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Sample records for adrenal androgen dehydroepiandrosterone

  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. Luteinizing hormone (LH)-releasing hormone agonist reduces serum adrenal androgen levels in prostate cancer patients: implications for the effect of LH on the adrenal glands.

    PubMed

    Nishii, Masahiro; Nomura, Masashi; Sekine, Yoshitaka; Koike, Hidekazu; Matsui, Hiroshi; Shibata, Yasuhiro; Ito, Kazuto; Oyama, Tetsunari; Suzuki, Kazuhiro

    2012-01-01

    Recently, adrenal androgens have been targeted as key hormones for the development of castration-resistant prostate cancer therapeutics. Although circulating adrenal androgens originate mainly from the adrenal glands, the testes also supply about 10%. Although widely used in androgen deprivation medical castration therapy, the effect of luteinizing hormone-releasing hormone (LH-RH) agonist on adrenal androgens has not been fully studied. In this study, changes in testicular and adrenal androgen levels were measured and compared to adrenocorticotropic hormone levels. To assess the possible role of LH in the adrenal glands, immunohistochemical studies of the LH receptor in normal adrenal glands were performed. Forty-seven patients with localized or locally progressive prostate cancer were treated with LH-RH agonist with radiotherapy. Six months after initiation of treatment, testosterone, dihydrotestosterone, and estradiol levels were decreased by 90%-95%, and dehydroepiandrosterone-sulfate, dehydroepiandrosterone, and androstenedione levels were significantly decreased by 26%-40%. The suppressive effect of LH-RH agonist at 12 months was maintained. Adrenocorticotropic hormone levels showed an increasing trend at 6 months and a significant increase at 12 months. LH receptors were positively stained in the cortex cells of the reticular layer of the adrenal glands. The long-term LH-RH agonist treatment reduced adrenal-originated adrenal androgens. LH receptors in the adrenal cortex cells of the reticular layer might account for the underlying mechanism of reduced adrenal androgens.

  3. The agonistic adrenal: melatonin elicits female aggression via regulation of adrenal androgens.

    PubMed

    Rendon, Nikki M; Rudolph, Lauren M; Sengelaub, Dale R; Demas, Gregory E

    2015-11-22

    Classic findings have demonstrated an important role for sex steroids as regulators of aggression, but this relationship is lacking within some environmental contexts. In mammals and birds, the adrenal androgen dehydroepiandrosterone (DHEA), a non-gonadal precursor of biologically active steroids, has been linked to aggression. Although females, like males, use aggression when competing for limited resources, the mechanisms underlying female aggression remain understudied. Here, we propose a previously undescribed endocrine mechanism regulating female aggression via direct action of the pineal hormone melatonin on adrenal androgens. We examined this in a solitary hamster species, Phodopus sungorus, in which both sexes are highly territorial across the seasons, and display increased aggression concomitant with decreased serum levels of sex steroids in short 'winter-like' days. Short- but not long-day females had increased adrenal DHEA responsiveness co-occurring with morphological changes in the adrenal gland. Further, serum DHEA and total adrenal DHEA content were elevated in short days. Lastly, melatonin increased DHEA and aggression and stimulated DHEA release from cultured adrenals. Collectively, these findings demonstrate that DHEA is a key peripheral regulator of aggression and that melatonin coordinates a 'seasonal switch' from gonadal to adrenal regulation of aggression by direct action on the adrenal glands.

  4. Adrenal androgen abnormalities in women with late onset and persistent acne.

    PubMed

    Aizawa, H; Niimura, M

    1993-01-01

    Androgens are an essential prerequisite for the development of acne. The present study was undertaken to characterize the androgen status of women with late onset and persistent acne only and, using the dexamethasone (dex) suppression test, to identify the source(s) of the androgen excess. We measured serum levels of total testosterone (T), free testosterone (FT), androstenedione (delta 4A), dihydrotestosterone (DHT), dehydroepiandrosterone sulphate (DHEA-S) and sex hormone binding globulin (SHBG) in 34 healthy control subjects, in 34 women with mild acne and in 29 women with moderate or severe acne. Serum FT, DHT and DHEA-S levels in patients of both acne groups were significantly higher than those in the control subjects. The other hormone levels showed no significant differences between patients and control subjects, and there were no significant differences between the two acne groups in any of the androgen levels. In order to evaluate the ovarian and adrenal contributions to serum androgens in the acne patients, the serum levels of delta 4A, T, DHT and DHEA-S were measured prior to and following 2 weeks of dex therapy. Following the dex test, the DHT and T of adrenal origin were significantly higher in the acne patients than in the control subjects. These results suggest that, in acne patients, hyperandrogenaemia is likely to develop as a result of adrenal androgen excess. In addition, since abnormally high androgen levels are frequently seen in late onset and persist acne, it seems that this condition is likely to be a sign of hyperandrogenism. PMID:8466282

  5. 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

  6. Plasma dehydroepiandrosterone sulfate levels in patients with hyperfunctioning and non-hyperfunctioning adrenal tumors before and after adrenal surgery.

    PubMed

    Tóth, M; Rácz, K; Varga, I; Adleff, V; Jakab, C; Fútó, L; Kiss, R; Gláz, E

    1997-03-01

    To investigate the clinical significance of plasma dehydroepiandrosterone sulfate (DHEAS) measurements, 175 patients with histologically confirmed adrenal tumors, 10 cortisol-producing adenomas, 59 aldosterone-producing adenomas, 56 non-hyperfunctioning adenomas, 13 adrenocortical carcinomas, 13 adrenal cysts, and 24 adrenomedullary tumors were studied. Plasma DHEAS levels were expressed as percentage of the mean of sex- and age-matched groups of healthy, normal subjects (DHEAS %). We found that before adrenal surgery, DHEAS % values were significantly reduced in patients with cortisol-producing (mean, 15.2% of control; 95% confidence interval (CI), 9.4-24.7%), non-hyperfunctioning (28.4%; 22.4-36.0%) as well as aldosterone-producing adrenocortical adenomas (55.4%; 47.1-65.1%) compared with controls, while values were normal in patients with adrenal cysts and in those with adrenomedullary tumors. Plasma DHEAS % values exhibited a great variability in adrenocortical carcinomas (mean, 84.0%; 95% CI, 33.2-212.5%). Death from adrenocortical carcinoma was more frequent in patients with high plasma DHEAS % values compared with those with low DHEAS %. During long-term postoperative monitoring, we found that plasma DHEAS levels of patients with aldosterone-producing and non-hyperfunctioning adenomas returned to normal in the second and fourth postoperative year respectively. In patients with cortisol-producing adenomas, plasma DHEAS remained suppressed for as long as 8 years after the operation. These findings show that except in adrenocortical carcinomas and cysts, plasma DHEAS levels are significantly decreased in all groups of adrenocortical tumors, including non-hyperfunctioning and aldosterone-producing tumors. The extent of this decrease and the postoperative persistence of suppressed plasma DHEAS levels may be related to the glucocorticoid production of adrenocortical tumors. PMID:9100554

  7. Novel dehydroepiandrosterone troche supplementation improves the serum androgen profile of women undergoing in vitro fertilization

    PubMed Central

    Keane, Kevin N; Hinchliffe, Peter M; Namdar, Navid; Conceicao, Jason L; Newsholme, Philip; Yovich, John L

    2015-01-01

    Dehydroepiandrosterone (DHEA) is the most abundant steroid hormone in the circulation and has potent multifunctional activity. Epidemiological evidence suggests that levels of serum DHEA decrease with advancing age, and this has been associated with onset or progression of various age-related ailments, including cognitive decline and dementia, cardiovascular disease, and obesity. Consequently, these findings have sparked intense research interest in DHEA supplementation as an “antiaging” therapy. Currently, DHEA is being used by 25% of in vitro fertilization (IVF) clinicians as an adjuvant in assisted reproductive programs, yet the therapeutic benefit of DHEA is unclear. Here, we examined the use of novel DHEA-containing oral troches in patients undertaking IVF and investigated the impact of these troches on their serum androgen profile. This retrospective study determined the androgen profile of 31 IVF patients before (baseline) and after DHEA supplementation (with DHEA). Baseline serum measurements of testosterone (total and free), DHEA sulfate (DHEAS), sex hormone-binding globulin (SHBG), and androstenedione were made before and after supplementation. Each patient received DHEA troches containing 25 mg of micronized DHEA, and troches were administered sublingually twice daily for a period of no greater than 4 months. Adjuvant treatment with DHEA boosted the serum concentration of a number of androgen-related analytes, including total and free testosterone, androstenedione, and DHEAS, while serum SHBG remained unchanged. Supplementation also significantly increased the free-androgen index in IVF patients. Interestingly, the increase in serum analyte concentration following DHEA supplementation was found to be dependent on body mass index (BMI), but not individual age. Patients with the lowest BMI (<20.0 kg/m2) tended to have lower testosterone and DHEAS, but higher SHBG and androstenedione levels in comparison with other BMI groups postsupplementation

  8. Novel dehydroepiandrosterone troche supplementation improves the serum androgen profile of women undergoing in vitro fertilization.

    PubMed

    Keane, Kevin N; Hinchliffe, Peter M; Namdar, Navid; Conceicao, Jason L; Newsholme, Philip; Yovich, John L

    2015-01-01

    Dehydroepiandrosterone (DHEA) is the most abundant steroid hormone in the circulation and has potent multifunctional activity. Epidemiological evidence suggests that levels of serum DHEA decrease with advancing age, and this has been associated with onset or progression of various age-related ailments, including cognitive decline and dementia, cardiovascular disease, and obesity. Consequently, these findings have sparked intense research interest in DHEA supplementation as an "antiaging" therapy. Currently, DHEA is being used by 25% of in vitro fertilization (IVF) clinicians as an adjuvant in assisted reproductive programs, yet the therapeutic benefit of DHEA is unclear. Here, we examined the use of novel DHEA-containing oral troches in patients undertaking IVF and investigated the impact of these troches on their serum androgen profile. This retrospective study determined the androgen profile of 31 IVF patients before (baseline) and after DHEA supplementation (with DHEA). Baseline serum measurements of testosterone (total and free), DHEA sulfate (DHEAS), sex hormone-binding globulin (SHBG), and androstenedione were made before and after supplementation. Each patient received DHEA troches containing 25 mg of micronized DHEA, and troches were administered sublingually twice daily for a period of no greater than 4 months. Adjuvant treatment with DHEA boosted the serum concentration of a number of androgen-related analytes, including total and free testosterone, androstenedione, and DHEAS, while serum SHBG remained unchanged. Supplementation also significantly increased the free-androgen index in IVF patients. Interestingly, the increase in serum analyte concentration following DHEA supplementation was found to be dependent on body mass index (BMI), but not individual age. Patients with the lowest BMI (<20.0 kg/m(2)) tended to have lower testosterone and DHEAS, but higher SHBG and androstenedione levels in comparison with other BMI groups postsupplementation. However

  9. Dehydroepiandrosterone alters vitamin E status and prevents lipid peroxidation in vitamin E-deficient rats

    PubMed Central

    Miyazaki, Hiroshi; Takitani, Kimitaka; Koh, Maki; Inoue, Akiko; Tamai, Hiroshi

    2016-01-01

    In humans, dehydroepiandrosterone and its sulfate ester metabolite DHEA-S are secreted predominantly from the adrenal cortex, and dehydroepiandrosterone is converted to steroid hormones, including androgens and estrogens, and neurosteroid. Dehydroepiandrosterone exerts protective effects against several pathological conditions. Although there are reports on the association between dehydroepiandrosterone and vitamins, the exact relationship between dehydroepiandrosterone and vitamin E remains to be determined. Therefore, we attempted to elucidate the effect of dehydroepiandrosterone on vitamin E status and the expression of various vitamin E-related proteins, including binding proteins, transporters, and cytochrome P450, in vitamin E-deficient rats. Plasma α-tocopherol levels in vitamin E-deficient rats increased in response to dehydroepiandrosterone administration. The expression of hepatic α-tocopherol transfer protein was repressed in vitamin E-deficient rats compared to that in control rats; however, dehydroepiandrosterone administration significantly upregulated this expression. Hepatic expression of CYP4F2, an α-tocopherol metabolizing enzyme, in vitamin E-deficient rats was decreased by dehydroepiandrosterone administration, whereas hepatic expression of ATP-binding cassette transporter A1, an α-tocopherol transporter, was not altered following dehydroepiandrosterone administration. Dehydroepiandrosterone repressed lipid peroxidation in the liver of vitamin E-deficient rats. Therefore, adequate dehydroepiandrosterone supplementation may improve lipid peroxidation under several pathological conditions, and dehydroepiandrosterone may modulate α-tocopherol levels through altered expression of vitamin E-related proteins. PMID:27257348

  10. Dehydroepiandrosterone increases the zone [correction of in zone] of glutamine synthetase-positive hepatocytes in female rat liver: a putative androgenic effect.

    PubMed

    Mayer, D; Buniatian, G; Metzger, C; Bannasch, P; Gebhardt, R

    1999-05-01

    The adrenal steroid dehydroepiandrosterone (DHEA) is a hepatocarcinogen and peroxisome proliferator in the rat, producing an increase in peroxisomes mainly in perivenular parts of the liver lobule. Glutamine synthetase (GS) is expressed exclusively in hepatocytes that directly surround the central terminal vein in rat liver. The GS-positive zone is wider in males than in females, covering about two to three cell layers in males and one to two cell layers in females. Treatment of rats with DHEA at a concentration of 0.6% in the diet for 4, 20, 32, 70 and 84 weeks resulted in an enlargement of the GS-positive zone in females, whereas no change was observed in males. In females treated for up to 32 weeks with DHEA, the relative mean width (RMW) of the GS-positive zone was as large as that observed in males. The increase in the RMW was paralleled by an increase in the number of GS-positive hepatocytes. Upon longer treatment, the width of GS expression decreased to that observed in untreated controls. The findings suggest an androgenic effect of DHEA. The areas of peroxisome proliferation, identified in haematoxylin and eosin- and periodic acid-Schiff-stained sections, and GS expression were not identical. Furthermore, preneoplastic and neoplastic liver lesions induced by DHEA were all negative for GS, indicating that they do not derive from the perivenular cells which show the most pronounced peroxisomal proliferation.

  11. Androgen therapy in women.

    PubMed

    Arlt, Wiebke

    2006-01-01

    Androgens in women either derive from direct ovarian production or from peripheral conversion of the adrenal sex steroid precursor, dehydroepiandrosterone, towards active androgens. Therefore, loss of adrenal or ovarian function, caused by Addison's disease or consequent to bilateral oophorectomy, results in severe androgen deficiency, clinically often associated with a loss of libido and energy. Importantly, physiological menopause does not necessarily lead to androgen deficiency, as androgen synthesis in the ovaries may persist despite the decline in estrogen production. However, the definition of female androgen deficiency, as recently provided by the Princeton consensus statement, is not precise enough and may lead to over-diagnosis due to the high prevalence of its diagnostic criteria: androgen levels below or within the lower quartile of the normal range and concurrent sexual dysfunction. Importantly, physiological menopause is not necessarily associated with androgen deficiency and therefore does not routinely require androgen therapy. Current replacement options include transdermal testosterone administration or dehydroepiandrosterone treatment, both of which have been shown to result in significant improvements, in particular in libido and mood, while effects on body composition and muscular function are not well documented. It is important to keep in mind that the number of randomized controlled trials is still limited and that currently none of the available preparations is officially approved for use in women. Currently, androgen replacement should be reserved for women with severe androgen deficiency due to an established cause and matching clinical signs and symptoms. PMID:16381985

  12. Salivary Dehydroepiandrosterone Responsiveness to Social Challenge in Adolescents with Internalizing Problems

    ERIC Educational Resources Information Center

    Shirtcliff, Elizabeth; Zahn-Waxler, Carolyn; Klimes-Dougan, Bonnie; Slattery, Marcia

    2007-01-01

    Background: Dehydroepiandrosterone (DHEA) is an adrenal androgen which is stress responsive and a trigger for pubertal maturation. Studies on basal DHEA suggest protective benefits against anxiety and depression, yet it is unknown whether DHEA responsivity is protective. Methods: Structural equation modeling examined salivary DHEA responses to a…

  13. Dehydroepiandrosterone sulfotransferase in the developing human fetus: quantitative biochemical and immunological characterization of the hepatic, renal, and adrenal enzymes.

    PubMed

    Barker, E V; Hume, R; Hallas, A; Coughtrie, W H

    1994-02-01

    The sulfation of the adrenal steroid dehydroepiandrosterone (DHEA) is a critical step in the provision of substrates for estrogen biosynthesis by the placenta during pregnancy. This enzyme reaction is catalyzed by a cytosolic sulfotransferase (ST) found in many key body tissues, and we have examined the ontogeny and localization of expression of this important enzyme in three tissues: the liver, adrenal, and kidney. Hepatic DHEA ST expression increased with advancing gestational age before reaching near-adult levels in the early postnatal period, suggesting an increased requirement for this enzyme in the liver as development progresses, whereas in the adrenal and kidney there was no obvious ontogenic pattern. The enzyme was expressed at a 5-fold higher level in the adrenal than in the liver and some 40-fold higher than in the kidney. Comparison of enzyme activity measurements and quantitation of the expression of DHEA ST by immunodot blot analysis with an anti-DHEA ST antibody preparation demonstrated the fragility of the enzyme activity and suggested that immunoquantitation was a superior method for assessment of levels of expression of this enzyme in widely different tissue sources. Examination of the localization of DHEA ST in these tissues by immunohistochemistry showed that in liver, DHEA ST was expressed in embryonic hepatocytes and continued to be expressed in these cells into adulthood, when there was some concentration of immunostaining around central veins. In the fetus, the adrenal enzyme was expressed in the fetal zone, whereas in adult tissue, staining was localized principally to the zona reticularis. Renal DHEA ST was present in the proximal and distal tubules, loops of Henle, collecting ducts, and their progenitors, but was at no time expressed in the vascular glomerulus. In light of the broad substrate specificity of this enzyme toward other steroids, in particular bile acids and cholesterol, the information presented forms a strong basis for

  14. Interleukin-6 inhibits adrenal androgen release from bovine adrenal zona reticularis cells by inhibiting the expression of steroidogenic proteins.

