTH) released from the pituitary stimulates the secretion of adrenal glucocorticoids, which in turn feedback at the level of the pituitary to rapidly inhibit ACTH secretion. In this study, we combine experimental physiology and mathematical modelling to investigate intra-adrenal mechanisms regulating glucocorticoid synthesis. Our modelling results suggest that glucocorticoids can inhibit their own synthesis through a very rapid (within minutes), presumably non-genomic, intra-adrenal pathway. We present further evidence for the existence of a short time delay in this intra-adrenal inhibition, and also that at the initiation of each ACTH stimulus, this local feedback mechanism is rapidly antagonized, presumably via activation of the specific ACTH receptor (MC2R) signalling pathway. This mechanism of intra-adrenal inhibition enables the gland to rapidly release glucocorticoids while at the same time preventing uncontrolled release of glucocorticoids in response to large surges in ACTH associated with stress. PMID:25392395

  17. The effects of stress on brain and adrenal stem cells.

    PubMed

    de Celis, M F R; Bornstein, S R; Androutsellis-Theotokis, A; Andoniadou, C L; Licinio, J; Wong, M-L; Ehrhart-Bornstein, M

    2016-05-01

    The brain and adrenal are critical control centers that maintain body homeostasis under basal and stress conditions, and orchestrate the body's response to stress. It is noteworthy that patients with stress-related disorders exhibit increased vulnerability to mental illness, even years after the stress experience, which is able to generate long-term changes in the brain's architecture and function. High levels of glucocorticoids produced by the adrenal cortex of the stressed subject reduce neurogenesis, which contributes to the development of depression. In support of the brain-adrenal connection in stress, many (but not all) depressed patients have alterations in the components of the limbic-hypothalamic-pituitary-adrenal (LHPA) axis, with enlarged adrenal cortex and increased glucocorticoid levels. Other psychiatric disorders, such as post-traumatic stress disorder, bipolar disorder and depression, are also associated with abnormalities in hippocampal volume and hippocampal function. In addition, hippocampal lesions impair the regulation of the LHPA axis in stress response. Our knowledge of the functional connection between stress, brain function and adrenal has been further expanded by two recent, independent papers that elucidate the effects of stress on brain and adrenal stem cells, showing similarities in the way that the progenitor populations of these organs behave under stress, and shedding more light into the potential cellular and molecular mechanisms involved in the adaptation of tissues to stress. PMID:26809844

  18. Androgens induce sebaceous differentiation in sebocyte cells expressing a stable functional androgen receptor.

    PubMed

    Barrault, Christine; Garnier, Julien; Pedretti, Nathalie; Cordier-Dirikoc, Sevda; Ratineau, Emeline; Deguercy, Alain; Bernard, François-Xavier

    2015-08-01

    Androgens act through non-genomic and androgen receptor (AR)-dependent genomic mechanisms. AR is expressed in the sebaceous gland and the importance of androgens in the sebaceous function is well established. However, the in vitro models used to date have failed to evidence a clear genomic effect (e.g., modification of gene expression profile) of androgens on human sebocyte cells. In order to study the impact of active androgens in sebocytes, we constructed a stable human sebocyte cell line derived from SEBO662 [17] constitutively expressing a fully functional AR. In these SEBO662 AR+ cells, dihydrotestosterone (DHT) induced AR nuclear translocation and the strong modulation of a set of transcripts (RASD1, GREB1...) known to be androgen-sensitive in other androgenic cells and tissues. Moreover, we observed that DHT precociously down-regulated markers for immature follicular cells (KRT15, TNC) and for hair lineage (KRT75, FST) and up-regulated the expression of genes potentially related to sebocyte differentiation (MUC1/EMA, AQP3, FADS2). These effects were fully confirmed at the protein level. In addition, DHT-stimulated SEBO662 AR+, cultured in a low-calcium defined keratinocyte medium without serum or any complement, neosynthesize lipids, including sebum lipids, and store increased amounts of triglycerides in lipid droplets. DHT also induces morphological changes, increases cell size, and treatments over 7 days lead to a time-dependent increase in the population of apoptotic DNA-fragmented cells. Taken together, these results show for the first time that active androgens alone can engage immature sebocytes in a clear lipogenic differentiation process (Graphical abstract). These effects depend on the expression of a functional AR in these cells. This model should be of interest for revisiting the mechanisms of the sebaceous function in vitro and for the design of relevant pharmacological models for drug or compound testing. PMID:25864624

  19. Androgens in human evolution. A new explanation of human evolution.

    PubMed

    Howard, J

    2001-01-01

    Human evolution consists of chronological changes in gene regulation of a continuous and relatively stable genome, activated by hormones, the production of which is intermittently affected by endogenous and exogenous forces. Periodic variations in the gonadal androgen, testosterone, and the adrenal androgen, dehydroepiandrosterone (DHEA), significantly participated in all hominid transformations. The hominid characteristics of early Australopithecines are primarily a result of increased testosterone. The first significant cold of the early Pleistocene resulted in an increase in DHEA that simultaneously produced Homo and the robust Australopithecines. Subsequent Pleistocene climatic changes and differential reproduction produced changes in DHEA and testosterone ratios that caused extinction of the robust Australopithecines and further changes and continuation of Homo. Changes in testosterone and DHEA produce allometric and behavioral changes that are identifiable and vigorous in modern populations. PMID:11702658

  20. Androgenic endocrine disruptors in wastewater treatment plant effluents in India: Their influence on reproductive processes and systemic toxicity in male rats

    SciTech Connect

    Kumar, Vikas; Chakraborty, Ajanta; Viswanath, Gunda; Roy, Partha

    2008-01-01

    Endocrine-disrupting chemicals (EDC) are linked to human health and diseases as they mimic or block the normal functioning of endogenous hormones. The present work dealt with a comparative study of the androgenic potential of wastewater treatment plant (WWTP) influents and effluents in Northern region of India, well known for its polluted water. Water samples were screened for their androgenic potential using the Hershberger assay and when they were found positive for androgenicity, we studied their mode of action in intact rats. The data showed a significant change in the weight and structure of sex accessory tissues (SATs) of castrated and intact rats. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis demonstrated a significant change in the expression patterns of the major steroidogenic enzymes in adrenal and testis: cytochrome P450{sub SCC}, cytochrome P450{sub C17}, 3{beta}-hydroxysteroid dehydrogenase, 17{beta}-hydroxysteroid dehydrogenase. This was further supported by increased enzymatic activities measured in vitro spectrophotometrically. Serum hormone profile showed a decreased level of gonadotrophic hormones and increased testosterone level. Further, increase in the serum level of alkaline phosphatase, SGPT and SGOT and histopathological changes in kidney and liver of treated animals, confirmed the toxic effects of contaminating chemicals. Analysis of water samples using HPLC and GC-MS showed the presence of various compounds and from them, four prominent aromatic compounds viz. nonylphenol, hexachlorobenzene and two testosterone equivalents, were identified. Our data suggest that despite rigorous treatment, the final treated effluent from WWTP still has enough androgenic and toxic compounds to affect general health.

  1. Prenatal hormones and childhood sex segregation: playmate and play style preferences in girls with congenital adrenal hyperplasia.

    PubMed

    Pasterski, Vickie; Geffner, Mitchell E; Brain, Caroline; Hindmarsh, Peter; Brook, Charles; Hines, Melissa

    2011-04-01

    We investigated playmate and play style preference in children with congenital adrenal hyperplasia (CAH) (26 females, 31 males) and their unaffected siblings (26 females, 17 males) using the Playmate and Play Style Preferences Structured Interview (PPPSI). Both unaffected boys and girls preferred same-sex playmates and sex-typical play styles. In the conflict condition where children chose between a same-sex playmate engaged in an other-sex activity or an other-sex playmate engaged in a same-sex activity, boys (both CAH and unaffected brothers) almost exclusively chose playmates based on the preferred play style of the playmate as opposed to the preferred gender label of the playmate. By contrast, unaffected girls used play style and gender label about equally when choosing playmates. Girls with CAH showed a pattern similar to that of boys: their playmate selections were more masculine than unaffected girls, they preferred a boy-typical play style and, in the conflict condition, chose playmates engaged in a masculine activity. These findings suggest that prenatal androgen exposure contributes to sex differences in playmate selection observed in typically developing children and that, among boys and girls exposed to high levels of androgens prenatally, play style preferences drive sex segregation in play. PMID:21338606

  2. Expression of nicotinic acetylcholine receptors in human and rat adrenal medulla.

    PubMed

    Mousavi, M; Hellström-Lindahl, E; Guan, Z Z; Bednar, I; Nordberg, A

    2001-12-21

    Neuronal nicotinic receptors (nAChRs) are expressed in the brain but also in the peripheral tissues including the adrenal medulla. However, it is unclear which nAChRs are present in the human adrenal medulla. In the study, receptor binding assay, Western blot and RT-PCR have been performed to investigate the expression of nAChRs in adrenal medulla from human, rat and mouse. The results showed that in human adult adrenal medulla, mRNAs for nAChR alpha3, alpha4, alpha5, alpha7, beta2, beta3, and beta4 subunits but not beta2 in the fetal human adrenal medulla were expressed. Saturation binding of [3H]epibatidine showed two binding sites in human aged adrenal medulla. The specific binding of [3H]epibatidine (0.1 nM) was significantly higher in human fetal compared to human aged adrenal medulla. mRNAs for the alpha3, alpha4, alpha5, alpha7, beta2, and beta4 subunits but not the beta3 were detectable in adult rat and mouse adrenal medulla. No differences in gene-expression of the nAChRs were observed between new born, adult and aged rat adrenal medulla. Saturation binding of [3H]epibatidine showed only one binding site in rat adrenal medulla. Lower protein levels for the nAChR subunits were observed in the rat adrenal medulla compared to rat brain. There was lower protein levels of the nAChRs in aged rat adrenal medulla compared to the young rats. Sub-chronic treatment of nicotine to rats did not influence level of the nAChRs in the adrenal medulla. In conclusion, the expression of nAChRs in adrenal medulla is age- related and species dependent. PMID:11811902

  3. Adrenal gland denervation and diving in ducks.

    PubMed

    Mangalam, H J; Jones, D R; Lacombe, A M

    1987-06-01

    The extreme elevation in plasma levels of free norepinephrine (NE) and free epinephrine (EP), which occurs during forced diving of ducks (Anas platyrhynchos), was studied before and after denervation of the adrenal glands. In intact animals both NE and EP concentration increased by up to two orders of magnitude in a 4-min dive but by a significantly lesser amount if the duck breathed O2 before the dive. Denervating the adrenal glands reduced the amounts of both catecholamines (CA) released during dives, plasma EP decreased to 10%, and NE to 50% of values obtained before denervation. Breathing O2 before a dive virtually eliminated CA release in denervates, indicating that hypoxia was the important non-neural releasing agent. Hypoxia was also the most important neural releasing agent compared with hypercapnia, acidosis, or hypoglycemia. Adrenal denervation did not cause significant changes in heart rate, blood pressure, arterial blood gas tensions, pH, or plasma glucose during dives, although denervation caused increased variation in some of these variables. In ducks CA release in dives is largely due to decreasing arterial O2 partial pressure, and full expression of the response is dependent on intact innervation of the adrenal gland. PMID:3591985

  4. Adrenal insufficiency presenting as hypercalcemia and acute kidney injury

    PubMed Central

    Ahn, Seung Won; Kim, Tong Yoon; Lee, Sangmin; Jeong, Jeong Yeon; Shim, Hojoon; Han, Yu min; Choi, Kyu Eun; Shin, Seok Joon; Yoon, Hye Eun

    2016-01-01

    Adrenal insufficiency is an uncommon cause of hypercalcemia and not easily considered as an etiology of adrenal insufficiency in clinical practice, as not all cases of adrenal insufficiency manifest as hypercalcemia. We report a case of secondary adrenal insufficiency presenting as hypercalcemia and acute kidney injury in a 66-year-old female. The patient was admitted to the emergency department with general weakness and poor oral intake. Hypercalcemia (11.5 mg/dL) and moderate renal dysfunction (serum creatinine 4.9 mg/dL) were shown in her initial laboratory findings. Studies for malignancy and hyperparathyroidism showed negative results. Basal cortisol and adrenocorticotropic hormone levels and adrenocorticotropic hormone stimulation test confirmed the diagnosis of adrenal insufficiency. With the administration of oral hydrocortisone, hypercalcemia was dramatically resolved within 3 days. This case shows that adrenal insufficiency may manifest as hypercalcemia and acute kidney injury, which implicates that adrenal insufficiency should be considered a cause of hypercalcemia in clinical practice. PMID:27536162

  5. Adrenal Insufficiency Associated with Small Cell Lung Cancer: A Case Report and Literature Review.

    PubMed

    Noguchi, Shingo; Torii, Ryo; Shimabukuro, Ikuko; Yamasaki, Kei; Kido, Takashi; Yoshii, Chiharu; Mukae, Hiroshi; Yatera, Kazuhiro

    2016-06-01

    A 78-year-old Japanese man with fatigue, appetite loss, skin hyperpigmentation, hypotension and hypoglycemia, visited our hospital to evaluate an abnormal chest X-ray and adrenal gland swelling in echography in February 2015. Chest computed tomography showed a mass lesion in the right lower lobe and bilateral adrenal swellings, and small cell lung cancer (SCLC) with bilateral adrenal metastasis was diagnosed after bronchoscopy. According to low levels of serum cortisol, elevated adrenocorticotropic hormone (ACTH) and rapid ACTH test, the diagnosis of adrenal insufficiency associated with SCLC was made. Treatment with hydrocortisone (20 mg/day) was started in addition to systemic chemotherapy with carboplatin and etoposide. The patient's symptoms were slightly improved, however, systemic chemotherapy was discontinued according to the patient's request after 1 course of chemotherapy. Thereafter, he received only supportive care, and his general condition gradually worsened and he ultimately died in August 2015. Adrenal insufficiency associated with SCLC, which is caused by tissue destruction more than 90% of the adrenal glands, is rare although adrenal metastasis is not rare in patients with lung cancer. The findings such as general fatigue, appetite loss, hypotension, and hyponatremia are often got follow up as findings of advanced cancer, but appropriate therapy for adrenal insufficiency, supplement of the adrenal corticosteroid hormone, may lead to a significant improvement in the symptoms and quality of life in clinical practice of lung cancer. Therefore, physicians must consider potential adrenal insufficiency in lung cancer patients with bilateral adrenal metastasis. PMID:27302729

  6. Adrenal hemangioma: a case report.

    PubMed

    Auh, Y H; Anand, J; Zirinsky, K; Kazam, E

    1986-01-01

    Adrenal hemangioma is a very rare tumor. Presented is the 18th case proved by autopsy or surgery reported in world literature. The tumor was incidentally discovered at autopsy. Unless this tumor has characteristic calcifications, phlebolith or phlebolithlike, its computed tomography appearance is nonspecific. Therefore, by computed tomography this tumor cannot be differentiated from other primary or secondary adrenal tumors. PMID:3943357

  7. Androgen inhibits the increases in hypothalamic corticotropin-releasing hormone (CRH) and CRH-immunoreactivity following gonadectomy.

    PubMed

    Bingaman, E W; Magnuson, D J; Gray, T S; Handa, R J

    1994-03-01

    To characterize the effect of androgens on the hypothalamo-pituitary-adrenal (HPA) axis we examined the regulation of corticotropin-releasing hormone (CRH) following gonadectomy and hormone replacement. Three-month-old male Fischer 344 (F344) rats were gonadectomized (GDX) or sham GDX. Control animals remained intact. Animals were sacrificed 1, 4, 7, 10, or 21 days following surgery. GDX rats had significantly elevated (p < 0.05) levels of hypothalamic CRH 21 days after surgery compared to intact and sham-operated rats. In a second study, 3-month-old male F344 rats were GDX and treated with the non-aromatizable androgen, dihydrotestosterone (DHT), using a Silastic capsule containing crystalline DHT propionate subcutaneously implanted in each animal's back. Control animals were GDX and sham-treated or left intact (INT). Three weeks following gonadectomy, CRH levels in the hypothalamus of GDX rats showed a significant increase (p < 0.05) compared to intact animals. DHT treatment, beginning at the time of gonadectomy prevented this increase. CRH or arginine vasopressin (AVP) immunoreactivity was examined using immunocytochemistry. The number of CRH-immunoreactive (IR) cells in the paraventricular nucleus (PVN) of GDX, DHT-treated animals was significantly decreased (p < 0.05) compared to GDX rats. No differences were seen between treatment groups in CRH-IR cell numbers in the bed nucleus of the stria terminalis or the central amygdaloid nucleus or in AVP-IR cell numbers in the PVN. These data demonstrate that long-term castration increases hypothalamic CRH content and CRH-IR cell numbers in the PVN by removal of an androgen-dependent repression. PMID:8159272

  8. Adrenal ganglioneuroma in a patient with polycystic ovarian disease (PCOD): a rare association.

    PubMed

    Kumar, Arvind; Singh, Vishwajeet; Sankhwar, Satyanarayan; Babu, Suresh

    2013-01-01

    Adrenal ganglioneuromas are rare, benign incidentalomas of a neural crest origin. A majority of these tumours are clinically silent and discovered on imaging for unrelated reasons. Polycystic ovarian disease (PCOD) is an endocrine disorder characterised by bilateral polycystic ovaries, anovulation leading to infertility, irregular menstrual cycles and features of androgen hormone excess. Herein we report a rare case of adrenal ganglioneuroma in a 14-year-old girl with PCOD. She was referred to us by the gynaecologist after incidental detection of adrenal mass on ultrasonography. Except for raised 24 h urinary metanephrines, rest of the hormones measured were in normal range. Transperitoneal adrenalectomy was performed and histopathology was suggestive of ganglioneuroma. Postoperative recovery was excellent and she is doing well. To our knowledge it is the first such type of case to be reported. PMID:24145507

  9. Increased 3β-hydroxysteroid dehydrogenase 2 and 17α-hydroxylase activities in a virilized adolescent female with adrenal adenoma: A case report

    PubMed Central

    YANG, GUOQING; DOU, JINGTAO; ZHANG, XIAOLIN; GU, WEIJUN; LV, ZHAOHUI; DU, JIN; BA, JIANMING; MU, YIMING; LU, JUMING

    2016-01-01

    In the present study, the case of a female patient with pseudo-hermaphrodism caused by an androgen-producing adrenocortical tumor is presented, and the possible mechanism is investigated. The expression of the luteinizing hormone/human chorionic gonadotrophin (LH/hCG) receptor in tumor tissues and normal adrenal tissues was analyzed using immunohistochemistry. Furthermore, the activities of 3β-hydroxysteroid dehydrogenase 2 (HSD2), cytochrome P450 17α-hydroxylase (CYP17) and 17β-hydroxysteroid dehydrogenase 3 (HSD3) enzymes were measured using enzyme-linked immunosorbent assay, and the expression levels of 3β-HSD2, 17β-HSD3, CYP17 and LH/hCG receptor mRNA were determined by quantitative polymerase chain reaction (qPCR). Immunohistochemical staining for the LH/hCG receptor was negative in the tumor tissue and positive in the normal adrenal tissue. The activities of 3β-HSD2 and CYP17 in the tumor tissue were higher than those in the normal tissue (P<0.01), whereas the activity of 17β-HSD3 was lower (P<0.01). The mRNA levels of 3β-HSD2 and CYP17 were higher (P<0.01) and the levels of 17β-HSD3 and LH/hCG receptor were lower (P<0.01) in the tumor tissue compared with those of the normal tissue. In conclusion, in the present study, a rare case of virilization by an androgen-producing adrenocortical tumor is present. The results indicate that it may be associated with increased activities of 3β-HSD2 and CYP17 but not with the expression of the LH/hCG receptor. PMID:26893641

  10. Androgen biosynthesis in castration-resistant prostate cancer

    PubMed Central

    Penning, Trevor M

    2014-01-01

    Prostate cancer is the second leading cause of death in adult males in the USA. Recent advances have revealed that the fatal form of this cancer, known as castration-resistant prostate cancer (CRPC), remains hormonally driven despite castrate levels of circulating androgens. CRPC arises as the tumor undergoes adaptation to low levels of androgens by either synthesizing its own androgens (intratumoral androgens) or altering the androgen receptor (AR). This article reviews the major routes to testosterone and dihydrotestosterone synthesis in CRPC cells and examines the enzyme targets and progress in the development of isoform-specific inhibitors that could block intratumoral androgen biosynthesis. Because redundancy exists in these pathways, it is likely that inhibition of a single pathway will lead to upregulation of another so that drug resistance would be anticipated. Drugs that target multiple pathways or bifunctional agents that block intratumoral androgen biosynthesis and antagonize the AR offer the most promise. Optimal use of enzyme inhibitors or AR antagonists to ensure maximal benefits to CRPC patients will also require application of precision molecular medicine to determine whether a tumor in a particular patient will be responsive to these treatments either alone or in combination. PMID:24829267

  11. Androgen receptor polymorphism (CAG repeats) and androgenicity.

    PubMed

    Canale, D; Caglieresi, C; Moschini, C; Liberati, C D; Macchia, E; Pinchera, A; Martino, E

    2005-09-01

    Objective Polymorphism of the androgen receptor (AR) has been related to various pathophysiological conditions, such as osteoporosis and infertility. The objectives of this study were to evaluate the frequency of distribution in a normal Italian population and to assess CAG repeats (CAGr) in other conditions, such as hypoandrogenism, potentially influenced by AR polymorphism. Patients and measurements CAGr polymorphism was determined in a group of 91 healthy normoandrogenized subjects, 29 hypoandrogenized patients (hypoplasia of prostate and seminal vesicles, reduced beard or body hair, etc.) and 29 infertile patients by direct sequencing. Results The mean (+/- SD) number of CAG repeats [(CAGr)n] was 21.5 (+/- 1.7) in the control group, 21.4 (+/- 2.0) in the infertile patients and 24.0 (+/- 2.9) in the hypoandrogenic males. The difference was statistically significant between this last group and the other two (P < 0.0001), while there was no difference between normal controls and infertile patients. The frequency distribution showed a shift towards higher CAG length in hypoandrogenized patients compared to controls and infertile patients. If we used a cut-off point of 24.9 (2 SD above the mean), the percentage of patients with 25 or more CAGr repeats was 38% among hypoandrogenized patients, 7% among infertile patients and 5% among the control group. In hypoandrogenized subjects (CAGr)n correlated slightly with testis and prostate volume. The number of CAG repeats was not associated with any of the hormonal parameters, including testosterone, evaluated in the three groups. Conclusions Our normal population, representing subjects from Central Italy, is superimposable on other European populations with regard to (CAGr)n distribution. Hypoandrogenic males have a shift in the frequency distribution towards longer (CAGr)n. Infertile patients are not statistically different from the control group. These findings suggest that, given the same amount of circulating

  12. Nonclassical Congenital Adrenal Hyperplasia and Pregnancy

    PubMed Central

    Cuhaci, Neslihan; Aydın, Cevdet; Yesilyurt, Ahmet; Pınarlı, Ferda Alpaslan; Ersoy, Reyhan; Cakir, Bekir

    2015-01-01

    Objective. The most common form of congenital adrenal hyperplasia (CAH) is 21-hydroxylase (21-OH) deficiency due to mutation of the CYP21A2 gene. Patients with nonclassical CAH (NC-CAH) are usually asymptomatic at birth and typically present in late childhood, adolescence, or adulthood with symptoms of excessive androgen secretion. Subfertility is relative in NC-CAH, but the incidence of spontaneous miscarriage is higher. Here, we report a previously undiagnosed female who gave birth to a normal male child and is planning to become pregnant again. Case Report. A 32-year-old female was referred to our clinic for obesity. Her medical history revealed that she had had three pregnancies. She was planning to become pregnant again. Her laboratory results revealed that she had NC-CAH. Since her husband is the son of her aunt and she had miscarriages and intrauterin exitus in her history, their genetic analyses were performed. Conclusion. Since most patients with NC-CAH have a severe mutation, these patients may give birth to a child with the classical CAH (C-CAH) if their partner is also carrying a severe mutation. Females with NC-CAH who desire pregnancy must be aware of the risk of having an infant with C-CAH. PMID:26558116

  13. Adrenal involvement in non-Hodgkin lymphoma

    SciTech Connect

    Paling, M.R.; Williamson, B.R.J.

    1983-08-01

    Adrenal masses are described in seven cases of non-Hodgkin lymphoma in a series of 173 patients. In all seven patients the lymphoma was diffuse rather than nodular. Three patients had adrenal masses at the time of presentation, whereas in four cases the adrenal gland was a site of tumor recurrence after therapy. Three patients had simultaneous bilateral adrenal involvement by tumor. No characteristic features were recognized that might have distinguished these tumors from other adrenal masses. Appropriate therapy successfully resolved the adrenal masses in all but one case. The latter patient was the only one with evidence of adrenal insufficiency.

  14. Unilateral adrenal tumor, erectile dysfunction and infertility in a patient with 21-hydroxylase deficiency: effects of glucocorticoid treatment and surgery.

    PubMed

    Scaroni, C; Favia, G; Lumachi, F; Opocher, G; Bonanni, G; Mantero, F; Armanini, D

    2003-02-01

    In untreated congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21OHDS) the presence of adrenal and testicular tumors had been described; however little is known about the effect of the enzymatic defect on fertility in males. We studied a male adult patient affected by 21OHDS for infertility, after a long period of discontinuation of glucocorticoid therapy and then during resumption of treatment and 8 months after monoadrenalectomy. The initial spermatic count revealed azoospermia and testicular needle aspiration showed a cytological picture consistent with prepuberty. The morphofunctional study revealed a right adrenal mass with reduced uptake at radioscan. Treatment was resumed with onset of impotency, which improved after reduction of the dose of glucocorticoids. The patient was monoadrenalectomised and his spermatic count increased. The patient shows that corticosteroid therapy in 21OHDS should be continued lifelong to avoid adrenal hyperplasia with possible areas of autonomy and to allow regular fertility. Impotence during treatment is probably due to a decrease of excessive adrenal androgens while testicular androgen production is still suppressed. PMID:12605349

  15. GnRH agonists and the rapidly increasing use of combined androgen blockade in prostate cancer.

    PubMed

    Labrie, Fernand

    2014-08-01

    The discovery of medical castration with GnRH agonists in 1979 rapidly replaced surgical castration and high doses of estrogens for the treatment of prostate cancer. Soon afterwards, it was discovered that androgens were made locally in the prostate from the inactive precursor DHEA of adrenal origin, a mechanism called intracrinology. Taking into account these novel facts, combined androgen blockade (CAB) using a pure antiandrogen combined with castration in order to block the two sources of androgens was first published in 1982. CAB was the first treatment shown in randomized and placebo-controlled trials to prolong life in prostate cancer, even at the metastatic stage. Most importantly, the results recently obtained with the novel pure antiandrogen enzalutamide as well as with abiraterone, an inhibitor of 17α-hydroxylase in castration-resistant prostate cancer, has revitalized the CAB concept. The effects of CAB observed on survival of heavily pretreated patients further demonstrates the importance of the androgens made locally in the prostate and are a strong motivation to apply CAB to efficiently block all sources of androgens earlier at start of treatment and, even better, before metastasis occurs. The future of research in this field thus seems to be centered on the development of more potent blockers of androgens formation and action in order to obtain better results at the metastatic stage and, for the localized stage, reduce the duration of treatment required to achieve complete apoptosis and control of prostate cancer proliferation before it reaches the metastatic or noncurable stage. PMID:24825748

  16. Intracrine Androgens Enhance Decidualization and Modulate Expression of Human Endometrial Receptivity Genes

    PubMed Central

    Gibson, Douglas A.; Simitsidellis, Ioannis; Cousins, Fiona L.; Critchley, Hilary O. D.; Saunders, Philippa T. K.

    2016-01-01

    The endometrium is a complex, steroid-dependent tissue that undergoes dynamic cyclical remodelling. Transformation of stromal fibroblasts (ESC) into specialised secretory cells (decidualization) is fundamental to the establishment of a receptive endometrial microenvironment which can support and maintain pregnancy. Androgen receptors (AR) are present in ESC; in other tissues local metabolism of ovarian and adrenal-derived androgens regulate AR-dependent gene expression. We hypothesised that altered expression/activity of androgen biosynthetic enzymes would regulate tissue availability of bioactive androgens and the process of decidualization. Primary human ESC were treated in vitro for 1–8 days with progesterone and cAMP (decidualized) in the presence or absence of the AR antagonist flutamide. Time and treatment-dependent changes in genes essential for a) intra-tissue biosynthesis of androgens (5α-reductase/SRD5A1, aldo-keto reductase family 1 member C3/AKR1C3), b) establishment of endometrial decidualization (IGFBP1, prolactin) and c) endometrial receptivity (SPP1, MAOA, EDNRB) were measured. Decidualization of ESC resulted in significant time-dependent changes in expression of AKR1C3 and SRD5A1 and secretion of T/DHT. Addition of flutamide significantly reduced secretion of IGFBP1 and prolactin and altered the expression of endometrial receptivity markers. Intracrine biosynthesis of endometrial androgens during decidualization may play a key role in endometrial receptivity and offer a novel target for fertility treatment. PMID:26817618

  17. Androgen receptor genomic regulation

    PubMed Central

    Jin, Hong-Jian; Kim, Jung

    2013-01-01

    The transcriptional activity of the androgen receptor (AR) is not only critical for the normal development and function of the prostate but also pivotal to the onset and progression of prostate cancer (PCa). The studies of AR transcriptional regulation were previously limited to a handful of AR-target genes. Owing to the development of various high-throughput genomic technologies, significant advances have been made in recent years. Here we discuss the discoveries of genome-wide androgen-regulated genes in PCa cell lines, animal models and tissues using expression microarray and sequencing, the mapping of genomic landscapes of AR using Combining Chromatin Immunoprecipitation (ChIP)-on-chip and ChIP-seq assays, the interplay of transcriptional cofactors in defining AR binding profiles, and the genomic regulation and AR reprogramming in advanced PCa. PMID:25237629

  18. Mechanism of androgen receptor action.

    PubMed

    Li, Jin; Al-Azzawi, Farook

    2009-06-20

    Recent research provides a much more detailed understanding of the role of the androgen receptor in normal human development and physiology, its structure, and its functioning. This review discusses genomic and non-genomic actions of the androgen receptor, as well as their co-regulators. We also explore several clinically relevant aspects of the molecular biology of the androgen receptor and its co-regulators. PMID:19372015

  19. Elevated expression levels of androgen receptors and matrix metalloproteinase-2 and -9 in 30 cases of hepatocellular carcinoma compared with adjacent tissues as predictors of cancer invasion and staging

    PubMed Central

    ZHANG, YAN; SHEN, YUCHENG; CAO, BIN; YAN, AITING; JI, HAOMING

    2015-01-01

    The aim of the present study was to investigate the potential roles of the androgen receptor (AR) and matrix metalloproteinase (MMP)-2 and MMP-9 in hepatocellular carcinoma (HCC) tissues and whether their expression could be used as a predictor of the invasion and stage of cancer. The expression levels of AR, MMP-2 and MMP-9 in HCC tissues and tissues adjacent to the tumor were measured by immunohistochemical staining assay. The expression rates of AR, MMP-2 and MMP-9 in the HCC tissue were 76.67, 73.33 and 76.67%, respectively, all of which were significantly higher than those in the tissues adjacent to the tumor. The expression of these proteins represents the local invasion and stage. AR, MMP-2 and MMP-9 expression levels in HCC tissues have the potential to be employed as predictors of the progression of local cancer invasion and the tumor stage. PMID:25667651

  20. Gendered occupational interests: prenatal androgen effects on psychological orientation to Things versus People.

    PubMed

    Beltz, Adriene M; Swanson, Jane L; Berenbaum, Sheri A

    2011-09-01

    There is considerable interest in understanding women's underrepresentation in science, technology, engineering, and mathematics careers. Career choices have been shown to be driven in part by interests, and gender differences in those interests have generally been considered to result from socialization. We explored the contribution of sex hormones to career-related interests, in particular studying whether prenatal androgens affect interests through psychological orientation to Things versus People. We examined this question in individuals with congenital adrenal hyperplasia (CAH), who have atypical exposure to androgens early in development, and their unaffected siblings (total N=125 aged 9 to 26 years). Females with CAH had more interest in Things versus People than did unaffected females, and variations among females with CAH reflected variations in their degree of androgen exposure. Results provide strong support for hormonal influences on interest in occupations characterized by working with Things versus People. PMID:21689657

  1. Stimulation of adrenal DNA synthesis in cadmium-treated male rats

    SciTech Connect

    Nishiyama, S.; Nakamura, K.

    1984-07-01

    Cadmium chloride (CdCl2) at a dose of 1 mg/kg body wt was injected into male rats of the Wistar strain, weighing 250 g on the average, twice a day (12-hr intervals) for 7 consecutive days. DNA and RNA contents and (/sup 3/H)-thymidine and (/sup 3/H)-uridine incorporation into the acid-insoluble fraction significantly increased in the adrenals of rats treated with Cd for 2 and 7 consecutive days. Adrenal protein content and weight also significantly increased. These results indicate that continued treatment with Cd stimulates DNA and RNA synthesis in the adrenal cortex, which in turn results in the increase of the total protein contents of the adrenal gland and subsequently in the enlargement of the gland. Serum adrenocorticotrophin (ACTH) and insulin levels in Cd-treated rats were not higher than control levels, suggesting that the stimulation of DNA synthesis in the adrenals of Cd-treated rats is due to factor(s) other than serum ACTH and insulin. Treatment with Cd inhibited DNA synthesis in cultured adrenocortical cells at concentrations of 10(-4) to 10(-8) M, suggesting that Cd does not directly stimulate DNA synthesis in the adrenal gland in vivo. Although the adrenal gland became enlarged, the total adrenal corticosterone content decreased significantly. The decrease of total adrenal corticosterone content may be due to the fall in serum ACTH level of Cd-treated rats.

  2. Adrenal Gland Disorders: Condition Information

    MedlinePlus

    ... of salt and water Controlling the "fight or flight" response to stress Maintaining pregnancy Initiating and controlling ... overview of the adrenal glands: Beyond fight or flight . Retrieved June 29, 2012 from http://www.endocrineweb. ...

  3. Radionuclide therapy of adrenal tumors.

    PubMed

    Carrasquillo, Jorge A; Pandit-Taskar, Neeta; Chen, Clara C

    2012-10-01

    Adrenal tumors arising from chromaffin cells will often accumulate radiolabeled metaiodobenzylguanidine (MIBG) and thus are amenable to therapy with I-131 MIBG. More recently, therapy studies have targeted the somatostatin receptors using Lu-177 or Y-90 radiolabeled somatostatin analogs. Because pheochromocytoma (PHEO)/paraganglioma (PGL) and neuroblastoma (NB), which often arise from the adrenals, express these receptors, clinical trials have been performed with these reagents. We will review the experience using radionuclide therapy for targeting PHEO/PGL and NBs. PMID:22718415

  4. 11-Ketotestosterone and 11-Ketodihydrotestosterone in Castration Resistant Prostate Cancer: Potent Androgens Which Can No Longer Be Ignored

    PubMed Central

    Pretorius, Elzette; Africander, Donita J.; Vlok, Maré; Quanson, Jonathan

    2016-01-01

    Dihydrotestosterone (DHT) is regarded as the most potent natural androgen and is implicated in the development and progression of castration resistant prostate cancer (CRPC). Under castrate conditions, DHT is produced from the metabolism of the adrenal androgen precursors, DHEA and androstenedione. Recent studies have shown that the adrenal steroid 11β-hydroxyandrostenedione (11OHA4) serves as the precursor to the androgens 11-ketotestosterone (11KT) and 11-ketodihydrotestosterone (11KDHT). In this study we comprehensively assess the androgenic activity of 11KT and 11KDHT. This is the first study, to our knowledge, to show that 11KT and 11KDHT, like T and DHT, are potent and efficacious agonists of the human androgen receptor (AR) and induced both the expression of representative AR-regulated genes as well as cellular proliferation in the androgen dependent prostate cancer cell lines, LNCaP and VCaP. Proteomic analysis revealed that 11KDHT regulated the expression of more AR-regulated proteins than DHT in VCaP cells, while in vitro conversion assays showed that 11KT and 11KDHT are metabolized at a significantly lower rate in both LNCaP and VCaP cells when compared to T and DHT, respectively. Our findings show that 11KT and 11KDHT are bona fide androgens capable of inducing androgen-dependant gene expression and cell growth, and that these steroids have the potential to remain active longer than T and DHT due to the decreased rate at which they are metabolised. Collectively, our data demonstrates that 11KT and 11KDHT likely play a vital, but overlooked, role in the development and progression of CRPC. PMID:27442248

  5. Laparoscopic Resection of Adrenal Teratoma

    PubMed Central

    Vitagliano, Gonzalo; Villeta, Matias; Arellano, Leonardo; Santis, Oscar

    2006-01-01

    Background: Teratoma is a germ-cell tumor that commonly affects the gonads. Its components originate in the ectoderm, endoderm, and mesoderm. Extragonadal occurrence is rare. Teratomas confined to the adrenal gland are exceptional; only 3 cases have been reported in the English-language literature. We report 2 cases of mature teratomas of the adrenal gland that were laparoscopically excised. Methods: Two patients (ages 8 and 61 years) were diagnosed with adrenal teratoma at our institution. Radiological examination showed a solid 8-cm adrenal lesion in both cases. Hormonal assessment was normal. Both patients underwent laparoscopic transperitoneal adrenalectomy. Results: Surgical time was 120 minutes and 50 minutes, respectively. One patient was discharged on postoperative day 2, and the other remained hospitalized until day 10. The latter patient required percutaneous drainage of a retroperitoneal collection. Both tumors were identified as mature cystic teratomas. No evidence was present of recurring disease in either patient. Conclusions: Adrenal teratoma is rare. Laparoscopic transperitoneal adrenalectomy is a feasible, effective technique that enables excellent oncologic results. To our knowledge, this is the first report of laparoscopic adrenalectomy for pure adrenal teratoma. PMID:17575773

  6. Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice Guideline in collaboration with the European Network for the Study of Adrenal Tumors.

    PubMed

    Fassnacht, Martin; Arlt, Wiebke; Bancos, Irina; Dralle, Henning; Newell-Price, John; Sahdev, Anju; Tabarin, Antoine; Terzolo, Massimo; Tsagarakis, Stylianos; Dekkers, Olaf M

    2016-08-01

    : By definition, an adrenal incidentaloma is an asymptomatic adrenal mass detected on imaging not performed for suspected adrenal disease. In most cases, adrenal incidentalomas are nonfunctioning adrenocortical adenomas, but may also represent conditions requiring therapeutic intervention (e.g. adrenocortical carcinoma, pheochromocytoma, hormone-producing adenoma or metastasis). The purpose of this guideline is to provide clinicians with best possible evidence-based recommendations for clinical management of patients with adrenal incidentalomas based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. We predefined four main clinical questions crucial for the management of adrenal incidentaloma patients, addressing these four with systematic literature searches: (A) How to assess risk of malignancy?; (B) How to define and manage low-level autonomous cortisol secretion, formerly called 'subclinical' Cushing's syndrome?; (C) Who should have surgical treatment and how should it be performed?; (D) What follow-up is indicated if the adrenal incidentaloma is not surgically removed? SELECTED RECOMMENDATIONS: (i) At the time of initial detection of an adrenal mass establishing whether the mass is benign or malignant is an important aim to avoid cumbersome and expensive follow-up imaging in those with benign disease. (ii) To exclude cortisol excess, a 1mg overnight dexamethasone suppression test should be performed (applying a cut-off value of serum cortisol ≤50nmol/L (1.8µg/dL)). (iii) For patients without clinical signs of overt Cushing's syndrome but serum cortisol levels post 1mg dexamethasone >138nmol/L (>5µg/dL), we propose the term 'autonomous cortisol secretion'. (iv) All patients with '(possible) autonomous cortisol' secretion should be screened for hypertension and type 2 diabetes mellitus, to ensure these are appropriately treated. (v) Surgical treatment should be considered in an individualized approach in patients with

  7. Genetics of primary macronodular adrenal hyperplasia.

    PubMed

    Fragoso, Maria Candida Barisson Villares; Alencar, Guilherme Asmar; Lerario, Antonio Marcondes; Bourdeau, Isabelle; Almeida, Madson Queiroz; Mendonca, Berenice Bilharinho; Lacroix, André

    2015-01-01

    ACTH-independent macronodular adrenal hyperplasia is a rare cause of Cushing's syndrome (CS), accounting for <2% of all endogenous CS cases; however it is more frequently identified incidentally with sub-clinical cortisol secretion. Recently, cortisol secretion has been shown to be regulated by ectopic corticotropin, which is in turn produced by clusters of steroidogenic cells of the hyperplastic adrenal nodules. Hence, the term 'ACTH-independent' is not entirely appropriate for this disorder. Accordingly, the disease is designated primary macronodular adrenal hyperplasia (PMAH) in this review article. The means by which cortisol production is regulated in PMAH despite the suppressed levels of ACTH of pituitary origin is exceedingly complex. Several molecular events have been proposed to explain the enhanced cortisol secretion, increased cell proliferation, and nodule formation in PMAH. Nonetheless, the precise sequence of events and the molecular mechanisms underlying this condition remain unclear. The purpose of this review is therefore to present new insights on the molecular and genetic profile of PMAH pathophysiology, and to discuss the implications for disease progression. PMID:25472909

  8. Insulin insensitivity in adrenal hyperplasia due to nonclassical steroid 21-hydroxylase deficiency.

    PubMed

    Speiser, P W; Serrat, J; New, M I; Gertner, J M

    1992-12-01

    To determine whether hyperandrogenism caused by an inborn error of adrenal steroidogenesis could produce insulin resistance, we examined insulin sensitivity in females with 21-hydroxylase deficiency. Minimal modelling was used to analyze the results of tolbutamide-modified, frequently sampled, iv glucose tolerance testing. Insulin sensitivity [Si; (min-1) (microU/mL)-1] was plotted against body mass index (BMI; defined as kilograms per m2). Six patients with nonclassical 21-hydroxylase deficiency (mean age, 27 yr; mean BMI, 23.2) underwent testing. None of these patients was in active puberty, nor was any patient being treated with glucocorticoids at the time of the study. Twelve eumenorrheic nonhyperandrogenic young adult female control subjects (mean age, 27 yr; mean BMI, 22.4) were also tested. The basal 17-hydroxyprogesterone concentration, but not the total serum testosterone level, was significantly different in the two groups (mean +/- SEM, 11,987 +/- 2,761 vs. 4,059 +/- 802 pmol/L; P < 0.05). As a group the patients' Si values were significantly lower than those of the controls (mean +/- SEM, 4.1 +/- 0.6 vs. 9.7 +/- 1.2; P < 0.05). There was no correlation between Si and basal serum 17-hydroxyprogesterone, testosterone, delta 4-androstenedione, or dehydroepiandrosterone. We conclude that chronic hypersecretion of androgen precursors due to an inborn error of metabolism can induce a reduction in insulin sensitivity. PMID:1464643

  9. Sensitization of androgen refractory prostate cancer cells to anti-androgens through re-expression of epigenetically repressed androgen receptor - Synergistic action of quercetin and curcumin.

    PubMed

    Sharma, Vikas; Kumar, Lokesh; Mohanty, Sujit K; Maikhuri, Jagdamba P; Rajender, Singh; Gupta, Gopal

    2016-08-15

    Epigenetic repression of Androgen Receptor (AR) gene by hypermethylation of its promoter causes resistance in prostate cancer (CaP) to androgen deprivation therapy with anti-androgens. Some dietary phytocompounds like quercetin (Q) and curcumin (C) with reported DNMT-inhibitory activity were tested for their ability to re-express the AR in AR-negative CaP cell lines PC3 and DU145. Combined treatment with Q+C was much more effective than either Q or C in inhibiting DNMT, causing global hypomethylation, restoring AR mRNA and protein levels and causing apoptosis via mitochondrial depolarization of PC3 and DU145. The functional AR protein expressed in Q+C treated cells sensitized them to dihydrotestosterone (DHT)-induced proliferation, bicalutamide-induced apoptosis, bound to androgen response element to increase luciferase activity in gene reporter assay and was susceptible to downregulation by AR siRNA. Bisulfite sequencing revealed high methylation of AR promoter CpG sites in AR-negative DU145 and PC3 cell lines that was significantly demethylated by Q+C treatment, which restored AR expression. Notable synergistic effects of Q+C combination in re-sensitizing androgen refractory CaP cells to AR-mediated apoptosis, their known safety in clinical use, and epidemiological evidences relating their dietary consumption with lower cancer incidences indicate their potential for use in chemoprevention of androgen resistance in prostate cancer. PMID:27132804

  10. Advantages and Limitations of Androgen Receptor-Based Methods for Detecting Anabolic Androgenic Steroid Abuse as Performance Enhancing Drugs

    PubMed Central

    Bailey, Kathy; Yazdi, Tahmineh; Masharani, Umesh; Tyrrell, Blake; Butch, Anthony; Schaufele, Fred

    2016-01-01

    Testosterone (T) and related androgens are performance enhancing drugs (PEDs) abused by some athletes to gain competitive advantage. To monitor unauthorized androgen abuse, doping control programs use mass spectrometry (MS) to detect androgens, synthetic anabolic-androgenic steroids (AASs) and their metabolites in an athlete’s urine. AASs of unknown composition will not be detected by these procedures. Since AASs achieve their anabolic effects by activating the Androgen Receptor (AR), cell-based bioassays that measure the effect of a urine sample on AR activity are under investigation as complementary, pan-androgen detection methods. We evaluated an AR BioAssay as a monitor for androgen activity in urine pre-treated with glucuronidase, which releases T from the inactive T-glucuronide that predominates in urine. AR BioAssay activity levels were expressed as ‘T-equivalent’ concentrations by comparison to a T dose response curve. The T-equivalent concentrations of androgens in the urine of hypogonadal participants supplemented with T (in whom all androgenic activity should arise from T) were quantitatively identical to the T measurements conducted by MS at the UCLA Olympic Analytical Laboratory (0.96 ± 0.22). All 17 AASs studied were active in the AR BioAssay; other steroids were inactive. 12 metabolites of 10 commonly abused AASs, which are used for MS monitoring of AAS doping because of their prolonged presence in urine, had reduced or no AR BioAssay activity. Thus, the AR BioAssay can accurately and inexpensively monitor T, but its ability to monitor urinary AASs will be limited to a period immediately following doping in which the active AASs remain intact. PMID:26998755

  11. Advantages and Limitations of Androgen Receptor-Based Methods for Detecting Anabolic Androgenic Steroid Abuse as Performance Enhancing Drugs.

    PubMed

    Bailey, Kathy; Yazdi, Tahmineh; Masharani, Umesh; Tyrrell, Blake; Butch, Anthony; Schaufele, Fred

    2016-01-01

    Testosterone (T) and related androgens are performance enhancing drugs (PEDs) abused by some athletes to gain competitive advantage. To monitor unauthorized androgen abuse, doping control programs use mass spectrometry (MS) to detect androgens, synthetic anabolic-androgenic steroids (AASs) and their metabolites in an athlete's urine. AASs of unknown composition will not be detected by these procedures. Since AASs achieve their anabolic effects by activating the Androgen Receptor (AR), cell-based bioassays that measure the effect of a urine sample on AR activity are under investigation as complementary, pan-androgen detection methods. We evaluated an AR BioAssay as a monitor for androgen activity in urine pre-treated with glucuronidase, which releases T from the inactive T-glucuronide that predominates in urine. AR BioAssay activity levels were expressed as 'T-equivalent' concentrations by comparison to a T dose response curve. The T-equivalent concentrations of androgens in the urine of hypogonadal participants supplemented with T (in whom all androgenic activity should arise from T) were quantitatively identical to the T measurements conducted by MS at the UCLA Olympic Analytical Laboratory (0.96 ± 0.22). All 17 AASs studied were active in the AR BioAssay; other steroids were inactive. 12 metabolites of 10 commonly abused AASs, which are used for MS monitoring of AAS doping because of their prolonged presence in urine, had reduced or no AR BioAssay activity. Thus, the AR BioAssay can accurately and inexpensively monitor T, but its ability to monitor urinary AASs will be limited to a period immediately following doping in which the active AASs remain intact. PMID:26998755

  12. No androgenic/anti-androgenic effects of bisphenol-A in Hershberger assay using immature castrated rats.

    PubMed

    Kim, Hyung Sik; Han, Soon Young; Kim, Tae Sung; Kwack, Seung Jun; Lee, Rhee Da; Kim, In Young; Seok, Ji-Hyun; Lee, Byung Mu; Yoo, Sun Dong; Park, Kui Lea

    2002-09-01

    Several studies have demonstrated that bisphenol A (BPA) exhibited weak estrogenic activity in the 3-day uterotrophic assay using ovariectomized (OVX) and immature rats (Toxicol. Lett. 115 (2000) 231; Regul. Toxicol. Pharmacol. 32 (2000) 118; J. Toxicol. Sci. 26 (2001) 111) and BPA also possessed anti-androgenic activity in in vitro yeast based assays (J. Endocrinol. 158 (1998) 327). To investigate anti-androgenic effects of BPA. a rodent Hershberger assay was carried out using immature Sprague-Dawley male rats. An androgen agonist, testosterone (0.4 mg/kg per day), was administered for 7 consecutive days by subcutaneous (s.c.) injection as a positive control. Additionally, a pure androgen antagonist, flutamide (1, 5. 10 mg/kg per day. oral) was co-administered with testosterone (0.4 mg/kg per day s.c.). BPA was also administered orally with or without testosterone (0.4 mg/kg per day, s.c.) for 7 consecutive days. In the testosterone treated groups, glans penis, seminal vesicles, ventral prostate, and levator ani plus bulbocavernosus muscles (LABC) weights were significantly increased compared with control. However. flulamide dose-dependently inhibited the testosterone-induced re-growth of seminal vesicles, ventral prostate, and LABC, with a significant decrease at flutamide 1.0 mg/kg and above (P<0.05). Serum LH levels were also significantly increased (5 mg/kg and above, P<0.05), but no changes in serum testosterone levels. In contrast, BPA had no effects on the re-growth of seminal vesicles, ventral prostate and LABC induced by testosterone, and no significant differences were observed in serum LH and testosterone levels. In summary, the Hershberger assay could be a sensitive method for detecting androgenic or anti-androgenic chemicals, but BPA did not exhibit any androgenic or anti-androgenic activities in Hershberger assay. PMID:12243870

  13. Adrenal Pheochromocytoma Incidentally Discovered in a Patient With Parkinsonism

    PubMed Central

    Petramala, Luigi; Concistrè, Antonio; Marinelli, Cristiano; Zinnamosca, Laura; Iannucci, Gino; Lucia, Piernatale; De Vincentis, Giuseppe; Letizia, Claudio

    2015-01-01

    Abstract To evaluate the diagnostic route of pheochromocytoma (PHEO) in a patient under dopaminergic treatment. A 70-year-old man with Parkinsonism and under treatment with levodopa and carbidopa came to our observation for evaluation of arterial hypertension and right adrenal mass discovered incidentally. To evaluate adrenal hormone levels we performed a dexamethasone suppression test, plasma aldosterone levels and 24-hr urinary metanephrine, which revealed elevated levels of catecholamines metabolities. 123-I-metaiodobenzylguanidine SPECT scintiscan revealed raised activity within the right adrenal gland concordant with the mass. The diagnosis of PHEO was posed and an elective laparoscopic adrenalectomy was performed; histopathological examination confirmed the PHEO diagnosis. Recently the coexistence of PHEO and Parkinsonism is a very rare association of diseases, with only 3 cases reported in literature. In this article, another case is reported and diagnostic procedures are discussed. PMID:26496334

  14. The physiological and pharmacological basis for the ergogenic effects of androgens in elite sports.

    PubMed

    Choong, Karen; Lakshman, Kishore M; Bhasin, Shalender

    2008-05-01

    Androgen doping in power sports is undeniably rampant worldwide. There is strong evidence that androgen administration in men increases skeletal muscle mass, maximal voluntary strength and muscle power. However, we do not have good experimental evidence to support the presumption that androgen administration improves physical function or athletic performance. Androgens do not increase specific force or whole body endurance measures. The anabolic effects of testosterone on the skeletal muscle are mediated through androgen receptor signaling. Testosterone promotes myogenic differentiation of multipotent mesenchymal stem cells and inhibits their differentiation into the adipogenic lineage. Testosterone binding to androgen receptor induces a conformational change in androgen receptor protein, causing it to associate with beta-catenin and TCF-4 and activate downstream Wnt target genes thus promoting myogenic differentiation. The adverse effects of androgens among athletes and recreational bodybuilders are under reported and include acne, deleterious changes in the cardiovascular risk factors, including a marked decrease in plasma high-density lipoproteins (HDL) cholesterol level, suppression of spermatogenesis resulting in infertility, increase in liver enzymes, hepatic neoplasms, mood and behavioral disturbances, and long term suppression of the endogenous hypothalamic-pituitary-gonadal axis. Androgens are often used in combination with other drugs which may have serious adverse events of their own. In spite of effective methods for detecting androgen doping, the policies for screening of athletes are highly variable in different countries and organizations and even existing policies are not uniformly enforced. PMID:18385897

  15. Profiling of androgen response in rainbow trout pubertal testis: relevance to male gonad development and spermatogenesis.

    PubMed

    Rolland, Antoine D; Lardenois, Aurélie; Goupil, Anne-Sophie; Lareyre, Jean-Jacques; Houlgatte, Rémi; Chalmel, Frédéric; Le Gac, Florence

    2013-01-01

    The capacity of testicular somatic cells to promote and sustain germ cell differentiation is largely regulated by sexual steroids and notably androgens. In fish species the importance of androgens is emphasized by their ability to induce sex reversal of the developing fries and to trigger spermatogenesis. Here we studied the influence of androgens on testicular gene expression in trout testis using microarrays. Following treatment of immature males with physiological doses of testosterone or 11-ketotestosterone, 418 genes that exhibit changes in expression were identified. Interestingly, the activity of testosterone appeared stronger than that of 11-ketotestosterone. Expression profiles of responsive genes throughout testis development and in isolated germ cells confirmed androgens to mainly affect gene expression in somatic cells. Furthermore, specific clusters of genes that exhibit regulation coincidently with changes in the natural circulating levels of androgens during the reproductive cycle were highlighted, reinforcing the physiological significance of these data. Among somatic genes, a phylogenetic footprinting study identified putative androgen response elements within the proximal promoter regions of 42 potential direct androgen target genes. Finally, androgens were also found to alter the germ line towards meiotic expression profiles, supporting the hypothesis of a role for the somatic responsive genes in driving germ cell fate. This study significantly increases our understanding of molecular pathways regulated by androgens in vertebrates. The highly cyclic testicular development in trout together with functions associated with regulated genes reveal potential mechanisms for androgen actions in tubule formation, steroid production, germ cell development and sperm secretion. PMID:23301058

  16. [Adrenal insufficiency in cirrhotic patients].

    PubMed

    Orozco, Federico; Anders, María; Mella, José; Antinucci, Florencia; Pagano, Patricia; Esteban, Paula; Cartier, Mariano; Romero, Gustavo; Francini, Bettina; Mastai, Ricardo

    2016-01-01

    Relative adrenal insufficiency (RAI) is a common finding in cirrhotic patients with severe sepsis, and increased mortality. Its significance is unknown in stable conditions. The aim of this study was to evaluate the prevalence of RAI in stable cirrhotic patients at different stages of the disease. Also, the impact of RAI on the survival was evaluated and basal cortisol levels between plasma and saliva was correlated in control subjects and cirrhotic patients. Forty seven ambulatory patients and 16 control subjects were studied. RAI was defined as a serum cortisol increase of less than 9 υg/dl from baseline after the stimulation with 250 mg of synthetic ACTH. Twenty two had Child-Pugh = 8 and 25 = 9. The prevalence of RAI in patients with stable cirrhosis was 22%. A higher incidence of RAI was observed in patients with a Child-Pugh = 9 (8/32) than in those with = 8 (3/13, p < 0.05). A correlation between salivary cortisol and basal plasma cortisol (r = 0.6, p < 0.0004) was observed. Finally, survival at 1 year (97%) and 3 years (91%) was significantly higher without RAI than those who developed this complication (79% and 51%, p < 0.05, respectively). In summary, the prevalence of RAI is frequent in patients with stable cirrhosis and that it is related to the severity of liver diseaseand increased mortality. PMID:27576278

  17. Genetics Home Reference: X-linked adrenal hypoplasia congenita

    MedlinePlus

    ... glands on top of each kidney called the adrenal glands . These glands produce a variety of hormones that ... disorder is adrenal insufficiency, which occurs when the adrenal glands do not produce enough hormones. Adrenal insufficiency typically ...

  18. Androgen dependence of hirsutism, acne, and alopecia in women: retrospective analysis of 228 patients investigated for hyperandrogenism.

    PubMed

    Karrer-Voegeli, Sandra; Rey, François; Reymond, Marianne J; Meuwly, Jean-Yves; Gaillard, Rolf C; Gomez, Fulgencio

    2009-01-01

    Hirsutism, acne, alopecia, and oligo-amenorrhea are clinical expressions of hyperandrogenism, one of the most frequent endocrine disorders in women of reproductive age. Women referred to our endocrine clinics for skin symptoms of hyperandrogenism underwent a laboratory workup to evaluate hormone measurements and received antiandrogen therapy. We retrospectively analyzed the outcome of 228 consecutive patients investigated over 6 years.Patients with hirsutism had higher levels of androstenedione, dehydroepiandrosterone sulfate (DHEAS), and salivary testosterone; lower levels of sex hormone-binding globulin (SHBG); and a higher prevalence of oligo-amenorrhea than patients with alopecia, while patients with acne showed intermediate values. Hirsutism score correlated positively with androstenedione, DHEAS, and salivary testosterone, and correlated negatively with SHBG; salivary testosterone showed the highest correlation coefficient. Total testosterone was not significantly different among patients with hirsutism, alopecia, or acne, and did not significantly correlate with hirsutism score. Hirsutism and oligo-amenorrhea were the most sensitive symptoms of hyperandrogenism, and no androgenic parameter alone allowed us to identify all cases of hyperandrogenism.Patients of central European origin sought consultation with milder hirsutism scores than patients of southern European origin. There was, however, no difference in the clinical-biological correlation between these groups, arguing against differences in skin sensitivity to androgens.Polycystic ovary syndrome, defined as hyperandrogenism (hirsutism or elevated androgens) and oligo-amenorrhea, was diagnosed in 63 patients (27.6%), an underestimate compared with other reports that include systematic ovarian ultrasound studies. Neither pelvic ultrasound, used in a limited number of cases, nor the luteinizing hormone/follicle-stimulating hormone ratio helped to distinguish patients with polycystic ovary syndrome from

  19. Elevated androgens during puberty in female rhesus monkeys lead to increased neuronal drive to the reproductive axis: a possible component of polycystic ovary syndrome

    PubMed Central

    McGee, W.K.; Bishop, C.V.; Bahar, A.; Pohl, C.R.; Chang, R.J.; Marshall, J.C.; Pau, F.K.; Stouffer, R.L.; Cameron, J.L.

    2012-01-01

    BACKGROUND Hyperandrogenemia is associated with several clinical disorders in which both reproductive dysfunction and metabolic changes may coexist [i.e. polycystic ovary syndrome (PCOS), obesity and congenital adrenal hyperplasia]. Moreover, there is growing evidence that the elevated levels of circulating androgens in obese girls may lead to an increased neuroendocrine drive to the reproductive axis, similar to that associated with PCOS. METHODS To test whether androgen exposure in the childhood and adolescent period could lead to pubertal alterations in LH secretory patterns, female rhesus monkeys received subcutaneous testosterone implants prepubertally beginning at 1 year of age, maintaining a 3.7-fold increase (P = 0.001) in circulating testosterone levels over cholesterol-implant controls (n = 6/group) into the post-pubertal period. In early adulthood, pulsatile secretion of LH was measured over 12 h during the early follicular phase of a menstrual cycle, and responsiveness of the pituitary to gonadotrophin-releasing hormone was determined. In addition, ultrasounds were performed to assess ovarian morphology and glucose tolerance testing was performed to assess insulin sensitivity. RESULTS The timing of menarche was similar between groups. Testosterone-treated animals had a significantly greater LH pulse frequency during the early follicular phase compared with controls (P = 0.039) when measured at 5 years of age. There was a larger LH response to GnRH when testosterone-treated animals were 4 years of age (P = 0.042), but not when the animals were 5 years old (P = 0.57). No differences were seen in insulin sensitivity or ovarian morphology, and the groups showed similar rates of ovulation in early adulthood. CONCLUSIONS Exposure to increased levels of androgens over the course of pubertal development appears to trigger physiological changes in the neural drive to the reproductive axis that resemble those of obese hyperandrogenemic girls in early adulthood

  20. Hypothalamic-pituitary-adrenal activity and pro-opiomelanocortin mRNA levels in the hypothalamus and pituitary of the rat are differentially modulated by acute intermittent morphine with or without water restriction stress.

    PubMed

    Zhou, Y; Spangler, R; Maggos, C E; Wang, X M; Han, J S; Ho, A; Kreek, M J

    1999-11-01

    Acute administration of morphine stimulates the secretion of hypothalamic-pituitary-adrenal (HPA) hormones, ACTH, beta-endorphin and corticosterone in the rat. In this study we investigated the effects of repeated multiple-dose morphine on HPA activity under two different conditions: without or with water restriction stress. Rats received six intermittent injections of morphine (6.25 mg/kg per injection, s.c.) every 2 h and were killed 30 min after the last injection. The results were as follows. (1) Morphine significantly elevated plasma ACTH and corticosterone levels; water restriction also significantly increased ACTH secretion, but with no significant increase of plasma corticosterone levels. In contrast, rats treated with morphine under the water restriction condition failed to show any increases of either ACTH or corticosterone levels. (2) Morphine did not change pro-opiomelanocortin (POMC) mRNA levels in the anterior pituitary; whereas water restriction significantly increased the POMC mRNA levels. The water restriction-induced increases of POMC mRNA in the anterior pituitary were absent in the rats which received morphine. (3) Morphine significantly increased POMC mRNA levels in the hypothalamus; water restriction had no effect. The morphine-induced increases in POMC mRNA in the hypothalamus were absent in the rat under the water restriction condition. These findings, that the effects of morphine on HPA activation or POMC mRNA expression depend on the presence of stress, suggest a counter-regulatory role of opiates on a stress response and opioid gene expression. PMID:10556776

  1. Compensatory adrenal growth - A neurally mediated reflex

    NASA Technical Reports Server (NTRS)

    Dallman, M. F.; Engeland, W. C.; Shinsako, J.

    1976-01-01

    The responses of young rats to left adrenalectomy or left adrenal manipulation were compared to surgical sham adrenalectomy in which adrenals were observed but not touched. At 12 h right adrenal wet weight, dry weight, DNA, RNA, and protein content were increased (P less than 0.05) after the first two operations. Left adrenal manipulation resulted in increased right adrenal weight at 12 h but no change in left adrenal weight. Sequential manipulation of the left adrenal at time 0 and the right adrenal at 12 h resulted in an enlarged right adrenal at 12 h (P less than 0.01), and an enlarged left adrenal at 24 h (P less than 0.05), showing that the manipulated gland was capable of response. Bilateral adrenal manipulation of the adrenal glands resulted in bilateral enlargement of 12 h (P less than 0.01). Taken together with previous results, these findings strongly suggest that compensatory adrenal growth is a neurally mediated reflex.

  2. Congenital adrenal hyperplasia--pharmacologic interventions from the prenatal phase to adulthood.

    PubMed

    Claahsen-van der Grinten, H L; Stikkelbroeck, N M M L; Otten, B J; Hermus, A R M M

    2011-10-01

    Congenital adrenal hyperplasia (CAH) is one of the most common inherited autosomal recessive disorders, caused by deficiency of one of the enzymes involved in steroid synthesis. The clinical picture of the most prevalent form, i.e. 21-hydroxylase deficiency, is characterized by cortisol and mostly aldosterone deficiency and androgen excess (leading to congenital virilization in girls). Treatment consists of glucocorticoids, aimed at substitution of cortisol deficiency and, decrease of androgen excess. Usually supraphysiological doses of glucocorticoids are required to effectively suppress adrenal androgens. Furthermore, with the currently available glucocorticoid preparations, it is not possible to simulate a normal circadian rhythm in CAH patients. Therefore, it is a difficult task for (pediatric) endocrinologists to find the best balance between under- and overtreatment thereby avoiding important long term complications. In this review we will discuss the current pharmacologic treatment options. We give age dependent dose recommendations and describe the limitations of current treatment strategies. We discuss effects on fertility, bone density and cardiovascular risks. Recommendations about the use of glucocorticoids in case of fever or stress situations are given. The principles of treatment of non classic (mild) CAH are discussed in a separate section. Also prenatal therapy, to prevent congenital virilization of a female CAH newborn, is discussed. Furthermore, an overview of alternative pharmacological treatment options in the future is given. PMID:21635919

  3. The PPAR{gamma} ligand ciglitazone regulates androgen receptor activation differently in androgen-dependent versus androgen-independent human prostate cancer cells

    SciTech Connect

    Moss, Patrice E.; Lyles, Besstina E.; Stewart, LaMonica V.

    2010-12-10

    The androgen receptor (AR) regulates growth and progression of androgen-dependent as well as androgen-independent prostate cancer cells. Peroxisome proliferator-activated receptor gamma (PPAR{gamma}) agonists have been reported to reduce AR activation in androgen-dependent LNCaP prostate cancer cells. To determine whether PPAR{gamma} ligands are equally effective at inhibiting AR activity in androgen-independent prostate cancer, we examined the effect of the PPAR{gamma} ligands ciglitazone and rosiglitazone on C4-2 cells, an androgen- independent derivative of the LNCaP cell line. Luciferase-based reporter assays and Western blot analysis demonstrated that PPAR{gamma} ligand reduced dihydrotestosterone (DHT)-induced increases in AR activity in LNCaP cells. However, in C4-2 cells, these compounds increased DHT-induced AR driven luciferase activity. In addition, ciglitazone did not significantly alter DHT-mediated increases in prostate specific antigen (PSA) protein or mRNA levels within C4-2 cells. siRNA-based experiments demonstrated that the ciglitazone-induced regulation of AR activity observed in C4-2 cells was dependent on the presence of PPAR{gamma}. Furthermore, overexpression of the AR corepressor cyclin D1 inhibited the ability of ciglitazone to induce AR luciferase activity in C4-2 cells. Thus, our data suggest that both PPAR{gamma} and cyclin D1 levels influence the ability of ciglitazone to differentially regulate AR signaling in androgen-independent C4-2 prostate cancer cells.

  4. Adrenalectomy for metastatic adrenal tumors.

    PubMed

    Kita, Masafumi; Tamaki, Gaku; Okuyama, Mitsuhiko; Saga, Yuji; Kakizaki, Hidehiro

    2007-11-01

    The indications for adrenalectomy in cases of metastatic adrenal tumor remain controversial. To clarify indications and outcomes of adrenalectomy for adrenal metastasis, we performed a retrospective review of all 8 patients who underwent adrenalectomy for adrenal metastasis between 1990 and 2006 in Asahikawa Medical College Hospital. The Primary tumor was renal cell carcinoma in 2 cases, and eccrine poro carcinoma, rectal cancer, lung cancer, melanoma, bladder cancer and cancer of unknown origin in 1 case each. Open adrenalectomy was performed in all cases, including 1 case that was converted from laparoscopic adrenalectomy. Of the 4 patients with solitary adrenal metastasis, 3 were considered tumor-free after adrenalectomy, while the remaining patient was not due to unresectable primary tumor. Of the 3 patients with complete resection, one remained alive as of 88 months after adrenalectomy but was then lost to follow-up, and the other 2 patients remain alive 12 and 7 months after adrenalectomy. Of the 2 patients with other resectable metastasis who were tumor-free after removal of all metastases, one was alive 31 months postoperatively and the other died 23 months after operation. The remaining 2 cases with other unresectable metastasis died within 6 months after adrenalectomy. At least in cases of solitary adrenal metastasis, adrenalectomy can be effective if other valid methods are unavailable. PMID:18051798

  5. Mifepristone Accelerates HPA Axis Recovery in Secondary Adrenal Insufficiency.

    PubMed

    Cohan, Pejman

    2016-01-01

    Context. Transient secondary adrenal insufficiency (SAI) is an expected complication following successful adenomectomy of ACTH-secreting pituitary adenomas or unilateral adrenalectomy for cortisol-secreting adrenal adenomas. To date, no pharmacological therapy has been shown to hasten recovery of the hypothalamic-pituitary-adrenal (HPA) axis in this clinical scenario. Case Description. A 33-year-old woman underwent uncomplicated unilateral adrenalectomy for a 3.7 cm cortisol-secreting adrenal adenoma. Postoperatively, she developed SAI and was placed on hydrocortisone 15 mg/day, given in divided doses. In the ensuing six years, the patient's HPA axis failed to recover and she remained corticosteroid-dependent. Quarterly biochemical testing (after withholding hydrocortisone for 18 hours) consistently yielded undetectable serum cortisol and subnormal plasma ACTH levels. While she was on hydrocortisone 15 mg/day, mifepristone was initiated and gradually titrated to a maintenance dose of 600 mg/day after 5 months. Rapid recovery of the HPA axis was subsequently noted with ACTH rising into the supranormal range at 4 months followed by a subsequent rise in cortisol levels into the normal range. After 6 months, the dose of hydrocortisone and mifepristone was lowered and both were ultimately stopped after 8 months. The HPA axis remains normal after an additional 16 months of follow-up. Conclusion. Mifepristone successfully restored the HPA axis in a woman with prolonged secondary adrenal insufficiency (SAI) after adrenalectomy for Cushing's syndrome (CS). PMID:27516913

  6. Mifepristone Accelerates HPA Axis Recovery in Secondary Adrenal Insufficiency

    PubMed Central

    2016-01-01

    Context. Transient secondary adrenal insufficiency (SAI) is an expected complication following successful adenomectomy of ACTH-secreting pituitary adenomas or unilateral adrenalectomy for cortisol-secreting adrenal adenomas. To date, no pharmacological therapy has been shown to hasten recovery of the hypothalamic-pituitary-adrenal (HPA) axis in this clinical scenario. Case Description. A 33-year-old woman underwent uncomplicated unilateral adrenalectomy for a 3.7 cm cortisol-secreting adrenal adenoma. Postoperatively, she developed SAI and was placed on hydrocortisone 15 mg/day, given in divided doses. In the ensuing six years, the patient's HPA axis failed to recover and she remained corticosteroid-dependent. Quarterly biochemical testing (after withholding hydrocortisone for 18 hours) consistently yielded undetectable serum cortisol and subnormal plasma ACTH levels. While she was on hydrocortisone 15 mg/day, mifepristone was initiated and gradually titrated to a maintenance dose of 600 mg/day after 5 months. Rapid recovery of the HPA axis was subsequently noted with ACTH rising into the supranormal range at 4 months followed by a subsequent rise in cortisol levels into the normal range. After 6 months, the dose of hydrocortisone and mifepristone was lowered and both were ultimately stopped after 8 months. The HPA axis remains normal after an additional 16 months of follow-up. Conclusion. Mifepristone successfully restored the HPA axis in a woman with prolonged secondary adrenal insufficiency (SAI) after adrenalectomy for Cushing's syndrome (CS). PMID:27516913

  7. Modulating the pituitary-adrenal response to stress

    NASA Technical Reports Server (NTRS)

    Vernikos-Danellis, J.

    1975-01-01

    Serotonin is believed to be a transmitter or regulator of neuronal function. A possible relationship between the pituitary-adrenal secretion of steroids and brain serotonin in the rat was investigated by evaluating the effects of altering brain 5-hydroxy tryptamine (HT) levels on the daily fluctuation of plasma corticosterone and on the response of the pituitary-adrenal system to a stressful or noxious stimulus in the rat. The approach was either to inhibit brain 5-HT synthesis with para-chlorophenyl alanine or to raise its level with precursors such as tryptophan or 5-hydroxy tryptophan.

  8. Genetic variants in hypothalamic-pituitary-adrenal axis genes and breast cancer risk in Caucasians and African Americans.

    PubMed

    Nan, Hongmei; Dorgan, Joanne F; Rebbeck, Timothy R

    2015-01-01

    Elevated circulating levels of the adrenal androgen dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are associated with increased breast cancer risk in prospective studies. Genetic variants in hypothalamic-pituitary-adrenal (HPA) axis genes may contribute to these circulating hormone levels, and consequently to breast cancer risk. No previous studies have examined the effects of genetic variants in HPA axis genes on breast cancer risk. We evaluated the associations of 49 single nucleotide polymorphisms (SNPs) in five HPA axis genes (NR3C1, NR3C2, CRH, CRHR1, and CRHBP) with the risk of breast cancer in the Women's Insights and Shared Experiences (WISE) Study of Caucasians (346 cases and 442 controls), as well as African Americans (149 cases and 246 controls). Of the 49 SNPs evaluated, one showed a nominal significant association (P for trend < 0.05) with breast cancer risk among Caucasians, and another two among African Americans. The age-adjusted additive odds ratio (OR) (95% confidence interval (95% CI)) of the SNP rs11747190[A] in the CRHBP gene for the risk of breast cancer among Caucasian women was 1.45 (1.09-1.94). The age-adjusted additive ORs (95% CIs) of two SNPs (CRHBP rs1700688[T] and CRHR1 rs17689471[C]) for the risk of breast cancer among African American women were 1.84 (1.13-2.98) and 2.48 (1.20-5.13), respectively. However, these SNPs did not show significant associations after correction for multiple testing. Our findings do not provide strong supportive evidence for the contribution of genetic variants in these HPA axis genes to the risk of developing breast cancer in either Caucasians or African Americans. PMID:26417403

  9. Genetic variants in hypothalamic-pituitary-adrenal axis genes and breast cancer risk in Caucasians and African Americans

    PubMed Central

    Nan, Hongmei; Dorgan, Joanne F; Rebbeck, Timothy R

    2015-01-01

    Elevated circulating levels of the adrenal androgen dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are associated with increased breast cancer risk in prospective studies. Genetic variants in hypothalamic-pituitary-adrenal (HPA) axis genes may contribute to these circulating hormone levels, and consequently to breast cancer risk. No previous studies have examined the effects of genetic variants in HPA axis genes on breast cancer risk. We evaluated the associations of 49 single nucleotide polymorphisms (SNPs) in five HPA axis genes (NR3C1, NR3C2, CRH, CRHR1, and CRHBP) with the risk of breast cancer in the Women’s Insights and Shared Experiences (WISE) Study of Caucasians (346 cases and 442 controls), as well as African Americans (149 cases and 246 controls). Of the 49 SNPs evaluated, one showed a nominal significant association (P for trend < 0.05) with breast cancer risk among Caucasians, and another two among African Americans. The age-adjusted additive odds ratio (OR) (95% confidence interval (95% CI)) of the SNP rs11747190[A] in the CRHBP gene for the risk of breast cancer among Caucasian women was 1.45 (1.09-1.94). The age-adjusted additive ORs (95% CIs) of two SNPs (CRHBP rs1700688[T] and CRHR1 rs17689471[C]) for the risk of breast cancer among African American women were 1.84 (1.13-2.98) and 2.48 (1.20-5.13), respectively. However, these SNPs did not show significant associations after correction for multiple testing. Our findings do not provide strong supportive evidence for the contribution of genetic variants in these HPA axis genes to the risk of developing breast cancer in either Caucasians or African Americans. PMID:26417403

  10. Adrenal oncoctyoma of uncertain malignant potential: a rare etiology of adrenal incidentaloma.

    PubMed

    Kedia, Rohit R; Muinov, Lucy; Lele, Subodh M; Shivaswamy, Vijay

    2016-03-01

    A rare cause for rapid adrenal enlargement is adrenal oncocytoma of uncertain malignant potential. A full biochemical evaluation is warranted to screen secreting adrenal adenomas as well as to evaluate adrenal cortical carcinoma. Careful pathologic evaluation is required as the diagnosis of AOC cannot be made by imaging. PMID:27014458

  11. Cushing syndrome due to adrenal tumor

    MedlinePlus

    ... syndrome. It occurs when a tumor of the adrenal gland releases excess amounts of the hormone cortisol. Causes ... hormone cortisol. This hormone is made in the adrenal glands . Too much cortisol can be due to various ...

  12. Giant adrenal cyst displacing the right kidney

    PubMed Central

    Chodisetti, Subbarao; Boddepalli, Yogesh; Kota, Malakondareddy

    2016-01-01

    Adrenal cysts are rare and should be considered in the differential diagnosis of retroperitoneal cysts. We present a case of a huge adrenal cyst displacing the right kidney anteriorly toward the left side in a young female. PMID:26941503

  13. Androgen receptor gene polymorphism in zebra species

    PubMed Central

    Ito, Hideyuki; Langenhorst, Tanya; Ogden, Rob; Inoue-Murayama, Miho

    2015-01-01

    Androgen receptor genes (AR) have been found to have associations with reproductive development, behavioral traits, and disorders in humans. However, the influence of similar genetic effects on the behavior of other animals is scarce. We examined the loci AR glutamine repeat (ARQ) in 44 Grevy's zebras, 23 plains zebras, and three mountain zebras, and compared them with those of domesticated horses. We observed polymorphism among zebra species and between zebra and horse. As androgens such as testosterone influence aggressiveness, AR polymorphism among equid species may be associated with differences in levels of aggression and tameness. Our findings indicate that it would be useful to conduct further studies focusing on the potential association between AR and personality traits, and to understand domestication of equid species. PMID:26236645

  14. [Osteoporosis in men and androgen replacement therapy].

    PubMed

    Tsujimura, Akira; Okuyama, Akihiko

    2003-11-01

    Androgen plays an important role in bone maturation and maintenance of bone mass. Androgen deficiency associated with aging causes osteoporosis for men. With respect to this disease, androgen replacement treatment has been performed for aging male. However, available preparations of androgen are limited in Japan and each of them has both merit and demerit. Establishment of guideline for androgen replacement treatment including criteria of serum testosterone concentration is the problem, which now confronts us. PMID:15775234

  15. Prenatal androgen exposure alters girls' responses to information indicating gender-appropriate behaviour.

    PubMed

    Hines, Melissa; Pasterski, Vickie; Spencer, Debra; Neufeld, Sharon; Patalay, Praveetha; Hindmarsh, Peter C; Hughes, Ieuan A; Acerini, Carlo L

    2016-02-19

    Individual variability in human gender-related behaviour is influenced by many factors, including androgen exposure prenatally, as well as self-socialization and socialization by others postnatally. Many studies have looked at these types of influences in isolation, but little is known about how they work together. Here, we report that girls exposed to high concentrations of androgens prenatally, because they have the genetic condition congenital adrenal hyperplasia, show changes in processes related to self-socialization of gender-related behaviour. Specifically, they are less responsive than other girls to information that particular objects are for girls and they show reduced imitation of female models choosing particular objects. These findings suggest that prenatal androgen exposure may influence subsequent gender-related behaviours, including object (toy) choices, in part by changing processes involved in the self-socialization of gendered behaviour, rather than only by inducing permanent changes in the brain during early development. In addition, the findings suggest that some of the behavioural effects of prenatal androgen exposure might be subject to alteration by postnatal socialization processes. The findings also suggest a previously unknown influence of early androgen exposure on later processes involved in self-socialization of gender-related behaviour, and thus expand understanding of the developmental systems regulating human gender development. PMID:26833843

  16. Approach to the Patient: The Adult With Congenital Adrenal Hyperplasia

    PubMed Central

    Arlt, Wiebke

    2013-01-01

    The most common form of congenital adrenal hyperplasia is steroid 21-hydroxylase deficiency (21OHD). When the nonclassical (mild) form is included, 21OHD is the most common genetic disease in human beings. With the advent of pharmaceutical preparation of glucocorticoids starting in the 1960s and newborn screening starting in the 1990s, the majority of children with 21OHD are reaching adulthood, which has yielded a cohort of patients with, in essence, a new disease. Only recently have some data emerged from cohorts of adults with 21OHD, and in some centers, experience with the management of these patients is growing. These patients suffer from poor health, infertility, characteristic tumors in the adrenal glands and gonads, and consequences of chronic glucocorticoid therapy. Their care is fragmented and inconsistent, and many stop taking their medications out of frustration. Internal medicine residents and endocrinology fellows receive little training in their care, which further discourages their seeking medical attention. Adults with 21OHD have a different physiology from patients with Addison's disease or other androgen excess states, and their needs are different than those of young children with 21OHD. Consequently, their care requires unorthodox treatment and monitoring strategies foreign to most endocrine practitioners. Our goal for this article is to review their physiology, complications, and needs in order to develop rational and effective treatment and monitoring strategies. PMID:23837188

  17. Serotonin involvement in pituitary-adrenal function

    NASA Technical Reports Server (NTRS)

    Vernikos-Danellis, J.; Kellar, K. J.; Kent, D.; Gonzales, C.; Berger, P. A.; Barchas, J. D.

    1977-01-01

    Experiments clarifying the effects of serotonin (5-HT) in the regulation of the hypothalamic-pituitary-adrenocortical system are surveyed. Lesion experiments which seek to determine functional maps of serotonergic input to areas involved in regulation are reported. Investigations of the effects of 5-HT levels on the plasma ACTH response to stress and the diurnal variation in basal plasma corticosterone are summarized, and the question of whether serotonergic transmission is involved in the regulation of all aspects of pituitary-adrenal function is considered with attention to the stimulatory and inhibitory action of 5-HT.

  18. Regulation of expression of Na+,K+-ATPase in androgen-dependent and androgen-independent prostate cancer

    PubMed Central

    Blok, L J; Chang, G T G; Steenbeek-Slotboom, M; Weerden, W M van; Swarts, H G P; Pont, J J H H M De; Steenbrugge, G J van; Brinkmann, A O

    1999-01-01

    The β1-subunit of Na+,K+-ATPase was isolated and identified as an androgen down-regulated gene. Expression was observed at high levels in androgen-independent as compared to androgen-dependent (responsive) human prostate cancer cell lines and xenografts when grown in the presence of androgens. Down-regulation of the β1-subunit was initiated at concentrations between 0.01 nM and 0.03 nM of the synthetic androgen R1881 after relatively long incubation times (> 24 h). Using polyclonal antibodies, the concentration of β1-subunit protein, but not of the α1-subunit protein, was markedly reduced in androgen-dependent human prostate cancer cells (LNCaP-FGC) cultured in the presence of androgens. In line with these observations it was found that the protein expression of total Na+,K+-ATPase in the membrane (measured by 3H-ouabain binding) was also markedly decreased. The main function of Na+,K+-ATPase is to maintain sodium and potassium homeostasis in animal cells. The resulting electrochemical gradient is facilitative for transport of several compounds over the cell membrane (for example cisplatin, a chemotherapeutic agent experimentally used in the treatment of hormone-refractory prostate cancer). Here we observed that a ouabain-induced decrease of Na+,K+-ATPase activity in LNCaP-FGC cells results in reduced sensitivity of these cells to cisplatin-treatment. Surprisingly, androgen-induced decrease of Na+,K+-ATPase expression, did not result in significant protection against the chemotherapeutic agent. © 1999 Cancer Research Campaign PMID:10487609

  19. Alterations in hypothalamic-pituitary-adrenal axis activity and in levels of proopiomelanocortin and corticotropin-releasing hormone-receptor 1 mRNAs in the pituitary and hypothalamus of the rat during chronic 'binge' cocaine and withdrawal.

    PubMed

    Zhou, Yan; Spangler, Rudolph; Schlussman, Stefan D; Ho, Ann; Kreek, Mary Jeanne

    2003-02-28

    Tolerance to the stimulatory effects of cocaine on the hypothalamic-pituitary-adrenal (HPA) axis develops after chronic 'binge' cocaine exposure in the rat. This blunting of HPA axis activity in response to cocaine is associated with a cocaine-induced reduction of corticotropin-releasing hormone (CRH) mRNA level in the hypothalamus. There is limited information about the effects of withdrawal from chronic cocaine on HPA activity. The present studies were undertaken to determine levels of the HPA hormones adrenocorticotropic hormone (ACTH) and corticosterone across 10 days of withdrawal following chronic 'binge' pattern cocaine administration (3 x 15 mg/kg/day at hourly intervals) for 14 days. Male Fischer rats showed a significantly attenuated HPA axis response to chronic 'binge' pattern cocaine administration 30 min after the last injection on the 14th day, as measured by both plasma ACTH and corticosterone levels at the nadir time point. Twenty-four hours following the final administration of 'binge' cocaine (the 1st day of withdrawal), a significant elevation of plasma ACTH levels and a modest, but significant, elevation of plasma corticosterone levels were found at the nadir time point. This acute withdrawal-related activation of the hormones of the HPA axis was no longer found on the 10th day of withdrawal. In the anterior pituitary, levels of both proopiomelanocortin (POMC) and CRH-receptor 1 (R1) mRNAs were significantly higher than saline controls on the 14th day of chronic 'binge' cocaine and were at control levels on the 4th day of withdrawal. In the neurointermediate lobe of the pituitary, a sustained reduction in POMC mRNA levels was observed on the 3rd, 7th and 14th day of chronic 'binge' cocaine, but POMC mRNA was at control levels by the 4th day of withdrawal. In the hypothalamus, POMC mRNA levels showed a transient decrease on the 1st day of 'binge' cocaine with no change during chronic 'binge' cocaine or its withdrawal. CRH mRNA levels in the

  20. Budesonide-related adrenal insufficiency.

    PubMed

    Arntzenius, Alexander; van Galen, Louise

    2015-01-01

    Iatrogenic adrenal insufficiency is a potential harmful side effect of treatment with corticosteroids. It manifests itself when an insufficient cortisol response to biological stress leads to an Addisonian crisis: a life-threatening situation. We describe a case of a patient who developed an Addisonian crisis after inappropriate discontinuation of budesonide (a topical steroid used in Crohn's disease) treatment. Iatrogenic adrenal insufficiency due to budesonide use has been rarely reported. Prescribers should be aware of the resulting risk for an Addisonian crisis. PMID:26430235

  1. Adrenal insufficiency in a woman secondary to standard-dose inhaled fluticasone propionate therapy

    PubMed Central

    Hay, Casey M; Spratt, Daniel I

    2014-01-01

    Summary A 55-year-old woman with asthma presented with adrenal insufficiency of unknown origin. She was referred to our Division of Reproductive Endocrinology to further evaluate an undetectable morning cortisol level discovered during the evaluation of a low serum DHEA-S level. She was asymptomatic other than having mild fatigue and weight gain. Her medication list included 220 μg of inhaled fluticasone propionate twice daily for asthma, which she was taking as prescribed. On presentation, the undetectable morning cortisol level was confirmed. A urinary measurement of fluticasone propionate 17β-carboxylic acid was markedly elevated. Fluticasone therapy was discontinued and salmeterol therapy initiated with supplemental hydrocortisone. Hydrocortisone therapy was discontinued after 2 months. A repeat urinary fluticasone measurement 4 months after the discontinuation of fluticasone therapy was undetectably low and morning cortisol level was normal at 18.0 μg/dl. Inhaled fluticasone is generally considered to be minimally systemically absorbed. This patient's only clinical evidence suggesting adrenal insufficiency was fatigue accompanying a low serum DHEA-S level. This case demonstrates that adrenal insufficiency can be caused by a routine dose of inhaled fluticasone. Missing this diagnosis could potentially result in adrenal crisis upon discontinuation of fluticasone therapy. Learning points Standard-dose inhaled fluticasone can cause adrenal insufficiency.Adrenal insufficiency should be considered in patients taking, or who have recently discontinued, inhaled fluticasone therapy and present with new onset of nonspecific symptoms such as fatigue, weakness, depression, myalgia, arthralgia, unexplained weight loss, and nausea that are suggestive of adrenal insufficiency.Adrenal insufficiency should be considered in postoperative patients who exhibit signs of hypoadrenalism after fluticasone therapy has been withheld in the perioperative setting.Routine screening

  2. Spontaneous Retroperitoneal Hemorrhage from Adrenal Artery Aneurysm

    SciTech Connect

    Gonzalez Valverde, F.M. Balsalobre, M.; Torregrosa, N.; Molto, M.; Gomez Ramos, M.J.; Vazquez Rojas, J.L.

    2007-04-15

    Spontaneous adrenal hemorrhage is a very rare but serious disorder of the adrenal gland that can require emergent treatment. We report on a 42-year-old man who underwent selective angiography for diagnosis and treatment of retroperitoneal hemorrhage from small adrenal artery aneurysm. This case gives further details about the value of transluminal artery embolization in the management of visceral aneurysm rupture.

  3. Spontaneous bilateral adrenal hemorrhage following cholecystectomy

    PubMed Central

    Dahan, Meryl; Lim, Chetana; Salloum, Chady

    2016-01-01

    Postoperative bilateral adrenal hemorrhage is a rare but potentially life-threatening complication. This diagnosis is often missed because the symptoms and laboratory results are usually nonspecific. We report a case of bilateral adrenal hemorrhage associated with acute primary adrenal insufficiency following laparoscopic cholecystectomy. The knowledge of this uncommon complication following any abdominal surgery allows timey diagnosis and rapid treatment. PMID:27275469

  4. Hair cortisol levels track phylogenetic and age related differences in hypothalamic-pituitary-adrenal (HPA) axis activity in non-human primates.

    PubMed

    Fourie, Nicolaas H; Bernstein, Robin M

    2011-11-01

    Hair has been shown to archive a uniquely time averaged signal of endocrine activity, and holds attractive advantages for both laboratory and field research. Prior research has explored the potential of hair hormone analysis to examine hormone-behavior relationships. To date, no research has focused on the potential of the technique to investigate age-related changes or taxon differences in endocrine function. It is known that non-human primate infants of many taxa exhibit high cortisol levels after parturition, which rapidly decline with age. It has also been shown that hypercortisolism generally characterizes platyrrhine (New World monkey) endocrine function. These endocrine trends have been characterized using cortisol levels determined from serum, plasma, and feces. Here we test whether cortisol levels determined from hair recover similar phylogenetic and age related patterns in endocrine function in non-human primates. In order to test whether hair cortisol reflect infant hypercortisolism with significant age-related decline, hair cortisol levels are measured in samples from wild vervet monkeys (Chlorocebus aethiops) and captive Guinea baboons (Papio hamadryas papio), ranging in age from infants through juveniles. Further, in order to test whether platyrrhines exhibit significantly higher hair cortisol levels compared to strepsirrhines and catarrhines, and therefore faithfully recover similar signals as more traditionally used substrates (e.g. serum), hair cortisol levels are quantified in adult female hair samples collected from a broad range of non-human primate taxa. Results confirm that hair cortisol levels accurately reflect known phylogenetic and age related patterns of circulating cortisol levels. Therefore, these results suggest that hair may be an ideal hormone bearing substrate for research focused on the examination of population endocrine profiles, cross-sectional studies of endocrine function and taxon variation in hormone levels, as well as

  5. Adrenal medullary regulation of rat renal cortical adrenergic receptors

    SciTech Connect

    Sundaresan, P.R.; Guarnaccia, M.M.; Izzo, J.L. Jr. )

    1987-11-01

    The role of the adrenal medulla in the regulation of renal cortical adrenergic receptors was investigated in renal cortical particular fractions from control rats and rats 6 wk after adrenal demedullation. The specific binding of ({sup 3}H)prazosin, ({sup 3}H)rauwolscine, and ({sup 125}I)iodocyanopindolol were used to quantitate {alpha}{sub 1}-, {alpha}{sub 2}-, and {beta}-adrenergic receptors, respectively. Adrenal demedullation increased the concentration of all three groups of renal adrenergic receptors; maximal number of binding sites (B{sub max}, per milligram membrane protein) for {alpha}{sub 1}-, and {alpha}{sub 2}-, and {beta}-adrenergic receptors were increased by 22, 18.5, and 25%, respectively. No differences were found in the equilibrium dissociation constants (K{sub D}) for any of the radioligands. Plasma corticosterone and plasma and renal norepinephrine levels were unchanged, whereas plasma epinephrine was decreased 72% by adrenal demedullation, renal cortical epinephrine was not detectable in control or demedullated animals. The results suggest that, in the physiological state, the adrenal medulla modulates the number of renal cortical adrenergic receptors, presumably through the actions of a circulating factor such as epinephrine.

  6. In Silico and In Vitro Investigation of the Piperine's Male Contraceptive Effect: Docking and Molecular Dynamics Simulation Studies in Androgen-Binding Protein and Androgen Receptor.

    PubMed

    Chinta, Gopichand; Ramya Chandar Charles, Mariasoosai; Klopčič, Ivana; Sollner Dolenc, Marija; Periyasamy, Latha; Selvaraj Coumar, Mohane

    2015-07-01

    Understanding the molecular mechanism of action of traditional medicines is an important step towards developing marketable drugs from them. Piperine, an active constituent present in the Piper species, is used extensively in Ayurvedic medicines (practiced on the Indian subcontinent). Among others, piperine is known to possess a male contraceptive effect; however, the molecular mechanism of action for this effect is not very clear. In this regard, detailed docking and molecular dynamics simulation studies of piperine with the androgen-binding protein and androgen receptors were carried out. Androgen receptors control male sexual behavior and fertility, while the androgen-binding protein binds testosterone and maintains its concentration at optimal levels to stimulate spermatogenesis in the testis. It was found that piperine docks to the androgen-binding protein, similar to dihydrotestosterone, and to androgen receptors, similar to cyproterone acetate (antagonist). Also, the piperine-androgen-binding protein and piperine-androgen receptors interactions were found to be stable throughout 30 ns of molecular dynamics simulation. Further, two independent simulations for 10 ns each also confirmed the stability of these interactions. Detailed analysis of the piperine-androgen-binding protein interactions shows that piperine interacts with Ser42 of the androgen-binding protein and could block the binding with its natural ligands dihydrotestosterone/testosterone. Moreover, piperine interacts with Thr577 of the androgen receptors in a manner similar to the antagonist cyproterone acetate. Based on the in silico results, piperine was tested in the MDA-kb2 cell line using the luciferase reporter gene assay and was found to antagonize the effect of dihydrotestosterone at nanomolar concentrations. Further detailed biochemical experiments could help to develop piperine as an effective male contraceptive agent in the future. PMID:26039262

  7. Targeting of androgen receptor in bone reveals a lack of androgen anabolic action and inhibition of osteogenesis A model for compartment-specific androgen action in the skeleton

    PubMed Central

    Wiren, Kristine M.; Semirale, Anthony A.; Zhang, Xiao-Wei; Woo, Adrian; Tommasini, Steven M.; Price, Christopher; Schaffler, Mitchell B.; Jepsen, Karl J.