    PubMed

    McIlmoil, S; Call, G B; Barney, M; Strickland, J; Judd, A M

    2015-10-01

    Interleukin-6 (IL-6) is secreted by adrenocortical cells and modifies cortisol secretion. In this study, the effects of IL-6 on adrenal androgen release were investigated. The zona reticularis (ZR) was generally isolated from bovine adrenal glands by dissection. In select experiments, the intact adrenal cortex (ie, all 3 adrenocortical zones) was dissected from the adrenal glands. For androgen release experiments, ZR and intact adrenocortical cubes were dispersed into isolated cells, the cells cultured and exposed to IL-6 and/or adrenocorticotropic hormone (ACTH), and androgen release determined by radioimmunoassay. Basal and ACTH-stimulated androgen release from the ZR was inhibited by IL-6 in a concentration-dependent (10-1000 pg/mL) and time-dependent (4-24 h) manner (P < 0.01 by 1-way analysis of variance and the Bonferroni test). In contrast, IL-6 increased basal and ACTH-stimulated androgen release from mixed adrenocortical cells (P < 0.01). The mechanism of IL-6 inhibition of androgen release was investigated by exposing ZR strips to IL-6 and measuring the expression of the messenger RNA (mRNA) and protein of steroidogenic factors. Basal and ACTH-stimulated expression of the mRNA and protein for steroidogenic acute regulatory protein, cholesterol side chain cleavage enzyme, 3-β-hydroxysteroid dehydrogenase type 2, steroid 17-α-hydroxylase/17,20 lyase/17,20 desmolase, and the nuclear factor steroidogenic factor 1 (SF-1), that stimulates steroidogenesis, were decreased by IL-6 (P < 0.01). In contrast IL-6 increased the mRNA and protein for dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1 (DAX-1), a nuclear factor that inhibits steroidogenesis (P < 0.01). In summary, IL-6 decreased androgen release and the expression of steroidogenic factors in the ZR, and this decrease may be mediated in part through increasing DAX-1 and decreasing SF-1. PMID:26218834

  15. 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.

  16. Adrenal androgen excess in the polycystic ovary syndrome: sensitivity and responsivity of the hypothalamic-pituitary-adrenal axis.

    PubMed

    Azziz, R; Black, V; Hines, G A; Fox, L M; Boots, L R

    1998-07-01

    Over 50% of patients with the polycystic ovary syndrome (PCOS) demonstrate excess levels of adrenal androgens (AAs), particularly dehydroepiandrosterone sulfate (DHS). Nonetheless, the mechanism for the AA excess remains unclear. It has been noted that in PCOS the pituitary and ovarian responses to their respective trophic factors (i.e. GnRH and LH, respectively) are exaggerated. Similarly, we have postulated that excess AAs in PCOS arises from dysfunction of the hypothalamic-pituitary-adrenal axis, due to 1) exaggerated pituitary secretion of ACTH in response to hypothalamic CRH, 2) excess sensitivity/responsivity of AAs to ACTH stimulation, or 3) both. To test this hypothesis we studied 12 PCOS patients with AA excess (HI-DHS; DHS, > 8.1 mumol/L or 3000 ng/mL), 12 PCOS patients without AA excess (LO-DHS; DHS, < 7.5 mumol/L or 2750 ng/mL), and 11 controls (normal subjects). Each subject underwent an acute 90-min ovine CRH stimulation test (1 microgram/kg) and an 8-h incremental i.v. stimulation with ACTH-(1-24) at doses ranging from 20-2880 ng/1.5 m2.h) with a final bolus of 0.25 mg. All patient groups had similar mean body mass indexes and ages, and both tests were performed in the morning during the follicular phase (days 3-10) of the same menstrual cycle, separated by 48-96 h. During the acute ovine CRH stimulation test, no significant differences in the net maximal response (i.e. change from baseline to peak level) for ACTH, dehydroepiandrosterone (DHA), androstenedione (A4), or cortisol (F) or for the DHA/ACTH, A4/ACTH, or F/ACTH ratios was observed. Nonetheless, the net response of DHA/F and the areas under the curve (AUCs) for DHA and DHA/F indicated a greater response for HI-DHS vs. LO-DHS or normal subjects. The AUC for A4 and A4/F and the delta A4/delta F ratio (delta = net maximum change) indicated that HI-DHS and LO-DHS had similar responses, which were greater than that of the normal subjects, although the difference between LO-DHS patients and normal

  17. Activation of two mutant androgen receptors from human prostatic carcinoma by adrenal androgens and metabolic derivatives of testosterone.

    PubMed

    Culig, Z; Stober, J; Gast, A; Peterziel, H; Hobisch, A; Radmayr, C; Hittmair, A; Bartsch, G; Cato, A C; Klocker, H

    1996-01-01

    The androgen receptor (AR) plays a central regulatory role in prostatic carcinoma and is a target of androgen ablation therapy. Recent detection of mutant receptors in tumor specimens suggest a contribution of AR alterations to progression towards androgen independence. In a specimen derived from metastatic prostate cancer we have reported a point mutation in the AR gene that leads to a single amino acid exchange in the ligand binding domain of the receptor. Another amino acid exchange resulting from a point mutation was also identified 15 amino acids away from our mutation. This mutation was detected in the AR gene isolated from an organ-confined prostatic tumor. Here we report the functional characterization of the two mutant receptors in the presence of adrenal androgens and testosterone metabolites. These studies were performed by cotransfecting androgen-responsive reporter genes and either the wild-type or mutant AR expression vectors into receptor negative DU-145 and CV-1 cells. The indicator genes used consisted of the promoter of the androgen-inducible prostate-specific antigen gene or the C' Delta9 enhancer fragment from the promoter of the mouse sex-limited protein driving the expression of the bacterial chloramphenicol acetyl transferase gene. Cotransfection-transactivation assays revealed that the adrenal androgen androstenedione and two products of testosterone metabolism, androsterone and androstandiol, induced reporter gene activity more efficiently in the presence of the mutant receptors than in the presence of the wild-type receptor. No difference between wild-type and mutant receptors was observed in the presence of the metabolite androstandione. The interaction of receptor-hormone complexes with target DNA was studied in vitro by electrophoretic mobility shift assays (EMSA). Dihydrotestosterone and the synthetic androgen mibolerone induced a faster migrating complex with all receptors, whereas the androgen metabolite androstandione induced this

  18. Dehydroepiandrosterone and sport.

    PubMed

    Corrigan, A B

    1999-08-16

    Dehydroepiandrosterone (DHEA) is a weak androgen, but is one of the main precursors of testosterone. Athletes use it for its androgenic and anticatabolic effects and it has been described as a "wonder drug", although there is little evidence to support these claims. There are no published studies of the long-term effects of taking DHEA, particularly in the large doses used by athletes, or of its possible interactions with other agents.

  19. 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

  20. Marked elevation of adrenal steroids, especially androgens, in saliva of prepubertal autistic children.

    PubMed

    Majewska, Maria Dorota; Hill, Martin; Urbanowicz, Ewa; Rok-Bujko, Paulina; Bieńkowski, Przemysław; Namysłowska, Irena; Mierzejewski, Paweł

    2014-06-01

    Autism is diagnosed on the basis of behavioral manifestations, but its biomarkers are not well defined. A strong gender bias typifying autism (it is 4-5 times more prevalent in males) suggests involvement of steroid hormones in autism pathobiology. In order to evaluate the potential roles of such hormones in autism, we compared the salivary levels of 22 steroids in prepubertal autistic male and female children from two age groups (3-4 and 7-9 years old) with those in healthy controls. The steroids were analyzed using gas chromatography-mass spectrometry and radioimmunoassay. Statistical analysis (ANOVA) revealed that autistic children had significantly higher salivary concentrations of many steroid hormones (both C21 and C19) than control children. These anomalies were more prominent in older autistic children and in boys. The levels of androgens (androstenediol, dehydroepiandrosterone, androsterone and their polar conjugates) were especially increased, indicative of precocious adrenarche and predictive of early puberty. The concentrations of the steroid precursor, pregnenolone, and of several pregnanolones were also higher in autistic than in healthy children, but cortisol levels were not different. Some steroids, whose levels are raised in autism (allopregnanolone, androsterone, pregnenolone, dehydroepiandrosterone and their sulfate conjugates) are neuroactive and modulate GABA, glutamate, and opioid neurotransmission, affecting brain development and functioning. These steroids may contribute to autism pathobiology and symptoms such as elevated anxiety, sleep disturbances, sensory deficits, and stereotypies among others. We suggest that salivary levels of selected steroids may serve as biomarkers of autism pathology useful for monitoring the progress of therapy.

  1. 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

  2. Adrenal adenoma and normal androgen levels in a young woman with polycystic ovaries: a case of idiopathic hirsutism?

    PubMed

    Orio, F; Palomba, S; Cascella, T; Tauchmanovà, L; Di Biase, S; Labella, D; Russo, T; Pellicano, M; Savastano, S; Zullo, F; Lombardi, G; Colao, A

    2004-01-01

    A case of unusual combination of polycystic ovaries (PCO), adrenal non-functioning adenoma and severe hirsutism in a young woman from Southern Italy is reported here. A 18-yr-old woman was referred to our Department because of oligomenhorrea, acne and severe hirsutism. During evaluation of the cause of her symptoms, PCO and small left adrenal adenoma were revealed. Although adrenal androgen excess has been shown to dysregulate the hypothalamic-pituitary-gonadal axis, causing PCO-like syndrome, normal circulating androgen values were found. Androgens and cortisol levels were completely suppressed by low-dose dexamethasone test, excluding autonomous steroid secretion by the adrenal mass. Normal response of cortisol and adrenal androgens to corticotropin stimulation test permitted the exclusion of functional adrenal hyperandrogenism. Despite normal LH/FSH ratio, anovulatory cycles were revealed by persistently low progesterone values. Glucose and insulin response to oral glucose tolerance test did not differ from those of normal population. The patient showed an improvement of acne and hirsutism on therapy with estro-progestins (EP). In conclusion, despite normal pattern of serum androgens and LH/FSH ratio, this patient had anovulatory cycles and good response to the EP treatment. These findings suggest that ultrasonography evidence of PCO together with anovulatory cycles contributed to her clinical picture whereas adrenal adenoma seemed to have no relevant role. This case report underlines the need of cautious interpretation of imaging results and clinical signs of severe hirsutism, reminding one that the true cause of a medical problem may not be the most evident.

  3. 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

  4. Ovarian and adrenal androgens and their link to high human chorionic gonadotropin levels: a prospective controlled study.

    PubMed

    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.

  5. Development of adrenal cortical zonation and expression of key elements of adrenal androgen production in the chimpanzee (Pan troglodytes) from birth to adulthood.

    PubMed

    Parker, C R; Grizzle, W E; Blevins, J K; Hawkes, K

    2014-04-25

    The basis for the pattern of adrenal androgen production in the chimpanzee, which resembles that of humans, is poorly defined. We characterized the developmental zonation and expression of elements of the androgen biosynthetic pathway in the chimpanzee adrenal. The newborn adrenal contained a broad fetal zone (FZ) expressing CYP17, SULT2A1, and Cytochrome B5 (CB5) but not HSD3B; the outer cortex expressed HSD3B but not SULT2A1 or CB5. During infancy, the FZ involuted and the HSD3B-expressing outer cortex broadened. By 3years of age, a thin layer of cells that expressed CB5, SULT2A1, and CYP17 adjoined the medulla and likely represented the zona reticularis; the outer cortex consisted of distinct zonae fasiculata and glomerulosa. Thereafter, the zona reticularis broadened as also occurs in the human. The adult chimpanzee adrenal displayed other human-like characteristics: intramedullary clusters of reticularis-like cells and also a cortical cuff of zona fasiculata-like cells adjoining the central vein.

  6. Early androgen exposure modulates spatial cognition in congenital adrenal hyperplasia (CAH)

    PubMed Central

    Mueller, S.C.; Temple, V.; Oh, E.; VanRyzin, C.; Williams, A.; Cornwell, B.; Grillon, C.; Pine, D.S.; Ernst, M.; Merke, DP

    2008-01-01

    Major questions remain about the exact role of hormones in cognition. Furthermore, the extent to which early perturbation in steroid function affects human brain development continues to be a wide open area of research. Congenital Adrenal Hyperplasia (CAH), a genetic disorder of steroid dysfunction characterized in part by in utero over-production of testosterone, was used as a natural model for addressing this question. Here, CAH (n=54, mean age = 17.53, 31 female) patients were compared to healthy age- and sex-matched individuals (n=55, mean age = 19.02, 22 female) on a virtual equivalent of the Morris Water Maze task (Morris, 1984), an established measure of sex differences in spatial cognition in rodents. Findings revealed that females with CAH with the most severe form of the disease and expected highest level of in utero exposure to androgens were found to perform similarly to both healthy males and CAH males, whereas strong sex differences were apparent in milder forms of the disorder and in controls. Moreover, advanced bone age, an indicator of long-term childhood exposure to testosterone was correlated with improved performance. The results indicate that individuals exposed to both excess androgens prenatally and prolonged exposure during childhood may manifest long-lasting changes in cognitive function. Such finding suggests a pivotal role of hormonal function on brain development in humans, mirroring results from the animal literature. PMID:18675711

  7. [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

  8. 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

  9. 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.

  10. Perturbations of hypothalamic-pituitary-gonadal axis and adrenal androgen functions in rheumatoid arthritis: an odyssey of hormonal relationships to the disease.

    PubMed

    Masi, A T; Chatterton, R T; Aldag, J C

    1999-06-22

    Rheumatoid arthritis (RA) is a heterogeneous disease with a diverse spectrum of manifestations and course of illness. Multiple factors are believed to contribute to its etiology. Nevertheless, consistent features are observed across populations, which include (1) increased familial or immunogenetic risk in younger-onset disease; (2) female predisposition, particularly during child-bearing ages; (3) predictable clinical improvement during pregnancy and worsening postpartum; and (4) increased incidence with aging, which suggest that hormonal factors influence the disease. In 1974, serum was prospectively obtained from pre-RA cases, 4 to 20 (mean = 12.0) years prior to onset of disease and concurrently from controls (CN) matched (4 CN per 1 RA) on age (+/- 2 years), race (all Caucasians), and entry menopausal status (EMS). CN have no known rheumatic disease. Pre-RA were divided into subgroups, according to EMS, i.e., premenopausal vs. non-premenopausal (peri- or post-menopausal), and either age at entry in 1974 or age at onset of RA. For example, one 3-way subgrouping includes: I. Entry premenopausal and RA onset < age 50 years; II. Entry premenopausal and RA onset age 50+ years, and III. Entry postmenopausal. The 11 youngest pre-RA (I) had a mean entry age of 29 years and RA onset of 41 years. An alternative 4-way subgrouping (a, b, c, d) divided the female subjects into premenopausal (last menstrual period [LMP], 0-31 days) and non-premenopausal major groups, as well as younger vs. older subgroups within the major EMS categories. The younger premenopausal women in each subgrouping system, that is, I or a, overlap almost entirely. Assays (RIA) of the major sex hormones were performed, e.g., luteinizing hormone (LH); follicle stimulating (FSH); estradiol (E2); progesterone (P4); and total testosterone (T); as well as adrenal hormones, including androstenendione (A4); dehydroepiandrosterone (DHEA); its sulfate (DHEAS); and cortisol (C). A significantly lower entry mean

  11. Should dehydroepiandrosterone replacement therapy be provided with glucocorticoids?

    PubMed

    Robinzon, B; Cutolo, M

    1999-06-01

    Adrenocorticotrophic hormone (ACTH) induces the concomitant secretion of glucocorticoids (GC) and dehydroepiandrosterone (DHEA) from the adrenal cortex. Whereas GC are catabolic, DHEA is anabolic. Long-term GC administration may result in some deleterious side-effects, such as muscular weakness, atrophy and necrosis, diabetes, fattiness, osteopenia, osteoporosis and avascular necrosis and susceptibility to infections. DHEA ameliorates some deleterious effects of GC, such as diabetes, amino acid deamination, fattiness, hypertension and susceptibility to viraemia. By its anabolic effects in muscles, bones and endothelium, DHEA may diminish the severity of GC-induced myopathy, osteopenia, osteoporosis and avascular necrosis. The natural concomitant secretion of DHEA with GC probably enables the latter to protect the body from ill-effects of stress without exerting their deleterious potency. DHEA secretion diminishes during aging and severe or chronic diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Anti-inflammatory and immunosuppressive effects of GC and androgens, including DHEA, are now well established. On the other hand, administration of GC inhibits ACTH secretion, involutes the adrenal cortex and results in further DHEA deficiency, particularly harmful in chronic autoimmune diseases (i.e. RA, SLE). Therefore, the deleterious side-effects of chronic administration of GC emerges from both their direct catabolic activity and the suppression of DHEA production. Whereas, in males, most androgens come from the testes, in females, under GC supplementation, DHEA deficiency leads to nullification of the androgen-dependent anabolism, leaving them exposed to the GC-catabolic effects to a larger extent. The viewpoint presented here claims that under chronic GC supplementation, DHEA replacement therapy may reduce damage caused by GC administration.

  12. Targeting of CYP17A1 Lyase by VT-464 Inhibits Adrenal and Intratumoral Androgen Biosynthesis and Tumor Growth of Castration Resistant Prostate Cancer

    PubMed Central

    Maity, Sankar N.; Titus, Mark A.; Gyftaki, Revekka; Wu, Guanglin; Lu, Jing-Fang; Ramachandran, S.; Li-Ning-Tapia, Elsa M.; Logothetis, Christopher J.; Araujo, John C.; Efstathiou, Eleni

    2016-01-01

    Cytochrome P450 17α-hydroxylase/17,20-lyase (CYP17A1) is a validated treatment target for the treatment of metastatic castration-resistant prostate cancer (CRPC). Abiraterone acetate (AA) inhibits both 17α-hydroxylase (hydroxylase) and 17,20-lyase (lyase) reactions catalyzed by CYP17A1 and thus depletes androgen biosynthesis. However, coadministration of prednisone is required to suppress the mineralocorticoid excess and cortisol depletion that result from hydroxylase inhibition. VT-464, a nonsteroidal small molecule, selectively inhibits CYP17A1 lyase and therefore does not require prednisone supplementation. Administration of VT-464 in a metastatic CRPC patient presenting with high tumoral expression of both androgen receptor (AR) and CYP17A1, showed significant reduction in the level of both dehydroepiandrosterone (DHEA) and serum PSA. Treatment of a CRPC patient-derived xenograft, MDA-PCa-133 expressing H874Y AR mutant with VT-464, reduced the increase in tumor volume in castrate male mice more than twice as much as the vehicle (P < 0.05). Mass spectrometry analysis of post-treatment xenograft tumor tissues showed that VT-464 significantly decreased intratumoral androgens but not cortisol. VT-464 also reduced AR signaling more effectively than abiraterone in cultured PCa cells expressing T877A AR mutant. Collectively, this study suggests that VT-464 therapy can effectively treat CRPC and be used in precision medicine based on androgen receptor mutation status. PMID:27748439

  13. 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

  14. Disposition and metabolic profile of the weak androgen Dehydroepiandrosterone (DHEA) following administration as part of a nutritional supplement to exercised horses.

    PubMed

    Knych, H K; Arthur, R M; Stanley, S D; McKemie, D S

    2015-01-01

    In order to ensure the welfare of performance horses and riders as well as the integrity of the sport, the use of both therapeutic and illegal agents in horse racing is tightly regulated. While Dehydroepiandrosterone (DHEA) is not specifically banned from administration to racehorses in the United States and no screening limit or threshold concentration exists, the metabolic conversion of DHEA to testosterone make its presence in nutritional supplements a regulatory concern. The recommended regulatory threshold for total testosterone in urine is 55 and 20 ng/mL for mares and geldings, respectively. In plasma, screening and confirmation limits for free testosterone (mares and geldings), of no greater than 0.1 and 0.025 ng/mL, respectively are recommended. DHEA was administered orally, as part of a nutritional supplement, to 8 exercised female thoroughbred horses and plasma and urine samples collected at pre-determined times post administration. Using liquid chromatography-mass spectrometry (LC-MS), plasma and urine samples were analyzed for DHEA, DHEA-sulfate, testosterone, testosterone-sulfate, pregnenolone, androstenedione, and androstenediol. DHEA was rapidly absorbed with maximal plasma concentrations reaching 52.0 ± 43.8 ng/mL and 32.1 ± 12.9 ng/mL for DHEA and DHEA sulfate, respectively. Free testosterone was not detected in plasma or urine samples at any time. Maximum sulfate conjugated testosterone plasma concentrations were 0.98 ± 1.09 ng/mL. Plasma testosterone-sulfate concentrations did not fall below 0.1 ng/mL and urine testosterone-sulfate below 55 ng/mL until 24-36 h post DHEA administration. Urine testosterone sulfate concentrations remained slightly above baseline levels at 48 h for most of the horses studied.

  15. 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

  16. Organizational role for pubertal androgens on adult hypothalamic-pituitary-adrenal sensitivity to testosterone in the male rat.

    PubMed

    Evuarherhe, O; Leggett, J D; Waite, E J; Kershaw, Y M; Atkinson, H C; Lightman, S L

    2009-06-15

    The inhibitory effect of androgens on the hypothalamic-pituitary-adrenal (HPA) axis in basal and stress conditions in adult male rats is well documented. Major sex-related neuroendocrine changes take place during puberty. There is a robust rise in production and secretion of gonadal steroids, which is thought to underlie numerous neural and behavioural changes brought on after puberty. The present study investigated the effect of the pubertal rise in gonadal steroid levels on the subsequent adult corticosterone profile, particularly the sensitivity of the adult HPA axis to testosterone. Animals were castrated either prepubertally (28 days) or in adulthood (11 weeks) and adult animals were subsequently treated with subcutaneous implants containing either testosterone or cholesterol. Using an automated blood sampling system, blood was collected from each freely moving, conscious rat every 10 min (i) over a 24 h period; (ii) in response to 10 min of noise stress, and (iii) following an immunological challenge with lipopolysaccharide (LPS). Analysis revealed that testosterone treatment did not significantly affect overall corticosterone release over the 24 h period in adult animals castrated before puberty in contrast to animals castrated in adulthood in which testosterone significantly suppressed corticosterone secretion. Following either a noise stress or LPS injection, testosterone treatment did not affect the hypothalamic or adrenal stress response in animals castrated prepubertally. Testosterone significantly suppressed the corticotrophin-releasing hormone and arginine vasopressin mRNA as well as the corticosterone response to LPS in castrated animals that had had their testes intact over puberty. These data provide evidence that puberty is a critical organizational period during which rising levels of gonadal steroids programme the sensitivity of the adult HPA axis to gonadal steroids in adulthood.

  17. Androgens alter corticotropin releasing hormone and arginine vasopressin mRNA within forebrain sites known to regulate activity in the hypothalamic-pituitary-adrenal axis.

    PubMed

    Viau, V; Soriano, L; Dallman, M F

    2001-05-01

    To reveal direct effects of androgens, independent of glucocorticoids, we studied the effects of gonadectomy (GDX) in adrenalectomized (ADX) rats with or without androgen replacement on corticotropin releasing hormone (CRH) and arginine vasopressin (AVP) mRNA expression within various forebrain sites known to regulate the hypothalamic-pituitary-adrenal axis. These included the medial parvocellular portion of the paraventricular nucleus of the hypothalamus (mp PVN), the central and medial nuclei of the amygdala and bed nuclei of the stria terminalis (BNST). In the mp PVN, ADX stimulated both CRH and AVP mRNA expression. Combined ADX + GDX inhibited only AVP, and testosterone and dihydrotestosterone (DHT) restored AVP mRNA. In the central nucleus of the amygdala, ADX decreased CRH mRNA expression, and this response was unaffected by GDX +/- testosterone or DHT replacement. In the medial amygdala, AVP mRNA expression was decreased by ADX, abolished by ADX + GDX, and restored by androgen replacement. ADX had no effect on CRH and AVP mRNA expression in the BNST. GDX + ADX, however, reduced CRH mRNA expression only within the fusiform nuclei of the BNST and reduced the number of AVP-expressing neurones in the posterior BNST. Androgen replacement reversed both responses. In summary, in ADX rats, AVP, but not CRH mRNA expression in the amygdala and mp PVN, is sensitive to GDX +/- androgen replacement. Both CRH- and AVP-expressing neurones in the BNST respond to GDX and androgen replacement, but not to ADX alone. Because androgen receptors are not expressed by hypophysiotropic PVN neurones, we conclude that glucocorticoid-independent, androgenic influences on medial parvocellular AVP mRNA expression are mediated upstream from the PVN, and may involve AVP-related pathways in the medial amygdala, relayed to and through CRH- and AVP-expressing neurones of the BNST.

  18. Dehydroepiandrosterone to enhance physical performance: myth and reality.

    PubMed

    Hahner, Stefanie; Allolio, Bruno

    2010-03-01

    Dehydroepiandrosterone (DHEA) is secreted by the zona reticularis of the adrenal cortex and is converted into potent sex steroids in peripheral target cells. As oral DHEA administration can lead to dose-dependent increases in circulating androgens, which may reach high supraphysiologic levels in women, it has been included in the list of prohibited substances by the World Anti-Doping Agency (WADA). However, evidence for an ergogenic activity of DHEA is still largely nonexistent. Randomized trials in elderly subjects with an age-dependent decrease in DHEA have provided little or no evidence for enhanced physical performance after long-term administration of DHEA, 50 mg/d, and smaller short-term studies in healthy male athletes using higher doses were completely negative. Thus the widely perceived performance-enhancing activity of DHEA is still more myth than reality. However, because studies in female athletes are still lacking, an ergogenic activity of high-dose DHEA in this population cannot be excluded but is expected to be associated with adverse events like hirsutism, acne, and alopecia.

  19. A novel androgen receptor gene mutation in a patient with congenital adrenal hyperplasia associated with penoscrotal hypospadias.

    PubMed

    Sharma, Vikas; Thangaraj, Kumarasamy; Jyothy, Akka

    2014-08-01

    Congenital adrenal hyperplasia (CAH) associated with penoscrotal hypospadias is a rare case of disorders of sex development. Here, we report clinical, genetic, biochemical, and molecular findings in a 2-year-old infant with CAH and penoscrotal hypospadias. Chromosomal analysis revealed 46,XX karyotype. Hormonal investigations indicated low levels of cortisol and elevated levels of testosterone, 17-hydroxyprogesterone, and androstenedione hormone. Molecular genetic testing of androgen receptor (AR) gene identified a novel homozygous missense mutation of single nucleotide transition G to A at position 2058 (GenBank accession number GU784855), resulting in amino acid interchange alanine to threonine at codon 566 in exon 2 (Ala566Thr) (GenBank Protein_id ADD26777.1). The nature of the mutation presented is in the highly conserved DNA-binding domain of the AR gene. The novel mutation identified in the rare genetic disorder provides additional support to the previously reported genotype-phenotype correlations, and our finding has expanded the spectrum of known mutations of the AR gene. PMID:24907477

  20. 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

  1. 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

  2. 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.

  3. Ovarian adrenal interactions during the menopausal transition

    PubMed Central

    Lasley, B. L.; Crawford, S. L.; Mcconnell, D. S.

    2015-01-01

    Observations over the past decade using longitudinal data reveal a gender-specific shift in adrenal steroid production. This shift is represented by an increase in the circulating concentrations of delta 5 steroids in 85% of all women and is initiated only after the menopausal transition has begun. While the associated rise in the major adrenal androgen, dehydroepiandrosterone sulfate (DHEAS), is modest, the parallel rises in dehydroepiandrosteone (DHEA) and androstenediol (Adiol) are much more robust. These increases in circulating steroid concentrations are qualitatively similar on average between ethnicities but quantitatively different between individual women. Both circulating testosterone (T) and androstenedione (Adione) also rise concomitantly but modestly by comparison. This phenomenon presents a new and provocative aspect to the endocrine foundations of the menopausal transition and may provide important clues to understanding the fundamentals of mid-aged women's healthy aging, particularly an explanation for the wide diversity in phenotypes observed during the MT as well as their different responses to hormone replacement therapies. Experimental studies using the nonhuman primate animal model show an acute adrenal response to human chorionic gonadotropin (hCG) challenge as well as the presence of luteinizing hormone receptors (LHR) in their adrenal cortices. These experimental results support the concept that LHRs are recruited to the adrenal cortices of mid-aged women that subsequently function to respond to increasing circulating LH to shunt pregnenolone metabolites towards the delta 5 pathway. Future investigations are required to determine the relationship of these changes in adrenal function to symptoms and health outcomes of mid-aged women. PMID:24346252

  4. Urinary androgens and cortisol metabolites in field-sampled bonobos (Pan paniscus).

    PubMed

    Dittami, John; Katina, Stanislav; Möstl, Erich; Eriksson, Jonas; Machatschke, Ivo H; Hohmann, Gottfried

    2008-02-01

    Urinary metabolites of androgens and cortisol were measured in free-living male and female bonobos. Sex differences and correlations between adrenal and gonadal steroid excretion were investigated. The immunoreactive concentrations of androgens were measured with two different androgen assays. One assay used a testosterone (T) antibody raised with a 17beta-hydroxy group, and the other employed an antibody raised against a reduced form, 5alpha-androstane-17alpha-ol-3-one-CM (17alpha) with cross reactivity for epitestosterone and 5alpha-androstanedione. Both assays have been used in bonobo and chimpanzee studies where non-invasive techniques were employed. The levels of 17alpha-androgen metabolites were 1.7- and 3-fold higher than those of T-metabolites in males and females. The two androgen assay results correlated in males but not females. There was a sex difference in the T-metabolites measured. Male levels were significantly higher. Levels of 17alpha in the two sexes were similar. Cortisol metabolite levels (CORT) were similar between the sexes. The T-metabolites were significantly correlated with CORT in males but not in females. In females, the 17alpha-androgen metabolites correlated with CORT. This suggests that either androgen secretion or metabolism differs between the sexes. A parsimonious interpretation of the androgen assay cortisol/androgen correlation differences would be that larger components of dehydroepiandrosterone (DHEA), androstenedione or epitestosterone from the adrenal androgens were being excreted and measured in the females. The CORT/T metabolite interactions in males may reflect male-specific social or metabolic endocrine conditions.

  5. Growth and adrenal androgen status at 7 years in very low birth weight survivors with and without bronchopulmonary dysplasia

    PubMed Central

    Korhonen, P; Hyodynmaa, E; Lenko, H; Tammela, O

    2004-01-01

    Aims: To evaluate whether 7 year old VLBW (very low birth weight, <1500 g) survivors with and without bronchopulmonary dysplasia (BPD) evince similar growth status and higher adrenal androgen (AA) levels than term controls, and whether AA levels are higher in VLBW children born small for gestational age (SGA) than in non-SGA cases. Methods: Assessment of height standard deviation score (SDs), body mass index (BMI), and serum androstenedione and dehydroepiandrostenedione sulphate levels in 31 VLBW children with BPD, 33 without BPD (no-BPD group), and 33 term controls. Results: Lower median (range) height SDs was found in BPD (-1.0 (-3.4 to 1.4) SD) and no-BPD (-0.9 (-2.9 to 2.2) SD) children than in term controls (0.3 (-1.5 to 1.9) SD). Low BMI (below 10th centile) was more common in both the BPD (18 (58%)) and no-BPD (16 (49%)) children compared to term cases (3 (9%)). The median (range) androstenedione levels tended to be higher in the BPD (0.8 (0 to 2.8) nmol/l) and no-BPD (0.8 (0 to 2.3) nmol/l) groups than in term controls (0.6 (0 to 1.8)). Higher median (range) dehydroepiandrostenedione sulphate levels were detected in the no-BPD compared to the term group (0.9 (0 to 4.1) v 0.3 (0 to 2.3) µmol/l). VLBW children born SGA had higher AA levels compared to non-SGA cases. Conclusions: At 7 years of age, VLBW children are shorter and tend to have higher AA levels than term controls, but VLBW children with and without BPD do not differ from each other in growth or AA status. Those born SGA have higher AA levels compared to non-SGA cases. The consequences of these findings to final height and to later metabolic and vascular health remain to be determined. PMID:15033838

  6. 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

  7. Low levels of dehydroepiandrosterone sulphate in plasma, and reduced sympathoadrenal response to hypoglycaemia in premenopausal women with rheumatoid arthritis

    PubMed Central

    Imrich, R; Rovensky, J; Malis, F; Zlnay, M; Killinger, Z; Kvetnansky, R; Huckova, M; Vigas, M; Macho, L; Koska, J

    2005-01-01

    Objectives: To evaluate the function of the hypothalamic-pituitary-adrenal axis and sympathoadrenal system in premenopausal women with rheumatoid arthritis (RA). Methods: Insulin-induced hypoglycaemia (0.1 IU/kg) was produced in 15 glucocorticoid-naive patients with long term RA with low disease activity and in 14 healthy women matched for age and body mass index. Concentrations of glucose, adrenocorticotropic hormone (ACTH), cortisol, Δ4-androstenedione (ASD), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEAS), 17α-hydroxyprogesterone (17OHP), epinephrine (EPI), norepinephrine (NE), interleukin 6 (IL6), and tumour necrosis factor α (TNFα) were analysed in plasma. Results: Patients had comparable responses of glucose, cortisol, ACTH, ASD, and 17OHP to hypoglycaemia, without any signs of hypothalamic insufficiency. Patients had lower basal DHEAS than controls (3.03 (0.37) µmol/l v 5.1 (0.9) µmol/l, respectively; p<0.05); borderline lower basal DHEA levels (p = 0.067); while the response of DHEA to hypoglycaemia was comparable to that of controls. Patients with RA had lower EPI (p = 0.005) and NE (p<0.001) responses to hypoglycaemia. TNFα and IL6 were higher (p<0.05) in patients with RA (TNFα 8 (2.8) pg/ml in RA v 1.1 (0.5) pg/ml in controls and IL6 15.1 (6.7) pg/ml v 1.4 (0.7) pg/ml). Conclusions: Lower basal DHEAS levels, without concomitant differences or changes in DHEA, ASD, 17OHP, and cortisol responses to hypoglycaemia in patients with RA, indicate an isolated decrease in adrenal androgen production. Significantly lower responses of EPI and NE to hypoglycaemia may suggest sympathoadrenal hyporeactivity in patients with RA. PMID:15647427

  8. 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

  9. 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

  10. Dehydroepiandrosterone decreases while cortisol increases in vitro growth and viability of Entamoeba histolytica.

    PubMed

    Carrero, Julio C; Cervantes, Claudia; Moreno-Mendoza, Norma; Saavedra, Emma; Morales-Montor, Jorge; Laclette, Juan P

    2006-02-01

    In vitro exposure of Entamoeba histolytica trophozoites to the sex steroids 17beta-estradiol, progesterone, and dehydrotestosterone had little effect on parasite viability or proliferation. However, treatment with the adrenal steroid dehydroepiandrosterone (DHEA) markedly inhibited parasite proliferation, adherence and motility, and at a certain dose it induced trophozoite lysis. The opposite effect on proliferation was found when the trophozoites were exposed to cortisol. Moreover, DHEA decreased while cortisol increased the parasite's DNA synthesis determined by 3H-thymidine incorporation. Trophozoite lysis by DHEA appeared to be caused by a necrotic rather than an apoptotic process, as observed in propidium iodide and terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling assays. A possible mechanisms of action was derived from experiments demonstrating that the activity of a putative 3-hydroxy-3-methyl glutaryl CoA reductase detected in trophozoite extracts was inhibited in the presence of DHEA. Contrary to its in vitro inhibitory effect, in vivo administration of DHEA to infected hamsters resulted in exacerbation of the amebic liver abscesses. These results demonstrated that androgen steroids act directly upon E. histolytica growth and viability, and may shed new light on some age and gender differences in disease progression, as well as finding application in the drug treatment of human amebiasis.