    2008-01-01

    Androgens are anabolic hormones that affect many tissues, including bone. However, an anabolic effect of androgen treatment on bone in eugonadal subjects has not been observed and clinical trials have been disappointing. The androgen receptor (AR) mediates biological responses to androgens. In bone tissue, both AR and the estrogen receptor (ER) are expressed. Since androgens can be converted into estrogen, the specific role of the AR in maintenance of skeletal homoeostasis remains controversial. The goal of this study was to use skeletally targeted overexpression of AR in differentiated osteoblasts as a means of elucidating the specific role(s) for AR transactivation in the mature bone compartment. Transgenic mice overexpressing AR under the control of the 2.3-kb α1(I)-collagen promoter fragment showed no difference in body composition, testosterone, or 17β-estradiol levels. However, transgenic males have reduced serum osteocalcin, CTx and TRAPC5b levels, and a bone phenotype was observed. In cortical bone, high-resolution micro-computed tomography revealed no difference in periosteal perimeter but a significant reduction in cortical bone area due to an enlarged marrow cavity. Endocortical bone formation rate was also significantly inhibited. Biomechanical analyses showed decreased whole bone strength and quality, with significant reductions in all parameters tested. Trabecular morphology was altered, with increased bone volume comprised of more trabeculae that were closer together but not thicker. Expression of genes involved in bone formation and bone resorption was significantly reduced. The consequences of androgen action are compartment-specific; anabolic effects are exhibited exclusively at periosteal surfaces, but in mature osteoblasts androgens inhibited osteogenesis with detrimental effects on matrix quality, bone fragility and whole bone strength. Thus, the present data demonstrate that enhanced androgen signaling targeted to bone results in low bone

  8. Are the Endocrine Society's Clinical Practice Guidelines on Androgen Therapy in Women misguided? A commentary.

    PubMed

    Traish, Abdulmaged; Guay, Andre T; Spark, Richard F

    2007-09-01

    The Endocrine Society Clinical Guidelines on Androgen Therapy in Women (henceforth referred to as the Guidelines) do not necessarily represent the opinion held by the many health-care professionals and clinicians who are specialized in the evaluation, diagnosis, and treatment of women's health in androgen insufficiency states. The recommendations provided in the published Guidelines are neither accurate nor complete. We disagree with the therapeutic nihilism promoted by these Guidelines. The members of the Guidelines Panel (henceforth referred to as the Panel), in their own disclaimer, stated that the Guidelines do not establish a standard of care. Based on data available in the contemporary literature, on the role of androgens in women's health, we provide in this commentary a point-by-point discussion of the arguments made by the Panel in arriving at their recommendations. It is our view that the Guidelines are not based on the preponderance of scientific evidence. Health-care professionals, physicians, and scientists often disagree when determining how best to address and manage new and emerging clinical issues. This is where we stand now as we endeavor to understand the role of androgens in a woman's health and welfare. Indeed, some basic facts are not in contention. All agree that dehydroepiandrosterone sulfate (DHEA-S) production from the adrenal gland begins during the preteen years, peaks in the mid 20s, then declines progressively over time. In contrast, ovarian androgen (i.e., testosterone) secretion commences at puberty, is sustained during a woman's peak reproductive years and declines as a woman ages, with a more rapid and steep decrease after surgical menopause. However, there are ample data to suggest that adrenal androgens play a role in the development of axillary and pubic hair, and that testosterone is critical for women's libido and sexual function. We take this opportunity to invite members of the Panel on Androgen Therapy in Women to discuss

  9. Anesthetic Considerations on Adrenal Gland Surgery

    PubMed Central

    Domi, Rudin; Sula, Hektor; Kaci, Myzafer; Paparisto, Sokol; Bodeci, Artan; Xhemali, Astrit

    2015-01-01

    Adrenal gland surgery needs a multidisciplinary team including endocrinologist, radiologist, anesthesiologist, and surgeon. The indications for adrenal gland surgery include hormonal secreting and non-hormonal secreting tumors. Adrenal hormonal secreting tumors present to the anesthesiologist unique challenges requiring good preoperative evaluation, perioperative hemodynamic control, corrections of all electrolytes and metabolic abnormalities, a detailed and careful anesthetic strategy, overall knowledge about the specific diseases, control and maintaining of postoperative adrenal function, and finally a good collaboration with other involved colleagues. This review will focus on the endocrine issues, as well as on the above-mentioned aspects of anesthetic management during hormone secreting adrenal gland tumor resection. PMID:25368694

  10. Endocrinopathies. Thyroid and adrenal disorders.

    PubMed

    Merchant, S R; Taboada, J

    1997-11-01

    This article focuses on common adrenal and thyroid diseases in the geriatric patient consisting of hypothyroidism in the dog, hyperthyroidism in the cat, and hyperadrenocorticism in the dog to include clinical signs, diagnosis, and management. A brief section on hyperadrenocorticism in the cat, thyroid tumors in the dog, and pheochromocytoma in the dog and cat are also included. PMID:9348631

  11. Hypoxia in the androgen-dependent Shionogi model for prostate cancer at three stages.

    PubMed

    Skov, Kirsten; Adomat, Hans; Bowden, Mary; Dragowska, Wieslawa; Gleave, Martin; Koch, Cameron J; Woo, Janet; Yapp, Donald T T

    2004-11-01

    The objective of this study was to investigate a possible relationship between androgen status and hypoxia in the Shionogi murine prostate tumor model, which is widely used to study the effects of androgen withdrawal on hormone resistance and radiation response. Binding of the nitroimidazole hypoxia marker EF5 was assessed using the Cy3-tagged monoclonal antibody ELK3-51. Three hours after injection of EF5 (30 mg/kg), tumors from the following three stages were excised: androgen-dependent, regressed tumors 7 days after castration, and androgen-independent. Half of each tumor was disaggregated for analysis by flow cytometry and the remainder was flash frozen. Statistically significant differences (P < 0.01) were found between androgen-dependent, regressed and androgen-dependent tumors: approximately 30, approximately 2 and approximately 50% hypoxic cells, respectively. Frozen sections from androgen-dependent tumors exhibited highly variable EF5 binding; regressed tumors showed very little or no binding; each section from androgen-dependent tumors showed high levels and uniformly distributed binding of EF5. There was no correlation between the degree of hypoxia and tumor weight (P > 0.1). The results from this preliminary study indicate that hypoxia may play an important role with respect to the timing of irradiation in prostate cancer treatments and possibly may be a useful prognostic tool. In addition, hypoxia may also be relevant to progression in this disease after androgen ablation. PMID:15624309

  12. Benefits of intermittent/continuous androgen deprivation in patients with advanced prostate cancer

    PubMed Central

    MURESANU, HORIA

    2016-01-01

    Background and aims In 1941 Huggins described the effect of castration on prostate cancer. gonadotropin-releasing hormone (GNRH) analogues were introduced in 1985. Complete androgen blockade (association of GNRH analogue with antiandrogen) was introduced by Fernand Labrie to achieve suppression of suprarenal testosterone. Long time androgen deprivation lead to androgen independence of the prostate cancer cell. Our principal aim was to demonstrate longer survival rates on prostate cancer patients with intermittent androgen deprivation. Methods 82 patients in the Urology Department of Vasile Goldis West University Arad were included into two groups, with continuous and intermittent androgen deprivation. Treatment efficiency was assessed by the level of testosterone and PSA. Adverse events (AE) and serious adverse events were reported according to Common Terminology Criteria of Adverse Events (CTCAE) of the National Cancer Institute (NCI). Results Evolution towards castrate resistant prostate cancer: 12.5% from the intermittent androgen deprivation group and 23.8% from the continuous androgen deprivation group Mortality rate: 15% of patients from the intermittent androgen deprivation group; 19% of patients from the continuous androgen deprivation group Conclusions Better quality of life (Qol) in periods without treatment due to testosteron recovery; Less AE’s and metabolic syndrome (MS) related complications; Better survival and longer time of disease control and Cost reduction. PMID:27547063

  13. Development of the human adrenal zona reticularis: morphometric and immunohistochemical studies from birth to adolescence.

    PubMed

    Hui, Xiao-Gang; Akahira, Jun-ichi; Suzuki, Takashi; Nio, Masaki; Nakamura, Yasuhiro; Suzuki, Hiroyoshi; Rainey, William E; Sasano, Hironobu

    2009-11-01

    Age-related morphologic development of human adrenal zona reticularis (ZR) has not been well examined. Therefore, in this study, 44 human young adrenal autopsy specimens retrieved from large archival files (n=252) were examined for immunohistochemical and morphometric analyses. Results demonstrated that ZR became discernible around 4 years of age, and both thickness and ratio per total cortex of ZR increased in an age-dependent fashion thereafter, although there was no significant increment in total thickness of developing adrenal cortex. We further evaluated immunoreactivity of both KI67 and BCL2 in order to clarify the equilibrium between cell proliferation and apoptosis in the homeostasis of developing human adrenals. Results demonstrated that proliferative adrenocortical cells were predominantly detected in the zona glomerulosa and partly in outer zona fasciculata (ZF) before 4 years of age and in ZR after 4 years of age, but the number of these cells markedly decreased around 20 years of age. The number of BCL2-positive cells increased in ZR and decreased in ZF during development. Adrenal androgen synthesizing type 5 17beta-hydroxysteroid dehydrogenase (HSD17B5 or AKR1C3 as listed in the Hugo Database) was almost confined to ZR of human adrenals throughout development. HSD17B5 immunoreactivity in ZR became discernible and increased from around 9 years of age. Results of our present study support the theory of age-dependent adrenocortical cell migration and also indicated that ZR development is not only associated with adrenarche, but may play important roles in an initiation of puberty. PMID:19723922

  14. Cardiovascular Disease Risk in Adult Women with Congenital Adrenal Hyperplasia Due to 21-hydroxylase Deficiency

    PubMed Central

    Kim, Mimi S.; Merke, Deborah P.

    2016-01-01

    Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a common autosomal recessive disorder characterized by impaired cortisol biosynthesis, with or without aldosterone deficiency, and androgen excess. Patients with the classic (severe) form also have epinephrine deficiency. Patients with CAH have an increased prevalence of risk factors for cardiovascular disease including obesity, hypertension and insulin resistance. Androgen excess in women appears to be an additional risk factor for cardiovascular disease. Carotid intima media thickness, a measure of subclinical atherosclerosis also has been found to be increased in adults with CAH. The multiple hormonal imbalances present in the adult woman with CAH, in combination with chronic glucocorticoid therapy, contribute to cardiovascular disease risk. Further investigation of the predisposition to cardiovascular disease in women with CAH is warranted. Longitudinal studies are needed and interventions targeting obesity, insulin resistance, hypertension and hyperandrogenism may offer improved outcome. PMID:19530065

  15. Genetics of androgen metabolism in women with infertility and hypoandrogenism.

    PubMed

    Shohat-Tal, Aya; Sen, Aritro; Barad, David H; Kushnir, Vitaly; Gleicher, Norbert

    2015-07-01

    Hypoandrogenism in women with low functional ovarian reserve (LFOR, defined as an abnormally low number of small growing follicles) adversely affects fertility. The androgen precursor dehydroepiandrosterone (DHEA) is increasingly used to supplement treatment protocols in women with LFOR undergoing in vitro fertilization. Due to differences in androgen metabolism, however, responses to DHEA supplementation vary between patients. In addition to overall declines in steroidogenic capacity with advancing age, genetic factors, which result in altered expression or enzymatic function of key steroidogenic proteins or their upstream regulators, might further exacerbate variations in the conversion of DHEA to testosterone. In this Review, we discuss in vitro studies and animal models of polymorphisms and gene mutations that affect the conversion of DHEA to testosterone and attempt to elucidate how these variations affect female hormone profiles. We also discuss treatment options that modulate levels of testosterone by targeting the expression of steroidogenic genes. Common variants in genes encoding DHEA sulphotransferase, aromatase, steroid 5α-reductase, androgen receptor, sex-hormone binding globulin, fragile X mental retardation protein and breast cancer type 1 susceptibility protein have been implicated in androgen metabolism and, therefore, can affect levels of androgens in women. Short of screening for all potential genetic variants, hormonal assessments of patients with low testosterone levels after DHEA supplementation facilitate identification of underlying genetic defects. The genetic predisposition of patients can then be used to design individualized fertility treatments. PMID:25942654

  16. An Update on Plant Derived Anti-Androgens

    PubMed Central

    Grant, Paul; Ramasamy, Shamin

    2012-01-01

    Anti-androgens are an assorted group of drugs and compounds that reduce the levels or activity of androgen hormones within the human body. Disease states in which this is relevant include polycystic ovarian syndrome, hirsutism, acne, benign prostatic hyperplasia, and endocrine related cancers such as carcinoma of the prostate. We provide an overview and discussion of the use of anti-androgen medications in clinical practice and explore the increasing recognition of the benefits of plant-derived anti-androgens, for example, spearmint tea in the management of PCOS, for which some evidence about efficacy is beginning to emerge. Other agents covered include red reishi, which has been shown to reduce levels 5-alpha reductase, the enzyme that facilitates conversion of testosterone to dihydrotestosterone (DHT); licorice, which has phytoestrogen effects and reduces testosterone levels; Chinese peony, which promotes the aromatization of testosterone into estrogen; green tea, which contains epigallocatechins and also inhibits 5-alpha reductase, thereby reducing the conversion of normal testosterone into the more potent DHT; black cohosh, which has been shown to kill both androgenresponsive and non-responsive human prostate cancer cells; chaste tree, which has a reduces prolactin from the anterior pituitary; and saw palmetto extract, which is used as an anti-androgen although it shown no difference in comparison to placebo in clinical trials. PMID:23843810

  17. Alternatively Spliced Androgen Receptor Variants

    PubMed Central

    Dehm, Scott M.; Tindall, Donald J.

    2011-01-01

    Alternative splicing is an important mechanism for increasing functional diversity from a limited set of genes. De-regulation of this process is common in diverse pathologic conditions. The androgen receptor (AR) is a steroid receptor transcription factor with functions critical for normal male development as well as the growth and survival of normal and cancerous prostate tissue. Studies of AR function in androgen insensitivity syndrome (AIS) and prostate cancer (PCa) have demonstrated loss-of-function AR alterations in AIS, and gain-of-function AR alterations in PCa. Over the past two decades, AR gene alterations have been identified in various individuals with AIS, which disrupt normal AR splicing patterns and yield dysfunctional AR protein variants. More recently, altered AR splicing patterns have been identified as a mechanism of PCa progression and resistance to androgen-depletion therapy. Several studies have described the synthesis of alternatively spliced transcripts encoding truncated AR isoforms that lack the ligand-binding domain, which is the ultimate target of androgen depletion. Many of these truncated AR isoforms function as constitutively active, ligand-independent transcription factors that can support androgen-independent expression of AR target genes, as well as the androgen-independent growth of PCa cells. In this review, we will summarize the various alternatively spliced AR variants that have been discovered, with a focus on their role and origin in the pathologic conditions of AIS and PCa. PMID:21778211

  18. Intraoperative identification of adrenal-renal fusion.

    PubMed

    Boll, Griffin; Rattan, Rishi; Yilmaz, Osman; Tarnoff, Michael E

    2015-01-01

    Adrenal - renal fusion is a rare entity defined as incomplete encapsulation of the adrenal gland and kidney with histologically adjacent functional tissue. This report describes the first published intraoperative identification of this anomaly during laparoscopic adrenalectomy. The patient was a 59-year-old man with chronic hypertension refractory to multiple antihypertensives found to be caused by a right-sided aldosterone-producing adrenal adenoma in the setting of bilateral adrenal hyperplasia. During laparoscopic adrenalectomy, the normal avascular plane between the kidney and adrenal gland was absent. Pathologic evaluation confirmed adrenal - renal fusion without adrenal heterotopia. Identified intraoperatively, this may be misdiagnosed as invasive malignancy, and thus awareness of this anomaly may help prevent unnecessarily morbid resection. PMID:26195881

  19. Hybrid Enzalutamide Derivatives with Histone Deacetylase Inhibitor Activity Decrease Heat Shock Protein 90 and Androgen Receptor Levels and Inhibit Viability in Enzalutamide-Resistant C4-2 Prostate Cancer Cells.

    PubMed

    Rosati, Rayna; Chen, Bailing; Patki, Mugdha; McFall, Thomas; Ou, Siyu; Heath, Elisabeth; Ratnam, Manohar; Qin, Zhihui

    2016-09-01

    Histone deacetylase inhibitors (HDACIs) can disrupt the viability of prostate cancer (PCa) cells through modulation of the cytosolic androgen receptor (AR) chaperone protein heat shock protein 90 (HSP90). However, toxicities associated with their pleiotropic effects could contribute to the ineffectiveness of HDACIs in PCa treatment. We designed hybrid molecules containing partial chemical scaffolds of enzalutamide and suberoylanilide hydroxamic acid (SAHA), with weakened intrinsic pan-HDACI activities, to target HSP90 and AR in enzalutamide-resistant PCa cells. The potency of the new molecules, compounds 2-75 [4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-N-(7-(hydroxyamino)-7-oxoheptyl)benzamide] and 1005 [(E)-3-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluorophenyl)-N-hydroxyacrylamide], as inhibitors of nuclear and cytosolic histone deacetylases was substantially lower than that of SAHA in cell-free and in situ assays. Compounds 2-75 and 1005 antagonized gene activation by androgen without inducing chromatin association of AR. Enzalutamide had no effect on the levels of AR or HSP90, whereas the hybrid compounds induced degradation of both AR and HSP90, similar to (compound 1005) or more potently than (compound 2-75) SAHA. Similar to SAHA, compounds 2-75 and 1005 decreased the level of HSP90 and induced acetylation in a predicted approximately 55 kDa HSP90 fragment. Compared with SAHA, compound 2-75 induced greater hyperacetylation of the HDAC6 substrate α-tubulin. In contrast with SAHA, neither hybrid molecule caused substantial hyperacetylation of histones H3 and H4. Compounds 2-75 and 1005 induced p21 and caused loss of viability in the enzalutamide-resistant C4-2 cells, with efficacies that were comparable to or better than SAHA. The results suggest the potential of the new compounds as prototype antitumor drugs that would downregulate HSP90 and AR in

  20. Case of metachronous bilateral isolated adrenal metastasis from colorectal adenocarcinoma and review of the literature.

    PubMed

    Liu, Yu-Yi; Chen, Zhi-Hui; Zhai, Er-Tao; Yang, Jie; Xu, Jian-Bo; Cai, Shi-Rong; Song, Wu

    2016-04-14

    Rarely has a solitary, metachronous bilateral adrenal metastasis of colorectal cancer been reported. We depict a 41-year-old man who underwent sigmoid colon cancer radical surgery followed by adjuvant chemotherapy for a locally ulcerative sigmoid adenocarcinoma with metachronous bilateral adrenal metastasis revealed by a computed tomography scan. Histopathological examination showed adenocarcinoma, compatible with metastasis from the rectal cancer. The level of serum carcinoembryonic antigen had indicative significance for the presence of adrenal metastasis in the reported series. We performed a literature analysis related to this pathological characteristic and attach importance to consistent, vigilant radiological surveillance of the adrenal glands in the patients' follow up for colorectal cancer with or without subsequent adrenal metastasis. PMID:27076775

  1. Thymic involution in the suspended rat - Adrenal hypertrophy and glucocorticoid receptor content

    NASA Technical Reports Server (NTRS)

    Steffen, J. M.; Musacchia, X. J.

    1986-01-01

    The relationship between thymic involution and adrenal hypertrophy is studied. The thymus, adrenal glands, and tissue water content are evaluated in male Sprague rats suspended in antiorthostatic (AO) or orthostatic (O) positions. A 50 percent decrease in the wet weight of the thymus and hypertrophy of the adrenal glands are observed during the seven days of AO suspension. After seven days of recovery the thymus weight is increased to control level; however, the hypertrophy of the adrenal glands remains unchanged. Thymic and renal responses in O postioned rats are similar to AO reactions. Thymic glucocorticoid (GC) receptor concentrations in the rats are analyzed; a 20 percent decrease in GC receptor site concentration, which is related to thymic involution, is detected in both AO and O rats. It is concluded that there is a temporal correlation between thymic involution and adrenal hypertrophy, which is not affected by AO positioning, and thymic involution is not associated with an increased sensitivity to GC.

  2. Diagnostic accuracy of computed tomography in detecting adrenal metastasis from primary lung cancer

    SciTech Connect

    Allard, P.

    1988-01-01

    The main study objective was to estimate the diagnostic accuracy of computed tomography (CT) for detection of adrenal metastases from primary lung cancer. A secondary study objective was to measure intra-reader and inter-reader agreement in interpretation of adrenal CT. Results were compared of CT film review and the autopsy findings of the adrenal glands. A five-level CT reading scale was used to assess the effect of various positivity criteria. The diagnostic accuracy of CT for detection of adrenal metastases was characterized by a tradeoff between specificity and sensitivity. At various positivity criteria, high specificity is traded against low sensitivity. The CT inability to detect many metastatic adrenals was related to frequent metastatic spread without morphologic changes of the gland.

  3. Case of metachronous bilateral isolated adrenal metastasis from colorectal adenocarcinoma and review of the literature

    PubMed Central

    Liu, Yu-Yi; Chen, Zhi-Hui; Zhai, Er-Tao; Yang, Jie; Xu, Jian-Bo; Cai, Shi-Rong; Song, Wu

    2016-01-01

    Rarely has a solitary, metachronous bilateral adrenal metastasis of colorectal cancer been reported. We depict a 41-year-old man who underwent sigmoid colon cancer radical surgery followed by adjuvant chemotherapy for a locally ulcerative sigmoid adenocarcinoma with metachronous bilateral adrenal metastasis revealed by a computed tomography scan. Histopathological examination showed adenocarcinoma, compatible with metastasis from the rectal cancer. The level of serum carcinoembryonic antigen had indicative significance for the presence of adrenal metastasis in the reported series. We performed a literature analysis related to this pathological characteristic and attach importance to consistent, vigilant radiological surveillance of the adrenal glands in the patients’ follow up for colorectal cancer with or without subsequent adrenal metastasis. PMID:27076775

  4. Congenital Adrenal Hyperplasia, Polycystic Ovary Syndrome and criminal behavior: A Swedish population based study.

    PubMed

    Ohlsson Gotby, Agnes; Nordenström, Anna; Falhammar, Henrik; Nordenskjöld, Agneta; Linden Hirschberg, Angelica; Frisén, Louise; Landén, Mikael; Lichtenstein, Paul

    2015-10-30

    Both prenatal and circulating testosterone and other androgens have been suggested to influence the individual's propensity to commit crime, but empirical evidence is limited and inconsistent. Congenital Adrenal Hyperplasia (CAH) and Polycystic Ovary Syndrome (PCOS) are both hyperandrogenic conditions but with an important difference; whereas subjects with CAH are exposed to high concentrations of androgens in utero, women with PCOS are subjected to high androgens in adulthood. Comparing these groups can therefore yield important insights of androgenic effects on behavior. In the current study, information on medical diagnoses and convicted crimes were gathered from Swedish population-based registers. The associations between diagnoses of CAH or PCOS and any crime, violent crime or sex crime were estimated with conditional logistic regression. Results showed that CAH in women and men did not predict criminality, whereas an increased risk for any crime and violent crime was found in PCOS women. Our findings indicate that female hyperandrogenism in adulthood, but not prenatal hyperandrogenism, is associated with risk for criminal behavior. Further research into hyperandrogenic conditions holds opportunities to deepen our understanding of the etiology of crime and psychopathology. PMID:26254797

  5. [Hypokalaemic paralysis as a presentation of adrenal tumor].

    PubMed

    Briere, C; Milhaud, D; Heroum, C; Ringeard, I; Blard, J-M; Pagès, M

    2003-12-01

    A 24-year-old patient presented with flaccid quadriplegia due to severe hypokaliemia, initially presumed to have been induced by glycyrrhizin. Persistence of low potassium levels and hypertension led to the diagnosis of primary hyperaldosteronism related to an adrenal cortical tumor. After surgery, the patient recovered from hypertension and hypokaliemia. PMID:14978420

  6. Primary aldosteronism caused by unilateral adrenal hyperplasia: rethinking the accuracy of imaging studies.

    PubMed

    Chen, Su-Yu; Shen, Sjen-Jung; Chou, Chien-Wen; Yang, Chwen-Yi; Cheng, Hon-Mei

    2006-03-01

    A rare type of aldosteronism, known as unilateral adrenal hyperplasia (UAH), is difficult to diagnose, not only because it fails to conform to the typical common subtypes, but also because imaging results are unreliable. We report 2 Taiwanese patients with UAH. Case 1 was a 44-year-old man with 2 episodes of hypokalemic paralysis. Hypertension and suppressed plasma renin activity (PRA) with elevated plasma aldosterone concentration (PAC) were observed. Abdominal computed tomography (CT) and magnetic resonance imaging (MRI) showed a right adrenal mass, but adrenal scintigraphy revealed no definite laterality. The patient underwent a laparoscopic right adrenalectomy. Adrenal cortical hyperplasia was discovered from results of the histologic analysis. Case 2 was a 33-year-old woman referred for hypokalemia, hypertension, and a left adrenal mass found on a CT scan. However, MRI revealed normal adrenal glands. The adrenal vein sampling for PAC showed overproduction of PAC from the left adrenal gland. A laparoscopic left adrenalectomy was done. Pathology results revealed micronodular cortical hyperplasia with central hemorrhage. Blood pressure, plasma potassium, aldosterone, and renin activity levels returned to normal after operation in both cases. Both patients have been well for 3 years and 16 months, respectively, after surgery. We review the literature and discuss the limitations of imaging studies. PMID:16599018

  7. Primary Adrenal Insufficiency Misdiagnosed as Hypothyroidism in a Patient with Polyglandular Syndrome

    PubMed Central

    Upala, Sikarin; Yong, Wai Chung; Sanguankeo, Anawin

    2016-01-01

    Context: Autoimmune polyglandular syndrome is a rare condition that causes a variety of clinical symptoms due to autoimmune processes involving multiple endocrine organs. Its vague presentation can cause missed or delayed treatment for adrenal insufficiency, resulting in a life-threatening adrenal crisis. Case Report: A 21-yr-old man presented with lethargy, hypotension, hyponatremia, hypoglycemia, and an elevated thyroid-stimulating hormone level. He was binge drinking the day before presentation. No significant response to initial treatment with levothyroxine and dextrose occurred. Diagnostic workup later revealed primary adrenal insufficiency. All initial symptoms completely resolved following treatment with hydrocortisone, fludrocortisone, and levothyroxine. Conclusion: Autoimmune polyglandular syndrome causes dysfunction of multiple endocrine organs such as the thyroid gland, adrenal gland, and pancreas. Initial diagnosis of APS is crucial and difficult because of its vague, acute presentation, which often involves hypothyroidism and adrenal insufficiency. Delayed treatment of adrenal insufficiency can result in a life-threatening adrenal crisis. A diagnostic workup for adrenal insufficiency should be performed in patients who do not respond to hypothyroidism treatment. PMID:27298818

  8. Androgen supplementation during aging: development of a physiologically appropriate protocol.

    PubMed

    Urbanski, Henryk F; Sorwell, Krystina G; Garyfallou, Vasilios T; Garten, Jamie; Weiss, Alison; Renner, Laurie; Neuringer, Martha; Kohama, Steven G

    2014-04-01

    Men show an age-related decline in the circulating levels of testosterone (T) and dehydroepiandrosterone sulfate (DHEAS). Consequently, there is interest in developing androgen supplementation paradigms for old men that replicate the hormone profiles of young adults. In the present study, we used old (21-26 years old) male rhesus monkeys as a model to examine the efficacy of an androgen supplementation paradigm that comprised oral T administration (12 mg/kg body weight, dissolved in sesame oil/chocolate) in the evening, and two oral DHEA administrations, 3 hr apart (0.04 mg/kg body weight, dissolved in sesame oil/chocolate) in the morning. After 5 days of repeated hormone supplementation, serial blood samples were remotely collected from each animal hourly across the 24-hr day, and assayed for cortisol, DHEAS, T, 5α-dihydrotestosterone (DHT), estrone (E1), and 17β-estradiol (E2). Following androgen supplementation, T levels were significantly elevated and this was associated with a more sustained nocturnal elevation of T's primary bioactive metabolites, DHT and E1 and E2. Plasma DHEAS levels were also significantly elevated after androgen supplementation; DHEAS levels rose in the early morning and gradually declined during the course of the day, closely mimicking the profiles observed in young adults (7-12 years old); in contrast, cortisol levels were unaltered by the supplementation. Together the data demonstrate a non-invasive androgen supplementation paradigm that restores youthful circulating androgen levels in old male primates. Because this paradigm preserves the natural circulating circadian hormone patterns, we predict that it will produce fewer adverse side effects, such as perturbed sleep or cognitive impairment. PMID:24134213

  9. Hypercholesterolemia in Male Power Lifters Using Anabolic-Androgenic Steroids.

    ERIC Educational Resources Information Center

    Cohen, Jonathan C.; And Others

    1988-01-01

    Measurement of serum cholesterol concentrations in male power lifters who used anabolic-androgenic steroids for eight weeks, three years, or eight years indicated that mean serum cholesterol levels increased with drug use, but decreased promptly to near pre-steroid levels after steroid use ended. (Author/CB)

  10. Anti-androgen treatments.

    PubMed

    Bachelot, Anne; Chabbert-Buffet, Nathalie; Salenave, Sylvie; Kerlan, Véronique; Galand-Portier, Marie-Béatrice

    2010-02-01

    1. Estrogen plus progestin contraceptives (EPP) are the first-line treatment of moderate hirsutism and acne in women of child bearing age (grade C). 2. CPA, 50mg/day, 20 days out of 28, associated with estrogen is the first-line treatment of "moderate to severe hirsutism" in women of childbearing age (grade C). 3. Spironolactone, given as a contraceptive, can be proposed as a second-line treatment in case of side effects or counter-indications to CPA in moderate to severe hirsutism (grade C) in women of childbearing age. No market authorization in this indication. 4. Flutamide or Finasteride are "only" to be used under the guise of contraception as a "thirdline therapy" in cases of severe hirsutism, the presence of side effects or counter-indications to EPP, CPA 50mg/day or spironolactone (grade C). No market authorization in this indication 5. There is no indication for GnRH analogs as an anti-androgen treatment in women of childbearing age given the current therapeutic alternatives (grade C) 6. Only long-term hair removal treatments can be proposed (grade C): electrolysis or laser hair removal. PMID:20096826

  11. Traumatic panhypopituitarism resulting in acute adrenal crisis.

    PubMed

    Ham, Phillip Benson; Cunningham, Aaron Joseph; Mentzer, Caleb James; Ahmad, Anbar; Young, Lester S; Abuzeid, Adel M

    2015-09-01

    Pituitary function plays an integral role in the physiologic response to traumatic injury. A significant proportion of trauma patients develop partial pituitary insufficiency. While isolated deficiencies of individual pituitary hormones are common, there are few reports in the literature of traumatic pan-pituitary failure with deficiency of all major pituitary hormones. We present a case of a patient involved in a motorcycle accident who sustained a sella turcica fracture, epidural hemorrhage, subdural hemorrhage, optic nerve palsy, and bilateral abducens nerve palsies. Three days after the accident, the patient became hypotensive and progressed to cardiopulmonary arrest. He was resuscitated and had spontaneous return of circulation. Despite adequate fluid resuscitation and vasopressor support, he remained profoundly hypotensive. Following administration of hydrocortisone, his blood pressures dramatically improved. He was found to have laboratory abnormalities, suggesting deficiencies of corticotropins, somatotropins, thyrotropins, gonadotropins, prolactin, and antidiuretic hormone. This is the first reported case of a patient with traumatic total panhypopituitarism complicated by acute adrenal crises during initial postinjury hospitalization. A review of the literature with comparison with other studies of trauma patients with deficiencies in five or more axes is presented. A high level of suspicion for central adrenal insufficiency and prompt administration of corticosteroids in the setting of symptomatic pituitary trauma can result in favorable outcomes. Screening for and treating posttraumatic hypopituitarism can result in improved rehabilitation and increased quality of life for trauma patients. PMID:26307884

  12. Long-Term DHEA Replacement in Primary Adrenal Insufficiency: A Randomized, Controlled Trial

    PubMed Central

    Gurnell, Eleanor M.; Hunt, Penelope J.; Curran, Suzanne E.; Conway, Catherine L.; Pullenayegum, Eleanor M.; Huppert, Felicia A.; Compston, Juliet E.; Herbert, Joseph; Chatterjee, V. Krishna K.

    2008-01-01

    Context: Dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) are the major circulating adrenal steroids and substrates for peripheral sex hormone biosynthesis. In Addison’s disease, glucocorticoid and mineralocorticoid deficiencies require lifelong replacement, but the associated near-total failure of DHEA synthesis is not typically corrected. Objective and Design: In a double-blind trial, we randomized 106 subjects (44 males, 62 females) with Addison’s disease to receive either 50 mg daily of micronized DHEA or placebo orally for 12 months to evaluate its longer-term effects on bone mineral density, body composition, and cognitive function together with well-being and fatigue. Results: Circulating DHEAS and androstenedione rose significantly in both sexes, with testosterone increasing to low normal levels only in females. DHEA reversed ongoing loss of bone mineral density at the femoral neck (P < 0.05) but not at other sites; DHEA enhanced total body (P = 0.02) and truncal (P = 0.017) lean mass significantly with no change in fat mass. At baseline, subscales of psychological well-being in questionnaires (Short Form-36, General Health Questionnaire-30), were significantly worse in Addison’s patients vs. control populations (P < 0.001), and one subscale of SF-36 improved significantly (P = 0.004) after DHEA treatment. There was no significant benefit of DHEA treatment on fatigue or cognitive or sexual function. Supraphysiological DHEAS levels were achieved in some older females who experienced mild androgenic side effects. Conclusion: Although further long-term studies of DHEA therapy, with dosage adjustment, are desirable, our results support some beneficial effects of prolonged DHEA treatment in Addison’s disease. PMID:18000094

  13. A clinical data validated mathematical model of prostate cancer growth under intermittent androgen suppression therapy

    NASA Astrophysics Data System (ADS)

    Portz, Travis; Kuang, Yang; Nagy, John D.

    2012-03-01

    Prostate cancer is commonly treated by a form of hormone therapy called androgen suppression. This form of treatment, while successful at reducing the cancer cell population, adversely affects quality of life and typically leads to a recurrence of the cancer in an androgen-independent form. Intermittent androgen suppression aims to alleviate some of these adverse affects by cycling the patient on and off treatment. Clinical studies have suggested that intermittent therapy is capable of maintaining androgen dependence over multiple treatment cycles while increasing quality of life during off-treatment periods. This paper presents a mathematical model of prostate cancer to study the dynamics of androgen suppression therapy and the production of prostate-specific antigen (PSA), a clinical marker for prostate cancer. Preliminary models were based on the assumption of an androgen-independent (AI) cell population with constant net growth rate. These models gave poor accuracy when fitting clinical data during simulation. The final model presented hypothesizes an AI population with increased sensitivity to low levels of androgen. It also hypothesizes that PSA production is heavily dependent on androgen. The high level of accuracy in fitting clinical data with this model appears to confirm these hypotheses, which are also consistent with biological evidence.

  14. Hypochlorite Oxidation of Select Androgenic Steroids

    EPA Science Inventory

    Steroid hormones are vital for regulation of various biological functions including sexual development. Elevated concentrations of natural and synthetic androgenic steroids have been shown to adversely affect normal development in indigenous aqueous species. Androgens and their s...

  15. Analysis of DAX1 (NR0B1) and steroidogenic factor-1 (SF1/Ad4BP, NR5A1) in children and adults with primary adrenal failure: ten years' experience

    PubMed Central

    Lin, Lin; Gu, Wen-Xia; Ozisik, Gokhan; To, Wing S.; Owen, Catherine J.; Jameson, J. Larry; Achermann, John C.

    2007-01-01

    Context Primary adrenal failure is a life-threatening condition that can be caused by a range of etiologies, including autoimmune, metabolic, and developmental disorders. The nuclear receptors DAX1 (NR0B1) and steroidogenic factor-1 (SF1/Ad4BP, NR5A1) play an important role in adrenal development and function, and mutations in these transcription factors have been found in patients with adrenal hypoplasia. Objective To investigate the prevalence of DAX1 and SF1 mutations in children and adults with primary adrenal failure of unknown etiology (i.e., not caused by congenital adrenal hyperplasia, adrenoleukodystrophy, autoimmune disease). Patients One-hundred and seventeen patients were included. Eighty-eight individuals presented in infancy or childhood with adrenal hypoplasia or primary adrenal failure of unknown etiology (n=64, 46,XY phenotypic males; n=17, 46,XY gonadal dysgenesis/impaired androgenization; n=7, 46,XX females). Twenty-nine individuals presented in adulthood with “Addison disease” of unknown etiology. Methods Mutational analysis of DAX1 (NR0B1) (including exon 2α/1A) and SF1 (NR5A1) by direct sequencing. Results DAX1 mutations were found in 58% (37/64) of 46,XY phenotypic boys referred with adrenal hypoplasia, and in all boys (8/8) with hypogonadotropic hypogonadism and a family history suggestive of adrenal failure in males. SF1 mutations causing adrenal failure were found only in two patients with 46,XY gonadal dysgenesis. No DAX1 or SF1 mutations were identified in the adult-onset group. Conclusions DAX1 mutations are a relatively frequent cause of adrenal failure in this group of boys. SF1 mutations causing adrenal failure in humans are rare and are more likely to be associated with significant underandrogenization and gonadal dysfunction in 46,XY individuals. PMID:16684822

  16. Androgens in a female primate: Relationships with reproductive status, age, dominance rank, fetal sex and secondary sexual color.

    PubMed

    Setchell, Joanna M; Smith, Tessa E; Knapp, Leslie A

    2015-08-01

    A comprehensive understanding of the role of androgens in reproduction, behavior and morphology requires the examination of female, as well as male, hormone profiles. However, we know far less about the biological significance of androgens in females than in males. We investigated the relationships between fecal androgen (immunoreactive testosterone) levels and reproductive status, age, dominance rank, fetal sex and a secondary sexual trait (facial color) in semi-free-ranging female mandrills (Mandrillus sphinx), using samples collected from 19 reproductively mature females over 13months. Fecal androgens varied with reproductive status, being highest during gestation. Fecal androgens began to increase at 3months of gestation, and peaked at 5months. This pattern is more similar to that found in a platyrrhine than in other cercopithecine species, suggesting that such patterns are not necessarily phylogenetically constrained. Fecal androgens did not vary systematically with rank, in contrast to the relationship we have reported for male mandrills, and in line with sex differences in how rank is acquired and maintained. Offspring sex was unrelated to fecal androgens, either prior to conception or during gestation, contrasting with studies of other primate species. Mean facial color was positively related to mean fecal androgens across females, reflecting the same relationship in male mandrills. However, the relationship between color and androgens was negative within females. Future studies of the relationship between female androgens and social behavior, reproduction and secondary sexual traits will help to elucidate the factors underlying the similarities and differences found between the sexes and among studies. PMID:25936819

  17. Androgen receptors in prostate cancer.

    PubMed

    Culig, Z; Klocker, H; Bartsch, G; Hobisch, A

    2002-09-01

    The androgen receptor (AR), a transcription factor that mediates the action of androgens in target tissues, is expressed in nearly all prostate cancers. Carcinoma of the prostate is the most frequently diagnosed neoplasm in men in industrialized countries. Palliative treatment for non-organ-confined prostate cancer aims to down-regulate the concentration of circulating androgen or to block the transcription activation function of the AR. AR function during endocrine therapy was studied in tumor cells LNCaP subjected to long-term steroid depletion; newly generated sublines could be stimulated by lower concentrations of androgen than parental cells and showed up-regulation of AR expression and activity as well as resistance to apoptosis. Androgenic hormones regulate the expression of key cell cycle regulators, cyclin-dependent kinase 2 and 4, and that of the cell cycle inhibitor p27. Inhibition of AR expression could be achieved by potential chemopreventive agents flufenamic acid, resveratrol, quercetin, polyunsaturated fatty acids and interleukin-1beta, and by the application of AR antisense oligonucleotides. In the clinical situation, AR gene amplification and point mutations were reported in patients with metastatic disease. These mutations generate receptors which could be activated by other steroid hormones and non-steroidal antiandrogens. In the absence of androgen, the AR could be activated by various growth-promoting (growth factors, epidermal growth factor receptor-related oncogene HER-2/neu) and pleiotropic (protein kinase A activators, interleukin-6) compounds as well as by inducers of differentiation (phenylbutyrate). AR function is modulated by a number of coactivators and corepressors. The three coactivators, TIF-2, SRC-1 and RAC3, are up-regulated in relapsed prostate cancer. New experimental therapies for prostate cancer are aimed to down-regulate AR expression and to overcome difficulties which occur because of the acquisition of agonistic properties

  18. Androgen Deficiency and Dry Eye Syndrome in the Aging Male

    PubMed Central

    Azcarate, Patrick M.; Venincasa, Vincent D.; Feuer, William; Stanczyk, Frank; Schally, Andrew V.; Galor, Anat

    2014-01-01

    Purpose. To evaluate the relationship between androgen levels and subjective and objective measures of dry eye syndrome (DES). Methods. A total of 263 male patients from the Miami Veterans Affairs Medical Center eye clinic aged ≥50 were recruited for this prospective cross-sectional study. Patients completed Dry Eye Questionnaire 5, underwent tear film evaluation, and had serum androgen levels measured. The correlations between androgen levels, DES composite scores, DES symptoms, and global, lipid, and aqueous tear film parameters were evaluated. Results. Two hundred sixty-three patients with a mean age of 69 (50–95) were examined. There was no linear association between composite DES scores (generated using latent class analysis) and androgen levels. However, eyes with high DES scores (0.95–1.0) had higher levels of sex hormone-binding globulin (P = 0.03) and lower levels of dehydroepiandrosterone sulfate (DHEAS) (P = 0.02), androstenedione (A) (P = 0.02), and androstane-3α,17β-diol glucuronide (P = 0.03) compared to eyes with intermediate (0.05–0.95) or low (0–0.05) scores. There were no strong correlations between tear film measures and androgen levels. Regarding global parameters, a weak inverse correlation was found between corneal staining and A (r = −0.17, P = 0.009). For lipid parameters, a weak correlation existed between tear breakup time (TBUT) and A (r = 0.15, P = 0.02). When considering aqueous and lipid deficiency independently, the association between TBUT and A existed only with aqueous tear deficiency (r = 0.66, P = 0.002). Regarding aqueous parameters, a weak correlation existed between Schirmer test and DHEAS (r = 0.13, P = 0.047) and A (r = 0.21, P = 0.001). Conclusions. There was a weak correlation between higher levels of androstenedione and healthier global, lipid, and aqueous tear film parameters. PMID:24994872

  19. Adrenal scan in 17-alpha-hydroxylase deficiency: false indication of adrenal adenoma

    SciTech Connect

    Shore, R.M.; Lieberman, L.M.; Newman, T.J.; Friedman, A.; Bargman, G.J.

    1981-07-01

    A patient who was thought to have testicular feminization syndrome and primary aldosteronism had an adrenal scan that suggested an adrenal adenoma. After later diagnosis of 17-alpha-hydroxylase deficiency, she was treated with glucocorticoids rather than surgery. Her clinical course and a repeat adrenal scan confirmed she did not have a tumor.

  20. Imaging of adrenal and renal hemorrhage.

    PubMed

    Hammond, Nancy A; Lostumbo, Antonella; Adam, Sharon Z; Remer, Erick M; Nikolaidis, Paul; Yaghmai, Vahid; Berggruen, Senta M; Miller, Frank H

    2015-10-01

    Hemorrhage of the kidneys and adrenal glands has many etiologies. In the adrenal glands, trauma, anticoagulation, stress, sepsis, surgery, and neoplasms are common causes of hemorrhage. In the kidneys, reasons for hemorrhage include trauma, bleeding diathesis, vascular diseases, infection, infarction, hemorrhagic cyst rupture, the Antopol-Goldman lesion, and neoplasms. Angiomyolipoma and renal cell carcinoma are the neoplasms most commonly associated with hemorrhage in the kidneys and adrenal cortical carcinoma, metastases, and pheochromocytoma are associated with hemorrhage in the adrenal glands. Understanding the computed tomography and magnetic resonance imaging features, and causes of hemorrhage in the kidneys and adrenal glands is critical. It is also important to keep in mind that mimickers of hemorrhage exist, including lymphoma in both the kidneys and adrenal glands, and melanoma metastases in the adrenal glands. Appropriate imaging follow-up of renal and adrenal hemorrhage should occur to exclude an underlying malignancy as the cause. If there is suspicion for malignancy that cannot be definitively diagnosed on imaging, surgery or biopsy may be warranted. Angiography may be indicated when there is a suspected underlying vascular disease. Unnecessary intervention, such as nephrectomy, may be avoided in patients with benign causes or no underlying disease. Appropriate management is dependent on accurate diagnosis of the cause of renal or adrenal hemorrhage and it is incumbent upon the radiologist to determine the etiology. PMID:26036792

  1. Androgen Receptor Repression of GnRH Gene Transcription

    PubMed Central

    Brayman, Melissa J.; Pepa, Patricia A.; Berdy, Sara E.

    2012-01-01

    Alterations in androgen levels lead to reproductive defects in both males and females, including hypogonadotropic hypogonadism, anovulation, and infertility. Androgens have been shown to down-regulate GnRH mRNA levels through an androgen receptor (AR)-dependent mechanism. Here, we investigate how androgen regulates expression from the GnRH regulatory region in the GT1-7 cell line, a model of GnRH neurons. A synthetic androgen, R1881, repressed transcription from the GnRH promoter (GnRH-P) in an AR-dependent manner, and liganded AR associated with the chromatin at the GnRH-P in live GT1-7 cells. The three known octamer-binding transcription factor-1 (Oct-1) binding sites in GnRH-P were required for AR-mediated repression, although other sequences were also involved. Although a multimer of the consensus Oct-1 binding site was not repressed, a multimer of the cluster of Oct-1, Pre-B cell leukemia transcription factor (Pbx)/Prep, and NK2 homeobox 1 (Nkx2.1) binding sites, found at −106/−91 in GnRH-P, was sufficient for repression. In fact, overexpression of any of these factors disrupted the androgen response, indicating that a balance of factors in this tripartite complex is required for AR repression. AR bound to this region in EMSA, indicating a direct interaction of AR with DNA or with other transcription factors bound to GnRH-P at this sequence. Collectively, our data demonstrate that GnRH transcription is repressed by AR via multiple sequences in GnRH-P, including three Oct-1 binding sites, and that this repression requires the complex interaction of several transcription factors. PMID:22074952

  2. AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS, AMERICAN COLLEGE OF ENDOCRINOLOGY, AND ANDROGEN EXCESS AND PCOS SOCIETY DISEASE STATE CLINICAL REVIEW: GUIDE TO THE BEST PRACTICES IN THE EVALUATION AND TREATMENT OF POLYCYSTIC OVARY SYNDROME--PART 1.