  11. 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.

  12. 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

  13. The hypothalamic-pituitary-adrenal and gonadal axes in rheumatoid arthritis.

    PubMed

    Cutolo, M; Villaggio, B; Foppiani, L; Briata, M; Sulli, A; Pizzorni, C; Faelli, F; Prete, C; Felli, L; Seriolo, B; Giusti, M

    2000-01-01

    The hypothalamic-pituitary-adrenal (HPA) and the hypothalamic-pituitary-gonadal (HPG) axes involvement or response to immune activation seems crucial for the control of excessive inflammatory and immune conditions such as autoimmune rheumatic diseases, including rheumatoid arthritis (RA). However, female patients seem to depend more on the HPA axis, whereas male patients seem to depend more on the HPG axis. In particular, hypoandrogenism may play a pathogenetic role in male RA patients because adrenal and gonadal androgens, both products of the HPA and HPG axes, are considered natural immunosuppressors. A significantly altered steroidogenesis of adrenal androgens (i.e., dehydroepiandrosterone sulfate, DHEAS and DHEA) in nonglucocorticoid-treated premenopausal RA patients has been described. The menopausal peak of RA suggests that estrogens and/or progesterone deficiency also play a role in the disease, and many data indicate that estrogens suppress cellular immunity, but stimulate humoral immunity (i.e., deficiency promotes cellular Th1-type immunity). A range of physical and psychosocial stressors are also implicated in the activation of the HPA axis and related HPG changes. Chronic and acute stressors appear to have different actions on immune mechanisms with experimental and human studies indicating that acute severe stressors may be even immunosuppressive, while chronic stress may enhance immune responses. The interactions between the immunological and neuroendocrine circuits is the subject of active and extensive ongoing research and might in the near future offer highly promising strategies for hormone-replacement therapies in RA.

  14. The influence of age and season on fecal dehydroepiandrosterone-sulfate (DHEAS) concentrations in Japanese macaques (Macaca fuscata).

    PubMed

    Takeshita, Rafaela Sayuri Cicalise; Huffman, Michael A; Bercovitch, Fred B; Mouri, Keiko; Shimizu, Keiko

    2013-09-15

    Dehydroepiandrosterone (DHEA) and its sulfate, DHEAS, are the most abundant steroid hormones in primates, providing a large reservoir of precursors for the production of androgens. DHEAS levels decline with age in adult humans and nonhuman primates, prompting its consideration as a biomarker of senescence. However, the mechanisms responsible for this age-related decrease and its relationship to reproduction remain elusive. This research investigated DHEAS concentrations in fecal samples in order to determine age-related changes in captive Japanese macaques, as well as to assess the possible influence of seasonality. The subjects were 25 female Japanese macaques (2weeks to 14years-old) housed outdoors in social groups at the Primate Research Institute. We collected three fecal samples from each animal during the breeding season (October to December) and three additional samples from adult females during the non-breeding season (May to June). The hormonal concentrations were determined using enzyme immunoassay. DHEAS concentration was negatively correlated with age, but we did not find a significant difference between breeding and non-breeding seasons. Neonatal macaques had the highest DHEAS concentrations of all age groups. We suggest that elevated neonatal DHEAS is possibly a residue from fetal adrenal secretion and that, as in humans, it might assist in neurobiological development.

  15. Androgen receptors, sex behavior, and aggression.

    PubMed

    Cunningham, Rebecca L; Lumia, Augustus R; McGinnis, Marilyn Y

    2012-01-01

    Androgens are intricately involved in reproductive and aggressive behaviors, but the role of the androgen receptor in mediating these behaviors is less defined. Further, activity of the hypothalamic-pituitary-gonadal axis and hypothalamic-pituitary-adrenal axis can influence each other at the level of the androgen receptor. Knowledge of the mechanisms for androgens' effects on behaviors through the androgen receptor will guide future studies in elucidating male reproductive and aggressive behavior repertoires.

  16. Development, validation and application of a stable isotope dilution liquid chromatography electrospray ionization/selected reaction monitoring/mass spectrometry (SID-LC/ESI/SRM/MS) method for quantification of keto-androgens in human serum.

    PubMed

    Tamae, Daniel; Byrns, Michael; Marck, Brett; Mostaghel, Elahe A; Nelson, Peter S; Lange, Paul; Lin, Daniel; Taplin, Mary-Ellen; Balk, Steven; Ellis, William; True, Larry; Vessella, Robert; Montgomery, Bruce; Blair, Ian A; Penning, Trevor M

    2013-11-01

    Prostate cancer is the most frequently diagnosed form of cancer in males in the United States. The disease is androgen driven and the use of orchiectomy or chemical castration, known as androgen deprivation therapy (ADT) has been employed for the treatment of advanced prostate cancer for over 70 years. Agents such as GnRH agonists and non-steroidal androgen receptor antagonists are routinely used in the clinic, but eventually relapse occurs due to the emergence of castration-resistant prostate cancer. With the appreciation that androgen signaling still persists in these patients and the development of new therapies such as abiraterone and enzalutamide that further suppresses androgen synthesis or signaling, there is a renewed need for sensitive and specific methods to quantify androgen precursor and metabolite levels to assess drug efficacy. We describe the development, validation and application of a stable isotope dilution liquid chromatography electrospray ionization selected reaction monitoring mass spectrometry (SID-LC/ESI/SRM/MS) method for quantification of serum keto-androgens and their sulfate and glucuronide conjugates using Girard-T oxime derivatives. The method is robust down to 0.2-4pg on column, depending on the androgen metabolite quantified, and can also quantify dehydroepiandrosterone sulfate (DHEA-S) in only 1μL of serum. The clinical utility of this method was demonstrated by analyzing serum androgens from patients enrolled in a clinical trial assessing combinations of pharmacological agents to maximally suppress gonadal and adrenal androgens (Targeted Androgen Pathway Suppression, TAPS clinical trial). The method was validated by correlating the results obtained with a hydroxylamine derivatization procedure coupled with tandem mass spectrometry using selected reaction monitoring that was conducted in an independent laboratory.

  17. Dehydroepiandrosterone (DHEA) supplementation in diminished ovarian reserve (DOR)

    PubMed Central

    2011-01-01

    Background With infertility populations in the developed world rapidly aging, treatment of diminished ovarian reserve (DOR) assumes increasing clinical importance. Dehydroepiandrosterone (DHEA) has been reported to improve pregnancy chances with DOR, and is now utilized by approximately one third of all IVF centers world-wide. Increasing DHEA utilization and publication of a first prospectively randomized trial now warrants a systematic review. Methods PubMed, Cochrane and Ovid Medline were searched between 1995 and 2010 under the following strategy: [<dehydroepiandrosterone or DHEA or androgens or testosterone > and ]. Bibliographies of relevant publications were further explored for additional relevant citations. Since only one randomized study has been published, publications, independent of evidence levels and quality assessment, were reviewed. Results Current best available evidence suggests that DHEA improves ovarian function, increases pregnancy chances and, by reducing aneuploidy, lowers miscarriage rates. DHEA over time also appears to objectively improve ovarian reserve. Recent animal data support androgens in promoting preantral follicle growth and reduction in follicle atresia. Discussion Improvement of oocyte/embryo quality with DHEA supplementation potentially suggests a new concept of ovarian aging, where ovarian environments, but not oocytes themselves, age. DHEA may, thus, represent a first agent beneficially affecting aging ovarian environments. Others can be expected to follow. PMID:21586137

  18. 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 ...

  19. 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

  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. Adrenal glands

    MedlinePlus

    ... disorders , infections, tumors, and bleeding. Related topics: Addison disease Adrenal insufficiency Congenital adrenal hyperplasia Cushing syndrome Diabetes mellitus - secondary Glucocorticoid medications Hirsutism Hump ...

  2. Sources of variation in plasma corticosterone and dehydroepiandrosterone in the male northern cardinal (Cardinalis cardinalis): I. Seasonal patterns and effects of stress and adrenocorticotropic hormone.

    PubMed

    Fokidis, H Bobby

    2016-09-01

    The secretion of steroids from the adrenal gland is a classic endocrine response to perturbations that can affect homeostasis. During an acute stress response, glucocorticoids (GC), such as corticosterone (CORT), prepare the metabolic physiology and cognitive abilities of an animal in a manner that promotes survival during changing conditions. Although GC functions during stress are well established, much less is understood concerning how adrenal androgens, namely dehydroepiandrosterone (DHEA) are influenced by stress. I conducted three field studies (one experimental and two descriptive) aimed at identifying how both CORT and DHEA secretion in free-living male northern cardinals (Cardinalis cardinalis), vary during acute stress; across different circulations (brachial vs. jugular); in response to ACTH challenge; and during the annual cycle. As predicted, restraint stress increased plasma CORT, but unexpectedly DHEA levels decreased, but the latter effect was only seen for blood sampled from the jugular vein, and not the brachial. The difference in DHEA between circulations may result from increased neural uptake of DHEA during stress. Injection with exogenous adrenocorticotropic hormone (ACTH) increased CORT concentrations, but failed to alter DHEA levels, thus suggesting ACTH is not a direct regulator of DHEA. Monthly field sampling revealed distinct seasonal patterns to both initial and restraint stress CORT and DHEA levels with distinct differences in the steroid milieu between breeding and non-breeding seasons. These data suggest that the CORT response to stress remains relatively consistent, but DHEA secretion is largely independent of the response by CORT. Although CORT functions have been well-studied in wild animals, little research exists for the role of DHEA and their variable relationship sets the stage for future experimental research addressing steroid stress responses. PMID:27255363

  3. Mechanisms of androgen deficiency in human immunodeficiency virus-infected women with the wasting syndrome.

    PubMed

    Grinspoon, S; Corcoran, C; Stanley, T; Rabe, J; Wilkie, S

    2001-09-01

    Although prior studies suggest reduced androgen levels in women with acquired immune deficiency syndrome wasting, little is known regarding the regulation of adrenal and ovarian androgen secretion in such patients. We investigated ovarian and adrenal function in 13 human immunodeficiency virus-infected women with acquired immune deficiency syndrome wasting and 21 age- and body mass index-matched healthy control subjects studied in the early follicular phase. Subjects received hCG (5000 U, im) on d 1 and Cosyntropin (0.25 mg, i.v.) on d 3 after dexamethasone (1 mg, orally, at 2400 h) pretreatment on d 2. At baseline, human immunodeficiency virus-infected subjects demonstrated significantly reduced T [18 +/- 2 vs. 25 +/- 2 ng/dl (0.6 +/- 0.1 vs. 0.9 +/- 0.1 nmol/liter); P = 0.02], free T [1.5 +/- 0.1 vs. 2.4 +/- 0.2 pg/ml (5.3 +/- 0.5 vs. 8.3 +/- 0.6 pmol/liter); P = 0.001], androstenedione [119 +/- 6 vs. 162 +/- 14 ng/dl (4.16 +/- 0.20 vs. 5.66 +/- 0.48 nmol/liter); P = 0.02], and dehydroepiandrosterone sulfate [0.96 +/- 0.17 vs. 1.55 +/- 0.19 microg/ml (2.6 +/- 0.5 vs. 4.2 +/- 0.5 micromol/liter); P = 0.047] levels compared with the control subjects. T [8 +/- 2 vs. 6 +/- 2 ng/dl (0.3 +/- 0.1 vs. 0.2 +/- 0.1 nmol/liter); P = 0.48], free T [0.5 +/- 0.2 vs. 0.4 +/- 0.1 pg/ml (1.7 +/- 0.7 vs. 1.5 +/- 0.5 pmol/liter); P = 0.85], 17 hydroxyprogesterone [0.5 +/- 0.2 vs. 0.7 +/- 0.2 microg/liter (1.6 +/- 0.6 vs. 2.0 +/- 0.6 nmol/liter); P = 0.63], and androstenedione [-1 +/- 12 vs. 8 +/- 11 ng/dl (-0.03 +/- 0.42 vs. 0.28 +/- 0.39 nmol/liter), P = 0.61] responses to hCG were not different between the groups. Cortisol responses were increased and dehydroepiandrosterone sulfate responses were decreased in the human immunodeficiency virus-infected vs. control subjects after ACTH stimulation. The ratio of DHEA to cortisol was significantly decreased at 60 (71 +/- 11 vs. 107 +/- 10; P = 0.02) and 90 (63 +/- 8 vs. 102 +/- 9; P = 0.004) min post-ACTH in the human immunodeficiency

  4. Central organization of androgen-sensitive pathways to the hypothalamic-pituitary-adrenal axis: implications for individual differences in responses to homeostatic threat and predisposition to disease.

    PubMed

    Williamson, Martin; Bingham, Brenda; Viau, Victor

    2005-12-01

    Despite clear evidence of the potency by which sex steroids operate on the hypothalamic-pituitary-adrenal (HPA) axis and genuine sex differences in disorders related to HPA dysfunction, the biological significance of this remains largely ignored. Stress-induced increases in circulating glucocorticoid levels serve to meet the metabolic demands of homeostatic threat head-on. Thus, the nature of the stress-adrenal axis is to protect the organism. As one develops, matures, and ages, still newer and competing physiological and environmental demands are encountered. These changing constraints are also met by shifts in sex steroid release, placing this class of steroids beyond the traditional realm of reproductive function. Here we focus on the dose-related and glucocorticoid-interactive nature by which testosterone operates on stress-induced HPA activation. This provides an overview on how to exploit these characteristics towards developing an anatomical framework of testosterone's actions in the brain, and expands upon the idea that centrally projecting arginine vasopressin circuits in the brain act to register and couple testosterone's effects on neuroendocrine and behavioural responses to stress. More generally, the work presented here underscores how a dual adrenal and gonadal systems approach assist in unmasking the bases by which individuals resist or succumb to stress.

  5. A case study of virilizing adrenal tumor in an adolescent female elite tennis player--insight into the use of anabolic steroids in young athletes.

    PubMed

    Eliakim, Alon; Cale-Benzoor, Mia; Klinger-Cantor, Beatrice; Freud, Enrique; Nemet, Dan; Feigin, Elad; Weintrob, Neomi

    2011-01-01

    A 14-year-old Caucasian girl was referred to the endocrine clinic for evaluation of voice deepening, facial hirsutism, and acne starting 2 years previously. She had been a competitive tennis player since age 7 years, practicing for 4-6 hours daily. On physical examination she was noticed to have a masculine appearance with mild facial acne and moderate hirsutism. Tanner stage was 1 for breast tissue and 5 for pubic hair. Her androgen levels (testosterone, androstenedione, dehydroepiandrosterone sulfate) were extremely elevated. Adrenal ultrasonography revealed a round left 4.6 × 5.3-cm adrenal mass. Laparoscopic left adrenalectomy was performed. The histologic findings were compatible with a benign adrenocortical tumor. Postoperatively, androgen levels dropped to within the normal range. Breast development proceeded normally, menarche occurred 2 months after tumor resection, and menses has been regular since then. Muscle strength of the dominant and nondominant upper and lower extremities was measured 1 month before surgery and 1 year later, using an isokinetic dynamometer (Biodex Systems II, Biodex, Shirley, NY, USA). There was no significant decrease in overall muscle strength after removal of the virilizing tumor and the marked drop in circulating androgens. In addition, the patient maintained her age category, number 1, national tennis ranking. The results suggest that even extremely high levels of tumor-related circulating androgens had no evident effect on muscle strength and competitive performance in a female adolescent tennis player. The lack of beneficial effect on performance in adolescents, combined with the potentially hazardous side effects of anabolic steroids, suggests that teenage athletes should avoid their use.

  6. Effect of leuprolide and dexamethasone on hair growth and hormone levels in hirsute women: the relative importance of the ovary and the adrenal in the pathogenesis of hirsutism.

    PubMed

    Rittmaster, R S; Thompson, D L

    1990-04-01

    Ten hirsute women with polycystic ovarian syndrome (PCO) and nine with idiopathic hirsutism (IH) underwent selective ovarian suppression with leuprolide for 5-6 months and then were randomized to receive, in addition, dexamethasone or placebo for 4 more months. Serum hormone levels and hair growth rates were determined before and after each treatment period. During the initial treatment period with leuprolide alone, testosterone decreased by 54 +/- 6% (mean +/- SEM) in PCO and by 36 +/- 3% in IH (P = 0.02). Androstenedione decreased by 53 +/- 6% in PCO and by 31 +/- 7% in IH (P = 0.02). Androstanediol glucuronide (Adiol-G) decreased by 14 +/- 6% in PCO and by 7 +/- 3% in IH. There was no change in dehydroepiandrosterone sulfate (DHEAS). While initial serum androgen levels were higher in PCO than in IH, they were similar after ovarian suppression in the two groups. After ovarian suppression, Adiol-G was more consistently correlated with testosterone and androstenedione than was DHEAS, suggesting that Adiol-G may be a better marker than DHEAS of adrenal androgen secretion. Hair growth rates decreased by 37 +/- 6% in PCO and by 14 +/- 10% in IH (P = 0.07). The change in hair growth correlated with the change in androstenedione (r = 0.66; P = 0.002), but not significantly with the change in testosterone (r = 0.29; P = 0.2). After the addition of dexamethasone therapy (0.5 mg daily), testosterone, androstenedione, and DHEAS levels fell to near or below assay detection limits, while Adiol-G decreased by 80 +/- 3%. Hair growth rates decreased slightly more in women during dexamethasone (46 +/- 6%) than during placebo (26 +/- 9%; P = 0.18). In summary, the ovary was the major source of circulating testosterone and androstenedione in PCO. The adrenal contributed a substantial minority of these hormones in PCO and was the major source of androgen secretion in IH. Adrenal hyperandrogenism was common in both IH and PCO. Hair growth rates correlated best with changes in serum

  7. Anti-androgens in gynaecological practice.

    PubMed

    Reed, M J; Franks, S

    1988-09-01

    Hirsutism and acne in women are common distressing problems. Unwanted hair growth, acne and seborrhoea result from the action of androgens on the skin. Such effects depend not only on increased androgen production by the ovary or adrenal gland but also on the bioavailability of androgen to peripheral tissues. This in turn is related to transport of androgens in plasma by specific binding proteins and to peripheral metabolism of testosterone and androstenedione to their more potent 5 alpha-reduced derivatives. An effective anti-androgen is one which blocks the androgen receptor-mediated actions of testosterone and DHT on skin. CPA, the treatment of choice in the UK, is a potent androgen receptor-blocking steroid which also has progestational properties. When combined with ethinyloestradiol it also suppresses ovarian function, thus reducing androgen production, and provides effective contraception. PMID:2976627

  8. A chromatography/tandem mass spectrometry method for the simultaneous profiling of ten endogenous steroids, including progesterone, adrenal precursors, androgens and estrogens, using low serum volume.

    PubMed

    Caron, Patrick; Turcotte, Véronique; Guillemette, Chantal

    2015-12-01

    Measurement of a large set of sex steroids in clinical epidemiology and laboratory research with reliable methods providing low quantification limits and using a limited volume of blood sample represents a significant challenge. We report a new validated gas chromatography selected reaction monitoring - tandem mass spectrometry assay (GC-MS/MS) for the simultaneous quantification of ten endogenous steroids including progesterone (PROG), dehydroepiandrosterone (DHEA), androstenediol (5-diol), androstenedione (4-dione), testosterone (T), dihydrotestosterone (DHT), androsterone (ADT), 5alpha-androstan-3beta-17beta-diol (3β-diol), estrone (E1) and estradiol (E2). After addition of stable isotope internal standards, the approach involved the combination of liquid-liquid extraction, derivatization and solid-phase extraction for injection into the GC system and multiple reaction monitoring (MRM). The method presents high reproducibility for all analytical parameters in 250 μl serum samples. The lower limit of quantification (LLOQ) were of 100 pg/ml for DHEA, 50 pg/ml for PROG, 5-diol, 4-dione and ADT, 30 pg/ml for T, 10 pg/ml for 3β-diol and DHT, 5 pg/ml for E1, and 1 pg/ml for E2. The applicability of the validated method to determine the concentrations of these 10 steroids was successfully tested on serum from men (n=15), premenopausal (n=10) and postmenopausal women (n=20), and is currently used for larger cancer-related epidemiology studies. One of the most considerable advantages over existing methods is the simultaneous determination of ten steroids in a limited volume of serum that will help conserve important clinical samples from existing biobanks.

  9. 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.

  10. Adrenal insufficiency.

    PubMed

    Li-Ng, Melissa; Kennedy, Laurence

    2012-10-01

    Adrenocortical insufficiency may arise through primary failure of the adrenal glands or due to lack of ACTH stimulation as a result of pituitary or hypothalamic dysfunction. Prolonged administration of exogenous steroids will suppress the hypothalamic-pituitary-adrenal axis, and hence cortisol secretion. We review briefly the causes, investigation, and treatment of adrenal insufficiency, and highlight aspects of particular relevance to patients with adrenal tumors.

  11. Congenital Adrenal Hyperplasia due to 17-alpha-hydoxylase/17,20-lyase Deficiency Presenting with Hypertension and Pseudohermaphroditism: First Case Report from Oman

    PubMed Central

    Mula-Abed, Waad-Allah S.; Pambinezhuth, Fathima B.; Al-Kindi, Manal K.; Al-Busaidi, Noor B.; Al-Muslahi, Hilal N.; Al-Lamki, Mohammad A.

    2014-01-01

    This is the first report of congenital adrenal hyperplasia (CAH) due to combined 17α-hydroxylase/17,20 lyase deficiency in an Omani patient who was initially treated for many years as a case of hypertension. CAH is an uncommon disorder that results from a defect in steroid hormones biosynthesis in the adrenal cortex. The clinical presentation depends on the site of enzymatic mutations and the types of accumulated steroid precursors. A 22-year-old woman who was diagnosed to have hypertension since the age of 10 years who was treated with anti-hypertensive therapy was referred to the National Diabetes and Endocrine Centre, Royal Hospital, Oman. The patient also had primary amenorrhea and features of sexual infantilism. Full laboratory and radio-imaging investigations were done. Adrenal steroids, pituitary function and karyotyping study were performed and the diagnosis was confirmed by molecular mutation study. Laboratory investigations revealed adrenal steroids and pituitary hormones profile in addition to 46XY karyotype that are consistent with the diagnosis of CAH due to 17α-hydroxylase deficiency. Extensive laboratory workup revealed low levels of serum cortisol (and its precursors 17α-hydroxyprogesterone and 11-deoxycortisol), adrenal androgens (dehydroepiandrosterone sulfate and androstenedione), and estrogen (estradiol); and high levels of mineralocorticoids precursors (11-deoxycorticosterone and corticosterone) with high levels of ACTH, FSH and LH. Mutation analysis revealed CYP17A1-homozygous mutation (c.287G>A p.Arg96Gln) resulting in the complete absence of 17α-hydroxylase/17,20-lyase activity. The patient was treated with dexamethasone and ethinyl estradiol with cessation of anti-hypertensive therapy. A review of the literature was conducted to identify previous studies related to this subtype of CAH. This is the first biochemically and genetically proven case of CAH due to 17α-hydroxylase/17,20-lyase deficiency in Oman and in the Arab World described

  12. Acne vulgaris related to androgens - a review.

    PubMed

    Khondker, L; Khan, S I

    2014-01-01

    Sebum production is stimulated by androgens and is the key in the development of acne vulgaris. Several investigators have looked for direct relationships between serum androgen levels, sebum secretion rate and the presence of acne. The presence of acne in prepubertal girls and sebum production in both sexes correlate with serum dehydroepiandrosterone sulfate (DHEAS) levels. Although increased serum androgen levels correlate with the presence of severe nodular acne in men and women, these levels are often within the normal range in mild to moderate acne. This raises the question of whether there is an increased local production of androgens within the sebaceous gland of patients with acne vulgaris that leads to increased sebum secretion.

  13. 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.

  14. Dehydroepiandrosterone, Its Sulfate and Cognitive Functions

    PubMed Central

    de Menezes, Karina Junqueira; Peixoto, Clayton; Nardi, Antonio Egidio; Carta, Mauro Giovanni; Machado, Sérgio; Veras, André Barciela

    2016-01-01

    To present a review of cross-sectional and longitudinal studies that investigate the relationship between the hormones Dehydroepiandrosterone (DHEA) and Dehydroepiandrosterone sulfate (DHEA-S) and cognition. Methods: The cognition items included in this review were global cognitive function, memory, attention, executive function, intelligence, perception and visuospatial ability. A systematic review was proceeded using three databases: PubMed, ISI Web of Science, and PsycINFO. Results: Two thousand fifty five references about cognition and hormones were found; 772 duplicated references were excluded, resulting in 1.283 references to be evaluated. According to exclusion and inclusion criteria, 25 references were selected. A positive correlation between DHEA-S blood levels and global cognition was found in women and men. Other positive correlations between DHEA-S and working memory, attention and verbal fluency were found only in women. The DHEA effect on cognition is limited to one study conducted among young men with high-doses. PMID:27346998

  15. Dehydroepiandrosterone Alters Retinol Status and Expression of the β-Carotene 15,15'-Monooxygenase and Lecithin:Retinol Acyltransferase Genes.

    PubMed

    Takitani, Kimitaka; Miyazaki, Hiroshi; Koh, Maki; Kishi, Kanta; Inoue, Akiko; Tamai, Hiroshi

    2016-01-01

    Dehydroepiandrosterone (DHEA) and its sulfate ester DHEA-sulfate (DHEA-S) are the most abundant adrenal steroids in humans. DHEA has a critical role as a steroidal precursor of androgens and/or estrogens, and in human studies and animal experiments, both DHEA and DHEA-S have multiple beneficial effects. However, there are few reports regarding the relationship between DHEA and nutrient status, especially for vitamins. Therefore, we elucidated the effect of DHEA administration on retinol status. Wistar rats were fed with a standard diet containing 0.4% (wt/wt) DHEA for 2 wk. We assessed retinol status and the expression of retinol-related proteins, including metabolic enzymes, binding proteins, cytochrome P450 (CYP) enzymes, and antioxidant enzymes. Retinol levels in the plasma and the liver of DHEA-fed rats were lower than those of controls. Expression of β-carotene 15,15'-monooxygenase (BCMO) in the liver and intestine of DHEA-fed rats was lower, whereas BCMO expression in the testes of DHEA-fed rats was higher than that of controls. Expression of the retinol-metabolizing aldehyde dehydrogenase (ALDH) enzyme ALDH1A2 was repressed in the liver of DHEA rats, whereas ALDH1A1 expression was unaltered. Hepatic expression of lecithin:retinol acyltransferase (LRAT) and CYP26A1 was lower in DHEA-fed rats than in controls. Retinol status in DHEA-fed rats might be affected by altered BCMO expression in the liver and intestine and hepatic LRAT expression, whereas BCMO expression in peripheral tissues may be regulated in a tissue-specific manner. We have shown that DHEA administration may influence retinol status and the expression of retinol-related proteins. PMID:27117846

  16. USP10 Expression in Normal Adrenal Gland and Various Adrenal Tumors.

    PubMed

    Zeng, Zhi; Zhou, Ziying; Zhan, Na; Yuan, Jingping; Ye, Baixin; Gu, Lijuan; Wang, Jun; Jian, Zhihong; Xiong, Xiaoxing

    2015-12-01

    Ubiquitin-specific protease 10 (USP10), a novel deubiquitinating enzyme, is associated with androgen receptor transcriptional activity and pathological processes of tumor. However, information between USP10 and the adrenal gland is limited. In particular, the role of USP10 in adrenal tumors has not been elucidated yet. This study aims to investigate the expression of USP10 in the human normal adrenal gland and various adrenal tumors. Tissue samples were obtained from 30 adrenocortical adenomas, nine adrenocortical adenocarcinomas, and 20 pheochromocytomas following laparoscopic surgery. Twenty normal adrenal glands were obtained from kidney surgical resection conducted due to renal cell carcinomas. USP10 expression was investigated on protein levels using immunohistochemistry and on mRNA levels using bioinformatics analysis in the Gene Expression Omnibus (GEO) Datasets. In the 20 cases of normal adrenal glands analyzed, USP10 protein was constantly expressed in situ in the cortex of the adrenal glands, but in the medulla of the gland, only the sustentacular cells were detected positive. In adrenal tumors, detectable levels of USP10 protein were found in 100 % (30/30) adrenocortical adenomas, 88.89 % (8/9) adrenocortical carcinomas, and 10 % (2/20) pheochromocytomas. Bioinformatics analysis did not show a significant difference in USP10 messenger RNA (mRNA) expression between adrenal tumors and normal adrenal gland tissues. A positive USP10 immunoreaction can be useful in distinguishing adrenal cortical tumors from pheochromocytoma.

  17. Nonsalt-losing congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase deficiency with normal glomerulosa function.

    PubMed

    Pang, S; Levine, L S; Stoner, E; Opitz, J M; Pollack, M S; Dupont, B; New, M I

    1983-04-01

    In studies of a 6-yr-old boy and his non-HLA identical 8-yr-old sister, we demonstrated 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) deficiency in the biosynthetic pathways of glucocorticoids and androgens, but not mineralocorticoids. The sister did not manifest abnormal genital development at birth, but developed premature adrenarche at the age of 4 yr, with clitoromegaly and advanced bone age. The brother had perineal hypospadias at birth and developed premature adrenarche at the age of 6 yr. In both siblings, baseline and ACTH-stimulated delta 5 steroids were markedly elevated. The baseline and ACTH-stimulated ratios of delta 5 to delta 4 steroids remained extremely high, and all steroids promptly suppressed with dexamethasone (DEX). Normal baseline PRA and serum and urinary aldosterone (Aldo) levels increased after stimulation with a low Na+ diet. Renal Na+ conservation was normal after dietary Na+ deprivation with and without DEX administration. The PRA to pH 1 Aldo ratio remained normal with normal and low Na+ diets, regardless of DEX administration, indicating normal glomerulosa function with renin stimulation. In both siblings, ACTH increased PRA and Aldo levels, maintaining the PRA to pH 1 Aldo ratio unchanged from the baseline value. In contrast, in control children, PRA was suppressed, while Aldo increased, resulting in a fall of the PRA to pH 1 Aldo ratio. The increase in PRA with exogenous ACTH in these siblings suggests there may be an ACTH-stimulable mineralocorticoid antagonist. During prolonged DEX administration, hCG administration caused a slight increase in 17-hydroxypregnenolone and dehydroepiandrosterone in both the siblings, while testosterone (T) rose poorly in the brother, and estradiol did not rise at all in the sister. These results suggest the possibility of a deficiency of 3 beta-HSD in the gonads as well as the adrenals. After [3H]dehydroepiandrosterone iv infusion, there was normal conversion to [3H]-conjugated testosterone

  18. Interrelationship between excessive levels of circulating androgens in blood and ovulatory failure.

    PubMed

    Parker, C R; Mahesh, V B

    1976-08-01

    The association of excessive circulating androgens in blood and ovulatory failure in women is well documented in a variety of clinical conditions. The restoration of ovulatory function by wedge resection of the polycystic ovary, by the administration of glucocorticoids or removal of tumors of the adrenal or ovary--measures that also reduce the level of circulating androgens--is also well documented. In view of the many hypotheses of adrenal and ovarian abnormalities and disorders of the hypothalamic-pituitary axis in the human, resulting in hirsutism and ovulatory failure, a normal intact rat model was developed to study the effect of androgens on ovulation. The administration of a weak androgen, dehydroepiandrosterone (DHA), to immature rats resulted in a single precocious ovulation followed by ovulatory failure. The conversion of DHA to estrogens appeared to be the principle mechanism for the precocious ovulation. The steps appeared to be an elevation in blood estradiol, followed by the depletion of cytoplasmic estradiol receptors of the hypothalamus and pituitary and the gonadotropin surge leading to ovulation. These events appeared to be similar to those occuring in the adult cycling rat, in precocious puberty induced by the administration of pregnant mare serum gonadotropins and during the onset of natural puberty. The role of estrogens in inducing the precocious ovulation was further supported by the absence of precocious ovulation in animals in which the conversion of DHA to estrogens was blocked or by administering androgens that could not be converted to estrogens. In contrast, the subsequent ovulatory failure could not be explained entirely by the conversion of DHA to estrogens. There was a considerable time lag between the withdrawal of DHA treatment and the replenishment of pituitary and hypothalamic cytoplasmic estradiol receptors. Unlike those of the cycling animal, the receptors were not replenished when the levels of circulating estradiol in blood

  19. Reduced quality and accelerated follicle loss with female reproductive aging - does decline in theca dehydroepiandrosterone (DHEA) underlie the problem?