    PubMed

    Goodman, Neil F; Cobin, Rhoda H; Futterweit, Walter; Glueck, Jennifer S; Legro, Richard S; Carmina, Enrico

    2015-11-01

    Polycystic Ovary Syndrome (PCOS) is recognized as the most common endocrine disorder of reproductive-aged women around the world. This document, produced by the collaboration of the American Association of Clinical Endocrinologists (AACE) and the Androgen Excess and PCOS Society (AES) aims to highlight the most important clinical issues confronting physicians and their patients with PCOS. It is a summary of current best practices in 2015. PCOS has been defined using various criteria, including menstrual irregularity, hyperandrogenism, and polycystic ovary morphology (PCOM). General agreement exists among specialty society guidelines that the diagnosis of PCOS must be based on the presence of at least two of the following three criteria: chronic anovulation, hyperandrogenism (clinical or biological) and polycystic ovaries. There is need for careful clinical assessment of women's history, physical examination, and laboratory evaluation, emphasizing the accuracy and validity of the methodology used for both biochemical measurements and ovarian imaging. Free testosterone (T) levels are more sensitive than the measurement of total T for establishing the existence of androgen excess and should be ideally determined through equilibrium dialysis techniques. Value of measuring levels of androgens other than T in patients with PCOS is relatively low. New ultrasound machines allow diagnosis of PCOM in patients having at least 25 small follicles (2 to 9 mm) in the whole ovary. Ovarian size at 10 mL remains the threshold between normal and increased ovary size. Serum 17-hydroxyprogesterone and anti-Müllerian hormone are useful for determining a diagnosis of PCOS. Correct diagnosis of PCOS impacts on the likelihood of associated metabolic and cardiovascular risks and leads to appropriate intervention, depending upon the woman's age, reproductive status, and her own concerns. The management of women with PCOS should include reproductive function, as well as the care of hirsutism

  3. Adrenal Venous Sampling: Where Is the Aldosterone Disappearing to?

    SciTech Connect

    Solar, Miroslav; Ceral, Jiri; Krajina, Antonin; Ballon, Marek; Malirova, Eva; Brodak, Milos; Cap, Jan

    2010-08-15

    Adrenal venous sampling (AVS) is generally considered to be the gold standard in distinguishing unilateral and bilateral aldosterone hypersecretion in primary hyperaldosteronism. However, during AVS, we noticed a considerable variability in aldosterone concentrations among samples thought to have come from the right adrenal glands. Some aldosterone concentrations in these samples were even lower than in samples from the inferior vena cava. We hypothesized that the samples with low aldosterone levels were unintentionally taken not from the right adrenal gland, but from hepatic veins. Therefore, we sought to analyze the impact of unintentional cannulation of hepatic veins on AVS. Thirty consecutive patients referred for AVS were enrolled. Hepatic vein sampling was implemented in our standardized AVS protocol. The data were collected and analyzed prospectively. AVS was successful in 27 patients (90%), and hepatic vein cannulation was successful in all procedures performed. Cortisol concentrations were not significantly different between the hepatic vein and inferior vena cava samples, but aldosterone concentrations from hepatic venous blood (median, 17 pmol/l; range, 40-860 pmol/l) were markedly lower than in samples from the inferior vena cava (median, 860 pmol/l; range, 460-4510 pmol/l). The observed difference was statistically significant (P < 0.001). Aldosterone concentrations in the hepatic veins are significantly lower than in venous blood taken from the inferior vena cava. This finding is important for AVS because hepatic veins can easily be mistaken for adrenal veins as a result of their close anatomic proximity.

  4. [Health status of adults with congenital adrenal hyperplasia due to 21-hydroxylase deficiency].

    PubMed

    Bachelot, Anne; Touraine, Philippe

    2014-04-01

    Congenital adrenal hyperplasia (CAH) is the commonest genetic endocrine disorder. Mutations in the 21-hydroxylase gene account for 95 % of cases. CAH is classified according to symptoms and signs and to age of presentation. The clinical phenotype is typically classified as classic, the severe form, or nonclassic (NCF), the mild or late-onset form. Classic CAH is a life-long chronic disorder. In childhood, treatment focuses on genital surgery and optimization of growth and pubertal development. Priorities change with increasing age, typically focusing on fertility in early adult life and prevention of metabolic syndrome and osteoporosis in middle and older age. Recent studies highlight the importance of long-term follow-up of these patients and of transitional care between childhoods to adult life. In nonclassic CAH women, subfertility is mild compared with the classic form and seems to be mainly due to hormonal imbalance. Menstrual cycle or ovulation disorders observed in these women who consulted for infertility are in most cases corrected by hydrocortisone treatment, which led to simultaneous lowering of plasma androgen levels and rapid occurrence of pregnancy. Hydrocortisone also reduces the incidence of miscarriages. Several studies have reported that near 60 % of nonclassic CAH patients are carriers of a severe mutation. These patients may therefore give birth to a child with the classical form of CAH if their partner is also carrying a severe mutation. Due to the high frequency of CYP21A2 mutations in the general population, it is essential to genotype the partner of NC-CAH patients with one severe mutation to offer genetic counselling. PMID:24630263

  5. Regulators of Androgen Action Resource: a one-stop shop for the comprehensive study of androgen receptor action.

    PubMed

    DePriest, Adam D; Fiandalo, Michael V; Schlanger, Simon; Heemers, Frederike; Mohler, James L; Liu, Song; Heemers, Hannelore V

    2016-01-01

    Androgen receptor (AR) is a ligand-activated transcription factor that is the main target for treatment of non-organ-confined prostate cancer (CaP). Failure of life-prolonging AR-targeting androgen deprivation therapy is due to flexibility in steroidogenic pathways that control intracrine androgen levels and variability in the AR transcriptional output. Androgen biosynthesis enzymes, androgen transporters and AR-associated coregulators are attractive novel CaP treatment targets. These proteins, however, are characterized by multiple transcript variants and isoforms, are subject to genomic alterations, and are differentially expressed among CaPs. Determining their therapeutic potential requires evaluation of extensive, diverse datasets that are dispersed over multiple databases, websites and literature reports. Mining and integrating these datasets are cumbersome, time-consuming tasks and provide only snapshots of relevant information. To overcome this impediment to effective, efficient study of AR and potential drug targets, we developed the Regulators of Androgen Action Resource (RAAR), a non-redundant, curated and user-friendly searchable web interface. RAAR centralizes information on gene function, clinical relevance, and resources for 55 genes that encode proteins involved in biosynthesis, metabolism and transport of androgens and for 274 AR-associated coregulator genes. Data in RAAR are organized in two levels: (i) Information pertaining to production of androgens is contained in a 'pre-receptor level' database, and coregulator gene information is provided in a 'post-receptor level' database, and (ii) an 'other resources' database contains links to additional databases that are complementary to and useful to pursue further the information provided in RAAR. For each of its 329 entries, RAAR provides access to more than 20 well-curated publicly available databases, and thus, access to thousands of data points. Hyperlinks provide direct access to gene

  6. Androgen receptor co-activator Hic-5/ARA55 as a molecular regulator of androgen sensitivity in dermal papilla cells of human hair follicles.

    PubMed

    Inui, Shigeki; Fukuzato, Yoko; Nakajima, Takeshi; Kurata, Sotaro; Itami, Satoshi

    2007-10-01

    Androgen site-specifically affects human hair growth after puberty through androgen receptors in the dermal papilla, which transactivate target genes acting in conjunction with co-activators. To examine the regulation of androgen sensitivity in hair follicles, we focused on androgen receptor co-activator Hic-5/ARA55. Its interaction with transfected androgen receptor in beard dermal papilla cells was confirmed with mammalian two-hybrid assays. The semiquantitative reverse transcriptase-polymerase chain reaction showed that Hic-5/ARA55 mRNA expression was high in dermal papilla cells from the beard and bald frontal scalp but low in cells from the occipital scalp. To determine whether Hic-5/ARA55 mRNA level correlates with its endogenous activity, we studied the effect of dominant negative Hic-5/ARA55 on transfected androgen receptor transactivation induced by R1881 using mouse mammary tumor virus-luciferase assays. We found that it suppressed the transactivation by 64.5 and 71.4% in dermal papilla cells from the beard and bald frontal scalp, respectively, whereas it showed no significant effect in cells from the occipital scalp. Our findings suggest that Hic-5/ARA55 is a molecular regulator for androgen sensitivity in human hair follicles. PMID:17508020

  7. A Rare Cavernous Hemangioma of the Adrenal Gland

    PubMed Central

    Pang, Cheng; Wu, Pengjie; Zhu, Gang

    2015-01-01

    Adrenal cavernous hemangiomas are rare nonfunctioning benign tumors. This case report presents a patient with a huge nonfunctioning adrenal cavernous hemangioma presenting as an adrenal incidentaloma suspicious for adrenal myelolipoma. Although adrenal cavernous hemangiomas are rare, they should be considered as a part of the differential diagnosis of adrenal neoplasms. The proper treatment is surgical excision due the risk of spontaneous tumor rupture and the difficulty of ruling out malignancy. PMID:26793524

  8. Role of Testosterone in Mediating Prenatal Ethanol Effects on Hypothalamic-Pituitary-Adrenal Activity in Male Rats

    PubMed Central

    Lan, Ni; Hellemans, Kim G. C.; Ellis, Linda; Viau, Victor; Weinberg, Joanne

    2009-01-01

    Summary Prenatal ethanol (E) exposure programs the fetal hypothalamic-pituitary-adrenal (HPA) and -gonadal (HPG) axes such that E rats show HPA hyperresponsiveness to stressors and altered HPG and reproductive function in adulthood. Importantly, prenatal ethanol may differentially alter stress responsiveness in adult male and female offspring compared to their control counterparts. To test the hypothesis that alterations in HPA activity in E males are mediated, at least in part, by ethanol-induced changes in the capacity of testosterone to regulate HPA activity, we explored dose-related effects of testosterone on HPA and HPG function in adult male offspring from prenatal E, pair-fed (PF) and ad libitum-fed control (C) dams. Our data suggest that E males show changes in both HPA and HPG regulation, as well as altered sensitivity to the inhibitory effects of testosterone. While gonadectomy (GDX) reduced weight gain in all animals, low testosterone replacement restored body weights in PF and C but not E males. Further, sensitivity of the thymus and adrenal to circulating testosterone was reduced in E rats. In addition, stress-induced corticosterone (CORT) levels were increased in PF and C but not E males following GDX, and while low dose testosterone replacement restored CORT levels for PF and C, high testosterone levels were needed to normalize CORT levels for E males. A negative correlation between pre-stress testosterone and post-stress CORT levels in C but not in E and PF males further supports the finding of reduced sensitivity to testosterone. Importantly, testosterone appeared to have reduced effects on central corticotrophin releasing hormone (CRH) pathways in E, but greater effects on central arginine vasopressin (AVP) pathways in E and/or PF compared to C males. Testosterone also had less of an inhibitory effect on stress-induced luteinizing hormone increases in E than in PF and C males following GDX. In addition, androgen receptor mRNA levels in the medial

  9. Dominant-Negative Androgen Receptor Inhibition of Intracrine Androgen-Dependent Growth of Castration-Recurrent Prostate Cancer

    PubMed Central

    Kantor, Boris; Li, Xiangping; Haack, Karin; Moore, Dominic T.; Wilson, Elizabeth M.

    2012-01-01

    Background Prostate cancer (CaP) is the second leading cause of cancer death in American men. Androgen deprivation therapy is initially effective in CaP treatment, but CaP recurs despite castrate levels of circulating androgen. Continued expression of the androgen receptor (AR) and its ligands has been linked to castration-recurrent CaP growth. Principal Finding In this report, the ligand-dependent dominant-negative ARΔ142–337 (ARΔTR) was expressed in castration-recurrent CWR-R1 cell and tumor models to elucidate the role of AR signaling. Expression of ARΔTR decreased CWR-R1 tumor growth in the presence and absence of exogenous testosterone (T) and improved survival in the presence of exogenous T. There was evidence for negative selection of ARΔTR transgene in T-treated mice. Mass spectrometry revealed castration-recurrent CaP dihydrotestosterone (DHT) levels sufficient to activate AR and ARΔTR. In the absence of exogenous testosterone, CWR-R1-ARΔTR and control cells exhibited altered androgen profiles that implicated epithelial CaP cells as a source of intratumoral AR ligands. Conclusion The study provides in vivo evidence that activation of AR signaling by intratumoral AR ligands is required for castration-recurrent CaP growth and that epithelial CaP cells produce sufficient active androgens for CaP recurrence during androgen deprivation therapy. Targeting intracrine T and DHT synthesis should provide a mechanism to inhibit AR and growth of castration-recurrent CaP. PMID:22272301

  10. Associations between peripheral androgens and cortisol in infertile women.

    PubMed

    Gleicher, Norbert; Seier, Kenneth; Kushnir, Vitaly A; Weghofer, Andrea; Wu, Yan-Guang; Wang, Qi; Albertini, David F; Barad, David H

    2016-04-01

    Testosterone has in recent years been proven essential for normal growth and maturation of small growing follicles. Concomitantly, low functional ovarian reserve (LFOR), characterized by a small growing follicle pool, has been associated with low testosterone levels, which can be of ovarian and/or adrenal origin. In this study we, therefore, investigated whether peripheral sex steroid precursors and testosterone levels potentially reflect on adrenal function. In a retrospective cohort study of 355 consecutive infertile women, who presented to an academically affiliated fertility center in New York City, we investigated in a series of statistical models whether low peripheral sex steroid precursors and testosterone are associated with peripheral cortisol (C) levels, reflecting adrenal function. To determine potential correlations, we investigated the dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), androstenedione (AD), total testosterone (TT), free testosterone (FT); sex hormone binding globulin (SHBG), anti-Müllerian hormone (AMH), thyroid stimulating hormone (TSH) and C in a series of multivariate and logistic regression analyses, utilizing C either as a continuous variable or with cut off <5.0μg/dL, and TT only as a continuous variable. Practically all models demonstrated significant predictability of peripheral sex hormone precursors for C levels, with DHEA demonstrating the strongest and most consistent predictability as an individual parameter and as part of the DHEAS/DHEA ratio. We conclude that in infertile women peripheral sex hormone precursors, especially DHEA, reflect C levels and, therefore, adrenal function. In infertile women, at all ages low levels of sex hormone precursors, therefore, should be considered indications for further adrenal assessments. PMID:26804970

  11. The diagnosis and treatment of adrenal insufficiency during childhood and adolescence.

    PubMed

    Park, Julie; Didi, Mohammed; Blair, Joanne

    2016-09-01

    The diagnosis and treatment of adrenal insufficiency in childhood and adolescence poses a number of challenges. Clinical features of chronic adrenal insufficiency are vague and non-specific, and mimic many other causes of chronic ill health. A range of diagnostic tests are available for the assessment of adrenal function, all of which have advantages and disadvantages. Cortisol responses to these tests may vary with age and between genders. Knowledge of normal cortisol levels during health and ill health in childhood is also limited, and the cortisol replacement therapies available in clinical practice enable only crude mimicry of physiological patterns of cortisol secretion. An awareness of the limitations of diagnostic tests and treatments is important, and critical clinical assessment, integrating clinical and biochemical data, is essential for the diagnosis and treatment of children with suspected adrenal insufficiency. The aim of this review is to draw on data from clinical studies to inform a pragmatic approach to the child presenting with symptoms of chronic adrenal insufficiency. Clinical features of primary and secondary adrenal insufficiency, and syndromes associated with these diagnoses are described. Factors to consider when selecting a diagnostic test of adrenal function and interpretation of test results are considered. Finally, the limitations of cortisol replacement therapy are also discussed. PMID:27083756

  12. Targeting intratumoral androgens: statins and beyond.

    PubMed

    Schweizer, Michael T; Yu, Evan Y

    2016-09-01

    While initially effective, androgen deprivation therapy (ADT) is not curative, and nearly all men with advanced prostate cancer will eventually progress to the more resistant, and ultimately lethal form of the disease, so called castration-resistant prostate cancer (CRPC). The maintenance of androgens within the prostate cancer microenvironment likely represents one of the key mechanisms by which this transition from hormone-sensitive to CRPC occurs. This can be accomplished either through intratumoral androgen biosynthesis or the active transport of androgens and androgenic precursors into the tumor microenvironment. More recently, preclinical and clinical data supported therapeutic strategies that seek to target these two mechanisms, either through the use of drugs that impair androgen biosynthesis (e.g. inhibiting the steroidogenic enzymes CYP17 and AKR1C3 with abiraterone and indomethacin, respectively) or drugs that inhibit the SLCO transporters responsible for importing androgens (e.g. statins). PMID:27583031

  13. Relative Adrenal Insufficiency in Cirrhotic Patients

    PubMed Central

    Anastasiadis, Sotirios N; Giouleme, Olga I; Germanidis, Georgios S; Vasiliadis, Themistoklis G

    2015-01-01

    Relative adrenal insufficiency (RAI) was demonstrated in patients with cirrhosis and liver failure. A relationship appears to exist between the severity of the liver disease and the presence of RAI. Neither the mechanism nor the exact prevalence of RAI is fully understood. There is though a hypothesis that low high-density lipoprotein (HDL) levels in this group of patients may be responsible for the insufficiency of cortisol. Several questions also arise about the way and the kind of cortisol (total cortisol, free cortisol, or even salivary cortisol) that should be measured. The presence of RAI in patients with cirrhosis is unquestionable, but still several studies should come up in order to properly define it and fully understand it. PMID:25780347

  14. Delayed Diagnosis of Graves' Thyrotoxicoisis Presenting as Recurrent Adrenal Crisis in Primary Adrenal Insufficiency.

    PubMed

    Naik, Dukhabandhu; Jebasingh, K Felix; Thomas, Nihal

    2016-04-01

    Adrenal crisis is a potential life threatening complication. The common causes of adrenal crisis are infections, surgical stress and abrupt cessation of steroid medications. Endocrine causes like Graves' disease with thyrotoxicosis is one of the less common causes of an adrenal crisis. We report a 42-year-old female who presented with recurrent episodes of adrenal crisis due to delayed diagnosis of thyrotoxicosis. She was initially treated with Carbimazole followed by Radio-iodine ablation and currently she is euthyroid. Her adrenal insufficiency was initially treated with hydrocortisone during the time of adrenal crisis followed by Prednisolone 5 mg once daily in the morning along with fludrocortisone 50 mcg once daily. This case highlights the need for high index of suspicion and less common causes like thyrotoxicosis should be ruled out in patients with adrenal crisis. PMID:27190873

  15. Delayed Diagnosis of Graves’ Thyrotoxicoisis Presenting as Recurrent Adrenal Crisis in Primary Adrenal Insufficiency

    PubMed Central

    Naik, Dukhabandhu; Jebasingh, K Felix

    2016-01-01

    Adrenal crisis is a potential life threatening complication. The common causes of adrenal crisis are infections, surgical stress and abrupt cessation of steroid medications. Endocrine causes like Graves’ disease with thyrotoxicosis is one of the less common causes of an adrenal crisis. We report a 42-year-old female who presented with recurrent episodes of adrenal crisis due to delayed diagnosis of thyrotoxicosis. She was initially treated with Carbimazole followed by Radio-iodine ablation and currently she is euthyroid. Her adrenal insufficiency was initially treated with hydrocortisone during the time of adrenal crisis followed by Prednisolone 5 mg once daily in the morning along with fludrocortisone 50 mcg once daily. This case highlights the need for high index of suspicion and less common causes like thyrotoxicosis should be ruled out in patients with adrenal crisis. PMID:27190873

  16. Androgen action in cultured dermal papilla cells from human hair follicles.

    PubMed

    Randall, V A; Thornton, M J; Hamada, K; Messenger, A G

    1994-01-01

    Androgens are major regulators of human hair growth with paradoxically different effects on hair follicles depending on their body site. They stimulate terminal growth in many regions including the face, have no effect on eyelashes, but may cause inhibition and balding on the scalp in genetically disposed individuals. How this occurs is unknown. However, androgens may act on the hair follicle via the cells of the dermal papilla; these would then influence the other cells of the hair follicle by altering the production of regulatory substances such as growth factors and/or extracellular matrix components. Therefore, primary lines of dermal papilla cells have been established from androgen-sensitive hair follicles, such as beard, and control, relatively androgen-independent, non-balding scalp cells and their mechanism of androgen action has been compared. Isolated beard dermal papillae were larger than those from scalp follicles. Although dermal papilla cells did not respond to in vitro androgens by alterations in growth, androgen-dependent dermal papilla cells contained higher levels of specific, low capacity, high affinity androgen receptors than non-balding scalp cells. The ability of the cells to metabolise testosterone to 5 alpha-dihydrotestosterone in culture also varied in parallel to that predicted from studies of hair growth in the 5 alpha-reductase deficiency syndrome. These results support the hypothesis that androgens act via the dermal papilla. They also show that dermal papilla cells retain differences in gene expression in culture which appear to correspond with their androgenic response in vivo. Further studies of such cells should help elucidate why bald men can grow beards! PMID:8003318

  17. Loss of exogenous androgen dependence by prostate tumor cells is associated with elevated glucuronidation potential.

    PubMed

    Zimmer, Brenna M; Howell, Michelle E; Wei, Qin; Ma, Linlin; Romsdahl, Trevor; Loughman, Eileen G; Markham, Jonathan E; Seravalli, Javier; Barycki, Joseph J; Simpson, Melanie A

    2016-08-01

    Prostate epithelial cells control the potency and availability of androgen hormones in part by inactivation and elimination. UDP-glucose dehydrogenase (UGDH) catalyzes the NAD(+)-dependent oxidation of UDP-glucose to UDP-glucuronate, an essential precursor for androgen inactivation by the prostate glucuronidation enzymes UGT2B15 and UGT2B17. UGDH expression is androgen stimulated, which increases the production of UDP-glucuronate and fuels UGT-catalyzed glucuronidation. In this study, we compared the glucuronidation potential and its impact on androgen-mediated gene expression in an isogenic LNCaP model for androgen-dependent versus castration-resistant prostate cancer. Despite significantly lower androgen-glucuronide output, LNCaP 81 castration-resistant tumor cells expressed higher levels of UGDH, UGT2B15, and UGT2B17. However, the magnitude of androgen-activated UGDH and prostate-specific antigen (PSA) expression, as well as the androgen receptor (AR)-dependent repression of UGT2B15 and UGT2B17, was blunted several-fold in these cells. Consistent with these results, the ligand-activated binding of AR to the PSA promoter and subsequent transcriptional activation were also significantly reduced in castration-resistant cells. Analysis of the UDP-sugar pools and flux through pathways downstream of UDP-glucuronate production revealed that these glucuronidation precursor metabolites were channeled through proteoglycan and glycosaminoglycan biosynthetic pathways, leading to increased surface expression of Notch1. Knockdown of UGDH diminished Notch1 and increased glucuronide output. Overall, these results support a model in which the aberrant partitioning of UDP-glucuronate and other UDP-sugars into alternative pathways during androgen deprivation contributes to the loss of prostate tumor cell androgen sensitivity by promoting altered cell surface proteoglycan expression. PMID:27307252

  18. Molecular cloning and characterization of a nuclear androgen receptor activated by 11-ketotestosterone

    PubMed Central

    Olsson, Per-Erik; Berg, A Håkan; von Hofsten, Jonas; Grahn, Birgitta; Hellqvist, Anna; Larsson, Anders; Karlsson, Johnny; Modig, Carina; Borg, Bertil; Thomas, Peter

    2005-01-01

    Although 11-ketotestosterone is a potent androgen and induces male secondary sex characteristics in many teleosts, androgen receptors with high binding affinity for 11-ketotestosterone or preferential activation by 11-ketotestosterone have not been identified. So, the mechanism by which 11-ketotestosterone exhibits such high potency remains unclear. Recently we cloned the cDNA of an 11-ketotestosterone regulated protein, spiggin, from three-spined stickleback renal tissue. As spiggin is the only identified gene product regulated by 11-ketotestosterone, the stickleback kidney is ideal for determination of the mechanism of 11-ketotestosterone gene regulation. A single androgen receptor gene with two splicing variants, belonging to the androgen receptor-β subfamily was cloned from stickleback kidney. A high affinity, saturable, single class of androgen specific binding sites, with the characteristics of an androgen receptor, was identified in renal cytosolic and nuclear fractions. Measurement of ligand binding moieties in the cytosolic and nuclear fractions as well as to the recombinant receptor revealed lower affinity for 11-ketotestosterone than for dihydrotestosterone. Treatment with different androgens did not up-regulate androgen receptor mRNA level or increase receptor abundance, suggesting that auto-regulation is not involved in differential ligand activation. However, comparison of the trans-activation potential of the stickleback androgen receptor with the human androgen receptor, in both human HepG2 cells and zebrafish ZFL cells, revealed preferential activation by 11-ketotestosterone of the stickleback receptor, but not of the human receptor. These findings demonstrate the presence of a receptor preferentially activated by 11-ketotestosterone in the three-spined stickleback, so far the only one known in any animal. PMID:16107211

  19. Orexin Decreases Aromatase Gene Expression in The Hypothalamus of Androgenized Female Rats

    PubMed Central

    Salimi, Maliheh; Alishah, Zahra; Khazali, Homayoun; Mahmoudi, Fariba

    2016-01-01

    Background Orexin is a hypothalamic orexigenic neuropeptide, which third cerebral injection of it mainly exerts inhibitory effects on reproductive functions. It increases significantly the Aromatase (Cyp19) gene expression in the hypothalamus of male rats. Aromatase is an enzyme which converts androgens to estradiol in the hypothalamus of rats. Prenatal or neonatal exposure of females to testosterone masculinizes the pattern of Cyp19 mRNA levels in adulthood. In the present study the effects of central injections of orexin-A on hypothalamic Cyp19 gene expression of adult female rats were investigated, while they had been androgenized on third day of postnatal life. Materials and Methods In this experimental study, twenty female Wistar rats received subcutaneous injections of testosterone propionate (50 µg/100 µl) on their third day of postnatal life. Adult androgenized rats weighing 180-220 g, received either 3 µl saline or one of 2, 4 or 8 µg/3 µl concentration of orexin via third cerebral ventricle. Five non-androgenized rats, as control group, received intra cerebral ventricle (ICV) injection of 3 µl saline. The hypothalamuses were dissected out and mean Cyp19 mRNA levels were determined by semi-quantitative real time-polymerase chain reaction (PCR) method. Data were analyzed by unpaired t test and one-way ANOVA using SPSS software, version 16. Results Mean relative Cyp19 mRNA level was significantly increased in the hypothalamus of androgenized compared to non-androgenized female rats. Central injec- tions of 2, 4 or 8 µg/3 µl orexin decreased significantly the hypothalamic Cyp19 mRNA level of androgenized rats compared to androgenized-control groups. Conclusion The results suggested that the orexin may exert inhibitory effects on the gene expression of Cyp19 in the hypothalamus of neonatal androgenized female rats in adulthood. PMID:27441052

  20. Images of pheochromocytoma in adrenal glands

    PubMed Central

    McCarthy, Colin J.; Blake, Michael A.

    2015-01-01

    Pheochromocytomas are relatively rare tumors of the adrenal medulla. A wide spectrum of imaging findings has been described. The aim of this article is to describe the multimodality imaging features of pheochromocytomas including diagnostic pearls that can help differentiate them from other adrenal lesions and pitfalls to avoid. PMID:26310999

  1. Computed tomographic findings in bilateral adrenal tuberculosis

    SciTech Connect

    Wilms, G.E.; Baert, A.L.; Kint, E.J.; Pringot, J.H.; Goddeeris, P.G.

    1983-03-01

    The computed tomographic (CT) features of bilateral adrenal tuberculosis are reported in two cases that demonstrate two typical different clinical and morphological manifestations of the disease. The incidence and CT appearance of adrenal tuberculosis are discussed, with emphasis on differential diagnosis.

  2. Regulators of Androgen Action Resource: a one-stop shop for the comprehensive study of androgen receptor action

    PubMed Central

    Fiandalo, Michael V.; Schlanger, Simon; Heemers, Frederike; Mohler, James L.; Liu, Song; Heemers, Hannelore V.

    2016-01-01

    Androgen receptor (AR) is a ligand-activated transcription factor that is the main target for treatment of non-organ-confined prostate cancer (CaP). Failure of life-prolonging AR-targeting androgen deprivation therapy is due to flexibility in steroidogenic pathways that control intracrine androgen levels and variability in the AR transcriptional output. Androgen biosynthesis enzymes, androgen transporters and AR-associated coregulators are attractive novel CaP treatment targets. These proteins, however, are characterized by multiple transcript variants and isoforms, are subject to genomic alterations, and are differentially expressed among CaPs. Determining their therapeutic potential requires evaluation of extensive, diverse datasets that are dispersed over multiple databases, websites and literature reports. Mining and integrating these datasets are cumbersome, time-consuming tasks and provide only snapshots of relevant information. To overcome this impediment to effective, efficient study of AR and potential drug targets, we developed the Regulators of Androgen Action Resource (RAAR), a non-redundant, curated and user-friendly searchable web interface. RAAR centralizes information on gene function, clinical relevance, and resources for 55 genes that encode proteins involved in biosynthesis, metabolism and transport of androgens and for 274 AR-associated coregulator genes. Data in RAAR are organized in two levels: (i) Information pertaining to production of androgens is contained in a ‘pre-receptor level’ database, and coregulator gene information is provided in a ‘post-receptor level’ database, and (ii) an ‘other resources’ database contains links to additional databases that are complementary to and useful to pursue further the information provided in RAAR. For each of its 329 entries, RAAR provides access to more than 20 well-curated publicly available databases, and thus, access to thousands of data points. Hyperlinks provide direct access to

  3. Modulation of the cytosolic androgen receptor in striated muscle by sex steroids

    NASA Technical Reports Server (NTRS)

    Rance, N. E.; Max, S. E.

    1982-01-01

    The influence of orchiectomy (GDX) and steroid administration on the level of the cytosolic androgen receptor in the rat levator ani muscle and in rat skeletal muscles (tibialis anterior and extensor digitorum longus) was studied. Androgen receptor binding to muscle cytosol was measured using H-3 methyltrienolone (R1881) as ligand, 100 fold molar excess unlabeled R1881 to assess nonspecific binding, and 500 fold molar excess of triamcinolone acetonide to prevent binding to glucocorticoid and progestin receptors. Results demonstrate that modification of the levels of sex steroids can alter the content of androgen receptors of rat striated muscle. Data suggest that: (1) cytosolic androgen receptor levels increase after orchiectomy in both levator ani muscle and skeletal muscle; (2) the acute increase in receptor levels is blocked by an inhibitor of protein synthesis; and (3) administration of estradiol-17 beta to castrated animals increases receptor binding in levator ani muscle but not in skeletal muscle.

  4. Gonadal steroid hormone receptors and sex differences in the hypothalamo-pituitary-adrenal axis.

    PubMed

    Handa, R J; Burgess, L H; Kerr, J E; O'Keefe, J A

    1994-12-01

    The rapid activation of stress-responsive neuroendocrine systems is a basic reaction of animals to perturbations in their environment. One well-established response is that of the hypothalamo-pituitary-adrenal (HPA) axis. In rats, corticosterone is the major adrenal steroid secreted and is released in direct response to adrenocorticotropin (ACTH) secreted from the anterior pituitary gland. ACTH in turn is regulated by the hypothalamic factor, corticotropin-releasing hormone. A sex difference exists in the response of the HPA axis to stress, with females reacting more robustly than males. It has been demonstrated that in both sexes, products of the HPA axis inhibit reproductive function. Conversely, the sex differences in HPA function are in part due to differences in the circulating gonadal steroid hormone milieu. It appears that testosterone can act to inhibit HPA function, whereas estrogen can enhance HPA function. One mechanism by which androgens and estrogens modulate stress responses is through the binding to their cognate receptors in the central nervous system. The distribution and regulation of androgen and estrogen receptors within the CNS suggest possible sites and mechanisms by which gonadal steroid hormones can influence stress responses. In the case of androgens, data suggest that the control of the hypothalamic paraventricular nucleus is mediated trans-synaptically. For estrogen, modulation of the HPA axis may be due to changes in glucocorticoid receptor-mediated negative feedback mechanisms. The results of a variety of studies suggest that gonadal steroid hormones, particularly testosterone, modulate HPA activity in an attempt to prevent the deleterious effects of HPA activation on reproductive function. PMID:7729815

  5. Adrenal function in patients with active tuberculosis.

    PubMed Central

    Barnes, D J; Naraqi, S; Temu, P; Turtle, J R

    1989-01-01

    Although tuberculosis is a recognised cause of adrenal insufficiency, little is known about adrenal function in patients with active tuberculosis. Ninety Melanesian adults with active tuberculosis (30 pulmonary, 30 miliary, 30 extrapulmonary) had adrenal function assessed prospectively before and three to four weeks after starting antituberculous chemotherapy. Basal serum cortisol concentrations were normal in 55 (61%) and raised in 35 (39%) of the subjects. No patient had a low basal cortisol concentration. After Synacthen stimulation, cortisol responses were normal in 81 (92%) of the patients and subnormal in seven (8%). After antituberculous chemotherapy the response to Synacthen stimulation was normal in all but one patient. It is concluded that adrenal dysfunction is an uncommon problem in patients with active tuberculosis, and that, contrary to recent reports, antituberculous chemotherapy regimens that include rifampicin do not have an adverse effect on adrenal function. PMID:2763243

  6. Adrenal steroid, cortisol, adrenocorticotropin, and beta-endorphin responses to human corticotropin-releasing hormone stimulation test in normal children and children with premature pubarche.

    PubMed

    Ghizzoni, L; Virdis, R; Ziveri, M; Lamborghini, A; Alberini, A; Volta, C; Bernasconi, S

    1989-10-01

    To determine whether CRH affects adrenal androgen, beta-endorphin (B-E), and ACTH secretion in normal children during sexual maturation, 17-hydroxyprogesterone (17-OHP), androstenedione (D4-A), dehydroepiandrosterone (DHEA), DHEA sulfate (DS), cortisol, B-E, and ACTH were measured after an iv injection of 1 microgram/kg human CRH. Children with premature pubarche were similarly analyzed to establish whether this condition is accompanied by altered hormonal responses to CRH. CRH produced consistent increases in ACTH, B-EP, and cortisol blood levels, which were comparable at all age intervals in all groups. 17-OHP increased after CRH injection, but its response linearly with age. D4-A levels were not influenced, while DHEA and DS levels were only partially influenced by CRH. The stimulated D4-A to 17-OHP ratio increased with sexual maturation, whereas ratios of cortisol to 17-OHP and D4-A to DHEA remained constant. Children with premature pubarche had hormonal responses similar in magnitude to those of prepubertal children of comparable age. In conclusion, an increase in 17,20-desmolase efficiency occurs with postnatal maturation after CRH challenge. Moreover, CRH does not appear to play an important role in premature pubarche. PMID:2550509

  7. Semen Quality, Hormonal Levels, and Androgen Receptor Gene Polymorphisms in a Population of Young Male Volunteers from Two Different Regions of Poland

    PubMed Central

    Kamieniczna, Marzena; Fraczek, Monika; Malcher, Agnieszka; Rozwadowska, Natalia; Czernikiewicz, Anna; Jedrzejczak, Piotr; Semczuk, Marian; Kurpisz, Maciej

    2015-01-01

    Background The population of healthy Polish men has not been frequently and systematically investigated for fertility status. The aim of this study was to assess the quality of semen in a randomly recruited population of young males. The most important task was to find a relationship between semen parameters, sex hormones, and AR gene polymorphism. Material/Methods Semen and blood samples from young men from the Poznan (n=113) and Lublin regions (n=89) were collected for semen analysis, assessment of hormonal concentrations, and calculation of the CAG and GGN repeats of the AR gene. Results Statistical comparisons of the hormones and circulating proteins and the seminological parameters revealed significant differences between the regional groups of males studied. Among the correlations found, we emphasize the positive relationship between inhibin B levels and both the number of spermatozoa per ml (R=0.37; p=0.0001) and the total sperm concentration (R=0.40; p=0.00003). Positive correlations between IGF1 and sperm morphology was also found (R=0.40; p=0.000004). The mean number of CAG repeats in our tested groups was 21.93±2.79, in a range from 16 to 31. The mean number of GGN repeats was 23.2±1.66 and ranged from 16 to 29. Numerous significant correlations were found between CAG or GGN repeats and blood hormones or circulating proteins and semen parameters; however, Spearman’s rank correlations revealed rather weak coefficients. Conclusions This report attempted to determine the quality of semen samples and sex hormones in a population of Polish young men. The results were found to be similar to data obtained in Scandinavia. The calculated means and range of CAG or GGN repeats of the AR gene in Polish males were similar to West European epidemiological data. PMID:26299772

  8. Hormone levels

    MedlinePlus

    Blood or urine tests can determine the levels of various hormones in the body. This includes reproductive hormones, thyroid hormones, adrenal hormones, pituitary hormones, and many others. For more information, see: ...

  9. CCAAT/Enhancer binding protein β controls androgen-deprivation-induced senescence in prostate cancer cells.

    PubMed

    Barakat, D J; Zhang, J; Barberi, T; Denmeade, S R; Friedman, A D; Paz-Priel, I

    2015-11-26

    The processes associated with transition to castration-resistant prostate cancer (PC) growth are not well understood. Cellular senescence is a stable cell cycle arrest that occurs in response to sublethal stress. It is often overcome in malignant transformation to confer a survival advantage. CCAAT/Enhancer Binding Protein (C/EBP) β function is frequently deregulated in human malignancies and interestingly, androgen-sensitive PC cells express primarily the liver-enriched inhibitory protein isoform. We found that C/EBPβ expression is negatively regulated by androgen receptor (AR) activity and that treatment of androgen-sensitive cell lines with anti-androgens increases C/EBPβ mRNA and protein levels. Accordingly, we also find that C/EBPβ levels are significantly elevated in primary PC samples from castration-resistant compared with therapy-naive patients. Chromatin immunoprecipitation demonstrated enhanced binding of the AR to the proximal promoter of the CEBPB gene in the presence of dihydroxytestosterone. Upon androgen deprivation, induction of C/EBPβ is facilitated by active transcription as evident by increased histone 3 acetylation at the C/EBPβ promoter. Also, the androgen agonist R1881 suppresses the activity of a CEBPB promoter reporter. Loss of C/EBPβ expression prevents growth arrest following androgen deprivation or anti-androgen challenge. Accordingly, suppression of C/EBPβ under low androgen conditions results in reduced expression of senescence-associated secretory genes, significantly decreased number of cells displaying heterochromatin foci and increased numbers of Ki67-positive cells. Ectopic expression of C/EBPβ caused pronounced morphological changes, reduced PC cell growth and increased the number of senescent LNCaP cells. Lastly, we found that senescence contributes to PC cell survival under androgen deprivation, and C/EBPβ-deficient cells were significantly more susceptible to killing by cytotoxic chemotherapy following androgen

  10. Classical forms of congenital adrenal hyperplasia due to 21-hydroxylase deficiency in adults.

    PubMed

    Bachelot, Anne; Chakthoura, Zeina; Rouxel, Agnès; Dulon, Jérome; Touraine, Philippe

    2008-01-01

    During childhood, the main aims of the medical treatment of congenital adrenal hyperplasia (CAH) secondary to 21-hydroxylase are to prevent salt loss and virilization and to attain normal stature and normal puberty. As such, there is a narrow therapeutic window through which the intended results can be achieved. In adulthood, the clinical management has received little attention, but recent studies have shown the relevance of long-term follow-up of these patients. The aims here are to review the multiple clinical, hormonal and metabolic abnormalities that could be found in adult CAH patients as such a decrease in bone mineral density, overweight and disturbed reproductive functions. In women with classic CAH, a low fertility rate is reported, and is probably the consequence of multiple factors including neuroendocrine and hormonal factors, feminizing surgery, and psychological factors. Men with CAH may present hypogonadism either through the effect of adrenal rests or from suppression of gonadotropins resulting in infertility. Therefore a multidisciplinary team with knowledge of CAH should carefully follow up these patients, from childhood through to adulthood, to avoid these complications and to ensure treatment compliance and tight control of the adrenal androgens. PMID:18204267

  11. Effects of androgen and leptin on behavioral and cellular responses in female rats.

    PubMed

    Feng, Yi; Shao, Ruijin; Weijdegård, Birgitta; Wang, Tienpei; Johansson, Julia; Sun, Shan; Wang, Wei; Egecioglu, Emil; Billig, Håkan; Stener-Victorin, Elisabet

    2011-09-01

    The causes of anxiety and depression in women with polycystic ovary syndrome (PCOS) remain elusive. To identify steps linking androgen signaling to the regulation of affective symptoms in vivo, we compared behavioral responses in female rats continuously exposed to DHT from puberty (a model of DHT-induced PCOS) and in rats exposed to DHT for 1week. Continuous and 1week of DHT exposure resulted in a general decrease in locomotor activity and time spent on the open arms in the elevated plus maze, indicating anxiety-like behavior. Rats with DHT-induced PCOS have increases in adiposity and circulating leptin levels accompanied by leptin resistance. One week of DHT exposure decreased androgen receptor (AR) expression in the hypothalamus and leptin synthesis and function in adipocytes; it also inhibited signal transducer and activator of transcription 3 (STAT3) and attenuated leptin activity by increasing levels of soluble leptin receptor, a leptin-binding protein, in the hypothalamus. This may affect the androgen-induced anxiety-related behavior in female rats. In conclusion, our results highlight the central role of androgens in behavioral function in female rats and suggest that androgens directly regulate the AR by decreasing its hypothalamic expression. Androgens also increase leptin synthesis in adipocytes, which drives central leptin signaling, and may regulate anxiety-related behaviors. Elucidating mechanisms by which androgens modulate female anxiety-like behavior may uncover useful approaches for treating women with PCOS who have symptoms of anxiety. PMID:21819988

  12. Protein phosphatase 1 suppresses androgen receptor ubiquitylation and degradation.

    PubMed

    Liu, Xiaming; Han, Weiwei; Gulla, Sarah; Simon, Nicholas I; Gao, Yanfei; Cai, Changmeng; Yang, Hongmei; Zhang, Xiaoping; Liu, Jihong; Balk, Steven P; Chen, Shaoyong

    2016-01-12

    The phosphoprotein phosphatases are emerging as important androgen receptor (AR) regulators in prostate cancer (PCa). We reported previously that the protein phosphatase 1 catalytic subunit (PP1α) can enhance AR activity by dephosphorylating a site in the AR hinge region (Ser650) and thereby decrease AR nuclear export. In this study we show that PP1α increases the expression of wildtype as well as an S650A mutant AR, indicating that it is acting through one or more additional mechanisms. We next show that PP1α binds primarily to the AR ligand binding domain and decreases its ubiquitylation and degradation. Moreover, we find that the PP1α inhibitor tautomycin increases phosphorylation of AR ubiquitin ligases including SKP2 and MDM2 at sites that enhance their activity, providing a mechanism by which PP1α may suppress AR degradation. Significantly, the tautomycin mediated decrease in AR expression was most pronounced at low androgen levels or in the presence of the AR antagonist enzalutamide. Consistent with this finding, the sensitivity of LNCaP and C4-2 PCa cells to tautomycin, as assessed by PSA synthesis and proliferation, was enhanced at low androgen levels or by treatment with enzalutamide. Together these results indicate that PP1α may contribute to stabilizing AR protein after androgen deprivation therapies, and that targeting PP1α or the AR-PP1α interaction may be effective in castration-resistant prostate cancer (CRPC). PMID:26636645

  13. A Prospective Multicenter Study of Adrenal Function in Critically Ill Children

    PubMed Central

    Menon, Kusum; Ward, Roxanne E.; Lawson, Margaret L.; Gaboury, Isabelle; Hutchison, James S.; Hébert, Paul C.

    2016-01-01

    Rationale Adrenal insufficiency is a clinical condition associated with fluid- and catecholamine-resistant hypotension. Objectives The objectives of this study were to determine the prevalence of adrenal insufficiency, risk factors and potential mechanisms for its development, and its association with clinically important outcomes in critically ill children. Methods A prospective, cohort study was conducted from 2005 to 2008 in seven tertiary-care, pediatric intensive care units in Canada on patients up to 17 years of age with existing vascular access. Adrenocorticotropic hormone stimulation tests (1 μg) were performed and adrenocorticotropic hormone levels measured in all participants. Measurements and Main Results A total of 381 patients had adrenal testing on admission. The prevalence of adrenal insufficiency was 30.2% (95% confidence interval, 25.9–35.1). Patients with adrenal insufficiency had higher baseline cortisol levels (28.6 μg/dl vs. 16.7 μg/dl, P < 0.001) and were significantly older (11.5 yr vs. 2.3 yr, P < 0.001) than those without adrenal insufficiency. Adrenal insufficiency was associated with an increased need for catecholamines (P <0.001) and more fluid boluses (P = 0.026). The sensitivity and specificity of the low-dose adrenocorticotropic hormone stimulation test were 100% and 84%, respectively. Conclusions Adrenal insufficiency occurs in many disease conditions in critically ill children and is associated with an increased use of catecholamines and fluid boluses. It is likely multifactorial in etiology and is associated with high baseline cortisol levels. Further research is necessary to determine which of these critically ill children are truly cortisol deficient before any treatment recommendations can be made. PMID:20299532

  14. Androgen Regulated Genes in Human Prostate Xenografts in Mice: Relation to BPH and Prostate Cancer

    PubMed Central

    Love, Harold D.; Booton, S. Erin; Boone, Braden E.; Breyer, Joan P.; Koyama, Tatsuki; Revelo, Monica P.; Shappell, Scott B.; Smith, Jeffrey R.; Hayward, Simon W.