    PubMed Central

    2013-01-01

    Infertility, spontaneous abortion and conception of trisomic offspring increase exponentially with age in mammals but in women there is an apparent acceleration in the rate from about age 37. The problems mostly commonly occur when the ovarian pool of follicles is depleted to a critical level with age but are also found in low follicular reserve of other etiologies. Since recent clinical studies have indicated that dehydroepiandrosterone (DHEA) supplementation may reverse the problem of oocyte quality, this review of the literature was undertaken in an attempt to find an explanation of why this is effective? In affected ovaries, oxygenation of follicular fluid is low, ultrastructural disturbances especially of mitochondria, occur in granulosa cells and oocytes, and considerable disturbances of meiosis occur. There is, however, no evidence to date that primordial follicles are compromised. In females with normal fertility, pre-antral ovarian theca cells respond to stimulation by inhibin B to provide androgen-based support for the developing follicle. With depletion of follicle numbers, inhibin B is reduced with consequent reduction in theca DHEA. Theca cells are the sole ovarian site of synthesis of DHEA, which is both a precursor of androstenedione and an essential ligand for peroxisome proliferator-activated receptor alpha (PPARα), the key promoter of genes affecting fatty acid metabolism and fat transport and genes critical to mitochondrial function. As well as inducing a plethora of deleterious changes in follicular cytoplasmic structure and function, the omega 9 palmitate/oleate ratio is increased by lowered activity of PPARα. This provides conditions for increased ceramide synthesis and follicular loss through ceramide-induced apoptosis is accelerated. In humans critical theca DHEA synthesis occurs at about 70 days prior to ovulation thus effective supplementation needs to be undertaken about four months prior to intended conception; timing which is also

  20. 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

  1. 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

  2. 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

  3. Adrenal myelolipoma. 6 cases and a review of the literature.

    PubMed

    Wagnerová, H; Lazúrová, I; Bober, J; Sokol, L; Zachar, M

    2004-01-01

    Adrenal myelolipoma is an uncommon, benign and hormonally inactive tumor. Most lesions are asymptomatic and usually are discovered incidentally at autopsy studies. Authors report on 6 patients (5 women, 1 man) with adrenal myelolipomas (5 right, 1 left), analyze their morphological findings and association with an adrenal hormonal overproduction. Five of the patients underwent surgery because of tumor size, in 3 of them histological evaluation confirmed myelolipoma and in 2 cases an adrenocortical adenoma with foci of myelolipoma. All the patients were asymptomatic and in 4 cases hormonal overproduction was not found. One female patient has oveproduction of dehydroepiandrosteron-sulphate (DHEAS) indicating a 3beta hydroxylase deficiency in this tumor and 1 patient has primary aldosteronism with a histological finding of an association of adrenocortical adenoma with foci of myelolipoma. Neither Cushings syndrome nor congenital adrenal hyperplasia were present in our group of patients.

  4. Bu-Shen-Ning-Xin decoction suppresses osteoclastogenesis via increasing dehydroepiandrosterone to prevent postmenopausal osteoporosis.

    PubMed

    Gui, Yuyan; Qiu, Xuemin; Xu, Yingping; Li, Dajin; Wang, Ling

    2015-06-01

    Bu-Shen-Ning-Xin decoction (BSNXD), a traditional Chinese medicine, has been used to prevent and treat age-related diseases such as postmenopausal osteoporosis (PMO) for decades. This study sought to investigate the underlying mechanisms of BSNXD in terms of receptor activation of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis in vitro because of the critical roles of bone resorption in the development and progression of osteoporosis. In mice, serum levels of dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), and 17-β-estradiol (E2) were evaluated with an enzyme immunoassay kit after ovariectomy. Levels of DHEA and DHEAS increased significantly following administration of BSNXD while the level of E2 did not. In addition, tartrate-resistance acid phosphatase staining showed that DHEA profoundly inhibited RANKL-induced osteoclastogenesis in vitro in a dose-dependent manner via estrogen receptor α (ERα) but not via estrogen receptor β or androgen receptors. Cytotoxicity was not detected in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. These data suggest that BSNXD prevents PMO by increasing DHEA via the ERαpathway to suppress osteoclastogenesis.

  5. Rise in dehydroepiandrosterone and oestrogens during clomiphene administration in normal men.

    PubMed

    Kampmann, J P; Jorgensen, F S; Bennett, E P; Johnsen, S G

    1976-09-01

    Serum concentrations of LH, FSH and testosterone, and urinary excretion of individual 17-ketosteroids, oestrogenic substances and free cortisol was investigated in 12 normal men after a daily administration of 50 mg clomiphene citrate for 14 days. A significant increase in the serum concentrations of LH, FSH and testosterone was seen after 8 days with a further increase when measured a week later. The percentual increase in urinary excretion of oestrogens and dehydroepiandrosterone was of the same order as the increase in serum testosterone concentrations whereas the increase in androsterone and a aetiocholanolone was significantly lower. The excretion of free cortisol was unaltered. The study that measurements of oestrogens in the urine might be used as a parameter of the stimulatory effect of clomiphene on the hypothalamic - pituitary - gonadal axis in man. In addition, of the results support the hypothesis of an independent effect of clomiphene on adrenal steroidogenesis, not related to the production of glucocorticoids.

  6. Androgen status in adolescent women with acne vulgaris.

    PubMed

    Aizawa, H; Nakada, Y; Niimura, M

    1995-07-01

    Androgens are essential for the development of acne. The object of this study was to elucidate the androgen status of women with adolescent (Tanner's stage IV-V) acne alone and compare them to age-matched normal controls. We measured serum levels of total testosterone (T), free testosterone (FT), dihydrotestosterone (DHT), and dehydroepiandrosterone sulfate (DHEA-S) in 15 women with adolescent acne and 13 age-matched healthy controls. No significant differences were found between the mean levels of T, FT or DHT levels in patients and controls. However, the mean levels of DHEA-S in the patient population (1886 +/- 829 ng/ml) were significantly (p < 0.05) higher than normal controls (1287 +/- 620 ng/ml). There was also no correlation between androgen levels and acne severity. Thus it is unlikely that serum androgens play a principal role in women with adolescent acne. PMID:7560449

  7. [Sexual and gonadal dysfunction in adrenal disorders].

    PubMed

    Horiba, N

    1997-11-01

    Among various diseases of the adrenals, major disorders that cause sexual and gonadal disturbances are congenital adrenal hyperplasia(CAH) and Cushing's syndrome, and the others include virilizing or feminizing adrenocortical tumors. CAH was reviewed based on the recent advances in molecular genetics. The most striking discovery was steroidogenic acute regulatory protein, mutations of which produce lipoid adrenal hyperplasia that was previously attributed to P-450scc deficiency. Reversible amenorrhea or impotence is found in patients with Cushing's syndrome. Low plasma estrogen and testosterone levels are associated with female and male patients, respectively. Elevated adrenal androgen accounts for mild virilization in female patients with ACTH-dependent subtypes. The sites of action at which hypercortisolemia suppresses the hypothalamic-pituitary-gonadal axis were discussed.

  8. [Morphometry in Development of Red Deer's Adrenal Glands].

    PubMed

    Ovcharenko, N D; Gribanova, O G; Bondyreva, L A

    2015-01-01

    Histological structures and morphometric and some histochemical indicators of elk's adrenal gland development as subspecies of red deer in prenatal and postnatal ontogenies stages was studied. It was found that the growth of the fetus adrenal glands weight and the thickness of the structures adrenal glands fragments continue throughout the prenatal period of ontogeny. The cells of androgenic zone with single wandering sympathogoniae are differentiated in the adrenal glands in the second month of development. The androgenic and definite zone and the adrenal medulla are differentiated by the third month of development. At the 4 months, adrenal gland cortex zona glomerulosa and zona fasciculate-reticularis are differentiated; zona reticularis is differentiated only by the seventh month. By the eighth month, the structure of adrenal glands corresponds to the adrenal glands of a newborn. Full structural formation of the adrenal glands takes place in young animals by age 1.5. Obvious structural changes were not found late in the postnatal stages of development.

  9. 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.

  10. [Adrenal mass and adrenal insufficiency].

    PubMed

    Martínez Albaladejo, M; García López, B; Serrano Corredor, S; Alguacil García, G

    1996-12-01

    Primary adrenal insufficiency is a non frequent disease, that is declared in young adults and in the most of the cases is produced from an autoimmune mechanism or a tuberculous disease. The incidence of these forms in the different geographic areas is dependent of degree of irradication of the tuberculosis. We report the case of a patient with latent chronic adrenal insufficiency of tuberculous origin who was affected for an addisonian crisis during an intercurrent infectious disease, which permitted the diagnosis of the addisonian crisis, and Mal of Pott was moreover detected. Evolution with corticosteroid and specific treatment was very favorable.

  11. Simultaneous measurement of testosterone, androstenedione and dehydroepiandrosterone (DHEA) in serum and plasma using Isotope-Dilution 2-Dimension Ultra High Performance Liquid-Chromatography Tandem Mass Spectrometry (ID-LC-MS/MS).

    PubMed

    Büttler, Rahel M; Martens, Frans; Kushnir, Mark M; Ackermans, Mariette T; Blankenstein, Marinus A; Heijboer, Annemieke C

    2015-01-01

    The adrenal and gonadal androgens, testosterone, androstenedione and dehydroepiandrosterone (DHEA) play an important role in sexual development as well as in other processes. We developed a method for simultaneous quantitative analysis of serum and plasma testosterone, androstenedione and DHEA levels using Isotope-Dilution Liquid-Chromatography Tandem Mass Spectrometry (ID-LC-MS/MS). Samples underwent liquid-liquid extraction and were analyzed on an Acquity 2D-UPLC-System and a Xevo TQ-S tandem mass spectrometer (Waters). The intra-assay and inter-assay coefficients of variation were <4.0%, <6.3% and <7.0% and <6.0%, <8.1% and <7.7% for testosterone, androstenedione and DHEA, respectively. Inter-assay CVs at the lower limit were 10.6%, 16.9% and 9.0% for testosterone (0.10nmol/L), androstenedione (0.10nmol/L) and DHEA (1.0nmol/L), respectively. Recoveries of spiked analytes were 93-107%. The present testosterone method compared well (y=1.00x-0.04; r=0.998) to a published ID-LC-MS/MS method for testosterone in our lab. The latter method being concordant with a published reference method (Bui et al., 2013). The present method compared well to a published ID-LC-MS/MS method (Kushnir et al., 2010) (y=1.06x-0.06; r=0.996 for testosterone; y=1.04x-0.04; r=0.995 for androstenedione and y=1.03x+0.01; r=0.991 for DHEA). In conclusion, we developed a sensitive and accurate ID-LC-MS/MS method to simultaneously measure serum testosterone, androstenedione and DHEA in serum and plasma.

  12. 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

  13. Adrenal glands of Spix's yellow-toothed cavy (Galea spixii, Wagler, 1831): morphological and morphometric aspects.

    PubMed

    Santos, A C; Viana, D C; Bertassoli, B M; Vasconcelos, B G; Oliveira, D M; Rici, R E G; Oliveira, M F; Miglino, M A; Assis-Neto, A C

    2016-05-01

    Considering the physiological importance and need of greater morphophysiological knowledge of adrenal glands, the aims of present study were compare the morphometric data between left and right adrenal of male and female; perform a histological, scanning and transmission electron microscopy study showing tissue constitution of glands; finally, in order to define the presence and correct site of the cytochrome P450c17 expression in adrenal glands, immunohistochemical study of this enzyme was performed in 18 adrenal glands (right n=9 and left n=9) of nine adult Galea spixii (four males and five females). Right adrenal was more cranially positioned than left adrenal; dimensions (weight, length and width) of right adrenal was larger than left adrenal; no differences between male and female body and adrenal measurements were found; the morphology of cells and different amounts of lipid droplets may be related to the different demands of steroid hormones production, related to each zone of the adrenal cortex; and, the cytochrome P450c17 immunolocalization in fasciculate and reticular zone may be related with synthesis of 17-hydroxy-pregnenolone, 17-hydroxy-progesterone, dehydroepiandrosterone or androstenedione. PMID:27143060

  14. Adrenal glands of Spix's yellow-toothed cavy (Galea spixii, Wagler, 1831): morphological and morphometric aspects.

    PubMed

    Santos, A C; Viana, D C; Bertassoli, B M; Vasconcelos, B G; Oliveira, D M; Rici, R E G; Oliveira, M F; Miglino, M A; Assis-Neto, A C

    2016-05-01

    Considering the physiological importance and need of greater morphophysiological knowledge of adrenal glands, the aims of present study were compare the morphometric data between left and right adrenal of male and female; perform a histological, scanning and transmission electron microscopy study showing tissue constitution of glands; finally, in order to define the presence and correct site of the cytochrome P450c17 expression in adrenal glands, immunohistochemical study of this enzyme was performed in 18 adrenal glands (right n=9 and left n=9) of nine adult Galea spixii (four males and five females). Right adrenal was more cranially positioned than left adrenal; dimensions (weight, length and width) of right adrenal was larger than left adrenal; no differences between male and female body and adrenal measurements were found; the morphology of cells and different amounts of lipid droplets may be related to the different demands of steroid hormones production, related to each zone of the adrenal cortex; and, the cytochrome P450c17 immunolocalization in fasciculate and reticular zone may be related with synthesis of 17-hydroxy-pregnenolone, 17-hydroxy-progesterone, dehydroepiandrosterone or androstenedione.

  15. Magnetic Resonance Imaging of the Vocal Folds in Women with Congenital Adrenal Hyperplasia and Virilized Voices

    ERIC Educational Resources Information Center

    Nygren, Ulrika; Isberg, Bengt; Arver, Stefan; Hertegård, Stellan; Södersten, Maria; Nordenskjöld, Agneta

    2016-01-01

    Purpose: Women with congenital adrenal hyperplasia (CAH) may develop a virilized voice due to late diagnosis or suboptimal suppression of adrenal androgens. Changes in the vocal folds due to virilization have not been studied in vivo. The purpose was to investigate if the thyroarytenoid (TA) muscle is affected by virilization and correlate…

  16. Infertility and Reproductive Function in Patients with Congenital Adrenal Hyperplasia: Pathophysiology, Advances in Management, and Recent Outcomes.

    PubMed

    Lekarev, Oksana; Lin-Su, Karen; Vogiatzi, Maria G

    2015-12-01

    Individuals with congenital adrenal hyperplasia have reduced fertility. However, reproductive outcomes have improved over the years. This review provides an update on the multiple pathologic processes that contribute to reduced fertility in both sexes, from alterations of the hypothalamic-pituitary-gonadal axis to the direct effect on gonadal function by elevated circulating adrenal androgens. In addition, elevated serum progesterone concentrations may hinder ovulation and embryo implantation in women, whereas in men testicular adrenal rest tumors can be a major cause of infertility. Suppression of adrenal androgen secretion represents the first line of therapy toward spontaneous conception in both sexes.

  17. Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulfate (DHEAS) and emotional processing - A behavioral and electrophysiological approach.

    PubMed

    do Vale, Sónia; Selinger, Lenka; Martins, João Martin; Bicho, Manuel; do Carmo, Isabel; Escera, Carles

    2015-07-01

    Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulfate (DHEAS) may have mood enhancement effects: higher DHEAS concentrations and DHEA/cortisol ratio have been related to lower depression scores and controlled trials of DHEA administration have reported significant antidepressant effects. The balance between DHEAS and DHEA has been suggested to influence brain functioning. We explored DHEAS, DHEA, cortisol, DHEA/cortisol and DHEAS/DHEA ratios relations to the processing of negative emotional stimuli at behavioral and brain levels by recording the electroencephalogram of 21 young women while performing a visual task with implicit neutral or negative emotional content in an audio-visual oddball paradigm. For each condition, salivary DHEA, DHEAS and cortisol were measured before performing the task and at 30 and 60min intervals. DHEA increased after task performance, independent of the implicit emotional content. With implicit negative emotion, higher DHEAS/DHEA and DHEA/cortisol ratios before task performance were related to shorter visual P300 latencies suggesting faster brain processing under a negative emotional context. In addition, higher DHEAS/DHEA ratios were related to reduced visual P300 amplitudes, indicating less processing of the negative emotional stimuli. With this study, we could show that at the electrophysiological level, higher DHEAS/DHEA and DHEA/cortisol ratios were related to shorter stimulus evaluation times suggesting less interference of the implicit negative content of the stimuli with the task. Furthermore, higher DHEAS/DHEA ratios were related to reduced processing of negative emotional stimuli which may eventually constitute a protective mechanism against negative information overload. PMID:26122298

  18. Androgens Regulate T47D Cells Motility and Invasion through Actin Cytoskeleton Remodeling

    PubMed Central

    Montt-Guevara, Maria Magdalena; Shortrede, Jorge Eduardo; Giretti, Maria Silvia; Giannini, Andrea; Mannella, Paolo; Russo, Eleonora; Genazzani, Alessandro David; Simoncini, Tommaso

    2016-01-01

    The relationship between androgens and breast cancer is controversial. Androgens have complex effects on breast cancer progression and metastasis. Moreover, androgen receptor (AR) is expressed in approximately 70 to 90% of invasive breast carcinomas, which has prognostic relevance in basal-like cancers and in triple-negative breast cancers. Recent studies have associated the actin-binding proteins of the ezrin–radixin–moesin (ERM) family with metastasis in endocrine-sensitive cancers. We studied on T47D breast cancer cells whether androgens with different characteristics, such as testosterone (T), dihydrotestosterone (DHT), and dehydroepiandrosterone (DHEA) may regulate breast cancer cell motility and invasion through the control of actin remodeling. We demonstrate that androgens promote migration and invasion in T47D via Moesin activation. We show that T and DHEA exert their actions via the AR and estrogen receptor (ER), while the non-aromatizable androgen – DHT – only recruits AR. We further report that androgen induced significant changes in actin organization with pseudopodia along with membrane ruffles formation, and this process is mediated by Moesin. Our work identifies novel mechanisms of action of androgens on breast cancer cells. Through the modulation of Moesin, androgens alter the architecture of cytoskeleton in T47D breast cancer cell and promote cell migration and invasion. These results could help to understand the biological actions of androgens on breast cancer and, eventually, to develop new strategies for breast cancer treatment. PMID:27746764

  19. Effect of isotretinoin on serum levels of precursor and peripherally derived androgens in patients with acne.

    PubMed

    Lookingbill, D P; Demers, L M; Tigelaar, R E; Shalita, A R

    1988-04-01

    Sebaceous glands are stimulated by androgens and can convert them to more active forms. Isotretinoin, however, has a profound inhibitory effect on sebaceous gland size and function. This study evaluated the effect of isotretinoin on serum levels of precursor and tissue-derived androgens. Twenty-four subjects (15 men and nine women) were treated for 20 weeks with 1 mg/kg/d of isotretinoin. Serum samples were obtained at baseline, 8, 16, and 24 weeks, and assayed for precursor androgens--total testosterone (TT), free testosterone (free T), dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEA-S); and tissue androgens--dihydrotestosterone (DHT), and its metabolite, 3 alpha-androstanediol glucuronide (3 alpha-diol G). Isotretinoin had no meaningful effects on precursor androgens, except for producing an elevation of free T in women. In contrast, isotretinoin produced depressions in the serum levels of DHT and 3 alpha-diol G in women and in 3 alpha-diol G in men. These decreases are believed to be the result, rather than the cause, of a reduction in the size of the sebaceous glands: The magnitude of the observed decreases may represent the amount of tissue-derived androgens that sebaceous glands normally contribute to the circulating pool. PMID:2965551

  20. Bone Mineral Status in Children with Congenital Adrenal Hyperplasia

    PubMed Central

    Fleischman, Amy; Ringelheim, Julie; Feldman, Henry A.; Gordon, Catherine M.