    2009-01-01

    Benign prostatic hyperplasia (BPH) and prostate carcinoma (CaP) are linked to aging and the presence of androgens, suggesting that androgen regulated genes play a major role in these common diseases. Androgen regulation of prostate growth and development depends on the presence of intact epithelial-stromal interactions. Further, the prostatic stroma is implicated in BPH. This suggests that epithelial cell lines are inadequate to identify androgen regulated genes that could contribute to BPH and CaP and which could serve as potential clinical biomarkers. In this study, we used a human prostate xenograft model to define a profile of genes regulated in vivo by androgens, with an emphasis on identifying candidate biomarkers. Benign transition zone (TZ) human prostate tissue from radical prostatectomies was grafted to the sub-renal capsule site of intact or castrated male immunodeficient mice, followed by the removal or addition of androgens, respectively. Microarray analysis of RNA from these tissues was used to identify genes that were; 1) highly expressed in prostate, 2) had significant expression changes in response to androgens, and, 3) encode extracellular proteins. A total of 95 genes meeting these criteria were selected for analysis and validation of expression in patient prostate tissues using quantitative real-time PCR. Expression levels of these genes were measured in pooled RNAs from human prostate tissues with varying severity of BPH pathologic changes and CaP of varying Gleason score. A number of androgen regulated genes were identified. Additionally, a subset of these genes were over-expressed in RNA from clinical BPH tissues, and the levels of many were found to correlate with disease status. Our results demonstrate the feasibility, and some of the problems, of using a mouse xenograft model to characterize the androgen regulated expression profiles of intact human prostate tissues. PMID:20027305

  15. Hyponatremia due to Secondary Adrenal Insufficiency Successfully Treated by Dexamethasone with Sodium Chloride

    PubMed Central

    Kazama, Itsuro; Tamada, Tsutomu; Nakajima, Toshiyuki

    2015-01-01

    Patient: Female, 60 Final Diagnosis: Hyponatremia due to secondary adrenal insufficiency Symptoms: prolonged general fatigue and anorexia Medication: — Clinical Procedure: Successfully treated by dexamethasone with sodium chloride Specialty: Nephrology Objective: Rare co-existance of disease or pathology Background: Patients who were surgically treated for Cushing’s syndrome postoperatively surrender to “primary” adrenal insufficiency. However, the preoperative over-secretion of cortisol or the postoperative administration of excessive glucocorticoids can cause “secondary” adrenal insufficiency, in which the prevalence of hyponatremia is usually lower than that of primary adrenal insufficiency. Case Report: A 60-year-old woman with a past medical history of Cushing’s syndrome developed hyponatremia with symptoms of acute glucocorticoid deficiency, such as prolonged general fatigue and anorexia, after upper respiratory tract infection. A decrease in the serum cortisol level and the lack of increase in the ACTH level, despite the increased demand for cortisol, enabled a diagnosis of “secondary” adrenal insufficiency. Although the initial fluid replacement therapy was not effective, co-administration of dexamethasone and sodium chloride quickly resolved her symptoms and ameliorated the refractory hyponatremia. Conclusions: In this case, the hypothalamic-pituitary axis of the patient was thought to have become suppressed long after the surgical treatment for Cushing’s syndrome. This case suggested a mechanism of refractory hyponatremia caused by secondary adrenal insufficiency, for which the administration of dexamethasone and sodium chloride exerted additional therapeutic efficacy. PMID:26319655

  16. Current status of imaging for adrenal gland tumors.

    PubMed

    Song, Julie H; Mayo-Smith, William W

    2014-10-01

    Adrenal glands are common sites of disease involved in a wide spectrum of pathology. Several imaging studies allow accurate diagnosis of adrenal masses, separating inconsequential benign masses from the lesions that require treatment. This article discusses contemporary adrenal imaging techniques, imaging appearance, and the optimal imaging algorithm for the workup of common adrenal masses. PMID:25246052

  17. Clinicopathological correlates of adrenal Cushing's syndrome.

    PubMed

    Duan, Kai; Hernandez, Karen Gomez; Mete, Ozgur

    2015-06-01

    Endogenous Cushing's syndrome is a rare endocrine disorder that incurs significant cardiovascular morbidity and mortality, due to glucocorticoid excess. It comprises adrenal (20%) and non-adrenal (80%) aetiologies. While the majority of cases are attributed to pituitary or ectopic corticotropin (ACTH) overproduction, primary cortisol-producing adrenal cortical lesions are increasingly recognised in the pathophysiology of Cushing's syndrome. Our understanding of this disease has progressed substantially over the past decade. Recently, important mechanisms underlying the pathogenesis of adrenal hypercortisolism have been elucidated with the discovery of mutations in cyclic AMP signalling (PRKACA, PRKAR1A, GNAS, PDE11A, PDE8B), armadillo repeat containing 5 gene (ARMC5) a putative tumour suppressor gene, aberrant G-protein-coupled receptors, and intra-adrenal secretion of ACTH. Accurate subtyping of Cushing's syndrome is crucial for treatment decision-making and requires a complete integration of clinical, biochemical, imaging and pathology findings. Pathological correlates in the adrenal glands include hyperplasia, adenoma and carcinoma. While the most common presentation is diffuse adrenocortical hyperplasia secondary to excess ACTH production, this entity is usually treated with pituitary or ectopic tumour resection. Therefore, when confronted with adrenalectomy specimens in the setting of Cushing's syndrome, surgical pathologists are most commonly exposed to adrenocortical adenomas, carcinomas and primary macronodular or micronodular hyperplasia. This review provides an update on the rapidly evolving knowledge of adrenal Cushing's syndrome and discusses the clinicopathological correlations of this important disease. PMID:26045561

  18. Clinicopathological correlates of adrenal Cushing's syndrome.

    PubMed

    Duan, Kai; Gomez Hernandez, Karen; Mete, Ozgur

    2015-03-01

    Endogenous Cushing's syndrome is a rare endocrine disorder that incurs significant cardiovascular morbidity and mortality, due to glucocorticoid excess. It comprises adrenal (20%) and non-adrenal (80%) aetiologies. While the majority of cases are attributed to pituitary or ectopic corticotropin (ACTH) overproduction, primary cortisol-producing adrenal cortical lesions are increasingly recognised in the pathophysiology of Cushing's syndrome. Our understanding of this disease has progressed substantially over the past decade. Recently, important mechanisms underlying the pathogenesis of adrenal hypercortisolism have been elucidated with the discovery of mutations in cyclic AMP signalling (PRKACA, PRKAR1A, GNAS, PDE11A, PDE8B), armadillo repeat containing 5 gene (ARMC5) a putative tumour suppressor gene, aberrant G-protein-coupled receptors, and intra-adrenal secretion of ACTH. Accurate subtyping of Cushing's syndrome is crucial for treatment decision-making and requires a complete integration of clinical, biochemical, imaging and pathology findings. Pathological correlates in the adrenal glands include hyperplasia, adenoma and carcinoma. While the most common presentation is diffuse adrenocortical hyperplasia secondary to excess ACTH production, this entity is usually treated with pituitary or ectopic tumour resection. Therefore, when confronted with adrenalectomy specimens in the setting of Cushing's syndrome, surgical pathologists are most commonly exposed to adrenocortical adenomas, carcinomas and primary macronodular or micronodular hyperplasia. This review provides an update on the rapidly evolving knowledge of adrenal Cushing's syndrome and discusses the clinicopathological correlations of this important disease. PMID:25425660

  19. The role of androgens in follicle maturation and ovulation induction: friend or foe of infertility treatment?

    PubMed Central

    2011-01-01

    Background Effects of androgens on follicle maturation have been controversial for some time. Here, we review the potential of their applications in improving human ovulation induction, based on human and animal data, reported in the literature. Methods We reviewed the published literature for the years 2005-2011, using relevant key words, in PubMed, Medline and Cochrane reviews, and then performed secondary reviews of referenced articles, which previously had not been known or preceded the searched time period. A total of 217 publications were reviewed. Results Contrary to widely held opinion, recent data, mostly developed in the mouse, convincingly demonstrate essential contribution of androgens to normal follicle maturation and, therefore, female fertility. Androgens appear most engaged at preantral and antral stages, primarily affect granulosa cells, and exert effects via androgen receptors (AR) through transcriptional regulation but also in non-genomic ways, with ligand-activated AR modulating follicle stimulating hormone (FSH) activity in granulosa cells. While some androgens, like testosterone (T) and dehydroepiandrosterone (DHEA), appear effective in improving functional ovarian reserve (FOR) in women with diminished ovarian reserve (DOR), others may even exert opposite effects. Such differences in androgens may, at least partially, reflect different levels of agonism to AR. Discussion Selective androgens appear capable of improving early stages of folliculogenesis. They, therefore, may represent forerunners of a completely new class of ovulation-inducing medications, which, in contrast to gonadotropins, affect follicle maturation at much earlier stages. PMID:21849061

  20. Camptothecin disrupts androgen receptor signaling and suppresses prostate cancer cell growth

    SciTech Connect

    Liu, Shicheng; Yuan, Yiming; Okumura, Yutaka; Shinkai, Norihiro; Yamauchi, Hitoshi

    2010-04-02

    The androgen receptor (AR) is the main therapeutic target for treatment of metastatic prostate cancers. The present study demonstrates that the topoisomerase I inhibitor camptothecin selectively inhibits androgen-responsive growth of prostate cancer cells. Camptothecin strikingly inhibited mutated and wild-type AR protein expression in LNCaP and PC-3/AR cells. This inhibition coincided with decreased androgen-mediated AR phosphorylation at Ser{sup 81} and reduced androgen-mediated AR transcriptional activity in a dose-dependent manner. Additionally, camptothecin disrupted the association between AR and heat shock protein 90 and impeded binding of the synthetic androgen [{sup 3}H]R1881 to AR in LNCaP cells. Camptothecin also blocked androgen-induced AR nuclear translocation, leading to downregulation of the AR target gene PSA. In addition to decreasing the intracellular and secreted prostate-specific antigen (PSA) levels, camptothecin markedly inhibited androgen-stimulated PSA promoter activity. Collectively, our data reveal that camptothecin not only serves as a traditional genotoxic agent but, by virtue of its ability to target and disrupt AR, may also be a novel candidate for the treatment of prostate cancer.

  1. RhoA as a Mediator of Clinically Relevant Androgen Action in Prostate Cancer Cells

    PubMed Central

    Schmidt, Lucy J.; Duncan, Kelly; Yadav, Neelu; Regan, Kevin M.; Verone, Alissa R.; Lohse, Christine M.; Pop, Elena A.; Attwood, Kristopher; Wilding, Gregory; Mohler, James L.; Sebo, Thomas J.; Tindall, Donald J.

    2012-01-01

    Recently, we have identified serum response factor (SRF) as a mediator of clinically relevant androgen receptor (AR) action in prostate cancer (PCa). Genes that rely on SRF for androgen responsiveness represent a small fraction of androgen-regulated genes, but distinguish benign from malignant prostate, correlate with aggressive disease, and are associated with biochemical recurrence. Thus, understanding the mechanism(s) by which SRF conveys androgen regulation to its target genes may provide novel opportunities to target clinically relevant androgen signaling. Here, we show that the small GTPase ras homolog family member A (RhoA) mediates androgen-responsiveness of more than half of SRF target genes. Interference with expression of RhoA, activity of the RhoA effector Rho-associated coiled-coil containing protein kinase 1 (ROCK), and actin polymerization necessary for nuclear translocation of the SRF cofactor megakaryocytic acute leukemia (MAL) prevented full androgen regulation of SRF target genes. Androgen treatment induced RhoA activation, increased the nuclear content of MAL, and led to MAL recruitment to the promoter of the SRF target gene FHL2. In clinical specimens RhoA expression was higher in PCa cells than benign prostate cells, and elevated RhoA expression levels were associated with aggressive disease features and decreased disease-free survival after radical prostatectomy. Overexpression of RhoA markedly increased the androgen-responsiveness of select SRF target genes, in a manner that depends on its GTPase activity. The use of isogenic cell lines and a xenograft model that mimics the transition from androgen-stimulated to castration-recurrent PCa indicated that RhoA levels are not altered during disease progression, suggesting that RhoA expression levels in the primary tumor determine disease aggressiveness. Androgen-responsiveness of SRF target genes in castration-recurrent PCa cells continued to rely on AR, RhoA, SRF, and MAL and the presence of

  2. Decreased adrenal medullary tyrosine hydroxylase mRNA in DMBA (7,12-dimethylbenz(a)anthracene)-induced mammary carcinoma

    SciTech Connect

    Bunce, O.R.; Badary, O.A.; Abou El-Ela, S.; Hartle, D.K. )

    1991-03-15

    Adrenal cortical hormones suppress initiation and promotion of DMBA-induced mammary tumorigenesis. The authors found a positive correlation between presence of DMBA-induced adrenal cortical necrosis and mammary tumor incidence. Because they find adrenal medullary as well as cortical lesions in tumor bearing (TB) DMBA-treated rats, they evaluated medullary function by quantitating hybridized cDNA- TH-S{sup 35} with in situ TH-mRNA u sing computer assisted quantitative autoradiographic technique. Virgin female Sprague-Dawley rats were given a 10 mg i.g. dose of DMBA. Three wks later, rats were placed on 20% polyunsaturated (PUFA) fat diets containing omega-6 and omega-3 fatty acids. All were killed 15 wks post-DMBA. TH-mRNA levels in adrenal medullae of TB animals were decreased compared to non-TB rats. Histopathology indicated a high incidence of medullary necrosis in TB rats, whereas, adrenal necrosis did not occur in non-TB animals. Adrenal necrosis correlated positively with tumor burden, but no correlation was found between incidence of adrenal lesions and type of PUFA in the diet. The authors suggest that DMBA adrenal necrosis may reduce TH-mRNA in the medulla, compromise its catecholamine synthetic capability, and thereby contribute to the overall metabolic stress condition of TB rats.

  3. Muscarine binding sites in bovine adrenal medulla.

    PubMed

    Barron, B A; Murrin, L C; Hexum, T D

    1986-03-18

    The presence of muscarinic binding sites in the bovine adrenal medulla was investigated using [3H]QNB and the bovine adrenal medulla. Scatchard analysis combined with computer analysis yielded data consistent with a two binding site configuration. KDs of 0.15 and 14 nM and Bmax s of 29 and 210 fmol/mg protein, respectively, were observed. Displacement of [3H]QNB by various cholinergic agents is, in order of decreasing potency: QNB, dexetimide, atropine, scopolamine, imipramine, desipramine, oxotremorine, pilocarpine, acetylcholine, methacholine and carbachol. These results demonstrate the presence of more than one muscarine binding site in the bovine adrenal gland. PMID:3709656

  4. Context-dependent effects of yolk androgens on nestling growth and immune function in a multibrooded passerine.

    PubMed

    Muriel, J; Salmón, P; Nunez-Buiza, A; de Salas, F; Pérez-Rodríguez, L; Puerta, M; Gil, D

    2015-08-01

    Female birds may adjust their offspring phenotype to the specific requirements of the environment by differential allocation of physiologically active substances into yolks, such as androgens. Yolk androgens have been shown to accelerate embryonic development, growth rate and competitive ability of nestlings, but they can also entail immunological costs. The balance between costs and benefits of androgen allocation is expected to depend on nestling environment. We tested this hypothesis in a multibrooded passerine, the spotless starling, Sturnus unicolor. We experimentally manipulated yolk androgen levels using a between-brood design and evaluated its effects on nestling development, survival and immune function. Both in first and replacement broods, the embryonic development period was shorter for androgen-treated chicks than controls, but there were no differences in second broods. In replacement broods, androgen-treated chicks were heavier and larger than those hatched from control eggs, but this effect was not observed in the other breeding attempts. Androgen exposure reduced survival with respect to controls only in second broods. Regarding immune function, we detected nonsignificant trends for androgen treatment to activate two important components of innate and adaptive immunity (IL-6 and Ig-A levels, respectively). Similarly, androgen-treated chicks showed greater lymphocyte proliferation than controls in the first brood and an opposite trend in the second brood. Our results indicate that yolk androgen effects on nestling development and immunity depend on the environmental conditions of each breeding attempt. Variation in maternal androgen allocation to eggs could be explained as the result of context-dependent optimal strategies to maximize offspring fitness. PMID:26079258

  5. Radiology of the adrenals with sonography and CT

    SciTech Connect

    Mitty, H.A.; Yeh, H.C.

    1982-01-01

    The basic science and application of clinical adrenal imaging is presented. The initial chapters deal with anatomic review and methods of adrenal imaging. The bulk of the book consists of individual chapters describing pathologic entities and syndromes of adrenal disease. The final chapter deals with differentiation of adrenal lesions from masses arising in adjacent organs. There is no other single source available which so concisely presents adrenal imaging. (KRM)

  6. Persistence of histoplasma in adrenals 7 years after antifungal therapy

    PubMed Central

    Kothari, Deepak; Chopra, Shweta; Bhardwaj, Minakshi; Ajmani, Ajay K.; Kulshreshtha, Bindu

    2013-01-01

    Adrenal histoplasmosis is an uncommon cause for adrenal insufficiency. The duration of treatment for adrenal histoplasmosis is not clear. Existing treatment regimens advocate antifungals given for periods ranging from 6 months to 2 years. We report here a rare case who showed persistence of histoplasma in adrenal biopsy 7 years after being initially treated with itraconazole for 9 months. This calls for a prolonged therapy with regular review of adrenal morphology and histology in these patients. PMID:23869317

  7. Androgen insensitivity syndrome

    MedlinePlus

    ... check levels of testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) Genetic testing (karyotype) to determine ... KJ, Bloom SL, et al. Fetal growth and development. In: Cunningham F, Leveno KJ, Bloom SL, et ...

  8. Loss of exogenous androgen dependence by prostate tumor cells is associated with elevated glucuronidation potential

    PubMed Central

    Zimmer, Brenna M.; Howell, Michelle E.; Wei, Qin; Ma, Linlin; Romsdahl, Trevor; Loughman, Eileen G.; Markham, Jonathan E.; Seravalli, Javier; Barycki, Joseph J.; Simpson, Melanie A.

    2016-01-01

    Prostate epithelial cells control the potency and availability of androgen hormones in part by inactivation and elimination. UDP-glucose dehydrogenase (UGDH) catalyzes the NAD+-dependent oxidation of UDP-glucose to UDP-glucuronate, an essential precursor for androgen inactivation by the prostate glucuronidation enzymes UGT2B15 and UGT2B17. UGDH expression is androgen stimulated, which increases the production of UDP-glucuronate, and fuels UGT-catalyzed glucuronidation. In this study, we compared the glucuronidation potential and its impact on androgen-mediated gene expression in an isogenic LNCaP model for androgen dependent versus castration resistant prostate cancer. Despite significantly lower androgen-glucuronide output, LNCaP 81 castration resistant tumor cells expressed higher levels of UGDH, UGT2B15, and UGT2B17. However, the magnitude of androgen-activated UGDH and PSA expression, as well as the AR-dependent repression of UGT2B15 and UGT2B17, was blunted several-fold in these cells. Consistent with these results, the ligand-activated binding of AR to the PSA promoter and subsequent transcriptional activation were also significantly reduced in castration resistant cells. Analysis of the UDP-sugar pools and flux through pathways downstream of UDP-glucuronate production revealed that these glucuronidation precursor metabolites were channeled through proteoglycan and glycosaminoglycan biosynthetic pathways, leading to increased surface expression of Notch 1. Knockdown of UGDH diminished Notch1 and increased glucuronide output. Overall, these results support a model in which the aberrant partitioning of UDP-glucuronate and other UDP-sugars into alternative pathways during androgen deprivation contributes to the loss of prostate tumor cell androgen sensitivity by promoting altered cell surface proteoglycan expression. PMID:27307252

  9. Sex-specific prenatal stress effects on the rat reproductive axis and adrenal gland structure.

    PubMed

    Ashworth, Cheryl J; George, Susan O; Hogg, Charis O; Lai, Yu-Ting; Brunton, Paula J

    2016-06-01

    Social stress during pregnancy has profound effects on offspring physiology. This study examined whether an ethologically relevant social stress during late pregnancy in rats alters the reproductive axis and adrenal gland structure in post-pubertal male and female offspring. Prenatally stressed (PNS) pregnant rats (n=9) were exposed to an unfamiliar lactating rat for 10 min/day from day 16 to 20 of pregnancy inclusive, whereas control pregnant rats (n=9) remained in their home cages. Gonads, adrenal glands and blood samples were obtained from one female and one male from each litter at 11 to 12-weeks of age. Anogenital distance was measured. There was no treatment effect on body, adrenal or gonad weight at 11-12 weeks. PNS did not affect the number of primordial, secondary or tertiary ovarian follicles, numbers of corpora lutea or ovarian FSH receptor expression. There was an indication that PNS females had more primary follicles and greater ovarian aromatase expression compared with control females (both P=0.09). PNS males had longer anogenital distances (0.01±0.0 cm/g vs 0.008±0.00 cm/g; P=0.007) and higher plasma FSH concentrations (0.05 ng/mL vs 0.006 ng/mL; s.e.d.=0.023; P=0.043) compared with control males. There were no treatment effects on the number of Sertoli cells or seminiferous tubules, seminiferous tubule area, plasma testosterone concentration or testis expression of aromatase, FSH receptor or androgen receptor. PNS did not affect adrenal size. These data suggest that the developing male reproductive axis is more sensitive to maternal stress and that PNS may enhance aspects of male reproductive development. PMID:27026714

  10. Disabled-2 is expressed in adrenal zona glomerulosa and is involved in aldosterone secretion.

    PubMed

    Romero, Damian G; Yanes, Licy L; de Rodriguez, Angela F; Plonczynski, Maria W; Welsh, Bronwyn L; Reckelhoff, Jane F; Gomez-Sanchez, Elise P; Gomez-Sanchez, Celso E

    2007-06-01

    The differentiation of the adrenal cortex into functionally specific zones is probably due to differential temporal gene expression during fetal growth, development, and adulthood. In our search for adrenal zona glomerulosa-specific genes, we found that Disabled-2 (Dab2) is expressed in the zona glomerulosa of the rat adrenal gland using a combination of laser capture microdissection, mRNA amplification, cDNA microarray hybridization, and real-time RT-PCR. Dab2 is an alternative spliced mitogen-regulated phosphoprotein with features of an adaptor protein and functions in signal transduction, endocytosis, and tissue morphogenesis during embryonic development. We performed further studies to analyze adrenal Dab2 localization, regulation, and role in aldosterone secretion. We found that Dab2 is expressed in the zona glomerulosa and zona intermedia of the rat adrenal cortex. Low-salt diet treatment increased Dab2-long isoform expression at the mRNA and protein level in the rat adrenal gland, whereas high-salt diet treatment did not cause any significant modification. Angiotensin II infusion caused a transient increase in both Dab2 isoform mRNAs in the rat adrenal gland. Dab2 overexpression in H295R human adrenocortical cells caused an increase in aldosterone synthase expression and up-regulated aldosterone secretion under angiotensin II-stimulated conditions. In conclusion, Dab2 is an adrenal gland zona glomerulosa- and intermedia-expressed gene that is regulated by aldosterone secretagogues such as low-salt diet or angiotensin II and is involved in aldosterone synthase expression and aldosterone secretion. Dab2 may therefore be a modulator of aldosterone secretion and be involved in mineralocorticoid secretion abnormalities. PMID:17303656

  11. Successful treatment for adrenocorticotropic hormone-independent macronodular adrenal hyperplasia with laparoscopic adrenalectomy: a case series

    PubMed Central

    2012-01-01

    Introduction Adrenocorticotropic hormone-independent macronodular adrenal hyperplasia, characterized by bilateral macronodular adrenal hypertrophy and autonomous cortisol production, is a rare cause of Cushing’s syndrome. Bilateral adrenalectomy is considered the standard treatment for adrenocorticotropic hormone-independent macronodular adrenal hyperplasia but obliges the patient to receive lifetime steroid replacement therapy subsequently, and may increase the patient’s risk of adrenal insufficiency. These circumstances require surgeons to carefully consider operative strategies on an individual basis. Case presentation We performed successful laparoscopic adrenalectomy on four patients with adrenocorticotropic hormone-independent macronodular adrenal hyperplasia. Computed tomography scans showed bilateral adrenal enlargement in all patients. Case 1: a 56-year-old Japanese woman presented with obvious Cushing’s symptoms during treatment for diabetes mellitus and hypertension. Case 2: a 37-year-old Japanese man also presented with Cushing’s symptoms during treatment for diabetes mellitus and hypertension. These patients were diagnosed as Cushing’s syndrome caused by adrenocorticotropic hormone-independent macronodular adrenal hyperplasia based on endocrinologic testing, and underwent bilateral laparoscopic adrenalectomy. Case 3: an 80-year-old Japanese woman was hospitalized due to unusual weight gain and heightened general fatigue, and was diagnosed as Cushing’s syndrome caused by adrenocorticotropic hormone-independent macronodular adrenal hyperplasia. She underwent unilateral laparoscopic adrenalectomy due to high operative risk. Case 4: a 66-year-old Japanese man was discovered to have bilateral adrenal tumors on medical examination. He did not have Cushing’s symptoms and was diagnosed as subclinical Cushing’s syndrome due to suppressed adrenocorticotropic hormone serum levels and loss of cortisol circadian rhythm without abnormal levels of

  12. New insights into the androgen biotransformation in prostate cancer: A regulatory network among androgen, androgen receptors and UGTs.

    PubMed

    Qin, Xuan; Liu, Mingyao; Wang, Xin

    2016-04-01

    Androgen, as one kind of steroid hormones, is pivotal in the hormone-sensitive cancer, such as prostate cancer (PCa). The synthesis, elimination, and bioavailability of androgen in prostate cells have been proved to be a main cause of the carcinogenesis, maintenance and deterioration of PCa. This review illustrates the outlines of androgen biotransformation, and further discusses the different enzymes, especially UDP-glucuronyltransferases (UGTs) embedded in both benign and malignant prostate cells, which catalyze the reactions. Although many inhibitors of the enzymes responsible for the synthesis of androgens have been developed into drugs to fight against PCa, the elimination procedures metabolized by the UGTs are less emphasized. Thus the regulatory network among androgen, androgen receptors (AR) and UGTs is carefully reviewed in this article, indicating the determinant effects of UGTs on prostatic androgens and the regulation of AR. Finally, the hypothesis is also put forward that the regulators of UGTs may be developed to accelerate the androgen elimination and benefit PCa therapy. PMID:26926093

  13. Anogenital distance as a marker of androgen exposure in humans.

    PubMed

    Thankamony, A; Pasterski, V; Ong, K K; Acerini, C L; Hughes, I A

    2016-07-01

    Abnormal foetal testis development has been proposed to underlie common disorders of the male reproductive system such as cryptorchidism, hypospadias, reduced semen quality and testicular germ cell tumour, which are regarded as components of a 'testicular dysgenesis syndrome'. The increasing trends and geographical variation in their incidence have been suggested to result from in utero exposure to environmental chemicals acting as endocrine disruptors. In rodents, the anogenital distance (AGD), measured from the anus to the base of genital tubercle, is a sensitive biomarker of androgen exposure during a critical embryonic window of testis development. In humans, several epidemiological studies have shown alterations in AGD associated with prenatal exposure to several chemicals with potential endocrine disrupting activity. However, the link between AGD and androgen exposure in humans is not well-defined. This review focuses on the current evidence for such a relationship. As in rodents, a clear gender difference is detected during foetal development of the AGD in humans which is maintained thereafter. Reduced AGD in association with clinically relevant outcomes of potential environmental exposures, such as cryptorchidism or hypospadias, is in keeping with AGD as a marker of foetal testicular function. Furthermore, AGD may reflect variations in prenatal androgen exposure in healthy children as shorter AGD at birth is associated with reduced masculine play behaviour in preschool boys. Several studies provide evidence linking shorter AGD with lower fertility, semen quality and testosterone levels in selected groups of adults attending andrology clinics. Overall, the observational data in humans are consistent with experimental studies in animals and support the use of AGD as a biomarker of foetal androgen exposure. Future studies evaluating AGD in relation to reproductive hormones in both infants and adults, and to gene polymorphisms, will help to further delineate

  14. Nonsteroidal Selective Androgen Receptor Modulators Enhance Female Sexual Motivation

    PubMed Central

    Jones, Amanda; Hwang, Dong Jin; Duke, Charles B.; He, Yali; Siddam, Anjaiah; Miller, Duane D.

    2010-01-01

    Women experience a decline in estrogen and androgen levels after natural or surgically induced menopause, effects that are associated with a loss of sexual desire and bone mineral density. Studies in our laboratories have shown the beneficial effects of selective androgen receptor modulators (SARMs) in the treatment of osteoporosis and muscle wasting in animal models. A series of S-3-(phenoxy)-2-hydroxy-2-methyl-N-(4-cyano-3-trifluoromethyl-phenyl)-propionamide analogs was synthesized to evaluate the effects of B-ring substitutions on in vitro and in vivo pharmacologic activity, especially female sexual motivation. The androgen receptor (AR) relative binding affinities ranged from 0.1 to 26.5% (relative to dihydrotestosterone) and demonstrated a range of agonist activity at 100 nM. In vivo pharmacologic activity was first assessed by using male rats. Structural modifications to the B-ring significantly affected the selectivity of the SARMs, demonstrating that single-atom substitutions can dramatically and unexpectedly influence activity in androgenic (i.e., prostate) and anabolic (i.e., muscle) tissues. (S)-N-(4-cyano-3-trifluoromethyl-phenyl)-3-(3-fluoro,4-chlorophenoxy)-2-hydroxy-2-methyl-propanamide (S-23) displayed full agonist activity in androgenic and anabolic tissues; however, the remaining SARMs were more prostate-sparing, selectively maintaining the size of the levator ani muscle in castrated rats. The partner-preference paradigm was used to evaluate the effects of SARMs on female sexual motivation. With the exception of two four-halo substituted analogs, the SARMs increased sexual motivation in ovariectomized rats, with potency and efficacy comparable with testosterone propionate. These results indicate that the AR is important in regulating female libido given the nonaromatizable nature of SARMs and it could be a superior alternative to steroidal testosterone preparations in the treatment of hypoactive sexual desire disorder. PMID:20444881

  15. Hyperkalemic paralysis in primary adrenal insufficiency

    PubMed Central

    Mishra, Ajay; Pandya, Himanshu V.; Dave, Nikhil; Sapre, Chinmaye M.; Chaudhary, Sneha

    2014-01-01

    Hyperkalemic paralysis due to Addison's disease is rare, and potentially life-threatening entity presenting with flaccid motor weakness. This case under discussion highlights Hyperkalemic paralysis as initial symptomatic manifestation of primary adrenal insufficiency. PMID:25136192

  16. The innervation of the mammalian adrenal gland.

    PubMed Central

    Parker, T L; Kesse, W K; Mohamed, A A; Afework, M

    1993-01-01

    Early conflicting reports and the lack of sensitive anatomical methods have led to an oversimplified view of adrenal gland innervation. It was not until the introduction of nerve fibre tracing techniques in the mid-1970s that the true complexity of adrenal innervation began to emerge. The first part of this article comprises a brief review of these and other relevant reports dealing with both medullary and cortical innervation. In the second part a detailed account is given of the work undertaken in Rex Coupland's Department relating to the innervation of the rodent and primate adrenal medulla using a retrograde fluorescent tracer technique. It was concluded that, in all 3 species studied, the adrenal medulla receives a sympathetic and parasympathetic efferent and an afferent innervation. The possible interrelationship between neural control of cortical and medullar secretions is discussed briefly. Images Fig. 1 Fig. 2 Fig. 5 PMID:8300416

  17. Effects of DDT on bobwhite quail adrenal gland

    USGS Publications Warehouse

    Lehman, J.W.; Peterle, T.J.; Mulls, C.M.

    1974-01-01

    A wide range of responses to sublethal levels of DDT exist, many of which are species specific and vary within each species depending upon age, sex, and physiological state. Sublethal levels of DDT do cause an increase in the adrenal cortical tissue of bobwhite quail, which may cause increased secretion of corticosteroids, and in turn affect reproduction. A delicate homeostatic balance exists within the avian endocrine system which may be disturbed by feeding sublethal levels of chlorinated hydrocarbon pesticides. This adverse effect on the endocrine system may cause subtle reproductive failures which go unnoticed until the population is greatly reduced.

  18. Adrenal hemangioma: computed tomogram and angiogram appearances.

    PubMed

    Wang, J H; Chiang, J H; Chang, T

    1992-08-01

    Adrenal hemangiomas are rare. To our knowledge, about 22 cases have been reported in the literature, of which 13 cases were surgically removed. We report probably the first case of CT and angiographically diagnosed and surgically confirmed adrenal hemangioma in Taiwan. We concluded that characteristic appearances on computed tomogram and angiogram associated with phlebolith-like calcification in the tumor may allow the radiologists to make correct preoperative diagnosis. PMID:1327475

  19. The effect of bedrest on adrenal function

    NASA Technical Reports Server (NTRS)

    Leach, C. S.; Hulley, S. B.; Rambaut, P. C.; Dietlein, L. F.

    1973-01-01

    Eight male subjects were subjected to continuous bedrest for 24-80 weeks for the purpose of studying metabolic responses. Three of the subjects did supine exercises daily during part of the study. Adrenal function was examined in relation to adrenal cortical and medullary excretions. The results reveal an increase in hydrocortisone throughout the test period, a decrease in norepinephrine and no change in epinephrine. These data suggest that exercise could decrease the severity of deconditioning caused by bedrest.

  20. The Role of Androgen and Androgen Receptor in the Skin-Related Disorders

    PubMed Central

    Lai, Jiann-Jyh; Chang, Philip; Lai, Kuo-Pao; Chen, Lumin; Chang, Chawnshang

    2013-01-01

    Androgen and androgen receptor (AR) may play important roles in several skin related diseases, such as androgenetic alopecia and acne vulgaris. Current treatments for these androgen/AR-involved diseases, which target the synthesis of androgens or prevent its binding to AR, can cause significant adverse side effects. Based on the recent studies using AR knockout mice, it has been suggested that AR and androgens play distinct roles in the skin pathogenesis, and AR seems to be a better target than androgens for the treatment of these skin diseases. Here we review recent studies of androgen/AR roles in several skin-related disorders, including acne vulgaris, androgenetic alopecia, and hirsutism, as well as cutaneous wound healing. PMID:22829074

  1. Congenital adrenal hyperplasia and risk for psychiatric disorders in girls and women born between 1915 and 2010: A total population study.

    PubMed

    Engberg, Hedvig; Butwicka, Agnieszka; Nordenström, Anna; Hirschberg, Angelica Lindén; Falhammar, Henrik; Lichtenstein, Paul; Nordenskjöld, Agneta; Frisén, Louise; Landén, Mikael

    2015-10-01

    Congenital adrenal hyperplasia (CAH) is a chronic condition and individuals are exposed to elevated androgen levels in utero as a result of the endogenous cortisol deficiency. Prenatal androgen exposure has been suggested to influence mental health, but population based studies on psychiatric morbidity among girls and women with CAH are lacking. Therefore, we performed a cohort study based on Swedish nationwide registers linked with the national CAH register. Girls and women with CAH due to 21-hydroxylase deficiency (n = 335) born between January 1915 and January 2010 were compared with aged-matched female (n = 33500) and male controls (n = 33500). Analyses were stratified by phenotype [salt wasting (SW), simple virilizing (SV), and non-classical type (NC)] and by CYP21A2 genotype subgroups (null, I2splice, I172N, and P30L). Results are presented as estimated risks (OR, 95%CI) of psychiatric disorders among girls and women with CAH compared with age-matched controls. Any psychiatric diagnoses were more common in CAH females compared with female and male population controls [1.9 (1.4-2.5), and 2.2 (1.7-2.9)]. In particular, the risk of alcohol misuse was increased compared with female and male population controls [2.8 (1.7-4.7) and 2.1 (1.2-3.5)], and appeared most common among the girls and women with the most severe null genotype [6.7 (2.6-17.8)]. The risk of stress and adjustment disorders was doubled compared with female population controls [2.1 (1.3-3.6)]. Girls and women with CAH have an increased risk of psychiatric disorders in general and substance use disorders in particular compared with unexposed females, with the highest risk among those with the most severe genotype. Prenatal androgen exposure and deficient endogenous cortisol and/or adrenaline production may provide explanations for these findings, but other factors related to CAH cannot be excluded. PMID:26184920

  2. Testosterone-secreting adrenal adenoma in a peripubertal girl

    SciTech Connect

    Kamilaris, T.C.; DeBold, C.R.; Manolas, K.J.; Hoursanidis, A.; Panageas, S.; Yiannatos, J.

    1987-11-13

    A 15-year-old girl who presented with primary amenorrhea and virilization had an adrenocortical adenoma that secreted predominantly testosterone. To the authors' knowledge, she is the first peripubertal and second youngest patient with a testosterone-secreting adrenal tumor described. Serum dehydroepiandrosterone sulfate and urinary 17-ketosteroid an 17-hydroxycorticosteroid levels were normal. A tumor was located by a computed tomographic (CT) scan and by uptake of 6-..beta..-(/sup 75/Se) selenomethylnorcholesterol. Microscopic examination of the tumor showed typical features of an adrenocortical adenoma with no histologic features characteristic of Leydig cells. Postoperatively, her hirsutism regressed, she rapidly went through puberty, and regular monthly menstruation started four months later. Finding the source of testosterone in a virilized patient can be difficult. Eleven of the 14 previously described patients with testosterone-secreting adrenal tumors initially underwent misdirected surgery on the ovaries. Review of these cases revealed that results of hormone stimulation and suppression tests are unreliable and that these tumors are usually large. Therefore, CT scanning of the adrenal glands is recommended in all patients suspected of having a testosterone-secreting tumor.

  3. Sympatho-adrenal activation by chronic intermittent hypoxia

    PubMed Central

    Kumar, Ganesh K.; Peng, Ying-Jie

    2012-01-01

    Recurrent apnea with chronic intermittent hypoxia (CIH) is a major clinical problem in adult humans and infants born preterm. Patients with recurrent apnea exhibit heightened sympathetic activity as well as elevated plasma catecholamine levels, and these phenotypes are effectively recapitulated in rodent models of CIH. This article summarizes findings from studies addressing sympathetic activation in recurrent apnea patients and rodent models of CIH and the underlying cellular and molecular mechanisms. Available evidence suggests that augmented chemoreflex and attenuated baroreflex contribute to sympathetic activation by CIH. Studies on rodents showed that CIH augments the carotid body response to hypoxia and attenuates the carotid baroreceptor response to increased sinus pressures. Processing of afferent information from chemoreceptors at the central nervous system is also facilitated by CIH. Adult and neonatal rats exposed to CIH exhibit augmented catecholamine secretion from the adrenal medulla. Adrenal demedullation prevents the elevation of circulating catecholamines in CIH-exposed rodents. Reactive oxygen species (ROS)-mediated signaling is emerging as the major cellular mechanism triggering sympatho-adrenal activation by CIH. Molecular mechanisms underlying increased ROS generation by CIH seem to involve transcriptional dysregulation of genes encoding pro-and antioxidant enzymes by hypoxia-inducible factor-1 and -2, respectively. PMID:22723632

  4. Protective effect of androgens against inflammation induced cartilage degradation in male rodents.

    PubMed Central

    Da Silva, J A; Larbre, J P; Spector, T D; Perry, L A; Scott, D L; Willoughby, D A

    1993-01-01

    OBJECTIVES--Rheumatoid arthritis (RA) is a disease which predominantly affects women. Interestingly, low serum androgen levels and clinical improvement with androgen replacement have been reported in male patients. The aetiopathogenic role of sex hormones in arthritis and their potential long term effects on joint destruction and disability remains unclear, however. This study was designed to investigate the potential influence of sex hormones on inflammation induced cartilage degradation in male rodents. METHODS--An in vivo model of cotton wrapped cartilage implants was used to assess the effects of androgen, oestradiol, and progesterone on inflammation induced cartilage degradation, and in vitro techniques were used to investigate the direct actions on cartilage metabolism and cytokine production in male animals. RESULTS--Orchidectomy resulted in accelerated cartilage damage which was reversed by replacement of physiological levels of androgens. Granulomatous tissue from castrated male rodents produced higher amounts of interleukin 1. Sex hormones reduced spontaneous proteoglycan loss in vitro but did not interfere with the effects of interleukin 1 on cultured cartilage. CONCLUSIONS--Androgens appear to protect cartilage from inflammation induced breakdown in male animals. These results support a pathogenic role for hypoandrogenism in rheumatoid arthritis and suggest that long term androgen replacement may help prevent joint damage and disability. PMID:8484695

  5. Disruption of androgen regulation in the prostate by the environmental contaminant hexachlorobenzene.

    PubMed Central

    Ralph, Jody L; Orgebin-Crist, Marie-Claire; Lareyre, Jean-Jacques; Nelson, Colleen C

    2003-01-01

    Hexachlorobenzene (HCB) is a persistent environmental contaminant that has the potential to interfere with steroid hormone regulation. The prostate requires precise control by androgens to regulate its growth and function. To determine if HCB impacts androgen action in the prostate, we used a number of methods. Our in vitro cell-culture-based assay used a firefly luciferase reporter gene driven by an androgen-responsive promoter. In the presence of dihydrotestosterone, low concentrations (0.5-5 nM) of HCB increased the androgen-responsive production of firefly luciferase and high concentrations of HCB (> 10 microM) suppressed this transcriptional activity. Results from a binding assay showed no evidence of affinity between HCB and the androgen receptor. We also tested HCB for in vivo effects using transgenic mice in which the transgene was a prostate-specific, androgen-responsive promoter upstream of a chloramphenicol acetyl transferase (CAT) reporter gene. In 4-week-old mice, the proportion of dilated prostate acini, a marker of sexual maturity, increased in the low HCB dose group and decreased in the high HCB dose mice. In the 8-week-old mice, there was a significant decrease in both CAT activity and prostate weight upon exposure to 20 mg/kg/day HCB. Therefore, in vitro and in vivo data suggest that HCB weakly agonizes androgen action, and consequently, low levels of HCB enhanced androgen action but high levels of HCB interfered. Environmental contaminants have been implicated in the rising incidence of prostate cancer, and insight into the mechanisms of endocrine disruption will help to clarify their role. PMID:12676599

  6. Androgen-mediated nurturing and aggressive behaviors during paternal care in bluegill sunfish (Lepomis macrochirus).

    PubMed

    Rodgers, Chandra M C; Neff, Bryan D; Knapp, Rosemary

    2013-03-01

    Male parental care in vertebrates often involves both defensive and nurturing behaviors. Whether androgens differentially mediate these two types of behaviors, or a trade-off exists between them, has been studied by behavioral endocrinologists for years but predominantly in species with biparental care. In such systems, potential detrimental effects of elevated androgens on parental care behaviors are often compensated for by changes in behavior of the unmanipulated parent. In contrast, for species where only one parent provides care, manipulation of androgen levels may more clearly determine if there are differential effects of androgens on these two types of behaviors and whether the proposed trade-off between defensive and nurturing behavior exists. Here, we manipulated androgen levels in two ways in bluegill sunfish (Lepomis macrochirus), a species where males provide sole parental care for the young. At the onset of the care period, males were implanted with 11-ketotestosterone, a major teleost androgen, the androgen receptor antagonist flutamide, or a blank implant. A separate control group experienced no manipulation. Males were then observed over several days and tested for their aggressiveness towards an experimentally-presented brood predator and for nurturing behavior (fanning of the eggs, removal of dead or fungal-infected eggs). Males implanted with 11-ketotestosterone displayed 64% more aggressive behaviors and 71% fewer nurturing behaviors than control groups. In contrast, males implanted with flutamide displayed 7% fewer aggressive behaviors and 126% more nurturing behaviors than control males. Taken together, these results show that aggression and nurturing behaviors are mediated by androgens and suggest that there is a trade-off between the two behaviors during parental care in this species. PMID:23268781

  7. Androgen response to social competition in a shoaling fish.

    PubMed

    Teles, Magda C; Oliveira, Rui F

    2016-02-01

    Androgens respond to social challenges and this response has been interpreted as a way for males to adjust androgen-dependent behavior to social context. However, the androgen responsiveness to social challenges varies across species and a conceptual framework has been developed to explain this variation according to differences in the mating system and parental care type, which determines the regimen of challenges males are exposed to, and concomitantly the scope (defined as the difference between the physiological maximum and the baseline levels) of response to a social challenge. However, this framework has been focused on territorial species and no clear predictions have been made to gregarious species (e.g. shoaling fish), which although tolerating same-sex individuals may also exhibit intra-sexual competition. In this paper we extend the scope of this conceptual framework to shoaling fish by studying the endocrine response of zebrafish (Danio rerio) to social challenges. Male zebrafish exposed to real opponent agonistic interactions exhibited an increase in androgen levels (11-ketotestosterone both in Winners and Losers and testosterone in Losers). This response was absent in Mirror-fighters, that expressed similar levels of aggressive behavior to those of winners, suggesting that this response is not a mere reflex of heightened aggressive motivation. Cortisol levels were also measured and indicated an activation of the hypothalamic-pituitary-interrenal axis in Winners of real opponent fighters, but not Losers or in Mirror-fighters. These results confirm that gregarious species also exhibit an endocrine response to an acute social challenge. PMID:26497408

  8. Failure to visualize adrenal glands in a patient with bilateral adrenal hyperplasia. [/sup 131/I

    SciTech Connect

    Gordon, L.; Mayfield, R.K.; Levine, J.H.; Lopes-Virella, M.F.; Sagel, J.; Buse, M.G.

    1980-01-01

    A patient with clinical and biochemical evidence of Cushing's disease and severe hyperlipidemia underwent an adrenal imaging procedure with NP-59 (6..beta..-(/sup 131/I)iodomethyl-19-norcholesterol), without visualization of either gland. Correction of the hyperlipidemia followed by repeated adrenal imaging resulted in bilateral visualization. A pituitary tumor was removed at surgery, confirming the diagnosis of Cushing's disease.

  9. Primary Bilateral Non-Hodgkin's Lymphoma of the Adrenal Gland Presenting as Incidental Adrenal Masses

    PubMed Central

    Rizzo, Christopher; Camilleri, David James; Gatt, Andre'

    2015-01-01

    Although lymphoma may occasionally involve the adrenal glands as part of a generalized disease process, primary adrenal lymphoma (PAL) is a rare disease. We present a case of a 62-year-old woman with a history of mild/moderate hereditary spherocytosis with a well-compensated baseline haemoglobin, who presented with rapidly progressive symptomatic anaemia. During the diagnostic workup, imaging revealed bilateral large adrenal masses and she was later diagnosed with diffuse large B-cell non-Hodgkin's lymphoma (DLBCL), with the adrenal glands being the dominant site of the disease. The patient was started on systemic chemotherapy, but her disease progressed with neurological involvement which responded to second-line therapy. Her adrenal disease however was refractory to further therapy. PMID:26681947

  10. Neuromedin-U inhibits unilateral adrenalectomy-induced compensatory adrenal growth in the rat.

    PubMed

    Malendowicz, Ludwik K; Guidolin, Diego; Trejter, Marcin; Rucinski, Marcin; Porzionato, Andrea; de Caro, Raffaele; Nowak, Magdalena

    2009-05-01

    Neuromedin-U (NMU) is a brain-gut peptide, which has been previously found to stimulate hypothalamic-pituitary-adrenal axis in the rat and to control the growth of the rat adrenal cortex. The present study aimed to investigate the possible involvement of NMU in the regulation of unilateral adrenalectomy-induced compensatory adrenal growth, a phenomenon known to be neurally mediated. The right adrenal gland of mature female rats was removed, the contralateral gland was then analyzed at 24 and 72h following surgery. Groups of rats were given 3 subcutaneous injections (24, 16 and 8h before decapitation) of NMU8 (1.5 or 3.0 nmol/100g/per injection). Three hours before sacrifice all rats received an intraperitoneal injection of 0.1mg/100g body weight of vincristin. By means of RT-PCR the presence of NMUR1 mRNA was detected in adrenal cortex of both intact and hemiadrenalectomized rats. As expected, unilateral adrenalectomy-induced an increase in adrenal weight, associated with increased plasma ACTH, aldosterone and corticosterone levels. The administration of NMU to hemiadrenalectomized rats did not significantly affect these parameters. NMU administration, however, notably inhibited the unilateral adrenalectomy-induced adrenocortical cell proliferation in both zona glomerulosa and zona fasciculata, as assessed by the metaphase index and the number of parenchymal cell nuclei per unit area of the tissue. When compared to hemiadrenalectomized animals receiving saline, a significant decrease of blood corticosterone levels was observed after 24h in rats treated with the highest dose of NMU. Since these effects were independent on changes in blood ACTH, they could reflect an interaction of NMU with the neural system innervating the adrenal gland. PMID:19428772

  11. Benign adrenal hemangiomas may mimic metastases on PET.

    PubMed

    Calata, Jed F; Sukerkar, Arun N; August, Carey Z; Maker, Ajay V

    2013-11-01

    CT or MRI are utilized in the initial evaluation of adrenal incidentalomas; however, overlap exists between benign and malignant lesions on these examinations. The American College of Radiology recommends PET scans to complement CT and MRI for patients with adrenal masses and a moderate-to-high likelihood of neoplastic disease. We present images of a PET-avid adrenal lesion in a patient with pulmonary and pancreatic neoplasms that mimicked metastasis, but was found to be a benign adrenal hemangioma on surgical resection. The use of PET for adrenal tumors, specifically adrenal hemangiomas, will be reviewed. PMID:24089061

  12. In Vitro Androgen Bioassays as a Detection Method for Designer Androgens

    PubMed Central

    Cooper, Elliot R.; McGrath, Kristine C. Y.; Heather, Alison K.