    2013-01-01

    Congenital adrenal hyperplasia (CAH) is caused by a deficiency in an adrenal enzyme resulting in alterations in Cortisol and aldosterone production. Bone status is affected by chronic glucocorticoid therapy and excess androgen exposure in children with CAH. This cross-sectional study enrolled participants with 21-hydroxylase deficiency from a pediatric referral center. Bone mineral density in the participants was normal when compared to age, gender and ethnicity adjusted standards, with respect to chronological age or bone age. Lean body mass was positively correlated with bone mineral content (BMC), independent of fat mass (p <0.001). There was no significant correlation between glucocorticoid dose or serum androgen levels and skeletal endpoints. In conclusion, lean body mass appears to be an important correlate of BMC in patients with CAH. The normal bone status may be explained by the differential effects of glucocorticoids on growing bone, beneficial androgen effects, or other disease specific factors. PMID:17396440

  1. Opioid-induced androgen deficiency (OPIAD).

    PubMed

    Smith, Howard S; Elliott, Jennifer A

    2012-07-01

    Opioid therapy is one of the most effective forms of analgesia currently in use. In the past few decades, the use of opioids as a long-term treatment for chronic pain has increased dramatically. Accompanying this upsurge in the use of long-term opioid therapy has been an increase in the occurrence of opioid associated endocrinopathy, most commonly manifested as an androgen deficiency and therefore referred to as opioid associated androgen deficiency (OPIAD). This syndrome is characterized by the presence of inappropriately low levels of gonadotropins (follicle stimulating hormone and luteinizing hormone) leading to inadequate production of sex hormones, particularly testosterone. Symptoms that may manifest in patients with OPIAD include reduced libido, erectile dysfunction, fatigue, hot flashes, and depression. Physical findings may include reduced facial and body hair, anemia, decreased muscle mass, weight gain, and osteopenia or osteoporosis. Additionally, both men and women with OPIAD may suffer from infertility. While the literature regarding OPIAD remains limited, it is apparent that OPIAD is becoming increasingly prevalent among chronic opioid consumers but often goes unrecognized. OPIAD can have a significant negative impact on the the quality of life of opioid users, and clinicians should anticipate the potential for its occurrence whenever long-term opioid prescribing is undertaken. Once diagnosed, treatment for OPIAD may be offered utilizing a number of androgen replacement therapy options including a variety of testosterone preparations and, for female patients with OPIAD, dehydroepiandrosterone (DHEA) supplementation. Follow-up evaluation of patients receiving androgen replacement therapy should include a review of any unresolved symptoms of hypogonadism, laboratory evaluation, and surveillance for potential adverse effects of androgen replacement therapy including prostate disease in males.: PMID:22786453

  2. Unveiling the crucial intermediates in androgen production

    PubMed Central

    Mak, Piotr J.; Gregory, Michael C.; Denisov, Ilia G.; Sligar, Stephen G.; Kincaid, James R.

    2015-01-01

    Ablation of androgen production through surgery is one strategy against prostate cancer, with the current focus placed on pharmaceutical intervention to restrict androgen synthesis selectively, an endeavor that could benefit from the enhanced understanding of enzymatic mechanisms that derives from characterization of key reaction intermediates. The multifunctional cytochrome P450 17A1 (CYP17A1) first catalyzes the typical hydroxylation of its primary substrate, pregnenolone (PREG) and then also orchestrates a remarkable C17–C20 bond cleavage (lyase) reaction, converting the 17-hydroxypregnenolone initial product to dehydroepiandrosterone, a process representing the first committed step in the biosynthesis of androgens. Now, we report the capture and structural characterization of intermediates produced during this lyase step: an initial peroxo-anion intermediate, poised for nucleophilic attack on the C20 position by a substrate-associated H-bond, and the crucial ferric peroxo-hemiacetal intermediate that precedes carbon–carbon (C-C) bond cleavage. These studies provide a rare glimpse at the actual structural determinants of a chemical transformation that carries profound physiological consequences. PMID:26668369

  3. Impaired oocyte quality induced by dehydroepiandrosterone is partially rescued by metformin treatment.

    PubMed

    Huang, Ying; Yu, Yang; Gao, Jiangman; Li, Rong; Zhang, Chunmei; Zhao, Hongcui; Zhao, Yue; Qiao, Jie

    2015-01-01

    The present study evaluated the influence of hyperandrogenism on oocyte quality using a murine PCOS model induced by dehydroepiandrosterone (DHEA) and further explored the effect of metformin treatment. Female BALB/c mice were treated with a vehicle control or DHEA (6 mg /100 g body weight) or DHEA plus metformin (50 mg /100 g body weight) for 20 consecutive days. DHEA-induced mice resembled some characters of human PCOS, such as irregular sexual cycles and polycystic ovaries. After the model validation was completed, metaphase II (MII) oocytes were retrieved and subsequent analyses of oocyte quality were performed. DHEA-treated mice yielded fewer MII oocytes, which displayed decreased mtDNA copy number, ATP content, inner mitochondrial membrane potential, excessive oxidative stress and impaired embryo development competence compared with those in control mice. Metformin treatment partially attenuated those damages, as evidenced by the increased fertilization and blastocyst rate, ATP content, GSH concentration and GSH/GSSG ratio, and decreased reactive oxygen species levels. No significant difference in normal spindle assembly was observed among the three groups. During in vitro maturation (IVM), the periods of germinal vesicle breakdown (GVBD) and the first polar body (PB1) extrusion were extended and the maturation rate of GVBD oocytes was decreased in DHEA mice compared with controls. Metformin treatment decreased the time elapsed of GVBD while had no effect on PB1 extrusion. These results indicated that excessive androgen is detrimental to oocyte quality while metformin treatment is, directly or indirectly, beneficial for oocyte quality improvement. PMID:25811995

  4. 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 ...

  5. Alzheimer's disease: pathophysiological implications of measurement of plasma cortisol, plasma dehydroepiandrosterone sulfate, and lymphocytic corticosteroid receptors.

    PubMed

    Armanini, Decio; Vecchio, Franco; Basso, Alfonso; Milone, Francesco Ferro; Simoncini, Maria; Fiore, Cristina; Mattarello, Mee Joung; Sartorato, Paola; Karbowiak, Isabella

    2003-11-01

    Alzheimer's disease is often characterized by an increase in plasma cortisol without clinical evidence of hypercorticism. Twenty-three consecutive patients with Alzheimer's disease and 23 age- and sex-matched healthy controls were studied by measuring plasma cortisol and dehydroepiandrosterone sulfate (DHEAS) (by enzyme immunoassay), the number of type I and type II corticosteroid receptors in mononuclear leukocytes (by radio-receptor-assay), and the lymphocyte subpopulations (by cytofluorimetry). Results are expressed in terms of median and range. In Alzheimer's disease, plasma cortisol was higher than in controls (median 0.74, range 0.47-1.21 vs 0.47, 0.36-0.77 mmol/L; p < 0.001). Plasma DHEAS, the DHEAS/cortisol ratio, and the number of type II corticosteroid receptors were significantly lower in AD than in controls (DHEAS: median 1.81, range 0.21-3.69 vs 3.51, 1.35-9.07 micromol/L; DHEAS/ cortisol: 2.04, range 0.3-5.8 vs 6.8, range 2.7-24 and type II receptors: 1219, 1000-2700 vs 1950, 1035- 2750 receptors per cell; p < 0.001). No correlation was found between the hormonal parameters, age, and mini-mental test score. These data support the hypothesis of a dysregulation of the adrenal pituitary axis in Alzheimer's disease, which is probably the consequence of damage to target tissues by corticosteroids. PMID:14665714

  6. Dehydroepiandrosterone Stimulation of Osteoblastogenesis in Human MSCs Requires IGF-I Signaling.

    PubMed

    Liang, Xiaonan; Glowacki, Julie; Hahne, Jochen; Xie, Li; LeBoff, Meryl S; Zhou, Shuanhu

    2016-08-01

    Dehydroepiandrosterone (DHEA) is an adrenal steroid that circulates in high concentrations in humans in its sulfated form, DHEAS. Clinical and epidemiological studies suggested that low DHEAS levels may be associated with low bone mass. Previously, we and others showed that the effects of DHEA on the skeleton may be conferred partly by their ability to inhibit skeletal catabolic agents, for example, bone resorptive cytokine IL-6. In this study, we tested the hypothesis that the anabolic effects of DHEA on osteoblastogenesis require IGF-I signaling pathways. Using both primary cultures and a cell line of human bone marrow-derived mesenchymal stem cells (hMSCs), we show that DHEA and other steroids stimulate osteoblastogenesis as shown by alkaline phosphatase activity and osteoblast gene induction. The stimulation by DHEA on both IGF-I gene expression and osteoblastogenesis in hMSCs requires IGF-I receptor, PI3K, p38 MAPK, or p42/44 MAPK signaling pathways. This study adds information to indicate that DHEA may be useful for treating bone diseases through its inhibition of skeletal catabolic IL-6 and stimulation of anabolic IGF-I-mediated mechanisms. J. Cell. Biochem. 117: 1769-1774, 2016. © 2015 Wiley Periodicals, Inc. PMID:26682953

  7. Association between megestrol acetate treatment and symptomatic adrenal insufficiency with hypogonadism in male patients with cancer.

    PubMed

    Dev, Rony; Del Fabbro, Egidio; Bruera, Eduardo

    2007-09-15

    Patients with advanced cancer may develop cachexia, which is often treated with megestrol acetate (MA). In addition to thromboembolic disease, MA may cause symptomatic suppression of the hypothalamic pituitary adrenal axis. In male patients with cancer, treatment with MA may also suppress the gonadal axis, resulting in symptomatic androgen deficiency. Three cases are presented to highlight the symptomatic burden of adrenal insufficiency and hypogonadism. Clinicians need an increased awareness of the complication of adrenal insufficiency secondary to MA treatment and a low threshold to test for adrenal and gonadal dysfunction in symptomatic male patients with advanced cancer.

  8. 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

  9. 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 ...

  10. 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 ...

  11. 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 - ...

  12. 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

  13. Disorders of adrenal development.

    PubMed

    Ferraz-de-Souza, Bruno; Achermann, John C

    2008-01-01

    Human adrenal development is a complex and relatively poorly understood process. However, significant insight into some of the mechanisms regulating adrenal development and function is being obtained through the analysis of individuals and families with adrenal hypoplasia. Adrenal hypoplasia can occur: (1) secondary to defects in pituitary adrenocorticotropin (ACTH) synthesis, processing and release (secondary adrenal hypoplasia; e.g. HESX1, LHX4, SOX3, TPIT, pituitary POMC, PC1); (2) as part of several ACTH resistance syndromes (e.g. MC2R/ACTHR, MRAP, Alacrima, Achalasia, Addison disease), or as (3) a primary defect in the development of the adrenal gland itself (primary adrenal hypoplasia; e.g. DAX1/NR0B1 - dosage-sensitive sex reversal, adrenal hypoplasia congenita critical region on the X chromosome 1). Indeed, the X-linked form of primary adrenal hypoplasia due to deletions or mutations in the orphan nuclear receptor DAX1 occurs in around half of male infants presenting with a salt-losing adrenal crisis, where no obvious steroidogenic defect (e.g. 21-hydroxylase deficiency), metabolic abnormality (e.g. neonatal adrenoleukodystrophy) or physical cause (e.g. adrenal haemorrhage) is found. Establishing the underlying basis of adrenal failure can have important implications for investigating associated features, the likely long-term approach to treatment, and for counselling families about the risk of other children being affected.

  14. Aspirin inhibits androgen response to chorionic gonadotropin in humans.

    PubMed

    Conte, D; Romanelli, F; Fillo, S; Guidetti, L; Isidori, A; Franceschi, F; Latini, M; di Luigi, L

    1999-12-01

    Eicosanoids play an important role in the regulation of the hypothalamic-pituitary axis; less clear is their role in testicular steroidogenesis. To evaluate the involvement of cyclooxygenase metabolites, such as prostaglandins, in the regulation of human testicular steroidogenesis, we examined the effects of a prostaglandin-blocker, aspirin, on plasma testosterone, pregnenolone, progesterone, 17OH-progesterone, androstenedione, dehydroepiandrosterone, and 17beta-estradiol response to human chorionic gonadotropin (hCG) in normal male volunteers in a placebo-controlled, single-blinded study. To test the efficacy of aspirin, seminal prostaglandin E(2) levels were also determined. hCG stimulation increased peripheral levels of testosterone, 17OH-progesterone, androstenedione, dehydroepiandrosterone, and 17beta-estradiol, without affecting circulating pregnenolone and progesterone values. Aspirin significantly lowered seminal prostaglandin E(2) levels, whereas it did not modify steroid concentrations not exposed to exogenous hCG. Moreover, the drug significantly reduced the response of testosterone, 17OH-progesterone, androstenedione, and dehydroepiandrosterone to hCG, as assessed by the mean integrated area under the curve, whereas it did not influence 17beta-estradiol response. In conclusion, aspirin treatment inhibits androgen response to chorionic gonadotropin stimulation in normal humans. The action of aspirin is probably mediated via an effective arachidonate cyclooxygenase block.

  15. Acne is not associated with abnormal plasma androgens.

    PubMed

    Levell, M J; Cawood, M L; Burke, B; Cunliffe, W J

    1989-05-01

    Plasma dehydroepiandrosterone sulphate, androstenedione, testosterone (T), dihydrotestosterone (DHT), and sex hormone binding globulin (SHBG) have been measured in 64 females and 26 males aged less than 25 years and with acne vulgaris. Oestradiol was measured in the males. Free T and free DHT were calculated. Acne was graded on three sites and the sebum excretion rate (SER) was measured in most patients. With the possible exception of free DHT, none of the plasma steroids or SHBG correlated with acne severity or with SER. Free DHT in the females showed a possible, but weak, correlation with total acne (r = 0.25, P = 0.07), but comparison with male data showed that this was not causative. The role of androgens in acne is permissive and plasma androgen measurements usually have no place in its management. PMID:2527050

  16. 21 CFR 862.1245 - Dehydroepiandrosterone (free and sulfate) test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1245 Dehydroepiandrosterone (free and sulfate) test system. (a)...

  17. 21 CFR 862.1245 - Dehydroepiandrosterone (free and sulfate) test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1245 Dehydroepiandrosterone (free and sulfate) test system. (a)...

  18. 21 CFR 862.1245 - Dehydroepiandrosterone (free and sulfate) test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1245 Dehydroepiandrosterone (free and sulfate) test system. (a)...

  19. 21 CFR 862.1245 - Dehydroepiandrosterone (free and sulfate) test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1245 Dehydroepiandrosterone (free and sulfate) test system. (a)...

  20. 21 CFR 862.1245 - Dehydroepiandrosterone (free and sulfate) test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1245 Dehydroepiandrosterone (free and sulfate) test system. (a)...

  1. 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

  2. Circulating androgens in women: exercise-induced changes.

    PubMed

    Enea, Carina; Boisseau, Nathalie; Fargeas-Gluck, Marie Agnès; Diaz, Véronique; Dugué, Benoit

    2011-01-01

    Physical exercise is known to strongly stimulate the endocrine system in both sexes. Among these hormones, androgens (e.g. testosterone, androstenedione, dehydroepiandrosterone) play key roles in the reproductive system, muscle growth and the prevention of bone loss. In female athletes, excessive physical exercise may lead to disorders, including delay in the onset of puberty, amenorrhoea and premature osteoporosis. The free and total fractions of circulating androgens vary in response to acute and chronic exercise/training (depending on the type), but the physiological role of these changes is not completely understood. Although it is commonly accepted that only the free fraction of steroids has a biological action, this hypothesis has recently been challenged. Indeed, a change in the total fraction of androgen concentration may have a significant impact on cells (inducing genomic or non-genomic signalling). The purpose of this review, therefore, is to visit the exercise-induced changes in androgen concentrations and emphasize their potential effects on female physiology. Despite some discrepancies in the published studies (generally due to differences in the types and intensities of the exercises studied, in the hormonal status of the group of women investigated and in the methods for androgen determination), exercise is globally able to induce an increase in circulating androgens. This can be observed after both resistance and endurance acute exercises. For chronic exercise/training, the picture is definitely less clear and there are even circumstances where exercise leads to a decrease of circulating androgens. We suggest that those changes have significant impact on female physiology and physical performance. PMID:21142281

  3. What is the best approach to the teenage patient presenting with nonclassical congenital adrenal hyperplasia: should we always treat with glucocorticoids?