    2013-01-01

    Androgens are the class of sex steroids responsible for male sexual characteristics, including increased muscle mass and decreased fat mass. Illicit use of androgen doping can be an attractive option for those looking to enhance sporting performance and/or physical appearance. The use of in vitro bioassays to detect androgens, especially designer or proandrogens, is becoming increasingly important in combating androgen doping associated with nutritional supplements. The nutritional sports supplement market has grown rapidly throughout the past decade. Many of these supplements contain androgens, designer androgens or proandrogens. Many designer or proandrogens cannot be detected by the standard highly-sensitive screening methods such as gas chromatography-mass spectrometry because their chemical structure is unknown. However, in vitro androgen bioassays can detect designer and proandrogens as these assays are not reliant on knowing the chemical structure but instead are based on androgen receptor activation. For these reasons, it may be advantageous to use routine androgen bioassay screening of nutraceutical samples to help curb the increasing problem of androgen doping. PMID:23389345

  13. How Is Adrenal Cancer Diagnosed?

    MedlinePlus

    ... levels before symptoms occur. Tests for high cortisol levels The levels of cortisol are measured in the ... cause high cortisol levels. Tests for high aldosterone levels The level of aldosterone will be measured and ...

  14. Diagnosis of adrenal tumors with radionuclide imaging

    SciTech Connect

    Beierwaltes, W.H.; Sisson, J.C.; Shapiro, B.

    1984-01-01

    The development of radiolabeled cholesterols in 1969 as precursors of adrenocortical steroid production allowed the first noninvasive imaging of the adrenal cortices. FDA-NDA approval in 1984 should allow routine use of these agents in most hospitals. NP-59 is most commonly used in the diagnosis and management of Cushing syndrome; the second most common use is in the diagnosis of primary aldosteronism. It is also helpful in the differential diagnosis of adrenal and ovarian hyperandrogenism and hirsutism, and is the only noninvasive method of detecting unilateral adrenocortical hypofunction. The newest and most popular use is in the differential diagnosis of asymptomatic masses in the region of the adrenal gland discovered incidentally with CT scan (incidentalomas). In this situation, the NP-59 scan can define whether the tumor is in the adrenal gland and if it is functional or nonfunctional. The authors believe that, in the future, radiolabeled enzyme inhibitors might offer better diagnostic imaging of the adrenal cortex, although these agents will probably not be available for routine use for some time. The development of a radioiodinated guanethidine analog, /sup 131/I-MIBG, has allowed differentiation of normal adrenal medullary function from bilateral adrenal medullary hyperplasia before the development of hypertension or tachycardia, diagnostic increases in plasma or urinary catecholamines, or abnormal CT scans. The search for a pheochromocytoma should begin with /sup 131/I-MIBG scintigraphy. While over 90% of primary pheochromocytomas occur in the abdomen, neither a survey of the abdomen nor the finding of a single tumor should conclude the search.

  15. Body condition influences sexual signal expression independent of circulating androgens in male red-backed fairy-wrens.

    PubMed

    Barron, Douglas G; Webster, Michael S; Schwabl, Hubert

    2013-03-01

    Androgens play a major role in the regulation of sexual signal expression of male vertebrates. In this study we assessed the prevalent, yet largely untested, assumption that signal honesty is maintained through condition-dependent androgen regulation by experimentally manipulating body condition of male red-backed fairy-wrens (Malurus melanocephalus) through trimming several flight feathers before the prenuptial molt. In their first reproductive season males of this species exhibit androgen-regulated plasticity in plumage coloration, ranging from red/black (high androgens) to brown (low androgens). Red/black plumage is preferred by females and might be constrained by a negative relationship between body condition and androgen levels. We also evaluated whether corticosterone changes to altered conditional state mediate the relationship between condition and androgens. While we predicted that males with trimmed feathers would expend greater energy and thus be in poorer condition at the time of molt, they were counter-intuitively in better condition compared to control birds, likely as a consequence of subtle behavioral changes. These birds in better condition molted a greater proportion of red/black plumage, as predicted, and also molted more heavily. However, experimental and control birds did not differ in their androgen or corticosterone concentrations. Furthermore, analysis of long-term data from the same population revealed no correlation between condition and androgen levels. Collectively, these results challenge the notion that condition-dependent androgen regulation alone is responsible for maintaining the honesty of sexual signals and highlights the necessity of considering alternate explanations. PMID:23261818

  16. The role of androgenic steroids in shaping social phenotypes across the lifespan in male marmosets (Callithrix spp.).

    PubMed

    French, Jeffrey A

    2013-03-01

    Steroid hormones, particularly androgens and their metabolic derivatives, play a prominent role in shaping morphological, behavioral, and social phenotypes in many organisms, including primates. This paper reviews the endocrine correlates of development in male marmoset monkeys of the genus Callithrix (C. kuhlii and C. geoffroyi). A lifespan developmental perspective is adopted, in which our knowledge of hormone effects and profiles from prenatal periods through old age is described. Prenatal steroid hormones appear to play a prominent role in shaping behavioral and morphological phenotypes both the prepartum and in the early postpartum periods of life, with exposure to high gestational androgen associated with reduced fetal growth and lower levels of juvenile play. Early postnatal elevations in androgen levels in males are ubiquitous in Callithrix, and play a role in the further differentiation of male genital morphology and behavior. Changes in androgens as males approach puberty are similar to the conventional primate pattern, and unlike in female marmosets, gonadal steroidogenesis appears to be independent of social context. In adults, androgens appear to be an important modulator of paternal responsiveness to infants, since androgens are low at times when males typically engage in maximal levels of care, and fathers that care for offspring extensively appear to have lower androgen levels than fathers that are less involved in offspring care. Finally, aging in male marmosets is associated with reduced androgen levels. This reduction appears to be attributable to deficits in central mechanisms, since experimental induction and inhibition of gonadal steroid synthesis and release appears to be normal in older males. Together, these results suggest a complex picture of lifetime involvement of androgens in shaping marmoset phenotypes. PMID:23335110

  17. Alteration in sexually dimorphic testosterone biotransformation profiles as a biomarker of chemically induced androgen disruption in mice.

    PubMed Central

    Wilson, V S; McLachlan, J B; Falls, J G; LeBlanc, G A

    1999-01-01

    Assessment of the impact of environmental chemicals on androgen homeostasis in rodent models is confounded by high intraindividual and interindividual variability in circulating testosterone levels. Our goal was to evaluate changes in testosterone biotransformation processes as a measure of androgen homeostasis and as a biomarker of exposure to androgen-disrupting chemicals. Sex-specific differences in hepatic testosterone biotransformation enzyme activities were identified in CD-1 mice. Gonadectomy followed by replacement of individual steroid hormones identified specific sex differences in biotransformation profiles that were due to the inductive or suppressive effects of testosterone. Notably, significant androgen-dependent differences in testosterone 6[alpha]- and 15[alpha]-hydroxylase activities were demonstrated, and the ratio of 6[alpha]- and 15[alpha]-hydroxylase activities proved to be an excellent indicator of the androgen status within the animal. The male or "masculinized" testosterone 6[alpha]/15[alpha]-hydroxylase ratio was significantly less than the female or "feminized" ratio. Male mice were exposed to both an antiandrogen, vinclozolin, and to a compound that modulates serum androgen levels, indole-3-carbinol, to test the utility of this ratio as a biomarker of androgen disruption. Treatment with the antiandrogen vinclozolin significantly increased the 6[alpha]/15[alpha]-hydroxylase ratio. Indole-3-carbinol treatment resulted in a dose-dependent, but highly variable, decrease in serum testosterone levels. The 6[alpha]/15[alpha]-hydroxylase ratio increased as serum testosterone levels decreased in these animals. However, the increase in the ratio was much less variable and more sensitive than serum testosterone levels. These investigations demonstrate that the 6[alpha]/15[alpha]-hydroxylase ratio is a powerful measure of androgen modulation and a sensitive indicator of exposure to androgen-disrupting chemicals in CD-1 mice. Images Figure 1 Figure 2

  18. Comparative effects of cadmium, zinc, and lead in vitro on pulmonary, adrenal, and hepatic microsomal metabolism in the guinea pig

    SciTech Connect

    Colby, H.D.; Johnson, P.B.; Zulkoski, J.S.; Pope, M.R.; Miles, P.R.

    1981-11-01

    The in vitro effects of Cd, Zn, and Pb on pulmonary, adrenal, and hepatic microsomal enzyme activities in guinea pigs were compared. Cd and Zn produced concentration-dependent (20-200 ..mu..M) decreases in benzphetamine demethylase and biphenyl hydrozylase activities in adrenal, liver, and lung. Pb had no significant effect on either enzyme in any of the tissues studied. Adrenal and pulmonary enzymes were more sensitive to the effects of Cd and Zn than were hepatic enzymes. Benzo(a)pyrene hydroxylase and ethoxycoumarin demethylase activities were decreased by Zn, Cd and Pb in adrenal, liver, and lung microsomes. The inhibitory effects on benzo(a)pyrene and ethoxycoumarin methabolism were far greater than those on benzphetamine or biphenyl metabolism. The relative potencies of the metals as inhibitors of xenobiotic metabolism were Zn > Cd > Pb. Cd and Zn also inhibited steroid 21-hydroxylase activity in adrenal microsomes, but Pb had no effect on steroid metabolism. In addition, microsomal epoxide hydratase activity in adrenal, liver, and lung was inhibited by Cd but not by Zn or Pb. The results demonstrate that adrenal and pulmonary microsomal enzyme, like those in liver, are inhibited by various metals. Inhibition of mixed-function oxidases by metals in vitro is apparently not related to changes in cytochrome P-450 levels or substrate binding to cytochrome P-450. In addition, the actions of Cd, Zn, and Pb in each tissue are highly dependent on the substrates employed.

  19. Cancer-Associated Fibroblasts Modify the Response of Prostate Cancer Cells to Androgen and Anti-Androgens in Three-Dimensional Spheroid Culture.

    PubMed

    Eder, Theresa; Weber, Anja; Neuwirt, Hannes; Grünbacher, Georg; Ploner, Christian; Klocker, Helmut; Sampson, Natalie; Eder, Iris E

    2016-01-01

    Androgen receptor (AR) targeting remains the gold standard treatment for advanced prostate cancer (PCa); however, treatment resistance remains a major clinical problem. To study the therapeutic effects of clinically used anti-androgens we characterized herein a tissue-mimetic three-dimensional (3D) in vitro model whereby PCa cells were cultured alone or with PCa-associated fibroblasts (CAFs). Notably, the ratio of PCa cells to CAFs significantly increased in time in favor of the tumor cells within the spheroids strongly mimicking PCa in vivo. Despite this loss of CAFs, the stromal cells, which were not sensitive to androgen and even stimulated by the anti-androgens, significantly influenced the sensitivity of PCa cells to androgen and to the anti-androgens bicalutamide and enzalutamide. In particular, DuCaP cells lost sensitivity to enzalutamide when co-cultured with CAFs. In LAPC4/CAF and LNCaP/CAF co-culture spheroids the impact of the CAFs was less pronounced. In addition, 3D spheroids exhibited a significant increase in E-cadherin and substantial expression of vimentin in co-culture spheroids, whereas AR levels remained unchanged or even decreased. In LNCaP/CAF spheroids we further found increased Akt signaling that could be inhibited by the phosphatidyl-inositol 3 kinase (PI3K) inhibitor LY294002, thereby overcoming the anti-androgen resistance of the spheroids. Our data show that CAFs influence drug response of PCa cells with varying impact and further suggest this spheroid model is a valuable in vitro drug testing tool. PMID:27598125

  20. Anti-androgenic effects of flavonols in prostate cancer

    PubMed Central

    Boam, Tristan

    2015-01-01

    Dietary-derived agents, such as the flavonoids, are of particular interest for prostate cancer (PCa) chemoprevention as they may offer a favourable safety and side-effect profile. An agent that demonstrates action on the androgen receptor (AR) axis may have value for preventing or treating castrate-resistant PCa. Four main flavonols – quercetin, myricetin, kaempferol, and fisetin – have been demonstrated in laboratory studies to have chemopreventive action in both castrate-resistant and castrate-sensitive PCa models. Mechanisms of flavonol action on the AR axis in PCa have been proposed to be inhibition of the 5α-reductase enzymes, direct androgen competition, suppression of the AR complex and transactivation by coregulators such as c-Jun, Sp1, and the PI3K/Akt pathway. It is, however, still unclear with current levels of evidence whether AR axis-mediated effects can fully account for the flavonols’ chemopreventive action. PMID:26557883

  1. Androgen and FSH synergistically stimulate lipoprotein degradation and utilization by ovary granulosa cells

    SciTech Connect

    Schreiber, J.R.; Nakamura, K.; Schmit, V.; Weinstein, D.B.

    1984-01-01

    Androgen can directly modulate the induction of steroidogenic enzymes by FSH (follicle stimulating hormone) in ovary granulosa cells. In studies of its mechanism of action, the authors examined the androgen effect on granulosa cell interaction with lipoproteins, the physiologic source of cholesterol. After granulosa cells were cultured for 48 hours with and without androgen and/or FSH, the cells were incubated for 24 hours with /sup 125/I-lipoproteins (human high density lipoprotein (HDL), rat HDL, or human low density lipoprotein (LDL)). The media were then analyzed for lipoprotein protein coat degradation products (mainly /sup 125/I-monoiodotyrosine) and progestin (mainly 20 alpha-dihydroprogesterone (20 alpha-DHP)). In the absence of FSH and androgen, 2 X 10(5) granulosa cells degraded basal levels of all three lipoproteins, but produced no measurable 20 alpha-DHP. The addition of 10(-7) M androstenedione (A), testosterone (T), or 5 alpha-dihydrotestosterone (DHT) had no effect on lipoprotein protein degradation or 20 alpha-DHP production. FSH alone stimulated lipoprotein protein degradation by 50 to 300% while the addition of androgen synergistically augmented the FSH-stimulated 20 alpha-DHP production as well as protein coat degradation of all three lipoproteins. DHT and T were both effective, indicating that androgens themselves, and not estrogen products, were responsible for the effect on lipoprotein protein degradation and 20 alpha-DHP production.

  2. Impaired spermatogenesis is not an obligate expression of receptor-defective androgen resistance.

    PubMed

    Pinsky, L; Kaufman, M; Killinger, D W

    1989-01-01

    We are studying a man who presented at age 21 years with severe extragenital subvirilization despite high-normal to above-normal levels of plasma testosterone for at least 5 years. At puberty, his penis, scrotum, and testes matured normally, and he did not develop gynecomastia; however, his voice, muscularity, and facial, sexual, and body hair remained immature. A 2.5-ml ejaculate yielded normal results for sperm density, morphology, and motility. Because persistent undervirilization was emotionally disabling, he has received pharmacologic doses of testosterone enanthate intramuscularly for 3.5 years. The treatment has improved his virilization and masculine self-image substantially, and his semen analysis has remained well within the normal range. The androgen receptor in his genital skin fibroblasts has a distinctively mutant phenotype: it has a low affinity (increased apparent equilibrium dissociation constant, Kd) for 5 alpha-dihydrotestosterone and two synthetic androgens, mibolerone (MB) and methyltrienolone (MT), and its binding capacity (Bmax) is normal for the other two ligands, but questionably low for MT. In addition, it up-regulates its activity normally in response to prolonged incubation with androgen, and its androgen-receptor complexes are not thermolabile. Our study of this man permits two conclusions: impaired spermatogenesis is not the irreducible expression of receptor-defective androgen resistance in man; and androgen pharmacotherapy may be remedial for those in whom extragenital subvirilization is emotionally costly and subnormal spermatogenesis is not an inevitable side effect of such therapy. PMID:2705470

  3. Research Resource: Hormones, Genes, and Athleticism: Effect of Androgens on the Avian Muscular Transcriptome.

    PubMed

    Fuxjager, Matthew J; Lee, Jae-Hyung; Chan, Tak-Ming; Bahn, Jae Hoon; Chew, Jenifer G; Xiao, Xinshu; Schlinger, Barney A

    2016-02-01

    Male vertebrate social displays vary from physically simple to complex, with the latter involving exquisite motor command of the body and appendages. Studies of these displays have, in turn, provided substantial insight into neuromotor mechanisms. The neotropical golden-collared manakin (Manacus vitellinus) has been used previously as a model to investigate intricate motor skills because adult males of this species perform an acrobatic and androgen-dependent courtship display. To support this behavior, these birds express elevated levels of androgen receptors (AR) in their skeletal muscles. Here we use RNA sequencing to explore how testosterone (T) modulates the muscular transcriptome to support male manakin courtship displays. In addition, we explore how androgens influence gene expression in the muscles of the zebra finch (Taenopygia guttata), a model passerine bird with a limited courtship display and minimal muscle AR. We identify androgen-dependent, muscle-specific gene regulation in both species. In addition, we identify manakin-specific effects that are linked to muscle use during the manakin display, including androgenic regulation of genes associated with muscle fiber contractility, cellular homeostasis, and energetic efficiency. Overall, our results point to numerous genes and gene networks impacted by androgens in male birds, including some that underlie optimal muscle function necessary for performing acrobatic display routines. Manakins are excellent models to explore gene regulation promoting athletic ability. PMID:26745669

  4. Selection for rapid embryo development correlates with embryo exposure to maternal androgens among passerine birds

    USGS Publications Warehouse

    Schwabl, H.; Palacios, M.G.; Martin, T.E.

    2007-01-01

    Greater offspring predation favors evolution of faster development among species. We hypothesized that greater offspring predation exerts selection on mothers to increase levels of anabolic androgens in egg yolks to achieve faster development. Here, we tested whether (1) concentrations of yolk androgens in passerine species were associated with offspring predation and (2) embryo and nestling development rates were associated with yolk androgen concentrations. We examined three androgens that increase in potency along the synthesis pathway: androstenedione (A4) to testosterone (T) to 5??- dihydrotestosterone (5??-DHT). Concentrations of none of these steroids were related to clutch size; only A4 was allometrically related to egg volume. Species that experience greater predation showed higher yolk concentrations of T and 5??-DHT. Higher concentrations of T and particularly 5??-DHT were strongly correlated with faster development during the embryo period and less so during the nestling period. Development rates were most strongly correlated with 5??-DHT, suggesting that potency increases along the androgen synthesis pathway and that effects are mediated by the androgen receptor pathway. These results are consistent with the hypothesis that selection for faster development by time-dependent offspring mortality may be achieved epigenetically by varying embryo exposure to maternal anabolic steroids. ?? 2007 by The University of Chicago. All rights reserved.

  5. p-Hydroxybenzyl Alcohol, an Active Phenolic Ingredient of Gastrodia elata, Reverses the Cycloheximide-Induced Memory Deficit by Activating the Adrenal Gland in Rats.

    PubMed

    Wu, Lung-Yuan; Chen, Wang-Chuan; Tsai, Fan-Shiu; Tsai, Chin-Chuan; Wu, Chi-Rei; Lin, Li-Wei

    2015-01-01

    The present study investigated the ameliorating effects of p-hydroxybenzyl alcohol (HBA), an active phenolic ingredient of Gastrodia elata, on cycloheximide (CXM)-induced impairment of passive avoidance response and clarified the role of adrenal glands on the effect of HBA in rats. An adrenalectomy (ADX) caused the memory deficit from 1 to 3 days after surgery. Administration of corticosterone (CORT) plus glucose completely recovered the memory deficit caused by ADX, and this effect was better than that of glucose or CORT alone. HBA ameliorated the memory deficit induced by CXM in sham and ADX rats, but ADX partially blocked it. Furthermore, plasma glucose, epinephrine and adrenal steroid levels of ADX rats significantly decreased. Sham rats who received HBA had an increase in plasma glucose and adrenal steroid levels. Therefore, we suggest that the reversal of CXM-induced memory deficit by HBA was partially dependent on adrenal glands through the increase of the levels of plasma adrenal steroids. PMID:26621444

  6. The androgen receptor in health and disease.

    PubMed

    Matsumoto, Takahiro; Sakari, Matomo; Okada, Maiko; Yokoyama, Atsushi; Takahashi, Sayuri; Kouzmenko, Alexander; Kato, Shigeaki

    2013-01-01

    Androgens play pivotal roles in the regulation of male development and physiological processes, particularly in the male reproductive system. Most biological effects of androgens are mediated by the action of nuclear androgen receptor (AR). AR acts as a master regulator of downstream androgen-dependent signaling pathway networks. This ligand-dependent transcriptional factor modulates gene expression through the recruitment of various coregulator complexes, the induction of chromatin reorganization, and epigenetic histone modifications at target genomic loci. Dysregulation of androgen/AR signaling perturbs normal reproductive development and accounts for a wide range of pathological conditions such as androgen-insensitive syndrome, prostate cancer, and spinal bulbar muscular atrophy. In this review we summarize recent advances in understanding of the epigenetic mechanisms of AR action as well as newly recognized aspects of AR-mediated androgen signaling in both men and women. In addition, we offer a perspective on the use of animal genetic model systems aimed at eventually developing novel therapeutic AR ligands. PMID:23157556

  7. [Acute adrenal insufficiency in the newborn].

    PubMed

    Limal, J-M; Bouhours-Nouet, N; Rouleau, S; Gatelais, F; Coutant, R

    2006-10-01

    Neonatal acute adrenal insufficiency is a rare condition. Congenital adrenal hyperplasia with 21-hydroxylase defect appears to be the most frequent cause, but the neonatal screening has improved its potential severe outcome. The other causes and the various clinical presentations have been exposed, with a special reference to the salt-wasting syndrome. Among them, the severity of X-linked adrenal hypoplasia congenita (AHC) deserves special attention. Two other causes of adrenal hypoplasia have been recently discovered, i.e. a mutation of the SF-1 gene and the syndrome IMAGe. Adrenal insufficiency secondary to ACTH deficiency is often unrecognised despite the risk of severe seizures and hypoglycaemia with brain damage. Finally, the hormonal diagnostic testing and the main therapeutic approach by corticosteroids have been indicated. The aim of this work is to focus the attention of paediatricians who examine a newborn because the risk of delayed diagnosis and fatal outcome may be limited if the clinical symptoms are soon recognized. PMID:16962294

  8. Role of adrenal imaging in surgical management

    SciTech Connect

    Lamki, L.M.; Haynie, T.P. )

    1990-03-01

    Adrenal imaging using radiopharmaceuticals is a functional test that can contribute significantly to surgical management and follow-up of patients with either benign or malignant conditions of the adrenal cortex and medulla. Imaging of the cortex is achieved by iodine-131-labeled iodomethyl nor-cholesterol (NP-59), while adrenal medulla imaging can be successfully accomplished by 131I-metaiodobenzylguanidine (MIBG), which localizes in the adrenergic nerve terminal with norepinephrine. Both tests carry high sensitivity and specificity for functional tumors and hyperplasia, and often better than CT scanning. This article reviews the current status and clinical utility of nuclear imaging of the adrenal cortex in congenital hyperplasia, low renin hypertension and aldosteronism, and Cushing's syndrome. Adrenal medulla imaging is reviewed in light of our experience at the University of Texas M.D. Anderson Cancer Center in pheochromocytoma, neuroblastoma, and other neuroectodermal tumors. Investigation of {sup 131}I-MIBG therapy of metastatic tumors of neuroectodermal origin potentially offers a means of at least controlling symptoms of hormonal secretion in these patients. 40 references.

  9. Endocytosis of connexin protein in adrenal cells.

    PubMed

    Murray, Sandra A; Nickel, B M; Gay, V L

    2004-11-01

    The ability of adrenocorticotropin (ACTH) to affect gap junctions was examined in adrenal cells in vivo and in vitro. Treatment with ACTH increased the size and number of gap junction plaques on the cell membranes in hypophysectomized animals and in adrenal culture. Intracellular (cytoplasmic) annular gap junctions were observed in cells of the inner adrenal cortical zones and in adrenal cell cultures. To investigate the relationship of annular gap junctions to surface junctions, adrenal cells in culture were transfected with cDNA encoding a green fluorescent protein tagged connexin 43 construct (Cx43-GFP), and subsequently studied by time-lapse video microscopy, immunocytochemistry, and transmission electron microscopy (TEM). Internalization of part or all of a surface gap junction plaque resulted in annular gap junction formation. These studies support the hypothesis that cytoplasmic vesicles, initially described with TEM methods, can result from removal of gap junction plaques from the cell surface. It is suggested that hormones can play a regulatory role in cell-cell communication by influencing the availability of gap junction protein at the cell surface and that hormonally-sensitive processes might serve as a means of altering intercellular communication. PMID:15666807

  10. Uptake and release of adrenal ascorbic acid in the guinea pig after injection of ACTH

    SciTech Connect

    Kipp, D.E.; Rivers, J.M.

    1987-09-01

    The effect of a single injection of ACTH (3 IU/100 g body weight) on the distribution of ascorbic acid (AA) and radiolabeled AA in 20 tissues was studied in adult male guinea pigs consuming 500 mg AA/kg diet. Saline- or ACTH-injected animals were simultaneously injected with (1-/sup 14/C)AA, and killed at 0.5, 1, 2, 4 and 6 h after injection. There was no significant difference between treatments in the weight of any tissue over the 6-h experimental period. As anticipated, the concentration of AA in the adrenals of animals injected with ACTH was 33% of that of animals injected with saline at 4 h. Unexpectedly, the concentration of radiolabeled AA in the adrenals at 0.5 h after ACTH injection was 172% of that after saline injection. The concentration of radiolabeled AA in the adrenal of the saline-injected animals increased slowly over time to reach a level similar to that of ACTH-injected animals by 6 h. There was no effect of ACTH on the level of AA or uptake in any of the other tissues examined. These results demonstrate that a single dose of ACTH markedly influences the retention of AA in the adrenal gland without similarly altering retention of AA in other tissues. Furthermore, ACTH treatment causes both accelerated uptake and release of AA into the adrenals.

  11. Expression of androgen receptor splice variants in clinical breast cancers

    PubMed Central

    Dvinge, Heidi; Tarulli, Gerard A.; Hanson, Adrienne R.; Ryan, Natalie K.; Pickering, Marie A.; Birrell, Stephen N.; Hu, Dong Gui; Mackenzie, Peter I.; Russell, Roslin; Caldas, Carlos; Raj, Ganesh V.; Dehm, Scott M.; Plymate, Stephen R.; Bradley, Robert K.; Tilley, Wayne D.; Selth, Luke A.

    2015-01-01

    The importance of androgen receptor (AR) signaling is increasingly being recognized in breast cancer, which has elicited clinical trials aimed at assessing the efficacy of androgen deprivation therapy (ADT) for metastatic disease. In prostate cancer, resistance to ADT is frequently associated with the emergence of androgen-independent splice variants of the AR (AR variants, AR-Vs) that lack the LBD and are constitutively active. Women with breast cancer may be prone to a similar phenomenon. Herein, we show that in addition to the prototypical transcript, the AR gene produces a diverse range of AR-V transcripts in primary breast tumors. The most frequently and highly expressed variant was AR-V7 (exons 1/2/3/CE3), which was detectable at the mRNA level in > 50% of all breast cancers and at the protein level in a subset of ERα-negative tumors. Functionally, AR-V7 is a constitutively active and ADT-resistant transcription factor that promotes growth and regulates a transcriptional program distinct from AR in ERα-negative breast cancer cells. Importantly, we provide ex vivo evidence that AR-V7 is upregulated by the AR antagonist enzalutamide in primary breast tumors. These findings have implications for treatment response in the ongoing clinical trials of ADT in breast cancer. PMID:26554309

  12. Expression of androgen receptor splice variants in clinical breast cancers.

    PubMed

    Hickey, Theresa E; Irvine, Connie M; Dvinge, Heidi; Tarulli, Gerard A; Hanson, Adrienne R; Ryan, Natalie K; Pickering, Marie A; Birrell, Stephen N; Hu, Dong Gui; Mackenzie, Peter I; Russell, Roslin; Caldas, Carlos; Raj, Ganesh V; Dehm, Scott M; Plymate, Stephen R; Bradley, Robert K; Tilley, Wayne D; Selth, Luke A

    2015-12-29

    The importance of androgen receptor (AR) signaling is increasingly being recognized in breast cancer, which has elicited clinical trials aimed at assessing the efficacy of androgen deprivation therapy (ADT) for metastatic disease. In prostate cancer, resistance to ADT is frequently associated with the emergence of androgen-independent splice variants of the AR (AR variants, AR-Vs) that lack the LBD and are constitutively active. Women with breast cancer may be prone to a similar phenomenon. Herein, we show that in addition to the prototypical transcript, the AR gene produces a diverse range of AR-V transcripts in primary breast tumors. The most frequently and highly expressed variant was AR-V7 (exons 1/2/3/CE3), which was detectable at the mRNA level in > 50% of all breast cancers and at the protein level in a subset of ERα-negative tumors. Functionally, AR-V7 is a constitutively active and ADT-resistant transcription factor that promotes growth and regulates a transcriptional program distinct from AR in ERα-negative breast cancer cells. Importantly, we provide ex vivo evidence that AR-V7 is upregulated by the AR antagonist enzalutamide in primary breast tumors. These findings have implications for treatment response in the ongoing clinical trials of ADT in breast cancer. PMID:26554309

  13. Cues to Androgens and Quality in Male Gibbon Songs

    PubMed Central

    Barelli, Claudia; Mundry, Roger; Heistermann, Michael; Hammerschmidt, Kurt

    2013-01-01

    Animal vocal signals may provide information about senders and mediate important social interactions like sexual competition, territory maintenance and mate selection. Hence, it is important to understand whether vocal signals provide accurate information about animal attributes or status. Gibbons are non-human primates that produce loud, distinctive and melodious vocalizations resembling more those of birds than of other non-human primates. Wild gibbons are characterized by flexibility in social organization (i.e., pairs and multimale units) as well as in mating system (i.e., monogamy and polyandry). Such features make them a suitable model to investigate whether the physiology (hormonal status) and socio-demographic features find their correspondence in the structure of their songs. By combining male solo song recordings, endocrine outputs using non-invasive fecal androgen measures and behavioral observations, we studied 14 groups (10 pair-living, 4 multimale) of wild white-handed gibbons (Hylobates lar) residing at Khao Yai National Park, Thailand. We collected a total of 322 fecal samples and recorded 48 songs from 18 adult animals. Our results confirmed inter-individuality in male gibbon songs, and showed a clear correlation between androgen levels and song structures. Gibbons with higher androgen levels produced calls having higher pitch, and similarly adult individuals produced longer calls than senior males. Thus, it is plausible that gibbon vocalizations provide receivers with information about singers' attributes. PMID:24367551

  14. Multiple roles for UDP-glucuronosyltransferase (UGT)2B15 and UGT2B17 enzymes in androgen metabolism and prostate cancer evolution.

    PubMed

    Gauthier-Landry, Louis; Bélanger, Alain; Barbier, Olivier

    2015-01-01

    In the prostate, approximately 50% of androgens are from adrenal steroids, mainly dehydroepiandrosterone (DHEA), its sulfate and androstenedione. These compounds are converted first into testosterone, and then into the active hormone dihydrotestosterone (DHT). After having activated the androgen receptor (AR), DHT is reduced into androstane-3α-DIOL (3α-DIOL) and androsterone (ADT), which are subsequently converted into 2 inactive and easily excretable metabolites: 3α-DIOL-17glucuronide (3α-DIOL-17G) and ADT-3glucuronide (ADT-3G). The formation of these last derivatives through the glucuronidation reaction involves 2 UDP-glucuronosyltransferase (UGT) enzymes, namely UGT2B15 and UGT2B17. The present review article aims at providing a comprehensive view of the physiological and pharmacological importance of these 2 enzymes for the control of androgen homeostasis. We will resume: (i) how UGT2B15 and UGT2B17 contribute to androgen elimination; (ii) how their glucuronidation capacity influences the androgen signaling pathway in prostate cells; (iii) how they contribute to the anti-proliferative properties of AR antagonists in prostate cancer cells; and (iv) how AR and its spliced variants regulate the UGT2B15 and/or UGT2B17 genes expression. Finally, whether the unexploited AR-UGT axis could serve as a prognostic maker or a pharmacological target for novel therapeutics in the treatment of prostate cancer is also discussed. This article is part of a special issue entitled 'Essential role of DHEA'. PMID:24861263

  15. Increase in collagen production with loss of androgen responsiveness in cultured androgen-responsive Shionogi carcinoma 115 cells.

    PubMed

    Terada, N; Wakimoto, H; Yamamoto, R; Uchida, N; Takatsuka, D; Takada, T; Taniguchi, H; Li, W; Kitamura, Y; Matsumoto, K

    1988-05-01

    The collagen production of androgen-responsive and -unresponsive Shionogi carcinoma 115 cells was investigated by culturing them in a medium with or without testosterone. Androgen-unresponsive cells were obtained by culturing a cloned androgen-responsive cell in a testosterone-free medium for 12 weeks. The collagen production of androgen-responsive cells slightly increased in the absence of testosterone, whereas testosterone did not affect the collagen production of androgen-unresponsive cells. Androgen-unresponsive cells produced 3-4 times more collagen than androgen-responsive cells. The major collagen produced by both androgen-responsive and - unresponsive cells migrated to the same position in sodium dodecylsulfate:polyacylamide gel electrophoresis. The present results indicate that the collagen production of androgen-responsive Shionogi carcinoma 115 cells increases with the loss of androgen responsiveness in culture. PMID:3169094

  16. Enobosarm (GTx-024) Modulates Adult Skeletal Muscle Mass Independently of the Androgen Receptor in the Satellite Cell Lineage.

    PubMed

    Dubois, Vanessa; Simitsidellis, Ioannis; Laurent, Michaël R; Jardi, Ferran; Saunders, Philippa T K; Vanderschueren, Dirk; Claessens, Frank

    2015-12-01

    Androgens increase skeletal muscle mass, but their clinical use is hampered by a lack of tissue selectivity and subsequent side effects. Selective androgen receptor modulators elicit muscle-anabolic effects while only sparingly affecting reproductive tissues. The selective androgen receptor modulator, GTx-024 (enobosarm), is being investigated for cancer cachexia, sarcopenia, and muscle wasting diseases. Here we investigate the role of muscle androgen receptor (AR) in the anabolic effect of GTx-024. In mice lacking AR in the satellite cell lineage (satARKO), the weight of the androgen-sensitive levator ani muscle was lower but was decreased further upon orchidectomy. GTx-024 was as effective as DHT in restoring levator ani weights to sham levels. Expression of the muscle-specific, androgen-responsive genes S-adenosylmethionine decarboxylase and myostatin was decreased by orchidectomy and restored by GTx-024 and DHT in control mice, whereas the expression was low and unaffected by androgen status in satARKO. In contrast, insulin-like growth factor 1Ea expression was not different between satARKO and control muscle, decreased upon castration, and was restored by DHT and GTx-024 in both genotypes. These data indicate that GTx-024 does not selectively modulate AR in the satellite cell lineage and that cells outside this lineage remain androgen responsive in satARKO muscle. Indeed, residual AR-positive cells were present in satARKO muscle, coexpressing the fibroblast-lineage marker vimentin. AR positive, muscle-resident fibroblasts could therefore be involved in the indirect effects of androgens on muscle. In conclusion, both DHT and GTx-024 target AR pathways in the satellite cell lineage, but cells outside this lineage also contribute to the anabolic effects of androgens. PMID:26393303

  17. How Do I Find an Experienced Adrenal Surgeon?

    MedlinePlus

    ... NICHD Research Information Clinical Trials Resources and Publications Adrenal Gland Disorders: Other FAQs Skip sharing on social media links Share this: Page ... do I find an experienced adrenal surgeon? Make sure that the surgeon you choose ...

  18. What Are the Treatments for Adrenal Gland Disorders?

    MedlinePlus

    ... Resources and Publications What are the treatments for adrenal gland disorders? Skip sharing on social media links Share ... a variety of surgical and medical treatments for adrenal gland disorders. These include 1 : Surgery to remove tumors ...

  19. What Should You Ask Your Doctor about Adrenal Cortical Cancer?

    MedlinePlus

    ... after treatment for adrenal cancer? What should you ask your doctor about adrenal cancer? As you deal ... frank, open discussions with your cancer care team. Ask any questions, no matter how trivial they might ...

  20. [Combined modality therapy for a patient with primary adrenal lymphoma].

    PubMed

    Matsuno, Teppei; Kuroda, Hiroyuki; Jomen, Wataru; Yoshida, Masahiro; Yamada, Michiko; Sato, Masanori; Abe, Tomoyuki; Sakurai, Tamaki; Fujii, Shigeyuki; Maeda, Masahiro; Fujita, Miri; Nagashima, Kazuo; Nojiri, Shuichi; Arihara, Yohei; Kato, Junji

    2014-04-01

    A 71-year-old man with malaise, anorexia, and weight loss was referred to our hospital from a clinic. Abdominal computed tomography(CT)revealed bilateral adrenal masses. An ultrasound-guided percutaneous needle biopsy of the adrenal grand indicated diffuse large B-cell lymphoma. A rapid adrenocorticotropic hormone(ACTH)test revealed primary adrenal failure. Rituximab-cyclophosphamide/doxorubicin/vincristine/prednisolone(common name, R-CHOP)therapy accompanied by intrathecal treatment was initiated along with steroid replacement therapy. After the fourth courses, a CT scan showed a reduction of the adrenal masses, and there was no[18F]-fluorodeoxyglucose(FDG)uptake in the adrenal masses. The patient has remained in metabolic complete remission. Subsequently, both adrenal lymphomas were irradiated. The patient has been disease-free for 6 months after the diagnosis of primary adrenal lymphoma. The combined modality of chemoradiation therapy plus intrathecal treatment could be effective for primary adrenal lymphoma with a poor prognosis. PMID:24743371

  1. Expression of a hyperactive androgen receptor leads to androgen-independent growth of prostate cancer cells.

    PubMed

    Hsieh, Chen-Lin; Cai, Changmeng; Giwa, Ahmed; Bivins, Aaronica; Chen, Shao-Yong; Sabry, Dina; Govardhan, Kumara; Shemshedini, Lirim

    2008-07-01

    Cellular changes that affect the androgen receptor (AR) can cause prostate cancer to transition from androgen dependent to androgen independent, which is usually lethal. One common change in prostate tumors is overexpression of the AR, which has been shown to lead to androgen-independent growth of prostate cancer cells. This led us to hypothesize that expression of a hyperactive AR would be sufficient for androgen-independent growth of prostate cancer cells. To test this hypothesis, stable lune cancer prostate (LNCaP) cell lines were generated, which express a virion phosphoprotein (VP)16-AR hybrid protein that contains full-length AR fused to the strong viral transcriptional activation domain VP16. This fusion protein elicited as much as a 20-fold stronger transcriptional activity than the natural AR. Stable expression of VP16-AR in LNCaP cells yielded androgen-independent cell proliferation, while under the same growth conditions the parental LNCaP cells exhibited only androgen-dependent growth. These results show that expression of a hyperactive AR is sufficient for androgen-independent growth of prostate cancer cells. To study the molecular basis of this enhanced growth, we measured the expression of soluble guanylyl cyclase-alpha1 (sGCalpha1), a subunit of the sGC, an androgen-regulated gene that has been shown to be involved in prostate cancer cell growth. Interestingly, the expression of sGCalpha1 is androgen independent in VP16-AR-expressing cells, in contrast to its androgen-induced expression in control LNCaP cells. RNA(I)-dependent inhibition of sGCalpha1 expression resulted in significantly reduced proliferation of VP16-AR cells, implicating an important role for sGCalpha1 in the androgen-independent growth of these cells. PMID:18469090

  2. [Mantle cell lymphoma markedly infiltrated into adrenal glands with adrenal insufficiency].

    PubMed

    Hashimoto, Ryo; Iwakiri, Rika; Tsutsumi, Hisashi; Ohta, Masatsugu; Mori, Mayumi

    2004-07-01

    A 66-year-old male was admitted to our hospital complaining of bilateral hypochondrial pain, back pain and loss of weight in May, 2002. Superficial lymph nodes were not palpable on admission. The leukocyte count was 3430/microl, hemoglobin concentration, 13.0g/dl, and platelet count, 174000/microl. LDH, soluble IL-2 receptor, ACTH and cortisol values were out of the normal range (LDH 1368IU/l, sIL-2R 2630U/ml, ACTH 132pg/ml, cortisol 7.4microg/dl). Abdominal CT scan showed bilateral adrenal masses, and abnormal uptake of Ga-scintigraphy was seen correspondent with the bilateral adrenal masses. The histological diagnosis of bilateral adrenal masses cannot be performed because of the bleeding tendency, but atypical cells were observed in the patient's bone marrow aspirate. Surface marker analysis of atypical cells showed CD5+, cyclin D1+, CD19+, CD20+ and HLA-DR+. From these results we diagnosed this case as a mantle cell lymphoma (stage IV B) markedly infiltrated into the adrenal glands with adrenal insufficiency. The bilateral adrenal masses dramatically reduced in size after CHOP chemotherapy with hydrocortisone supplementation. We report on the present case and summarize the reports of adrenal grand-infiltrating lymphomas. PMID:15359915

  3. Prenatal ethanol exposure-induced adrenal developmental abnormality of male offspring rats and its possible intrauterine programming mechanisms.

    PubMed

    Huang, Hegui; He, Zheng; Zhu, Chunyan; Liu, Lian; Kou, Hao; Shen, Lang; Wang, Hui

    2015-10-01

    Fetal adrenal developmental status is the major determinant of fetal tissue maturation and offspring growth. We have previously proposed that prenatal ethanol exposure (PEE) suppresses fetal adrenal corticosterone (CORT) synthesis. Here, we focused on PEE-induced adrenal developmental abnormalities of male offspring rats before and after birth, and aimed to explore its intrauterine programming mechanisms. A rat model of intrauterine growth retardation (IUGR) was established by PEE (4g/kg·d). In PEE fetus, increased serum CORT concentration and decreased insulin-like growth factor 1 (IGF1) concentration, with lower bodyweight and structural abnormalities as well as a decreased Ki67 expression (proliferative marker), were observed in the male fetal adrenal cortex. Adrenal glucocorticoid (GC)-metabolic activation system was enhanced while gene expression of IGF1 signaling pathway with steroidogenic acute regulatory protein (StAR), 3β-hydroxysteroid dehydrogenase (3β-HSD) was decreased. Furthermore, in the male adult offspring of PEE, serum CORT level was decreased but IGF1 was increased with partial catch-up growth, and Ki67 expression demonstrated no obvious change. Adrenal GC-metabolic activation system was inhibited, while IGF1 signaling pathway and 3β-HSD was enhanced with the steroidogenic factor 1 (SF1), and StAR was down-regulated in the adult adrenal. Based on these findings, we propose a "two-programming" mechanism for PEE-induced adrenal developmental toxicity: "the first programming" is a lower functional programming of adrenal steroidogenesis, and "the second programming" is GC-metabolic activation system-related GC-IGF1 axis programming. PMID:26188107

  4. Principles and management of adrenal cancer

    SciTech Connect

    Javadpour, N.

    1987-01-01

    This book provides information on adrenal diseases of latest developments and guides the clinicians in the care of their patients. The book is divided into two parts. The first section gives an overview of the embryology, anatomy, physiology, markers, pathology, imaging and the current progress in the field. The second edition covers specific diseases of the adrenal cortex and medulla. The increasingly significant roles played by steroids, catecholamines, blockers, computed tomography and magnetic resonance are elucidated and discussed. The contents include: Overview of progress; current problems, and perspectives - embryology anatomy, physiology, and biologic markers; pathology; advances in diagnosis; imaging techniques; adrenal disorders in childhood; primary aldosteronism; Cushing's syndrome; carcinoma; pheochromocytoma; neuroblastoma; metastatic disease; surgical management; and subject index.

  5. Myxoid adrenal adenoma with focal pseudoglandular pattern.

    PubMed

    De Padua, Michelle; Rajagopal, V

    2008-05-01

    Adrenal cortical tumors with myxoid change are rare tumors. To our knowledge, only 22 cases have been described so far in literature, which include 13 carcinomas and 9 adenomas. A pseudoglandular pattern has been described in 9 of these tumors. We report a case of a myxoid adenoma of the left adrenal gland in a 67-year-old woman, with a focal pseudoglandular pattern involving about 20% of the studied tumor. Rest of the tumor was composed of anastomosing cords of tumor cells. Abundant myxoid stroma was present, which stained positively with alcian blue and was weakly focally positive with periodic acid Schiff. Immunophenotype was consistent with an adrenal tumor, i.e., positive for vimentin, inhibin, and melan A. Cytokeratin AE1/AE3 and chromogranin were negative. MIB-1 index was < 0.1%. PMID:18579979

  6. Role of phospholipases in adrenal steroidogenesis.

    PubMed

    Bollag, Wendy B

    2016-04-01

    Phospholipases are lipid-metabolizing enzymes that hydrolyze phospholipids. In some cases, their activity results in remodeling of lipids and/or allows the synthesis of other lipids. In other cases, however, and of interest to the topic of adrenal steroidogenesis, phospholipases produce second messengers that modify the function of a cell. In this review, the enzymatic reactions, products, and effectors of three phospholipases, phospholipase C, phospholipase D, and phospholipase A2, are discussed. Although much data have been obtained concerning the role of phospholipases C and D in regulating adrenal steroid hormone production, there are still many gaps in our knowledge. Furthermore, little is known about the involvement of phospholipase A2, perhaps, in part, because this enzyme comprises a large family of related enzymes that are differentially regulated and with different functions. This review presents the evidence supporting the role of each of these phospholipases in steroidogenesis in the adrenal cortex. PMID:26878860

  7. Adrenal Schwannomas: Rare Tumor of the Retroperitoneum.

    PubMed

    Grasso, Emanuele; Simone, Michele

    2015-01-01

    Schwannoma is a benign neurogenic tumor originating from Schwann cells. These produce the myelin sheath that covers peripheral nerves that are often affected. This latter localization is extremely rare, and only a few case reports can be found in the medical literature. Studies have shown that approximately 0.5% to 5% of schwannomas are retroperitoneal, constituting 0.2% of adrenal incidental tumors. These usually present as incidental findings, nonsecreting adrenal masses in asymptomatic patients. Diagnosis of a schwannoma is based on detection of spindle cells with Antoni A and Antoni B regions in histological sections and positive staining for S-100 protein by immunohistochemical analysis. We report a case of an incidentally identified during an abdominal ultrasound examination with schwannoma localized in the left adrenal gland. PMID:26101687

  8. Image-Guided Adrenal and Renal Biopsy

    PubMed Central

    Sharma, Karun V.; Venkatesan, Aradhana M.; Swerdlow, Daniel; DaSilva, Daniel; Beck, Avi; Jain, Nidhi; Wood, Bradford J.

    2010-01-01

    Image-guided biopsy is a safe and well-established technique that is familiar to most interventional radiologists (IRs). Improvements in image-guidance, biopsy tools and biopsy techniques now routinely allow for safe biopsy of renal and adrenal lesions which traditionally were considered difficult to reach or technically challenging. Image-guided biopsy is used to establish the definitive tissue diagnosis in adrenal mass lesions that can not be fully characterized with imaging or laboratory tests alone. It is also used to establish definitive diagnosis in some cases of renal parenchymal disease and has an expanding role in diagnosis and characterization of renal masses prior to treatment. Although basic principles and techniques for image-guided needle biopsy are similar regardless of organ, this paper will highlight some technical considerations, indications and complications which are unique to the adrenal gland and kidney because of their anatomic location and physiologic features. PMID:20540919

  9. Bioanalytical LC-MS Method for the Quantification of Plasma Androgens and Androgen Glucuronides in Breast Cancer.

    PubMed

    Kalogera, Eleni; Pistos, Constantinos; Provatopoulou, Xeni; Christophi, Costas A; Zografos, George C; Stefanidou, Maria; Spiliopoulou, Chara; Athanaselis, Sotirios; Gounaris, Antonia

    2016-04-01

    The physiological and pathological development of the breast is strongly affected by the hormonal milieu consisting of steroid hormones. Mass spectrometry (MS) technologies of high sensitivity and specificity enable the quantification of androgens and consequently the characterization of the hormonal status. The aim of this study is the assessment of plasma androgens and androgen glucuronides, in the par excellence hormone-sensitive tissue of the breast, through the application of liquid chromatography-mass spectrometry (LC-MS). A simple and efficient fit-for-purpose method for the simultaneous identification and quantification of dehydroepiandrosterone sulfate (DHEAS), androstenedione (A4), androsterone glucuronide (ADTG) and androstane-3α, 17β-diol-17-glucuronide (3α-diol-17G) in human plasma was developed and validated. The presented method permits omission of derivatization, requires a single solid-phase extraction procedure and the chromatographic separation can be achieved on a single C18 analytical column, for all four analytes. The validated method was successfully applied for the analysis of 191 human plasma samples from postmenopausal women with benign breast disease (BBD), lobular neoplasia (LN), ductal carcinoma in situ and invasive ductal carcinoma (IDC). DHEAS plasma levels exhibited significant differences between LN, IDC and BBD patients (P < 0.05). Additionally, ADTG levels were significantly higher in patients with LN compared with those with BBD (P < 0.05). PMID:26762957

  10. Localization of metastatic adrenal cortical carcinoma with Ga-67

    SciTech Connect

    Ward, F.T.; Anderson, J.H.; Jelinek, J.; Anderson, D.W. )

    1991-02-01

    Data are limited on the localization of Ga-67 in primary or metastatic adrenal cortical carcinoma. We report the localization of Ga-67 to pathologically confirmed adrenal cortical carcinoma metastatic to the lung. A review of the literature revealed four patients have previously been reported to have metastatic adrenal cortical carcinoma detected on Ga-67 scan. Gallium imaging may be useful in the evaluation of patients with adrenal cortical carcinoma. SPECT imaging should further improve lesion resolution and localization.

  11. Adrenal glands in patients with cogenital renal anomalies: CT appearance

    SciTech Connect

    Kenney, P.J.; Robbins, G.L.; Ellis, D.A.; Spirt, B.A.

    1985-04-01

    The CT appearance of the adrenal glands was investigated in 30 patients with congenital renal anomalies. The ipsilateral adrenal was clearly identified in 83% of these patients; in all of them, the adrenal was a paraspinal disk-shaped organ, which appeared linear on CT. Conversely, the adrenals retained their normal shape in a control group of 20 patients with acquired renal atrophy or prior simple nephrectomy.

  12. Laser autofluorescent spectroscopy in adrenal tumor surgery

    NASA Astrophysics Data System (ADS)

    Vetshev, Petr S.; Ippolitov, Leonid I.; Loschenov, Victor B.; Kazaryan, Airazat M.; Minnibaev, Marat T.; Vetshev, Sergei P.

    1999-12-01

    Determination of a histological type of adrenal lesion at the preoperative or intraoperative stage allows to choose the optimal volume of surgery and in the short time effectively correct the postoperative hormonal therapy. 12 patients with different adrenal tumours (3 - lightcellular adenoma, 3 - mixedcellular adenoma, 1 - darkcellular adenoma, 1 - trabecular adenoma, 1 - malignant lymphoma, 3 - aldosteroma, 1 - pheochromocytoma, including the chance of combination of mixedcellular adenoma and aldosteroma of left adrenal) were operated on. The patients' aged varied from 33 to 62 years. For the first time we made intraoperative laser autofluorescent spectroscopy (IOLAS). The laser ve1ength was 632.8 nm. We defined a autofluorescent intensity. Portable equipment was used. The duration of the procedure did not exceed 2mm. The autofluorescent peak of adrenal tissue was 1.33+/-0.05 relativistic unit (RU) at 685 nm. The autofiurescent peaks of adrenal adenomas were 1 .07 RU, 0.9-1 .15 RU, 1.7-1 .9 RU, 3.4 RU accordingly for trabecular adenoma, lightcellular adenoma, mixedcellular adenoma, darkcellular adenoma Besides greater contribution of longwave component to auflurescence is characteristic for mixecellular adenoma and especially for darkcellular adenoma. The autofiurescent peaks of aldosteroma and pheochromocytoma were accordingly 1.2-1.4 RU and 2.2 RU. Spectral distribution of intensity was like mixedcellular adenoma's one. In the case of malignant lymphoma the autofiurescence peak was 2,3 RU and we also noted displacement of maximum of autoflurescence (-15 nm, from 685 nm to 670 nm).The results of IOLAS application as a adjuvant diagnosticmethod point to promise for intraoperative rapid diagnostics of adrenal tumours.

  13. Preventing female virilisation in congenital adrenal hyperplasia: The controversial role of antenatal dexamethasone.

    PubMed

    Heland, Sarah; Hewitt, Jacqueline K; McGillivray, George; Walker, Susan P

    2016-06-01

    Congenital adrenal hyperplasia (CAH) refers to a group of recessively inherited disorders of cortisol production, which in the classical form results in virilisation of female fetuses. Since the 1980s, antenatal treatment with dexamethasone has been recommended in high-risk pregnancies to minimise the risk of virilising the female genitalia of affected fetuses. To be effective, this treatment requires implementation in early pregnancy, prior to the commencement of autonomous fetal adrenal androgen synthesis. Using this approach, seven of eight high-risk pregnancies are treated unnecessarily, prior to establishing the fetal gender or the confirmed diagnosis of a genetically affected pregnancy. In the face of ongoing concerns regarding potential adverse maternal-fetal effects of antenatal dexamethasone exposure, a review of this practice has been advocated by expert advisory groups. In this review, we summarise current controversies, potential improvements and future directions in the management of pregnancies at risk of CAH. In high-risk families, recent genomic advances include early prenatal diagnosis utilising noninvasive genetic techniques to minimise unnecessary dexamethasone exposure to unaffected fetuses. In affected pregnancies when families elect for antenatal treatment, optimal antenatal dosing regimens need to be defined and a standardised treatment and follow-up protocol are recommended. Establishment of a national registry with standardised follow-up will allow future families to be better informed of the risks and benefits of both treated and untreated fetal CAH. PMID:26661642

  14. Synthetic androgens as designer supplements.

    PubMed

    Joseph, Jan Felix; Parr, Maria Kristina

    2015-01-01

    Anabolic androgenic steroids (AAS) are some of the most common performance enhancing drugs (PED) among society. Despite the broad spectrum of adverse effects and legal consequences, AAS are illicitly marketed and distributed in many countries. To circumvent existing laws, the chemical structure of AAS is modified and these designer steroids are sold as nutritional supplements mainly over the Internet. Several side effects are linked with AAS abuse. Only little is known about the pharmacological effects and metabolism of unapproved steroids due to the absence of clinical studies. The large number of designer steroid findings in dietary supplements and the detection of new compounds combined with legal loopholes for their distribution in many countries show that stricter regulations and better information policy are needed. PMID:26074745

  15. Synthetic Androgens as Designer Supplements

    PubMed Central

    Joseph, Jan Felix; Parr, Maria Kristina

    2015-01-01

    Anabolic androgenic steroids (AAS) are some of the most common performance enhancing drugs (PED) among society. Despite the broad spectrum of adverse effects and legal consequences, AAS are illicitly marketed and distributed in many countries. To circumvent existing laws, the chemical structure of AAS is modified and these designer steroids are sold as nutritional supplements mainly over the Internet. Several side effects are linked with AAS abuse. Only little is known about the pharmacological effects and metabolism of unapproved steroids due to the absence of clinical studies. The large number of designer steroid findings in dietary supplements and the detection of new compounds combined with legal loopholes for their distribution in many countries show that stricter regulations and better information policy are needed. PMID:26074745

  16. Hormones, context, and "brain gender": a review of evidence from congenital adrenal hyperplasia.

    PubMed

    Jordan-Young, Rebecca M

    2012-06-01

    Brain organization theory suggests that steroid hormones during fetal development permanently organize the brain for gender, including patterns of sexuality, cognition, temperament, and interests that differ by sex. This widely-accepted theory has important implications for health, ranging from medical management of infants with intersex conditions to suggested etiologies for sex differences in autism, depression, and other mental health problems. Studies of genetic females with congenital adrenal hyperplasia (CAH), in which high prenatal androgens have been linked to both atypical genitals and "masculine" patterns of gender and sexuality, are particularly important. Based on a comprehensive review of research on CAH, this article demonstrates that such studies have neglected four broad categories of variables that plausibly affect psychosexual development: (1) physiological effects of CAH, including complex disruption of steroid hormones from early development onwards; (2) intensive medical intervention and surveillance, which many women with CAH describe as traumatic; (3) direct effects of genital morphology on sexuality (versus indirect effects that "masculine" genitals may have on gender socialization); and (4) expectations of masculinization that likely affect both the development and evaluation of gender and sexuality in CAH. Complex and iterative interactions among postnatal biological variables, medical interventions, and social context provide a more plausible explanation for atypicalities in psychology and behavior that have been reported for genetic females with CAH than the conventional explanation that early androgens have "masculinized" their brains. PMID:21962724

  17. AB079. Phenotype variation in untreated 46,XX congenital adrenal hyperplasia

    PubMed Central

    Faradz, Sultana MH; Utari, Agustini; Ediati, Annastasia; Ariani, Mahayu Dewi; Juniarto, Achmad Zulfa

    2015-01-01

    Simple virilizing congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder characterized by 21 hydroxylase deficiency leading to excessive androgen production. In infants with 46,XX karyotype, prenatal exposure of androgen overproduction leads to a gradual virilization of the external genital. Consequently, babies are born with an ambiguous genital which complicates sex assignment. Genital virilization will be progressive if these babies remain untreated. In country where newborn screening is available, patients with CAH are identified soon after birth and receive medication afterward, unlike in Indonesia. Many parents and patients with CAH did not seek healthcare professionals due to lack of information about inheritance and clinical manifestation of CAH. In Indonesia, newborn screening has not been applied yet; management and therapy for CAH are only available in some big cities but glucocorticoid medications need to be imported. Diagnosis was established using karyotype, hormonal and gene mutation analysis. In this study, we reported 30 patients with different physical appearance i.e., big phallus, one or two ending perineum, very severe chordae, labioscrotal fusion, complete labial fusion with scrotalization, masculization, no breast development, severe hyperpigmentation, appears Adam’s apple and short stature. Sex assignment is still a dilemma; some of the children were raised as males, females, or left undefined. The complex management of children and adults with CAH highlights the importance of raising awareness among medical personnels to promote early detection and treatment for CAH patients. Genetic counseling is essential for these families.

  18. Prenatal Diagnosis of Congenital Adrenal Hyperplasia.

    PubMed

    Yau, Mabel; Khattab, Ahmed; New, Maria I

    2016-06-01

    Congenital adrenal hyperplasia (CAH) owing to 21-hydroxylase deficiency is a monogenic disorder of adrenal steroidogenesis. To prevent genital ambiguity, in girls, prenatal dexamethasone treatment is administered early in the first trimester. Prenatal genetic diagnosis of CAH and fetal sex determination identify affected female fetuses at risk for genital virilization. Advancements in prenatal diagnosis are owing to improved understanding of the genetic basis of CAH and improved technology. Cloning of the CYP21A2 gene ushered in molecular genetic analysis as the current standard of care. Noninvasive prenatal diagnosis allows for targeted treatment and avoids unnecessary treatment of males and unaffected females. PMID:27241964

  19. Ewing's Sarcoma of the Adrenal Gland.

    PubMed

    Pal, Dilip Kumar; Chandra, Vipin; Ranjan, Kumar Rajiv; Chakrabortty, Debasis; Banerjee, Manju

    2016-01-01

    Ewing's sarcoma (ES) or primitive neuro-ectodermal tumor (PNET) typically occurs in long or flat bones, the chest wall, extra-skeletal soft tissue, and rarely in solid organs. Incidence of adrenal Ewing's sarcoma is very rare. Here we report a case of Ewing's sarcoma of the right adrenal gland in an 8-year-old girl who presented with an abdominal mass. The huge tumor was managed by preoperative neo-adjuvant chemotherapy followed by surgical resection. She died due to metastasis after five months of surgery. PMID:27398321

  20. Diagnosis and Management of Hereditary Adrenal Cancer.

    PubMed

    Angelousi, Anna; Zilbermint, Mihail; Berthon, Annabel; Espiard, Stéphanie; Stratakis, Constantine A

    2016-01-01

    Benign adrenocortical tumours (ACT) are relatively frequent lesions; on the contrary, adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with unfavourable prognosis. Recent advances in the molecular understanding of adrenal cancer offer promise for better therapies in the future. Many of these advances stem from the molecular elucidation of genetic conditions predisposing to the development of ACC. Six main clinical syndromes have been described to be associated with hereditary adrenal cancer. In these conditions, genetic counselling plays an important role for the early detection and follow-up of the patients and the affected family members. PMID:27075352

  1. Noncholinergic control of adrenal catecholamine secretion.

    PubMed Central

    Livett, B G; Marley, P D

    1993-01-01

    It has been known for over 70 years that adrenal catecholamine secretion can be modulated or elicited by noncholinergic neurotransmitters and hormones. However, our understanding of the cellular mechanisms by which these agents produce their effects and the physiological conditions under which they act are not well characterised. Here we briefly review the mechanisms by which one such agent (the neuropeptide substance P) modulates the cholinergic secretory response of adrenal chromaffin cells, and another agent (angiotensin II) elicits catecholamine secretion independently of the cholinergic innervation. PMID:7507911

  2. Biopsy of the right adrenal gland by the transhepatic approach

    SciTech Connect

    Price, R.B.; Bernardino, M.E.; Berkman, W.A.; Sones, P.J. Jr.; Torres, W.E.

    1983-08-01

    A transhepatic computed-tomographic-guided biopsy of a right adrenal mass is described. This method is simpler to perform than the usual posterior biopsy carried out with the patient prone and is less likely to cause a complicating pneumothorax. In seven of eight patients with right adrenal masses, adrenal tissue was obtained and an accurate diagnosis was possible. No complications resulted.

  3. Imaging of an adrenal cortical carcinoma and its skeletal metastasis

    SciTech Connect

    Drane, W.E.; Graham, M.M.; Nelp, W.B.

    1983-08-01

    Though the typical scintigraphic appearance in adrenal cortical carcinoma is bilateral nonvisualization of the adrenal glands, a case with simultaneous visualization of both an adrenal cortical carcinoma and its skeletal metastasis using 6-..beta..-(/sup 131/I)iodomethyl-19-norcholesterol is reported.

  4. Adrenal pseudotumors on CT due to dilated portosystemic veins

    SciTech Connect

    Mitty, H.M.; Cohen, B.A.; Sprayregen, S.; Schwartz, K.

    1983-10-01

    The adrenal and periadrenal venous systems are part of the portosystemic collateral pathways that may enlarge in portal hypertension. The cross-sectional image of the resulting enlarged venous channels may simulate an adrenal msss. Three examples of such computed tomographic (CT) scans are presented with selective venographic correlation. Patients with portal hypertension and suspected adrenal pathology may require enhanced or dynamic CT scans.

  5. Imaging of an adrenal cortical carcinoma and its skeletal metastasis

    SciTech Connect

    Drane, W.E.; Graham, M.M.; Nelp, W.B.

    1983-08-01

    Though the typical scintigraphic appearance in adrenal cortical carcinoma is bilateral nonvisualization of the adrenal glands, we report a case with simultaneous visualization of both an adrenal cortical carcinoma and its skeletal metastasis using 6-beta-(/sup 131/I)iodomethyl-19-norcholesterol.

  6. Ultrasonographic appearance of adrenal glands in healthy and sick cats.

    PubMed

    Combes, Anaïs; Pey, Pascaline; Paepe, Dominique; Rosenberg, Dan; Daminet, Sylvie; Putcuyps, Ingrid; Bedu, Anne-Sophie; Duchateau, Luc; de Fornel-Thibaud, Pauline; Benchekroun, Ghita; Saunders, Jimmy H

    2013-06-01

    The first part of the study aimed to describe prospectively the ultrasonographic features of the adrenal glands in 94 healthy cats and 51 chronically sick cats. It confirmed the feasibility of ultrasonography of adrenal glands in healthy and chronically sick cats, which were not statistically different. The typical hypoechoic appearance of the gland surrounded by hyperechoic fat made it recognisable. A sagittal plane of the gland, not in line with the aorta, may be necessary to obtain the largest adrenal measurements. The reference intervals of adrenal measurements were inferred from the values obtained in the healthy and chronically sick cats (mean ± 0.96 SD): adrenal length was 8.9-12.5 mm; cranial height was 3.0-4.8 mm; caudal height was 3.0-4.5 mm. The second part of the study consisted of a retrospective analysis of the ultrasonographic examination of the adrenal glands in cats with adrenal diseases (six had hyperaldosteronism and four had pituitary-dependent hyperadrenocorticism) and a descriptive comparison with the reference features obtained in the control groups from the prospective study. Cats with hyperaldosteronism presented with unilateral severely enlarged adrenal glands. However, a normal contralateral gland did not preclude a contralateral infiltration in benign or malignant adrenal neoplasms. The ultrasonographic appearance of the adrenal glands could not differentiate benign and malignant lesions. The ultrasonographic appearance of pituitary-dependent hyperadrenocorticism was mainly a symmetrical adrenal enlargement; however, a substantial number of cases were within the reference intervals of adrenal size. PMID:23234721

  7. Gene array analysis of adrenal glands in broiler chickens following ACTH treatment

    PubMed Central

    Bureau, Clara; Hennequet-Antier, Christelle; Couty, Michel; Guémené, Daniel

    2009-01-01

    Background Difference in adaptability responses to stress has been observed amongst bird species, strains, and individuals. Components of the HPA axis, one of the internal systems involved in homeostasis re-establishment following stress, could play a role in this variability of responses. The aim of the present study was 1) to identify genes involved in the regulation of adrenal activity following ACTH stimulation and 2) to examine adrenal genes differentially expressed in individuals with high and low plasma corticosterone response following ACTH treatment. Results Analysis with 21 K poultry oligo microarrays indicated that ACTH treatment affected the expression of 134 genes. Several transcripts assigned to genes involved in the adrenal ACTH signaling pathway and steroidogenic enzymes were identified as differentially expressed by ACTH treatment. Real-time PCR on 18 selected genes confirmed changes in transcript levels of 11 genes, including MC2R, CREM, Cry, Bmal1, Sqle, Prax1, and StAR. Only 4 genes revealed to be differentially expressed between higher and lower adrenal responders to ACTH treatment. Conclusion The results from the present study reveal putative candidate genes; their role in regulation of adrenal functions and adaptability to stress should be further investigated. PMID:19751509

  8. High-fat diet prevents adaptive peripartum-associated adrenal gland plasticity and anxiolysis

    PubMed Central

    Perani, Clara V.; Neumann, Inga D.; Reber, Stefan O.; Slattery, David A.

    2015-01-01

    Maternal obesity is associated with lower basal plasma cortisol levels and increased risk of postpartum psychiatric disorders. Given that both obesity and the peripartum period are characterized by an imbalance between adrenocorticotropic hormone (ACTH) and cortisol, we hypothesized that the adrenal glands undergo peripartum-associated plasticity and that such changes would be prevented by a high-fat diet (HFD). Here, we demonstrate substantial peripartum adrenal gland plasticity in the pathways involved in cholesterol supply for steroidogenesis in female rats. In detail, the receptors involved in plasma lipid uptake, low density lipoprotein (LDL) receptor (LDLR) and scavenger receptor class B type 1 (SRB1), are elevated, intra-adrenal cholesterol stores are depleted, and a key enzyme in de novo cholesterol synthesis, hydroxymethylglutaryl coenzyme A reductase (HMGCR), is downregulated; particularly at mid-lactation. HFD prevented the lactation-associated anxiolysis, basal hypercorticism, and exaggerated the corticosterone response to ACTH. Moreover, we show that HFD prevented the downregulation of adrenal cholesterol stores and HMGCR expression, and LDLR upregulation at mid-lactation. These findings show that the adrenal gland is an important regulator of peripartum-associated HPA axis plasticity and that HFD has maladaptive consequences for the mother, partly by preventing these neuroendocrine and also behavioural changes. PMID:26442440

  9. Genetics Home Reference: androgen insensitivity syndrome

    MedlinePlus

    ... typically raised as females and have a female gender identity. Affected individuals have male internal sex organs ( ... and may have a male or a female gender identity. People with mild androgen insensitivity are born ...

  10. Erroneous prenatal diagnosis of congenital adrenal hyperplasia owing to a duplication of the CYP21A2 gene.

    PubMed

    Lekarev, O; Tafuri, K; Lane, A H; Zhu, G; Nakamoto, J M; Buller-Burckle, A M; Wilson, T A; New, M I

    2013-01-01

    Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder where steroidogenesis in the adrenal cortex is impaired. The most common form is caused by 21-hydroxylase deficiency (21OHD). Classical 21OHD is characterized by glucocorticoid and mineralocorticoid deficiency and by overproduction of adrenal androgens. The diagnosis rests on biochemical and genetic analyses. In families with history of CAH, prenatal genetic diagnosis is offered. We herein present a case of an infant whose parents were identified to carry mutations on the CYP21A2 gene. The fetal DNA analysis demonstrated that the fetus carried a paternal exon 8 (Q318X) mutation and a maternal exon 8 (R356X) mutation. The fetus was presumed to be affected with CAH, yet his clinical presentation at birth was not consistent with the diagnosis. Repeated genetic analysis identified a paternal CYP21A2 gene duplication with Q318X mutation on one copy of CYP21A2. We conclude that a duplication of the CYP21A2 gene should be suspected when clinical and hormonal findings do not support the genetic diagnosis. Furthermore, because individuals with Q318X mutation frequently have a duplication of the CYP21A2 gene, when Q318X is detected, it is important to distinguish the severe point mutation in single gene copy alleles from the non-deficient variant in gene-duplicated alleles. PMID:23269230

  11. A brain sexual dimorphism controlled by adult circulating androgens.

    PubMed

    Cooke, B M; Tabibnia, G; Breedlove, S M

    1999-06-22

    Reports of structural differences between the brains of men and women, heterosexual and homosexual men, and male-to-female transsexuals and other men have been offered as evidence that the behavioral differences between these groups are likely caused by differences in the early development of the brain. However, a possible confounding variable is the concentration of circulating hormones seen in these groups in adulthood. Evaluation of this possibility hinges on the extent to which circulating hormones can alter the size of mammalian brain regions as revealed by Nissl stains. We now report a sexual dimorphism in the volume of a brain nucleus in rats that can be completely accounted for by adult sex differences in circulating androgen. The posterodorsal nucleus of the medial amygdala (MePD) has a greater volume in male rats than in females, but adult castration of males causes the volume to shrink to female values within four weeks, whereas androgen treatment of adult females for that period enlarges the MePD to levels equivalent to normal males. This report demonstrates that adult hormone manipulations can completely reverse a sexual dimorphism in brain regional volume in a mammalian species. The sex difference and androgen responsiveness of MePD volume is reflected in the soma size of neurons there. PMID:10377450

  12. Minoxidil may suppress androgen receptor-related functions.

    PubMed

    Hsu, Cheng-Lung; Liu, Jai-Shin; Lin, An-Chi; Yang, Chih-Hsun; Chung, Wen-Hung; Wu, Wen-Guey

    2014-04-30

    Although minoxidil has been used for more than two decades to treat androgenetic alopecia (AGA), an androgen-androgen receptor (AR) pathway-dominant disease, its precise mechanism of action remains elusive. We hypothesized that minoxidil may influence the AR or its downstream signaling. These tests revealed that minoxidil suppressed AR-related functions, decreasing AR transcriptional activity in reporter assays, reducing expression of AR targets at the protein level, and suppressing AR-positive LNCaP cell growth. Dissecting the underlying mechanisms, we found that minoxidil interfered with AR-peptide, AR-coregulator, and AR N/C-terminal interactions, as well as AR protein stability. Furthermore, a crystallographic analysis using the AR ligand-binding domain (LBD) revealed direct binding of minoxidil to the AR in a minoxidil-AR-LBD co-crystal model, and surface plasmon resonance assays demonstrated that minoxidil directly bound the AR with a K(d) value of 2.6 µM. Minoxidil also suppressed AR-responsive reporter activity and decreased AR protein stability in human hair dermal papilla cells. The current findings provide evidence that minoxidil could be used to treat both cancer and age-related disease, and open a new avenue for applications of minoxidil in treating androgen-AR pathway-related diseases. PMID:24742982

  13. Minoxidil may suppress androgen receptor-related functions

    PubMed Central

    Hsu, Cheng-Lung; Liu, Jai-Shin; Lin, An-Chi; Yang, Chih-Hsun; Chung, Wen-Hung; Wu, Wen-Guey

    2014-01-01

    Although minoxidil has been used for more than two decades to treat androgenetic alopecia (AGA), an androgen-androgen receptor (AR) pathway-dominant disease, its precise mechanism of action remains elusive. We hypothesized that minoxidil may influence the AR or its downstream signaling. These tests revealed that minoxidil suppressed AR-related functions, decreasing AR transcriptional activity in reporter assays, reducing expression of AR targets at the protein level, and suppressing AR-positive LNCaP cell growth. Dissecting the underlying mechanisms, we found that minoxidil interfered with AR-peptide, AR-coregulator, and AR N/C-terminal interactions, as well as AR protein stability. Furthermore, a crystallographic analysis using the AR ligand-binding domain (LBD) revealed direct binding of minoxidil to the AR in a minoxidil-AR-LBD co-crystal model, and surface plasmon resonance assays demonstrated that minoxidil directly bound the AR with a Kd value of 2.6 μM. Minoxidil also suppressed AR-responsive reporter activity and decreased AR protein stability in human hair dermal papilla cells. The current findings provide evidence that minoxidil could be used to treat both cancer and age-related disease, and open a new avenue for applications of minoxidil in treating androgen-AR pathway-related diseases. PMID:24742982

  14. Visinin-like peptide 1 in adrenal gland of the rat. Gene expression and its hormonal control.

    PubMed

    Trejter, Marcin; Hochol, Anna; Tyczewska, Marianna; Ziolkowska, Agnieszka; Jopek, Karol; Szyszka, Marta; Malendowicz, Ludwik K; Rucinski, Marcin

    2015-01-01

    VSNL1 encodes the calcium-sensor protein visinin-like 1 and was identified previously as an upregulated gene in a sample set of aldosterone-producing adenomas. Recently, by means of microarray studies we demonstrated high expression of Vsnl1 gene in rat adrenal zona glomerulosa (ZG). Only scanty data are available on the role of this gene in adrenal function as well as on regulation of its expression by factors affecting adrenal cortex structure and function. Therefore we performed relevant studies aimed at clarifying some of the above issues. By Affymetrix(®) Rat Gene 1.1 ST Array Strip, QPCR and immunohistochemistry we demonstrated that expression levels of Vsnl1 in the rat adrenal ZG are notably higher than in the fasciculata/reticularis zone. In QPCR assay this difference was approximately 10 times higher. Expression of this gene in the rat adrenal gland or adrenocortical cells was acutely down regulated by ACTH, while chronic administration of corticotrophin or dexamethasone did not change Vsnl1 mRNA levels. In enucleation-induced adrenocortical regeneration expression levels of both Vsnl1 and Cyp11b2 were notably lowered and positively correlated. Despite these findings, the physiological significance of adrenal Vsnl1 remains unclear, and requires further investigation. PMID:25451331

  15. Androgen deprivation treatment of sexual behavior.

    PubMed

    Houts, Frederick W; Taller, Inna; Tucker, Douglas E; Berlin, Fred S

    2011-01-01

    Gonadotropin-releasing hormone agonists are underutilized in patients seeking diminution of problematic sexual drives. This chapter reviews the literature on surgical castration of sex offenders, anti-androgen use and the rationale for providing androgen deprivation therapy, rather than selective serotonin reuptake inhibitors or more conservative interventions, for patients with paraphilias and excessive sexual drive. Discussions of informed consent, side effects, contraindications and case examples are provided. PMID:22005210

  16. Maternal Undernutrition Programs Offspring Adrenal Expression of Steroidogenic Enzymes

    PubMed Central

    Khorram, Naseem M.; Magee, Thomas R.; Wang, Chen; Desai, Mina; Ross, Michael; Khorram, Omid

    2011-01-01

    The aim of this study was to determine the influence of maternal undernutrition (MUN) on maternal and offspring adrenal steoridogenic enzymes. Pregnant Sprague-Dawley rats were 50% food-restricted from day 10 of gestation until delivery. Control animals received ad libitum food. Offspring were killed on day 1 of life (P1) and at 9 months. We determined the messenger RNA (mRNA) expression of steroidogneic enzymes by real-time reverse transcriptase polymerized chain reaction (RT-PCR). Maternal undernutrition inhibited maternal adrenal expression of P450 cholesterol side-chain cleavage enzyme (CYP11A1), 11 beta-hydroxylase (CYP11B1), aldosterone synthase (CYP11B2), and adrenocorticotropic hormone (ACTH) receptor (ACTH-R; MC2 gene) compared with control offspring. There was a marked downregulation in the expression of CYP11B1, CYP11B2, 11 β-hydroxysteroid dehydrogenase type 1 and 2 (HSD1 and HSD2), CYP11A1, ACTH receptor, steroidogenic acute regulatory protein (STAR), and mineralocorticoid receptor (MCR; NR3C2 gene) mRNA in P1 MUN offspring (both genders), with no changes in glucocorticoid receptor (GCR). Quantitative immunohistochemical analysis confirmed the PCR data for GCR and MCR in P1 offspring and demonstrated lower expression of leptin receptor protein (Ob-Ra/Ob-Rb) and mRNA in P1 MUN offspring. In 9-month adult male MUN offspring, the expression of HSD1, CYP11A1, CYP11B2, Ob-Ra/Ob-Rb, and GCR mRNA were significantly upregulated with a trend toward an increase in ACTH-R and a decrease in 17 alpha-hydroxylase (CYP17A1) expression. In adult female MUN offspring, similar to males, the expression of CYP11A1, ACTH-R, and Ob-Rb mRNA were increased, whereas GCR and CYP17A1 mRNA were decreased. These results indicate that the adrenal gland is a target of nutritional programming. In utero undernutrition has a global suppressive effect on maternal and P1 offspring adrenal steroidogenic enzymes in association with reduced circulating corticosterone levels in P1 offspring

  17. Targeted Androgen Pathway Suppression in Localized Prostate Cancer: A Pilot Study

    PubMed Central

    Mostaghel, Elahe A.; Nelson, Peter S.; Lange, Paul; Lin, Daniel W.; Taplin, Mary Ellen; Balk, Steven; Ellis, William; Kantoff, Philip; Marck, Brett; Tamae, Daniel; Matsumoto, Alvin M.; True, Lawrence D.; Vessella, Robert; Penning, Trevor; Hunter Merrill, Rachel; Gulati, Roman; Montgomery, Bruce

    2014-01-01

    Purpose Ligand-mediated activation of the androgen receptor (AR) is critical for prostate cancer (PCa) survival and proliferation. The failure to completely ablate tissue androgens may limit suppression of PCa growth. We evaluated combinations of CYP17A and 5-α-reductase inhibitors for reducing prostate androgen levels, AR signaling, and PCa volumes. Patients and Methods Thirty-five men with intermediate/high-risk clinically localized PCa were randomly assigned to goserelin combined with dutasteride (ZD), bicalutamide and dutasteride (ZBD), or bicalutamide, dutasteride, and ketoconazole (ZBDK) for 3 months before prostatectomy. Controls included patients receiving combined androgen blockade with luteinizing hormone-releasing hormone agonist and bicalutamide. The primary outcome measure was tissue dihydrotestosterone (DHT) concentration. Results Prostate DHT levels were substantially lower in all experimental arms (0.02 to 0.04 ng/g v 0.92 ng/g in controls; P < .001). The ZBDK group demonstrated the greatest percentage decline in serum testosterone, androsterone, and dehydroepiandrosterone sulfate (P < .05 for all). Staining for AR and the androgen-regulated genes prostate-specific antigen and TMPRSS2 was strongly suppressed in benign glands and moderately in malignant glands (P < .05 for all). Two patients had pathologic complete response, and nine had ≤ 0.2 cm3 of residual tumor (defined as a near-complete response), with the largest numbers of complete and near-complete responses in the ZBDK group. Conclusion Addition of androgen synthesis inhibitors lowers prostate androgens below that achieved with standard therapy, but significant AR signaling remains. Tissue-based analysis of steroids and AR signaling is critical to informing the search for optimal local and systemic control of high-risk prostate cancer. PMID:24323034

  18. Protective Effects of KH-204 in the Bladder of Androgen-Deprived Rats

    PubMed Central

    Bae, Woong Jin; Ha, U Syn; Choi, Jin Bong; Kim, Kang Sup; Kim, Su Jin; Cho, Hyuk Jin; Hong, Sung Hoo; Lee, Ji Youl; Wang, Zhiping; Hwang, Sung Yeoun

    2015-01-01

    Purpose We investigated the protective effects of the herbal formulation KH-204 in the bladder of androgen-deprived rats. Materials and Methods Male rats aged eight weeks were randomly divided into four groups, containing eight rats each: sham operation only (normal control group), androgen-deprived only (androgen-deprived control group), and androgen-deprived followed by treatment with 200 mg/kg or 400 mg/kg of KH-204. After 0.5 mg/kg of leuprorelin was subcutaneously injected in the androgen-deprived groups, the oral administration of either distilled water in the two control groups or KH-204 in the treatment group was continued for four weeks. Serum testosterone levels, RhoGEF levels, nitric oxide (NO)-cyclic guanosine monophosphate (cGMP)-related parameters, oxidative stress, and histologic changes were evaluated after treatment. Results Treatment with the herbal formulation KH-204 (1) increased serum testosterone levels; (2) restored the expression of RhoGEFs, endothelial NO synthase, and neuronal NO synthase; (3) increased the expression of superoxide dismutase; and (4) decreased bladder fibrosis. Conclusions Our results suggest that the positive effects of KH-204 on the urinary bladder may be attributed to its antioxidant effects or to an elevation in NO-cGMP activity. PMID:26331123

  19. [A rare form of adrenal tuberculosis presenting as an asymptomatic adrenal mass].

    PubMed

    Sarf, Ismail; el Mejjad, Amine; Badre, Latifa; Dakir, Mohamed; Aboutaieb, Rachid; Meziane, Fethi

    2003-02-01

    The authors report a case of adrenal tuberculosis discovered during staging of a biopsy-confirmed bladder tumour, in a 70-year-old patient consulting for haematuria. Cystoscopy with biopsy revealed a high-grade papillary urothelial carcinoma invading the detrusor. Staging abdominopelvic computed tomography revealed a necrotic, multilobed right adrenal mass. Histological examination of the adrenalectomy specimen revealed adrenal tuberculosis. Antituberculous therapy was administered for 9 months and comprised streptomycin, isoniazid, rifampicin and pyrazinamide for 2 months, followed by rifampicin and isoniazid for 7 months. In the light of this case and with the increasing incidence of AIDS, the diagnosis of adrenal tuberculosis must be considered in any case of incidentaloma. PMID:12703369

  20. Opioid-Induced Androgen Deficiency (OPIAD): Diagnosis, Management, and Literature Review.

    PubMed

    O'Rourke, Timothy K; Wosnitzer, Matthew S

    2016-10-01

    Opioid-induced androgen deficiency (OPIAD) was initially recognized as a possible consequence of opioid use roughly four decades ago. Long-acting opioid use carries risks of addiction, tolerance, and systemic side effects including hypogonadotropic hypogonadism with consequent testosterone depletion leading to multiple central and peripheral effects. Hypogonadism is induced through direct inhibitory action of opioids on receptors within the hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-adrenal (HPA) axes as well as testosterone production within the testes. Few studies have systematically investigated hormonal changes induced by long-term opioid administration or the effects of testosterone replacement therapy (TRT) in patients with OPIAD. Clomiphene citrate, a selective estrogen receptor modulator (SERM), is a testosterone enhancement treatment which upregulates endogenous hypothalamic function. This review will focus on the pathophysiology, diagnosis, and management of OPIAD, including summary of literature evaluating OPIAD treatment with TRT, and areas of future investigation. PMID:27586511

  1. Androgen secreting giant adrenocortical carcinoma with no metastases: A case report and review of the literature

    PubMed Central

    Uruc, Fatih; Urkmez, Ahmet; Yuksel, Ozgur Haki; Sahin, Aytac; Verit, Ayhan

    2015-01-01

    Functional adrenocortical carcinoma (ACC) is a very rare disease with a poor prognosis. Over half (60%) of ACCs bigger than 6 cm synthesize hormones; hormone-secreting ACCs generally include virilization, feminization or Cushing syndrome. Besides, 82% of ACCs are metastatic at the time of diagnosis. While a 48-year-old female patient was examined for abdominal pain and flushing, we detected a non-metastasizing mass (23 × 18 × 16 cm) in the adrenal lodge. The mass was extracted en bloc during open exploration and its histopathology was reported as ACC. We review the literature and report the largest androgen-producing, clinically silent ACC mass cited in the literature so far. PMID:26425231

  2. Mechanistic relationship between androgen receptor polyglutamine tract truncation and androgen-dependent transcriptional hyperactivity in prostate cancer cells.

    PubMed

    Wang, Qianben; Udayakumar, T S; Vasaitis, Tadas S; Brodie, Angela M; Fondell, Joseph D

    2004-04-23

    Androgen receptor (AR) signaling pathways mediate critical events in normal and neoplastic prostate growth. Shortening of the polymorphic N-terminal polyglutamine (poly(Q)) tract of the AR gene leads to transcriptional hyperactivity and has been correlated with an increased risk of prostate cancer. The underlying mechanisms for these effects are poorly understood. We show here that androgen-dependent cellular proliferation and transcription in prostate cancer cells is inversely correlated to the length of the AR poly(Q) region. We further show that AR proteins containing a shortened poly(Q) region functionally respond to lower concentrations of androgens than wild type AR. Whereas DNA binding activity is relatively unaffected by AR poly(Q) variation, we found that ligand binding affinity and the ligand-induced NH(2)- to COOH-terminal intramolecular interaction is enhanced when the poly(Q) region is shortened. Importantly, we show that AR proteins containing a shortened poly(Q) region associate in vivo with higher levels of specific p160 coactivators and components of the SWI/SNF chromatin remodeling complex as compared with the wild type AR. Collectively, our findings suggest that the AR transcriptional hyperactivity associated with shortened poly(Q) length stems from altered ligand-induced conformational changes that enhance coactivator recruitment. PMID:14966121

  3. Growth hormone-releasing hormone (GHRH) antagonists inhibit the proliferation of androgen-dependent and -independent prostate cancers.

    PubMed

    Letsch, Markus; Schally, Andrew V; Busto, Rebeca; Bajo, Ana M; Varga, Jozsef L

    2003-02-01

    The antiproliferative effects of an antagonist of growth hormone-releasing hormone (GHRH) JV-1-38 were evaluated in nude mice bearing s.c. xenografts of LNCaP and MDA-PCa-2b human androgen-sensitive and DU-145 androgen-independent prostate cancers. In the androgen-sensitive models, JV-1-38 greatly potentiated the antitumor effect of androgen deprivation induced by surgical castration, but was ineffective when given alone. Thus, in castrated animals bearing MDA-PCa-2b cancers, the administration of JV-1-38 for 35 days virtually arrested tumor growth (94% inhibition vs. intact control, P < 0.01; and 75% vs. castrated control, P < 0.05). The growth of LNCaP tumors was also powerfully suppressed by JV-1-38 combined with castration (83% inhibition vs. intact control, P < 0.01; and 68% vs. castrated control, P < 0.05). However, in androgen-independent DU-145 cancers, JV-1-38 alone could inhibit tumor growth by 57% (P < 0.05) after 45 days. In animals bearing MDA-PCa-2b and LNCaP tumors, the reduction in serum prostate-specific antigen levels, after therapy with JV-1-38, paralleled the decrease in tumor volume. Inhibition of MDA-PCa-2b and DU-145 cancers was associated with the reduction in the expression of mRNA and protein levels of vascular endothelial growth factor. The mRNA expression for GHRH receptor splice variants was found in all these models of prostate cancer. Our results demonstrate that GHRH antagonists inhibit androgen-independent prostate cancers and, after combination with androgen deprivation, also androgen-sensitive tumors. Thus, the therapy with GHRH antagonist could be considered for the management of both androgen-dependent or -independent prostate cancers. PMID:12538852

  4. Growth hormone-releasing hormone (GHRH) antagonists inhibit the proliferation of androgen-dependent and -independent prostate cancers

    PubMed Central

    Letsch, Markus; Schally, Andrew V.; Busto, Rebeca; Bajo, Ana M.; Varga, Jozsef L.

    2003-01-01

    The antiproliferative effects of an antagonist of growth hormone-releasing hormone (GHRH) JV-1-38 were evaluated in nude mice bearing s.c. xenografts of LNCaP and MDA-PCa-2b human androgen-sensitive and DU-145 androgen-independent prostate cancers. In the androgen-sensitive models, JV-1-38 greatly potentiated the antitumor effect of androgen deprivation induced by surgical castration, but was ineffective when given alone. Thus, in castrated animals bearing MDA-PCa-2b cancers, the administration of JV-1-38 for 35 days virtually arrested tumor growth (94% inhibition vs. intact control, P < 0.01; and 75% vs. castrated control, P < 0.05). The growth of LNCaP tumors was also powerfully suppressed by JV-1-38 combined with castration (83% inhibition vs. intact control, P < 0.01; and 68% vs. castrated control, P < 0.05). However, in androgen-independent DU-145 cancers, JV-1-38 alone could inhibit tumor growth by 57% (P < 0.05) after 45 days. In animals bearing MDA-PCa-2b and LNCaP tumors, the reduction in serum prostate-specific antigen levels, after therapy with JV-1-38, paralleled the decrease in tumor volume. Inhibition of MDA-PCa-2b and DU-145 cancers was associated with the reduction in the expression of mRNA and protein levels of vascular endothelial growth factor. The mRNA expression for GHRH receptor splice variants was found in all these models of prostate cancer. Our results demonstrate that GHRH antagonists inhibit androgen-independent prostate cancers and, after combination with androgen deprivation, also androgen-sensitive tumors. Thus, the therapy with GHRH antagonist could be considered for the management of both androgen-dependent or -independent prostate cancers. PMID:12538852

  5. Adrenal response to ACTH stimulation in Rusa deer (Cervus rusa timorensis).

    PubMed

    van Mourik, S; Stelmasiak, T

    1984-01-01

    Resting cortisol values in immobilized mature Rusa stags (Cervus rusa timorensis) and the response to synthetic ACTH were investigated. The mean level of cortisol in mature Rusa stags was found to be 3.80 ng/ml (SD = 0.87, N = 18). Over the range 0.37-6.0 i.u. the adrenal response to ACTH challenge was linearly related to the log dose ACTH administered (r = 0.998). More than 6 i.u. of ACTH caused maximal stimulation of the adrenal gland. Rusa deer appear to be much more sensitive to ACTH administration than other species. PMID:6150796

  6. [Quantitative evaluation of ultrastructural restructuring in the adrenal cortex of rats under stress].

    PubMed

    Bogdanova, T I

    1987-01-01

    Quantitative and qualitative analysis has revealed that submicroscopic changes of the rat adrenal cortex in dynamics of the stress reaction examined at the level of "functional element" which combines basic structural components of the parenchyma and stroma are of the polyphase character and agree with data from the biochemical analysis of 11-OCS in blood plasma. At the stage of exhaustion of the stress reaction (72 hours of immobilization) the ultrastructure of the adrenal cortex testifies to the preservation of functional reserves in the secretory cells. PMID:3672636

  7. Dopamine-secreting giant adrenal ganglioneuroma: clinical and diffusion-weighted magnetic resonance imaging findings.

    PubMed

    Polat, A V; Polat, A Kamali; Aslan, K; Atmaca, H; Karagoz, F

    2014-01-01

    We report a case of a dopamine-secreting giant primary adrenal ganglioneuroma (GN) in a 29-year-old male patient. Although the patient was clinically silent, the 24-hour urine levels of dopamine, normetanephrine, homovanillic acid and vanillyl mandelic acid were elevated. Abdominal ultrasonography and magnetic resonance imaging showed a large solid tumor with calcifications and a slightly lobular edge on the left adrenal gland. A tumor, 13 x 23 x 25 cm in size, was completely resected without morbidity. A 2-year follow-up with computed tomography showed that the postoperative course of the patient was uneventful. PMID:25073244

  8. An Adrenal Mass and Increased Catecholamines: Monoamine Oxidase or Pheochromocytoma Effect?

    PubMed Central

    Bosscher, Marianne R. F.; Wentholt, Iris M.; Ackermans, Mariette T.; Nieveen van Dijkum, Els J. M.

    2015-01-01

    Hormonal evaluation in patients with an adrenal incidentaloma can be difficult in patients with comorbidities or in patients using interfering drugs. We present a case of a 54-year-old man who was evaluated for an adrenal mass. The medical history reported treatment with a monoamine oxidase (MAO) inhibitor for recurrent psychoses. Hormonal screening showed elevated levels of normetanephrine and metanephrine in plasma and urine, suggesting a diagnosis of pheochromocytoma (PHEO), and an adrenalectomy was performed. Histologic examination showed that the tumor had an origin of the adrenal cortex. MAO inhibitors are also known to cause elevated levels of catecholamines. In this case, a PHEO seemed more likely the cause due to repeatedly elevated levels of metanephrines and normal levels of catecholamines. Since the tumor had an origin of the adrenal cortex, the use of MAO inhibitors was the most likely explanation for the elevated levels of metanephrines. This case illustrated the difficulties in diagnosing PHEO, especially in patients with comorbidities and interfering drugs. PMID:25584109

  9. The neural androgen receptor: a therapeutic target for myelin repair in chronic demyelination.

    PubMed

    Hussain, Rashad; Ghoumari, Abdel M; Bielecki, Bartosz; Steibel, Jérôme; Boehm, Nelly; Liere, Philippe; Macklin, Wendy B; Kumar, Narender; Habert, René; Mhaouty-Kodja, Sakina; Tronche, François; Sitruk-Ware, Regine; Schumacher, Michael; Ghandour, M Said

    2013-01-01

    Myelin regeneration is a major therapeutic goal in demyelinating diseases, and the failure to remyelinate rapidly has profound consequences for the health of axons and for brain function. However, there is no efficient treatment for stimulating myelin repair, and current therapies are limited to anti-inflammatory agents. Males are less likely to develop multiple sclerosis than females, but often have a more severe disease course and reach disability milestones at an earlier age than females, and these observations have spurred interest in the potential protective effects of androgens. Here, we demonstrate that testosterone treatment efficiently stimulates the formation of new myelin and reverses myelin damage in chronic demyelinated brain lesions, resulting from the long-term administration of cuprizone, which is toxic for oligodendrocytes. In addition to the strong effect of testosterone on myelin repair, the number of activated astrocytes and microglial cells returned to low control levels, indicating a reduction of neuroinflammatory responses. We also identify the neural androgen receptor as a novel therapeutic target for myelin recovery. After the acute demyelination of cerebellar slices in organotypic culture, the remyelinating actions of testosterone could be mimicked by 5α-dihydrotestosterone, a metabolite that is not converted to oestrogens, and blocked by the androgen receptor antagonist flutamide. Testosterone treatment also failed to promote remyelination after chronic cuprizone-induced demyelination in mice with a non-functional androgen receptor. Importantly, testosterone did not stimulate the formation of new myelin sheaths after specific knockout of the androgen receptor in neurons and macroglial cells. Thus, the neural brain androgen receptor is required for the remyelination effect of testosterone, whereas the presence of the receptor in microglia and in peripheral tissues is not sufficient to enhance remyelination. The potent synthetic

  10. [Neonatal adrenal hemorrhage revealed by jaundice: a case report].

    PubMed

    Oulmaati, A; Hays, S; Mory-Thomas, N; Bretones, P; Bensaid, M; Jordan, I; Bonfils, M; Godbert, I; Picaud, J-C

    2012-04-01

    The clinical presentation of adrenal hemorrhage varies, depending on the extent of hemorrhage as well as the amount of adrenal cortex involved by the hemorrhage. We report here a case of neonatal adrenal hemorrhage revealed by late onset of neonatal jaundice. This adrenal hemorrhage most probably resulted from shoulder dystocia. The aim of this work was to focus on the fact that jaundice can be caused by adrenal hemorrhage and to emphasize the crucial importance of abdominal ultrasound in cases of persistent jaundice. PMID:22424898

  11. CT manifestations of adrenal trauma: experience with 73 cases.

    PubMed

    Sinelnikov, Alex O; Abujudeh, Hani H; Chan, David; Novelline, Robert A

    2007-03-01

    Adrenal injuries, although an uncommon consequence of abdominal trauma, are important to recognize. If bilateral, adrenal trauma could result in life-threatening adrenal insufficiency. Furthermore, in the setting of trauma, adrenal injury can point to other concomitant injuries and has been associated with overall increased morbidity and mortality. In the past, before the advent of computed tomography (CT), detection was difficult, and the diagnosis was often made only at surgery or postmortem. Today, the diagnosis of adrenal injuries can be quickly and accurately made with CT. This retrospective review was carried out to identify, describe, and analyze different CT appearances of adrenal injuries and correlated with associated injuries and observed clinical context and outcomes. A patient cohort of CT-detected adrenal injuries was identified through a radiology software research tool by searching for keywords in radiology reports. The identified CT scans were reviewed and correlated with the patients' available clinical chart data and follow-up. Between April 1995 and October 2004, 73 cases of CT-detected adrenal injuries were identified, including 48 men and 25 women, with an age range 6 to 90 years and a mean age of 42.7 years. Of the cases, 77% were right-sided, 15% were left-sided, and 8% were bilateral. The causes of injuries were motor vehicle collisions (75%), falls (14%), sports related (4%), and miscellaneous causes (7%). Associated trauma included injuries of the liver (43%), spleen (23%), lung (19%), and kidney (18%), as well as pneumothoraces/hemothoraces (22%). Skeletal injuries included fractures of the ribs, clavicles, and/or scapulae (39%), pelvis and hips (30%), and the spine (23%). Isolated adrenal trauma was seen in only 4% of the cases. The CT findings of adrenal trauma were focal hematoma (30%), indistinct (27%) or enlarged (18%) adrenal gland, gross (15%) or focal (7%) adrenal hemorrhage, and adrenal mass (11%). Associated CT findings

  12. Genetics Home Reference: primary macronodular adrenal hyperplasia

    MedlinePlus

    ... germline and somatic mutations are associated with both primary macronodular adrenal hyperplasia and meningioma. J Clin Endocrinol Metab. 2015 Jan;100(1):E119-28. doi: 10.1210/jc.2014-2648. Citation on PubMed or Free article on PubMed Central Faucz FR, Zilbermint M, Lodish ...

  13. Adrenal metabolism of mitotane and related compounds

    SciTech Connect

    Djanegara, T.K.S.

    1989-01-01

    Mitotane (o,p{prime}-DDD; 1-(2-chlorophenyl)-1-(4-chlorophenyl)-2,2-dichloroethane) has been used in the treatment of Cushing's syndrome due to adrenal hyperfunction and it the drug of choice for adrenocortical carcinoma. The object of this investigation is to study the biotransformation of o,p{prime}-DDD and p,p{prime}-DDD in dogs and bovine adrenal cortex to explain its selective toxicity and mechanism of action. The in vitro biotransformation of {sup 14}C-labeled o,p{prime}-DDD and p,p{prime}-DDD by dog and bovine adrenal cortex as studied. Of the cortex subcellular fractions, the cytosol fraction was found to be the most active in metabolizing the substrates, followed by the mitochondrial fraction. This metabolism including that in cytosolic fractions, did not take place with boiled enzyme preparations and required an NADPH generating system. This study has been directed towards establishing the metabolic activation mechanism which may account for the adrenocorticolytic effect of mitotane in contrast to detoxication by the liver. HPLC and TLC metabolic profiles have been generated from incubations of bovine and dog adrenal cortex homogenates and their subfractions for {sup 14}C-labeled p,p{prime}-DDD, o,p{prime}-DDD and its monochloroethylene derivative, o,p{prime}-DDMU.

  14. Primary adrenal lymphoma: a systematic review.

    PubMed

    Rashidi, Armin; Fisher, Stephen I

    2013-12-01

    Fewer than 200 cases of primary adrenal lymphoma (PAL) have been reported. We have systematically reviewed all 187 cases of PAL reported in the English literature until June 2013, from which we drew the following conclusions: PAL is typically a highly symptomatic and aggressive, metabolically hyperactive, hypovascular, hypoechoic (and heterogeneous on ultrasound), hypodense (with slight to moderate enhancement on computed tomography), high-grade lymphoma, primarily affecting elderly males and presenting with large bilateral adrenal masses. Most cases have adrenal insufficiency, B-symptoms, and elevated lactate dehydrogenase. Hepatosplenomegaly, lymphadenopathy, concurrent or prior immune dysregulation, and bone marrow involvement are uncommon. Epstein-Barr virus positivity is observed in more than half of cases and the disease is disseminated at presentation in 18 % of cases. The two most common WHO 2008-defined PAL subtypes are diffuse large B cell lymphoma (78 %) and peripheral T cell lymphoma (7 %). The prognosis of PAL has improved with the advent of rituximab-containing chemotherapeutic regimens. According to our results, administration of chemotherapy and adrenal insufficiency are significant independent predictors of prognosis. PMID:23771429

  15. A case of congenital lipoid adrenal hyperplasia.

    PubMed

    Hashemipour, Mahin; Ghasemi, Mahmoud; Hovsepian, Silva

    2012-07-01

    Lipoid congenital adrenal hyperplasia (lipoid CAH), a rare disorder of steroid biosynthesis, is the most severe form of CAH. In this disorder the synthesis of glucocorticoids, mineralocorticoids and sex steroids is impaired which result in adrenal failure, severe salt wasting crisis and hyperpigmentation in phenotypical female infants irrespective of genetic sex. In this report, we presented a 28-day-old phenotypic female infant, which referred with lethargy, failure to thrive and electrolyte abnormalities. Considering the clinical and biochemical findings, lipoid CAH was diagnosed and replacement therapy with standard doses of glucocorticoid and mineralocorticoid and sodium chloride was initiated. During follow-up, she had good clinical condition, but at 6 years of age, she refers with hypertension and adrenal insufficiency because of arbitrary drug discontinuation by mother. In ultrasonography an abdominal mass (the testicles) was reported. Chromosome study showed 46XY pattern. Orchiectomy was performed. We recommended that in cases with clinical presentation of adrenal insufficiency if there is not the facility to determine the karyotype, repeated ultrasonography perform during follow-up. In addition, investigating the genetic bases of the disorder would help us to determine the pathogenesis of lipoid CAH in our community. It would be helpful in prenatal diagnosis and treatment of the disorder to prevent its related comorbidities. PMID:22891154

  16. Steroidogenic pathways involved in androgen biosynthesis in eumenorrheic women and patients with polycystic ovary syndrome.

    PubMed

    Saito, Kazuki; Matsuzaki, Toshiya; Iwasa, Takeshi; Miyado, Mami; Saito, Hidekazu; Hasegawa, Tomonobu; Homma, Keiko; Inoue, Eisuke; Miyashiro, Yoshimichi; Kubota, Toshiro; Irahara, Minoru; Ogata, Tsutomu; Fukami, Maki

    2016-04-01

    The conventional Δ5 and Δ4 steroidogenic pathways mediate androgen production in females. While multiple non-conventional pathways to dihydrotestosterone (DHT) have recently been postulated in humans, the functional significance of these pathways remains to be elucidated. The aim of this study was to clarify the origin of androgens in healthy women and in patients with polycystic ovary syndrome (PCOS), a multifactorial disorder characterized by androgen overproduction. We measured 13 steroids in blood samples of 31 eumenorrheic females and 28 PCOS patients using liquid chromatography-tandem mass spectrometry and chemiluminescent enzyme immunoassay. We found that 17-hydroxy (17-OH) progesterone (17-OHP), androstenedione (Δ4A), testosterone, androstanedione, androsterone, and androstanediol levels were higher in the patient group than in the eumenorrheic group, while levels of other steroids were comparable between the two groups. In the eumenorrheic group, DHT levels were correlated with testosterone, androstanedione, and androstanediol. Quantitative correlations were also observed among 17-OH allopregnanolone, androsterone, androstanediol, and DHT, and among Δ4A, androstanedione, androsterone, and androstanediol. In the patient group, DHT levels were correlated with testosterone levels, but not with androstanedione or androstanediol levels. Δ4A and testosterone paralleled 17-OHP. Androstanedione, androsterone, androstanediol, and 17-OH allopregnanolone were quantitatively correlated. In both groups, multivariable linear regression analyses suggested relationships between androsterone and androstanedione, as well as between androsterone and 17-OH allopregnanolone. These results indicate that multiple androgen biosynthesis pathways are operating in eumenorrheic females and PCOS patients. In PCOS patients, excessive androgens are produced primarily via the conventional pathways, while two alternative pathways; i.e., an androstanedione-mediated pathway and a so

  17. Diverse dose-response effects of yolk androgens on embryo development and nestling growth in a wild passerine.

    PubMed

    Muriel, Jaime; Pérez-Rodríguez, Lorenzo; Puerta, Marisa; Gil, Diego

    2015-07-01

    Avian egg yolks contain various amounts of maternally derived androgens that can modify offspring phenotype and adjust their development to the post-hatching environment. Seemingly adaptive variation in yolk androgen levels with respect to breeding density conditions or male attractiveness has been found in numerous studies. One important consideration that has been overlooked in previous research is the likely non-linear nature of hormone effects. To examine possible complex dose-response effects of maternal androgens on chick development, we experimentally administered three different androgen doses of the naturally occurring mixture of yolk testosterone and androstenedione to spotless starling eggs (Sturnus unicolor). We found that yolk androgens induce a non-linear dose-response pattern in several traits. Androgens had a stimulatory effect on hatchling body mass and nestling skeletal growth, but maximum values were found at intermediate doses, whereas our highest dose resulted in a decrease. However, the opposite U-shaped effect was found on nestling body mass. We also detected linear negative and positive effects on embryonic development period and nestling gape width, respectively. Our results suggest differential tissue responsiveness to yolk androgens, which may result in compromises in maternal allocation to produce adapted phenotypes. Because of the non-linear dose-response pattern, future investigations should carefully consider a wide range of concentrations, as the balance of costs and benefits may strongly differ depending on concentration. PMID:25987739

  18. Isolation, characterization, and differentiation of progenitor cells from human adult adrenal medulla.

    PubMed

    Santana, Magda M; Chung, Kuei-Fang; Vukicevic, Vladimir; Rosmaninho-Salgado, Joana; Kanczkowski, Waldemar; Cortez, Vera; Hackmann, Klaus; Bastos, Carlos A; Mota, Alfredo; Schrock, Evelin; Bornstein, Stefan R; Cavadas, Cláudia; Ehrhart-Bornstein, Monika

    2012-11-01

    Chromaffin cells, sympathetic neurons of the dorsal ganglia, and the intermediate small intensely fluorescent cells derive from a common neural crest progenitor cell. Contrary to the closely related sympathetic nervous system, within the adult adrenal medulla a subpopulation of undifferentiated progenitor cells persists, and recently, we established a method to isolate and differentiate these progenitor cells from adult bovine adrenals. However, no studies have elucidated the existence of adrenal progenitor cells within the human adrenal medulla. Here we describe the isolation, characterization, and differentiation of chromaffin progenitor cells obtained from adult human adrenals. Human chromaffin progenitor cells were cultured in low-attachment conditions for 10-12 days as free-floating spheres in the presence of fibroblast growth factor-2 (FGF-2) and epidermal growth factor. These primary human chromosphere cultures were characterized by the expression of several progenitor markers, including nestin, CD133, Notch1, nerve growth factor receptor, Snai2, Sox9, Sox10, Phox2b, and Ascl1 on the molecular level and of Sox9 on the immunohistochemical level. In opposition, phenylethanolamine N-methyltransferase (PNMT), a marker for differentiated chromaffin cells, significantly decreased after 12 days in culture. Moreover, when plated on poly-l-lysine/laminin-coated slides in the presence of FGF-2, human chromaffin progenitor cells were able to differentiate into two distinct neuron-like cell types, tyrosine hydroxylase (TH)(+)/β-3-tubulin(+) cells and TH(-)/β-3-tubulin(+) cells, and into chromaffin cells (TH(+)/PNMT(+)). This study demonstrates the presence of progenitor cells in the human adrenal medulla and reveals their potential use in regenerative medicine, especially in the treatment of neuroendocrine and neurodegenerative diseases. PMID:23197690

  19. Isolation, Characterization, and Differentiation of Progenitor Cells from Human Adult Adrenal Medulla

    PubMed Central

    Santana, Magda M.; Chung, Kuei-Fang; Vukicevic, Vladimir; Rosmaninho-Salgado, Joana; Kanczkowski, Waldemar; Cortez, Vera; Hackmann, Karl; Bastos, Carlos A.; Mota, Alfredo; Schrock, Evelin; Bornstein, Stefan R.; Cavadas, Cláudia

    2012-01-01

    Chromaffin cells, sympathetic neurons of the dorsal ganglia, and the intermediate small intensely fluorescent cells derive from a common neural crest progenitor cell. Contrary to the closely related sympathetic nervous system, within the adult adrenal medulla a subpopulation of undifferentiated progenitor cells persists, and recently, we established a method to isolate and differentiate these progenitor cells from adult bovine adrenals. However, no studies have elucidated the existence of adrenal progenitor cells within the human adrenal medulla. Here we describe the isolation, characterization, and differentiation of chromaffin progenitor cells obtained from adult human adrenals. Human chromaffin progenitor cells were cultured in low-attachment conditions for 10–12 days as free-floating spheres in the presence of fibroblast growth factor-2 (FGF-2) and epidermal growth factor. These primary human chromosphere cultures were characterized by the expression of several progenitor markers, including nestin, CD133, Notch1, nerve growth factor receptor, Snai2, Sox9, Sox10, Phox2b, and Ascl1 on the molecular level and of Sox9 on the immunohistochemical level. In opposition, phenylethanolamine N-methyltransferase (PNMT), a marker for differentiated chromaffin cells, significantly decreased after 12 days in culture. Moreover, when plated on poly-l-lysine/laminin-coated slides in the presence of FGF-2, human chromaffin progenitor cells were able to differentiate into two distinct neuron-like cell types, tyrosine hydroxylase (TH)+/β-3-tubulin+ cells and TH−/β-3-tubulin+ cells, and into chromaffin cells (TH+/PNMT+). This study demonstrates the presence of progenitor cells in the human adrenal medulla and reveals their potential use in regenerative medicine, especially in the treatment of neuroendocrine and neurodegenerative diseases. PMID:23197690

  20. Bilateral Adrenal Adenoma Presented As Multiple Metatarsal And Phalangeal Fractures

    PubMed Central

    LiYeung, L L; Lui, T H

    2015-01-01

    Introduction: Symptomatic adrenal adenoma usually presents with systemic symptoms. Depending on the function of the adenoma, the patient can present with pheochromocytoma-like symptoms; primary hyperaldosteronism and Cushing syndrome (weight gain, weakness, depression, and bruising). Case report: A 41 year-old lady presented with multiple metatarsal and phalangeal fractures of the both feet without significant injury. DEXA scan showed evidence of osteoporosis. Investigations showed that the picture was compatible with adrenal Cushing syndrome. Computed tomogram showed bilateral adrenal adenoma. Adrenal cortex scintigraphy with NP-59 scan showed hyperfunctioning right adrenal adenoma. Laproscopic R adrenalectomy was performed and histological study confirmed adrenal cortical adenoma with adjacent cortical atrophy suggestive of a functioning adenoma. Post-operatively, she was put on hydrocortisone replacement and recovered well. Conclusion: Adrenal adenoma can present with insufficiency fractures of the feet. PMID:27299107

  1. Histoplasmosis of the adrenal glands studied by CT

    SciTech Connect

    Wilson, D.A.; Muchmore, H.G.; Tisdal, R.G.; Fahmy, A.; Pitha, J.V.

    1984-03-01

    Computed tomography (CT) of the adrenal glands was performed on seven patients who had histologically proved disseminated histoplasmosis. All seven patients showed some degree of adrenal gland abnormality. The range of CT findings included minimal enlargement with faint flecks of calcium, moderate enlargement with focal low attenuation nodules, and massive enlargement with large areas of necrosis or dense calcification. The changes in each patient were bilateral and symmetrical. Adrenal gland shape was usually preserved. Finding of percutaneous adrenal biopsy, which was performed under CT guidance, made the diagnosis in one patient. Five of seven patients had adrenal insufficiency. It is concluded that the diagnosis of disseminated histoplasmosis should be considered in any patient who has bilateral adrenal gland enlargement and who resides in an endemic area, especially if there is evidence of adrenal insufficiency.

  2. Adrenal myelolipoma: Controversies in its management

    PubMed Central

    Shenoy, Vasanth G.; Thota, Anuroop; Shankar, Ravi; Desai, Mallikarjun G.

    2015-01-01

    Adrenal myelolipomas (AMLs) are rare, benign neoplasms of the adrenal gland with varied clinical presentations. The rarity of these tumors precludes any case-controlled or randomized study into their management. The available literature is limited to case reports and short series from referral centers. This review is an effort to put the available literature into perspective such that clinical decision making can be done with some clarity. The PubMed and Cochrane databases were searched with key words Adrenal Myelolipoma, Adrenal Incidentaloma (AI) and Adrenal Collision Tumor (ACT). From over 1300 search results, 547 relevant publications dating from 1954 to 2014 were reviewed. Details of about 1231 AMLs in the indexed literature were analyzed. Increasing usage of imaging studies has significantly increased the discovery of AMLs. Although AMLs are benign tumors, those measuring larger than 6 cm are prone to rupture and hemorrhage. Thorough endocrine work-up may benefit a selected group of patients, especially those who are hypertensive, diabetic/pre-diabetic, young patients (<50 years) and those with bilateral AML. Regular observation is needed for AML patients who are being treated non-operatively, as many of them may require surgery during follow-up. Although the AACE/AAES guidelines for AI (2009) exclude AML from mandatory metabolic work-up for a newly discovered AI, we feel that a significant number of patients with AML would benefit from metabolic work-up. In the literature, endocrine dysfunction in AML is 7% as compared with 11% in AI. Endocrine dysfunction in AML is probably underdiagnosed. PMID:25878407

  3. [Changes in the activity of sympathetic-adrenal medullary system and hypothalamic-pituitary-adrenal system in humans exposed to psychogenic stressors and their effects on immunoreactivity].

    PubMed

    Simić, Natasa

    2010-10-01

    This paper gives an account of the functioning of the two systems in different stress induced situations. The activation of the sympathetic-adrenal medullary system is accompanied by the release of catecholamines, while the increased activity of the hypothalamic-pituitary-adrenal system results in the increased release of corticosteroids, especially cortisol. The role of the sympathetic-adrenal medullary system was investigated in immunologic changes induced by laboratory stressors. In the real, as in laboratory conditions, the effects of different stressors on the level of cortisol were studied, as it is the final product of the hypothalamic-pituitary-adrenal system activity. Additional (negative) effects on the functioning of these systems could induce some variables, as an increased consumption of alcohol, smoking, and sleeping disorder. Furthermore, the methodological shortcomings and the selection of subjects in previous studies are discussed. Previous results are also discussed, such as the immunosuppressive effects of cortisol, as well as the mediator and moderator variables in relation to stress and immunoreactivity. PMID:21688610

  4. To be or not to be in sexual desire: the androgen dilemma.

    PubMed

    Nappi, R E

    2015-10-01

    The androgen milieu and sexual desire in women seem to be tightly linked because they both decline with age. However, we are still missing a cut-off plasma level for androgens (total testosterone, free testosterone) or androgen precursors (androstenedione, dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS)) to diagnose androgen deficiency in clinical practice. Apart from the complex multidimensional nature of sexual desire across the reproductive lifespan, the correlation between measurements of testosterone and specific signs and symptoms has been difficult because, according to guidelines, most available assays are unreliable at baseline and under hormonal treatments. Recent data obtained with accurate methods based on mass spectrometry to measure total testosterone levels found a significant positive association with sexual desire, arousal and masturbation in midlife US women across the menopausal transition. Even in a European cohort of healthy women aged 19-65 years, sexual desire, measured with a validated questionnaire, correlated overall with free testosterone and androstenedione measured with mass spectrometry. Collectively, these data support the therapeutic use of testosterone for low desire and sexual dysfunction in those clinical conditions in which androgen deficiency may be accurately diagnosed. PMID:26176767

  5. Androgen Receptor as a Driver of Therapeutic Resistance in Advanced Prostate Cancer

    PubMed Central

    Kahn, Barbara; Collazo, Joanne; Kyprianou, Natasha

    2014-01-01

    The role of the androgen receptor (AR) signaling axis in the progression of prostate cancer is a cornerstone to our understanding of the molecular mechanisms causing castration-resistant prostate cancer (CRPC). Resistance of advanced prostate cancer to available treatment options makes it a clinical challenge that results in approximately 30,000 deaths of American men every year. Since the historic discovery by Dr. Huggins more than 70 years ago, androgen deprivation therapy (ADT) has been the principal treatment for advanced prostate cancer. Initially, ADT induces apoptosis of androgen-dependent prostate cancer epithelial cells and regression of androgen-dependent tumors. However, the majority of patients with advanced prostate cancer progress and become refractory to ADT due to emergence of androgen-independent prostate cancer cells driven by aberrant AR activation. Microtubule-targeting agents such as taxanes, docetaxel and paclitaxel, have enjoyed success in the treatment of metastatic prostate cancer; although new, recently designed mitosis-specific agents, such as the polo-kinase and kinesin-inhibitors, have yielded clinically disappointing results. Docetaxel, as a first-line chemotherapy, improves prostate cancer patient survival by months, but tumor resistance to these therapeutic agents inevitably develops. On a molecular level, progression to CRPC is characterized by aberrant AR expression, de novo intraprostatic androgen production, and cross talk with other oncogenic pathways. Emerging evidence suggests that reactivation of epithelial-mesenchymal-transition (EMT) processes may facilitate the development of not only prostate cancer but also prostate cancer metastases. EMT is characterized by gain of mesenchymal characteristics and invasiveness accompanied by loss of cell polarity, with an increasing number of studies focusing on the direct involvement of androgen-AR signaling axis in EMT, tumor progression, and therapeutic resistance. In this article, we

  6. The effect of changes in adrenal blood flow on adrenal cortical responses to adrenocorticotrophin in conscious calves.

    PubMed Central

    Jones, C T; Edwards, A V; Bloom, S R

    1990-01-01

    1. The effect of varying adrenal blood flow on the rate at which it was estimated that adrenocorticotrophin (ACTH) was presented to the adrenal gland was related to right adrenal cortisol output in conscious calves fitted with 'adrenal clamps'. 2. Intra-aortic infusions of endothelin at either 15.0 or 7.5 pmol min-1 kg-1 produced a substantial fall in right adrenal blood flow which was dose-related over this range. There was an associated fall in right adrenal cortisol output and cortisol output was linearly related to estimated ACTH presentation to the gland over the whole range investigated. The changes in adrenal cortisol output were reflected by changes in the concentration of cortisol in the peripheral plasma, which could be attributed entirely to the fluctuations in adrenal cortisol output. 3. It is concluded that delivery of ACTH to the adrenal gland is flow dependent over the physiological range in these animals and that changes in adrenal cortical blood flow can therefore be expected to result in changes in adrenal output due to variations in the presentation rate of ACTH. PMID:2177504

  7. Androgen Control in Prostate Cancer.

    PubMed

    Pelekanou, Vasiliki; Castanas, Elias

    2016-10-01

    Research on prostate cancer has extensively advanced in the past decade, through an improved understanding for its genetic basis and risk-stratification. Molecular classification of prostate cancer into distinct subtypes and the recognition of new histologic entities promise the development of tailored-made management strategies of patients. Nowadays, various alternatives are available for clinical management of localized disease ranging from observation alone through radical prostatectomy. In patients with castration-resistant prostate cancer, the approval of new drugs for the management of metastatic disease has offered promising results improving the survival of these patients. In this context, androgen receptors (AR) remain at the epicenter of prostate cancer research holding a prominent role in the biology and therapeutic regimens of prostate cancer. As many of castration-resistant tumors retain hormone-responsiveness, AR is a clinical relevant, druggable target. However, AR paradoxically remains neglected as a prostate cancer biomarker. The great advancements in prostate cancer preclinical and clinical research, imply further improvement in clinical and translational data, for patient selection and treatment optimization. For a precision medicine-guided clinical management of prostate cancer, AR evaluation has to be implemented in companion and complementary diagnostics, as discussed here. J. Cell. Biochem. 117: 2224-2234, 2016. © 2016 Wiley Periodicals, Inc. PMID:27104784

  8. Resveratrol alleviates endotoxemia-associated adrenal insufficiency by suppressing oxidative/nitrative stress.

    PubMed

    Duan, Guo-Li; Wang, Chang-Nan; Liu, Yu-Jian; Yu, Qing; Tang, Xiao-Lu; Ni, Xin; Zhu, Xiao-Yan

    2016-06-30

    We have recently demonstrated that endotoxin causes oxidative stress and overproduction of nitric oxide in adrenal glands, thereby leading to adrenocortical insufficiency. The aim of this study is to investigate the effects of resveratrol, a natural plant polyphenol with anti-oxidant and anti-nitrative properties, on endotoxemia-associated adrenocortical insufficiency. Resveratrol was administered immediately before injection of lipopolysaccharide (LPS). Twenty four hours later, the adrenocorticotropic hormone (ACTH) stimulation tests was been performed to measure the plasma corticosterone level and the adrenal gland tissues were collected for histopathologic examination, and determination of malondialdehyde (MDA), total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity, catalase (CAT) activity, inducible nitric oxide synthase (iNOS) expression, nitric oxide (NO) and peroxynitrite production. Treatment with resveratrol significantly inhibited endotoxemia-induced iNOS expression, NO production, and peroxynitrite formation and also attenuated LPS-induced oxidative stress in the adrenal gland, as evidenced by the decrease of pro-oxidant biomarker (MDA), and the increases of anti-oxidant biomarkers (T-AOC, CAT and SOD activity). H&E staining demonstrated that administration of LPS resulted in increased into the adrenal gland. H&E-stained sections of adrenal glands demonstrated signs of leukocyte infiltration and hemorrhage during endotoxemia, which were significantly improved by resveratrol treatment. In addition, resveratrol reversed the LPS-induced downregulation of ACTH receptor and silent information regulator 1 (SIRT1) in adrenal gland, as well as adrenocortical hyporesponsiveness to ACTH. Resveratrol exerts protective effects against endotoxemia-associated adrenocortical insufficiency by suppressing oxidative/nitrative stress. These findings support the potential for resveratrol as a possible pharmacological agent to improve adrenocortical

  9. A Rare Case of Adrenal Pheochromocytoma with Unusual Clinical and Biochemical Presentation: 
A Case Report and Literature Review

    PubMed Central

    Mula-Abed, Waad-Allah S.; Ahmed, Riyaz; Ramadhan, Fatima A.; Al-Kindi, Manal K.; Al-Busaidi, Noor B.; Al-Muslahi, Hilal N.; Al-Lamki, Mohammad A.

    2015-01-01

    A 50-year-old Omani woman presented to the Outpatient Clinic, Royal Hospital, Oman with right upper abdominal pain and backache that had lasted 10 days. She had no palpitation, sweating, or hypertension (blood pressure 122/78mmHg). The patient’s history revealed that she had a similar incidence of abdominal pain two months prior, which was a "dull ache" in nature and somewhat associated with headache. The pain was relieved using a mild analgesic drug. Abdominal ultrasonography showed a right adrenal mass, and both computed tomography and magnetic resonance imaging of the adrenal glands confirmed a right adrenal mass consistent with adrenal pheochromocytoma. However, clinical biochemistry tests revealed normal levels of plasma catecholamines (dopamine, norepinephrine, and epinephrine) and metanephrine, which are unusual findings in adrenal pheochromocytoma. Meanwhile, the patient had markedly raised plasma normetanephrine (10-fold) which, together with the normal metanephrine, constitutes a metabolic profile that is compatible with extra-adrenal pheochromocytoma. The patient also had markedly raised chromogranin A (16-fold), consistent with the presence of a neuroendocrine tumor. Laparoscopic right adrenalectomy was done and the adrenal tumor was excised and retrieved in total. Histopathology and immunohistochemistry confirmed the diagnosis of adrenal pheochromocytoma; the tumor cells being positive for chromogranin, synaptophysin, and S-100 protein. Following surgery, the patient did well and showed full recovery at follow-up after three months. Molecular genetic testing showed no pathogenic mutation in pheochromocytoma genes: MAX, SDHA, SDHAF2, SDHB, SDHC, SDHD, VHL, and PRKAR1A. A review of the literature was conducted to identify the pathophysiology and any previous reports of such case. To our knowledge, this is the first report in Oman of the extremely rare entity of pheochromocytoma with an unusual clinical and biochemical scenario. PMID:26421121

  10. A Rare Case of Adrenal Pheochromocytoma with Unusual Clinical and Biochemical Presentation: 
A Case Report and Literature Review.

    PubMed

    Mula-Abed, Waad-Allah S; Ahmed, Riyaz; Ramadhan, Fatima A; Al-Kindi, Manal K; Al-Busaidi, Noor B; Al-Muslahi, Hilal N; Al-Lamki, Mohammad A

    2015-09-01

    A 50-year-old Omani woman presented to the Outpatient Clinic, Royal Hospital, Oman with right upper abdominal pain and backache that had lasted 10 days. She had no palpitation, sweating, or hypertension (blood pressure 122/78mmHg). The patient's history revealed that she had a similar incidence of abdominal pain two months prior, which was a "dull ache" in nature and somewhat associated with headache. The pain was relieved using a mild analgesic drug. Abdominal ultrasonography showed a right adrenal mass, and both computed tomography and magnetic resonance imaging of the adrenal glands confirmed a right adrenal mass consistent with adrenal pheochromocytoma. However, clinical biochemistry tests revealed normal levels of plasma catecholamines (dopamine, norepinephrine, and epinephrine) and metanephrine, which are unusual findings in adrenal pheochromocytoma. Meanwhile, the patient had markedly raised plasma normetanephrine (10-fold) which, together with the normal metanephrine, constitutes a metabolic profile that is compatible with extra-adrenal pheochromocytoma. The patient also had markedly raised chromogranin A (16-fold), consistent with the presence of a neuroendocrine tumor. Laparoscopic right adrenalectomy was done and the adrenal tumor was excised and retrieved in total. Histopathology and immunohistochemistry confirmed the diagnosis of adrenal pheochromocytoma; the tumor cells being positive for chromogranin, synaptophysin, and S-100 protein. Following surgery, the patient did well and showed full recovery at follow-up after three months. Molecular genetic testing showed no pathogenic mutation in pheochromocytoma genes: MAX, SDHA, SDHAF2, SDHB, SDHC, SDHD, VHL, and PRKAR1A. A review of the literature was conducted to identify the pathophysiology and any previous reports of such case. To our knowledge, this is the first report in Oman of the extremely rare entity of pheochromocytoma with an unusual clinical and biochemical scenario. PMID:26421121

  11. Changes in estrogen receptor ERalpha and ERbeta expression in chicken (Gallus domesticus) adrenal gland during short-fasting and refeeding.

    PubMed

    Błachuta, Małgorzata; Wrońska-Fortuna, Danuta

    2012-01-01

    Estrogen receptors have been found in the adrenal gland of rodents, monkeys, mares and sheep, indicating a connection between sex steroids and the activity of the adrenal gland. In the present study, the expression of estrogen receptors alpha (ERalpha) and beta (ERbeta) in the chicken adrenal gland during stress induced by 24 h fasting and after refeeding was determined using reverse transcription and the polymerase chain reaction (RT-PCR). The presence of both ER mRNAs in the adrenal gland of all examined groups was found. The relative expression of ERalpha mRNA was higher than ERbeta mRNA. There were no significant differences in ERalpha mRNA expression among the examined groups. On the contrary, we observed changes in ERbeta expression during stress conditions. These findings indicate different pathways of estrogen action in the avian adrenal gland. Furthermore, changes in ERbeta level suggest that this form of estrogen receptor plays a predominant role for estrogen action in the chicken adrenal gland during stress. PMID:23342917

  12. Enucleation-induced rat adrenal gland regeneration: expression profile of selected genes involved in control of adrenocortical cell proliferation.

    PubMed

    Tyczewska, Marianna; Rucinski, Marcin; Ziolkowska, Agnieszka; Szyszka, Marta; Trejter, Marcin; Hochol-Molenda, Anna; Nowak, Krzysztof W; Malendowicz, Ludwik K

    2014-01-01

    Enucleation-induced adrenal regeneration is a highly controlled process; however, only some elements involved in this process have been recognized. Therefore, we performed studies on regenerating rat adrenals. Microarray RNA analysis and QPCR revealed that enucleation resulted in a rapid elevation of expression of genes involved in response to wounding, defense response, and in immunological processes. Factors encoded by these genes obscure possible priming effects of various cytokines on initiation of regeneration. In regenerating adrenals we identified over 100 up- or downregulated genes involved in adrenocortical cell proliferation. The changes were most significant at days 2-3 after enucleation and their number decreased during regeneration. For example, expression analysis revealed a notable upregulation of the growth arrest gene, Gadd45, only 24 hours after surgery while expression of cyclin B1 and Cdk1 genes was notably elevated between days 1-8 of regeneration. These changes were accompanied by changes in expression levels of numerous growth factors and immediate-early transcription factors genes. Despite notable differences in mechanisms of adrenal and liver regeneration, in regenerating adrenals we identified genes, the expression of which is well recognized in regenerating liver. Thus, it seems legitimate to suggest that, in the rat, the general model of liver and adrenal regeneration demonstrate some degree of similarity. PMID:25431590

  13. Enucleation-Induced Rat Adrenal Gland Regeneration: Expression Profile of Selected Genes Involved in Control of Adrenocortical Cell Proliferation

    PubMed Central

    Tyczewska, Marianna; Rucinski, Marcin; Ziolkowska, Agnieszka; Szyszka, Marta; Trejter, Marcin; Hochol-Molenda, Anna; Nowak, Krzysztof W.; Malendowicz, Ludwik K.

    2014-01-01

    Enucleation-induced adrenal regeneration is a highly controlled process; however, only some elements involved in this process have been recognized. Therefore, we performed studies on regenerating rat adrenals. Microarray RNA analysis and QPCR revealed that enucleation resulted in a rapid elevation of expression of genes involved in response to wounding, defense response, and in immunological processes. Factors encoded by these genes obscure possible priming effects of various cytokines on initiation of regeneration. In regenerating adrenals we identified over 100 up- or downregulated genes involved in adrenocortical cell proliferation. The changes were most significant at days 2-3 after enucleation and their number decreased during regeneration. For example, expression analysis revealed a notable upregulation of the growth arrest gene, Gadd45, only 24 hours after surgery while expression of cyclin B1 and Cdk1 genes was notably elevated between days 1–8 of regeneration. These changes were accompanied by changes in expression levels of numerous growth factors and immediate-early transcription factors genes. Despite notable differences in mechanisms of adrenal and liver regeneration, in regenerating adrenals we identified genes, the expression of which is well recognized in regenerating liver. Thus, it seems legitimate to suggest that, in the rat, the general model of liver and adrenal regeneration demonstrate some degree of similarity. PMID:25431590

  14. Androgen actions on the human hair follicle: perspectives.

    PubMed

    Inui, Shigeki; Itami, Satoshi

    2013-03-01

    Androgens stimulate beard growth but suppress hair growth in androgenetic alopecia (AGA). This condition is known as 'androgen paradox'. Human pilosebaceous units possess enough enzymes to form the active androgens testosterone and dihydrotestosterone. In hair follicles, 5α-reductase type 1 and 2, androgen receptors (AR) and AR coactivators can regulate androgen sensitivity of dermal papillae (DP). To regulate hair growth, androgens stimulate production of IGF-1 as positive mediators from beard DP cells and of TGF-β1, TGF-β2, dickkopf1 and IL-6 as negative mediators from balding DP cells. In addition, androgens enhance inducible nitric oxide synthase from occipital DP cells and stem cell factor for positive regulation of hair growth in beard and negative regulation of balding DP cells. Moreover, AGA involves crosstalk between androgen and Wnt/β-catenin signalling. Finally, recent data on susceptibility genes have provided us with the impetus to investigate the molecular pathogenesis of AGA. PMID:23016593

  15. Androgen receptor expression and morphology of forebrain and neuromuscular systems in male green anoles displaying individual differences in sexual behavior.

    PubMed

    Neal, Jennifer K; Wade, Juli

    2007-08-01

    Investigating individual differences in sexual performance in unmanipulated males is important for understanding natural relationships between behavior and morphology, and the mechanisms regulating them. Among male green anole lizards, some court and copulate frequently (studs) and others do not (duds). To evaluate potential factors underlying differences in the level of these behaviors, morphology and androgen receptor expression in neuromuscular courtship and copulatory structures, as well as in the preoptic area and amygdala, were compared in males displaying varying degrees of sexual function. This study revealed that individual differences in behavior among unmanipulated males, in particular the extension of a throat fan (dewlap) used during courtship, were positively correlated with the size of fibers in the associated muscle and with soma size in the amygdala. The physiological response to testosterone, as indicated by the height of cells in an androgen-sensitive portion of the kidney, was also correlated with male sexual behavior, and predicted it better than plasma androgen levels. Androgen receptor expression was not related to the display of courtship or copulation in any of the tissues examined. The present data indicate that higher levels of male courtship behavior result in (or are the result of) enhanced courtship muscle and amygdala morphology, and that androgen-sensitive tissue in studs may be more responsive to testosterone than duds. However, some mechanism(s) other than androgen receptor expression likely confer this difference in responsiveness. PMID:17531996

  16. Androgen receptor expression and morphology of forebrain and neuromuscular systems in male green anoles displaying individual differences in sexual behavior

    PubMed Central

    Neal, Jennifer K.; Wade, Juli

    2010-01-01

    Investigating individual differences in sexual performance in unmanipulated males is important for understanding natural relationships between behavior and morphology, and the mechanisms regulating them. Among male green anole lizards, some court and copulate frequently (studs) and others do not (duds). To evaluate potential factors underlying differences in the level of these behaviors, morphology and androgen receptor expression in neuromuscular courtship and copulatory structures, as well as in the preoptic area and amygdala, were compared in males displaying varying degrees of sexual function. This study revealed that individual differences in behavior among unmanipulated males, in particular the extension of a throat fan (dewlap) used during courtship, were positively correlated with the size of fibers in the associated muscle and with soma size in the amygdala. The physiological response to testosterone, as indicated by the height of cells in an androgen-sensitive portion of the kidney, was also correlated with male sexual behavior, and predicted it better than plasma androgen levels. Androgen receptor expression was not related to the display of courtship or copulation in any of the tissues examined. The present data indicate that higher levels of male courtship behavior result in (or are the result of) enhanced courtship muscle and amygdala morphology, and that androgen-sensitive tissue in studs may be more responsive to testosterone than duds. However, some mechanism(s) other than androgen receptor expression likely confer this difference in responsiveness. PMID:17531996

  17. Image Registration of Cone-Beam Computer Tomography and Preprocedural Computer Tomography Aids in Localization of Adrenal Veins and Decreasing Radiation Dose in Adrenal Vein Sampling

    SciTech Connect

    Busser, Wendy M. H. Arntz, Mark J.; Jenniskens, Sjoerd F. M.; Deinum, Jaap; Hoogeveen, Yvonne L.; Lange, Frank de; Schultze Kool, Leo J.

    2015-08-15

    PurposeWe assessed whether image registration of cone-beam computed tomography (CT) (CBCT) and contrast-enhanced CT (CE-CT) images indicating the locations of the adrenal veins can aid in increasing the success rate of first-attempts adrenal vein sampling (AVS) and therefore decreasing patient radiation dose.Materials and Methods CBCT scans were acquired in the interventional suite (Philips Allura Xper FD20) and rigidly registered to the vertebra in previously acquired CE-CT. Adrenal vein locations were marked on the CT image and superimposed with live fluoroscopy and digital-subtraction angiography (DSA) to guide the AVS. Seventeen first attempts at AVS were performed with image registration and retrospectively compared with 15 first attempts without image registration performed earlier by the same 2 interventional radiologists. First-attempt AVS was considered successful when both adrenal vein samples showed representative cortisol levels. Sampling time, dose-area product (DAP), number of DSA runs, fluoroscopy time, and skin dose were recorded.ResultsWithout image registration, the first attempt at sampling was successful in 8 of 15 procedures indicating a success rate of 53.3 %. This increased to 76.5 % (13 of 17) by adding CBCT and CE-CT image registration to AVS procedures (p = 0.266). DAP values (p = 0.001) and DSA runs (p = 0.026) decreased significantly by adding image registration guidance. Sampling and fluoroscopy times and skin dose showed no significant changes.ConclusionGuidance based on registration of CBCT and previously acquired diagnostic CE-CT can aid in enhancing localization of the adrenal veins thereby increasing the success rate of first-attempt AVS with a significant decrease in the number of used DSA runs and, consequently, radiation dose required.

  18. Increased cytosolic androgen receptor binding in rat striated muscle following denervation and disuse

    NASA Technical Reports Server (NTRS)

    Bernard, P. A.; Fishman, P. S.; Max, S. R.; Rance, N. E.

    1984-01-01

    The effects of denervation and disuse on cytosolic androgen receptor binding by rat striated muscle are investigated. Denervation of the extensor digitorum longus and tibialis anterior muscles caused by a 40-50-percent increase in cytosolic androgen receptor concentration with no change in apparent binding affinity. This effect was evident at 6 h postdenervation, maximal at 24 h, and declined to 120 percent of the control level 72 h after denervation. A 40-percent increase in cytosolic androgen receptor concentration was also noted 24 hr after denervation of the hormone-sensitive levator ani muscle. The effect of denervation on androgen receptors was blocked by in vivo injection of cycloheximide; therefore, de novo receptor synthesis probably is not involved in the observed increase. Disuse, produced by subperineurial injection of tetrodotoxin into the tibial and common peroneal branches of the sciatic nerve, mimicked the effect of denervation on androgen receptor binding, suggesting that neuromuscular activity is important in regulation of receptor concentration. Possible mechanisms subserving this effect are discussed.

  19. Drug Insight: testosterone and selective androgen receptor modulators as anabolic therapies for chronic illness and aging

    PubMed Central

    Bhasin, Shalender; Calof, Olga M; Storer, Thomas W; Lee, Martin L; Mazer, Norman A; Jasuja, Ravi; Montori, Victor M; Gao, Wenqing; Dalton, James T

    2007-01-01

    SUMMARY Several regulatory concerns have hindered development of androgens as anabolic therapies, despite unequivocal evidence that testosterone supplementation increases muscle mass and strength in men; it induces hypertrophy of type I and II muscle fibers, and increases myonuclear and satellite cell number. Androgens promote differentiation of mesenchymal multipotent cells into the myogenic lineage and inhibit their adipogenic differentiation, by facilitating association of androgen receptors with β-catenin and activating T-cell factor 4. Meta-analyses indicate that testosterone supplementation increases fat-free mass and muscle strength in HIV-positive men with weight loss, glucocorticoid-treated men, and older men with low or low-normal testosterone levels. The effects of testosterone on physical function and outcomes important to patients have not, however, been studied. In older men, increased hematocrit and increased risk of prostate biopsy and detection of prostate events are the most frequent, testosterone-related adverse events. Concerns about long-term risks have restrained enthusiasm for testosterone use as anabolic therapy. Selective androgen-receptor modulators that are preferentially anabolic and that spare the prostate hold promise as anabolic therapies. We need more studies to determine whether testosterone or selective androgen-receptor modulators can induce meaningful improvements in physical function and patient-important outcomes in patients with physical dysfunction associated with chronic illness or aging. PMID:16932274

  20. Criminality and the 2D:4D ratio: testing the prenatal androgen hypothesis.

    PubMed

    Ellis, Lee; Hoskin, Anthony W

    2015-03-01

    A decade old theory hypothesizes that brain exposure to androgens promotes involvement in criminal behavior. General support for this hypothesis has been provided by studies of postpubertal circulating levels of testosterone, at least among males. However, the theory also predicts that for both genders, prenatal androgens will be positively correlated with persistent offending, an idea for which no evidence currently exists. The present study used an indirect measure of prenatal androgen exposure-the relative length of the second and fourth fingers of the right hand (r2D:4D)-to test the hypothesis that elevated prenatal androgens promote criminal tendencies later in life for males and females. Questionnaires were administered to 2,059 college students in Malaysia and 1,291 college students in the United States. Respondents reported their r2D:4D relative finger lengths along with involvement in 13 categories of delinquent and criminal acts. Statistically significant correlations between the commission of most types of offenses and r2D:4D ratios were found for males and females even after controlling for age. It is concluded that high exposure to androgens during prenatal development contributes to most forms of offending following the onset of puberty. PMID:24013770