    PubMed

    Matthews, Deborah; Cheetham, Tim

    2013-03-01

    Patients with Congenital adrenal hyperplasia due to partial deficiency in the enzyme 21-hydroxylase can present in childhood or adolescence with signs of adrenal androgen excess. Strategies to reduce the impact of androgen excess in females include cosmetic measures as well as antiandrogens and agents such as the combined oral contraceptive pill. Glucocorticoid may not be appropriate straightaway but can be introduced if other measures are ineffective or when pregnancy is planned.

  4. The diurnal patterns of cortisol and dehydroepiandrosterone in relation to intense aerobic exercise in recreationally trained soccer players.

    PubMed

    Labsy, Z; Prieur, F; Le Panse, B; Do, M C; Gagey, O; Lasne, F; Collomp, K

    2013-03-01

    Diurnal patterns of cortisol and dehydroepiandrosterone (DHEA) secretion, the two main peripheral secretory products of the hypothalamic-pituitary-adrenal neuroendocrine stress axis, have been well characterized in rest conditions but not in relation to physical exercise. The purpose of this investigation was therefore to determine the effects of an intense 90-min aerobic exercise on the waking diurnal cortisol and DHEA cycles on three separate days [without exercise, with morning exercise (10:00-11:30 h), and with afternoon exercise (14:00-15:30 h)] in nine recreationally trained soccer players. Saliva samples were collected at awakening, 30 min after awakening, and then every 2 h from 08:00 to 22:00 h. A burst of secretory activity was found for cortisol (p < 0.01) but not for DHEA after awakening. Overall, diurnal decline for both adrenal steroids was observed on resting and exercise days under all conditions. However, there was a significant increase in salivary cortisol concentrations on the morning-exercise and afternoon-exercise days at, respectively, 12:00 h (p < 0.05) and 16:00 h (p < 0.01), versus the other trials. This acute response to exercise was not evident for DHEA. The results of this investigation indicate that 90 min of intense aerobic exercise does not affect the circadian pattern of salivary adrenal steroids in recreationally trained athletes over a 16-h waking period, despite a transitory increase in post-exercise cortisol concentration. Further studies are necessary to determine whether these results are applicable to elite athletes or patients with cortisol or DHEA deficiency.

  5. 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

  6. Hemorrhagic adrenal cyst.

    PubMed

    Cunningham, M D

    1993-05-01

    Adrenal cysts are uncommon. They may be fatal if they hemorrhage and are not rapidly diagnosed. Most adrenal cysts are small and asymptomatic. When they are symptomatic, it is usually because the cyst has enlarged, causing flank discomfort, gastrointestinal complaints, and hemorrhage. Occasionally, a palpable mass may be found. It is thought that hemorrhage occurs secondary to trauma or some toxic or infectious process. The author describes a case in which a previously healthy man had a sudden hemorrhage within a benign adrenal cyst with infarction of the kidney. A discussion of adrenal cysts follows.

  7. 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

  8. Dehydroepiandrosterone (DHEA) restrains intestinal inflammation by rendering leukocytes hyporesponsive and balancing colitogenic inflammatory responses.

    PubMed

    Alves, Vanessa Beatriz Freitas; Basso, Paulo José; Nardini, Viviani; Silva, Angélica; Chica, Javier Emílio Lazo; Cardoso, Cristina Ribeiro de Barros

    2016-09-01

    Dehydroepiandrosterone (DHEA) is a hormone that plays an important role in the modulation of inflammatory responses. However, the precise mechanisms that link the actions of this androgen with protection or susceptibility to inflammatory bowel diseases (IBD) remain uknown. Here we showed that low dose DHEA inhibited proliferation of spleen cells and IFN-у production. The hormone was not toxic to myeloid lineage cells, although it caused necrosis of spleen cells at the intermediate and highest doses in vitro (50 and 100μM). The treatment of C57BL/6 mice with DHEA during colitis induction by dextran sodium sulfate (DSS) led to a reduction in weight loss and clinical signs of disease. There were decreased peripheral blood monocytes on day 6 of DSS exposure and treatment, besides increase in circulating neutrophils in the tissue repair phase. DHEA also led to reduced lamina propria cellularity and restoration of normal colon length. These results were accompanied by decreased expression of IL-6 and TGF-β mRNA, while IL-13 was augmented in the colon on day 6, which was probably related to attenuation of inflammation. There was retention of CD4(+) cells in the spleen after use of DHEA, along with augmented frequency of CD4(+)IL-4(+) cells, decreased CD4(+)IFN-ɣ(+) in spleen and constrained CD4(+)IL-17(+) population in the mesenteric lymph nodes. Moreover, splenocytes of mice treated with DHEA became hyporesponsive, as observed by reduced proliferation after re-stimulation ex-vivo. In conclusion, DHEA modifyies leukocyte activity and balances the exacerbated immune responses which drive local and systemic damages in IBD.

  9. Dehydroepiandrosterone (DHEA) restrains intestinal inflammation by rendering leukocytes hyporesponsive and balancing colitogenic inflammatory responses.

    PubMed

    Alves, Vanessa Beatriz Freitas; Basso, Paulo José; Nardini, Viviani; Silva, Angélica; Chica, Javier Emílio Lazo; Cardoso, Cristina Ribeiro de Barros

    2016-09-01

    Dehydroepiandrosterone (DHEA) is a hormone that plays an important role in the modulation of inflammatory responses. However, the precise mechanisms that link the actions of this androgen with protection or susceptibility to inflammatory bowel diseases (IBD) remain uknown. Here we showed that low dose DHEA inhibited proliferation of spleen cells and IFN-у production. The hormone was not toxic to myeloid lineage cells, although it caused necrosis of spleen cells at the intermediate and highest doses in vitro (50 and 100μM). The treatment of C57BL/6 mice with DHEA during colitis induction by dextran sodium sulfate (DSS) led to a reduction in weight loss and clinical signs of disease. There were decreased peripheral blood monocytes on day 6 of DSS exposure and treatment, besides increase in circulating neutrophils in the tissue repair phase. DHEA also led to reduced lamina propria cellularity and restoration of normal colon length. These results were accompanied by decreased expression of IL-6 and TGF-β mRNA, while IL-13 was augmented in the colon on day 6, which was probably related to attenuation of inflammation. There was retention of CD4(+) cells in the spleen after use of DHEA, along with augmented frequency of CD4(+)IL-4(+) cells, decreased CD4(+)IFN-ɣ(+) in spleen and constrained CD4(+)IL-17(+) population in the mesenteric lymph nodes. Moreover, splenocytes of mice treated with DHEA became hyporesponsive, as observed by reduced proliferation after re-stimulation ex-vivo. In conclusion, DHEA modifyies leukocyte activity and balances the exacerbated immune responses which drive local and systemic damages in IBD. PMID:27263829

  10. Adrenarche in bonobos (Pan paniscus): evidence from ontogenetic changes in urinary dehydroepiandrosterone-sulfate levels.

    PubMed

    Behringer, Verena; Hohmann, Gottfried; Stevens, Jeroen M G; Weltring, Anja; Deschner, Tobias

    2012-07-01

    Adrenarche is characterized by the onset of adrenal secretions of increasing amounts of dehydroepiandrosterone-sulfate (DHEA-S). While the function of adrenarche remains a matter of speculation, evidence suggests that the morphological and physiological changes related to it are restricted to humans and closely related primates. Within the primate order, adrenarche has been described only in humans and chimpanzees, but bonobos, the sister species of chimpanzees, have not yet been studied regarding the early ontogenetic changes such as adrenarche. While bonobos and chimpanzees share many morphological and behavioral characteristics, they differ in a number of behavioral traits, and there is a growing interest in terms of the physiological differences that can be linked to species-specific patterns of social behavior. In this study, we measured urinary DHEA-S levels to determine whether bonobos experience physiological changes that are indicative of adrenarche. We measured DHEA-S in urine using ELISA and analyzed its levels in the samples from 53 bonobos aged 1-18 years. Our results show that bonobos experience an increase in DHEA-S levels after 5 years of age, which is comparable with the patterns observed in humans and chimpanzees. This indicates that bonobos do undergo adrenarche and that the timing of onset is similar to that of the two Pan species. The extraction procedures described in this report demonstrate the use of urine for monitoring ontogenetic changes in DHEA-S excretion. If applicable to other species, the technique would facilitate more research on the evolutionary origin of adrenarche and other developmental processes.

  11. Mechanisms of drug resistance that target the androgen axis in castration resistant prostate cancer (CRPC).

    PubMed

    Penning, Trevor M

    2015-09-01

    Castrate resistant prostate cancer (CRPC) is the fatal-form of prostate cancer and remains androgen dependent. The reactivation of the androgen axis occurs due to adaptive intratumoral androgen biosynthesis which can be driven by adrenal androgens and/or by changes in the androgen receptor (AR) including AR gene amplification. These mechanisms are targeted with P450c17 inhibitors e.g., abiraterone acetate and AR super-antagonists e.g., enzalutamide, respectively. Clinical experience indicates that with either agent an initial response is followed by drug resistance and the patient clinically progresses on these agents. This article reviews the mechanisms of intrinsic and acquired drug resistance that target the androgen axis and how this might be surmounted.

  12. Noncovalent intermolecular interactions between dehydroepiandrosterone and the active site of human dehydroepiandrosterone sulphotransferase: A density functional theory based treatment

    NASA Astrophysics Data System (ADS)

    Astani, Elahe; Heshmati, Emran; Chen, Chun-Jung; Hadipour, Nasser L.; Shekarsaraei, Setareh

    2016-04-01

    A theoretical study was performed to characterize noncovalent intermolecular interactions, especially hydrogen bond (HB), in the active site of enzyme human dehydroepiandrosterone sulphotransferase (SULT2A1/DHEA) using the local (M06-L) and hybrid (M06, M06-2X) meta-GGA functionals of density functional theory (DFT). Results revealed that DHEA is able to form HBs with residues His99, Tyr231, Met137 and Met16 in the active site of the SULT2A1/DHEA. It was found that DHEA interacts with the other residues through electrostatic and Van der Waals interactions.

  13. Immunolocalization of steroidogenic enzymes in equine fetal adrenal glands during mid-late gestation.

    PubMed

    Weng, Qiang; Tanaka, Yumiko; Taniyama, Hiroyuki; Tsunoda, Nobuo; Nambo, Yasuo; Watanabe, Gen; Taya, Kazuyoshi

    2007-10-01

    To elucidate the relationship between steroidogenic hormones and developing adrenal glands, we investigated the immunolocalization of steroidogenic enzymes in equine fetal adrenal glands during mid-late gestation. Fetal adrenal glands were obtained from three horses at 217, 225 and 235 days of gestation. Steroidogenic enzymes were immunolocalized using polyclonal antisera raised against bovine adrenal cholesterol side-chain cleavage cytochrome P450 (P450scc), human placental 3beta-hydroxysteroid dehydrogenase (3betaHSD), porcine testicular 17alpha-hydroxylase cytochrome P450 (P450c17) and human placental aromatase cytochrome P450 (P450arom). Histologically, cortex and medulla cells were clearly observed in the three fetal adrenal gland tissue samples. P450scc and P450c17 were identified in cortex cells close to medulla cells and in some medulla cells in the fetal adrenal glands. P450arom was present in both cortex and medulla cells in the fetal adrenal glands. However, 3betaHSD was not found in any of the equine fetal adrenal gland tissue samples. These results suggest that equine fetal adrenal glands have the ability to synthesize androgen and estrogen, which may play an important physiological role in the development of equine fetal adrenal glands.

  14. A rare adrenal incidentaloma: adrenal schwannoma.

    PubMed

    Adas, Mine; Ozulker, Filiz; Adas, Gokhan; Koc, Bora; Ozulker, Tamer; Sahin, Ilknur Mansuroglu

    2013-01-01

    Adrenal schwannoma is an extremely uncommon cause of incidentaloma. It originates from neural sheath Schwann cells of the adrenal gland. We report the case of a left adrenal schwannoma incidentally discovered in a 32-year-old woman during examination of bloated feeling and stomach ache. The patient was incidentally found to have a left adrenal mass of 9 cm on abdominal ultrasonography. Computed tomography (CT) of the abdomen and [(18)F] fluorodeoxyglucose positron emission tomography (PET) were also performed. Metabolic evaluation was unremarkable. Due to the large size of the tumor, left adrenalectomy was performed. The postoperative course was uneventful. Histological examination established the diagnosis of schwannoma. This diagnosis was supported by immunohistochemistry of S-100 and vimentin positivity. In conclusion, adrenal schwannoma is an extremely rare entity and can grow considerably in size. The present case report emphasizes that clinicians should be aware of the possibility of retroperitoneal schwannoma. Total excision of benign schwannoma is associated with a favorable outcome. To our knowledge, there are case reports of schwannoma with CT and magnetic resonance imaging findings in the literature, although this is the first schwannoma case with PET-CT imaging. PMID:24403879

  15. A Rare Adrenal Incidentaloma: Adrenal Schwannoma

    PubMed Central

    Adas, Mine; Ozulker, Filiz; Adas, Gokhan; Koc, Bora; Ozulker, Tamer; Sahin, Ilknur Mansuroglu

    2013-01-01

    Adrenal schwannoma is an extremely uncommon cause of incidentaloma. It originates from neural sheath Schwann cells of the adrenal gland. We report the case of a left adrenal schwannoma incidentally discovered in a 32-year-old woman during examination of bloated feeling and stomach ache. The patient was incidentally found to have a left adrenal mass of 9 cm on abdominal ultrasonography. Computed tomography (CT) of the abdomen and [18F] fluorodeoxyglucose positron emission tomography (PET) were also performed. Metabolic evaluation was unremarkable. Due to the large size of the tumor, left adrenalectomy was performed. The postoperative course was uneventful. Histological examination established the diagnosis of schwannoma. This diagnosis was supported by immunohistochemistry of S-100 and vimentin positivity. In conclusion, adrenal schwannoma is an extremely rare entity and can grow considerably in size. The present case report emphasizes that clinicians should be aware of the possibility of retroperitoneal schwannoma. Total excision of benign schwannoma is associated with a favorable outcome. To our knowledge, there are case reports of schwannoma with CT and magnetic resonance imaging findings in the literature, although this is the first schwannoma case with PET-CT imaging. PMID:24403879

  16. 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.

  17. Circulating LH, FSH, prolactin, testosterone, delta 4-androstenedione, dehydroepiandrosterone sulfate and cortisol levels in the fetus in late gestation and in newborn male and female lambs.

    PubMed

    Savoie, S; Bourel, B; Hamel, R; Buithieu, M; Jéquier, J C; Bertrand, J; Saez, J M; Collu, R; Ducharme, J R

    1981-01-01

    Gonadotropins, prolactin (PRL), testosterone (T), delta 4-androstenedione, dehydroepiandrosterone sulfate and cortisol (F) levels were determined from 14 days before birth to term in 3 female and 3 male ovine fetuses with a chronically implanted venous catheter, and in the same animals from birth to 72 h of age. In both sexes, plasma gonadotropins and androgens were low throughout the period of study while plasma F increased with gestational age. After birth, plasma gonadotropins and PRL tended to increase progressively with time while PRL concentrations were significantly higher in female than in male lambs. F and T concentrations decreased significantly within the first 12 and 6 h of postnatal life. Higher T values were again observed at 36 h in male lambs. These data indicate that the fetal hypothalamic-pituitary-gonadal axis is relatively quiescent in the last 14 days of gestation but is activated within the first 72 h after birth.

  18. Placental estrogen suppresses cyclin D1 expression in the nonhuman primate fetal adrenal cortex.

    PubMed

    Dumitrescu, Adina; Aberdeen, Graham W; Pepe, Gerald J; Albrecht, Eugene D

    2014-12-01

    We have previously shown that estrogen selectively suppresses growth of the fetal zone of the baboon fetal adrenal cortex, which produces the C19-steroid precursors, eg, dehydroepiandrosterone sulfate, which are aromatized to estrogen within the placenta. In the present study, we determined whether fetal adrenal expression of cell cycle regulators are altered by estrogen and thus provide a mechanism by which estrogen regulates fetal adrenocortical development. Cyclin D1 mRNA levels in the whole fetal adrenal were increased 50% (P < .05), and the number of cells in the fetal adrenal definitive zone expressing cyclin D1 protein was increased 2.5-fold (P < .05), whereas the total number of cells in the fetal zone and fetal serum dehydroepiandrosterone sulfate levels were elevated 2-fold (P < .05) near term in baboons in which fetal serum estradiol levels were decreased by 95% (P < .05) after maternal administration of the aromatase inhibitor letrozole and restored to normal by concomitant administration of letrozole plus estradiol throughout second half of gestation. However, fetal adrenocortical expression of cyclin D2, the cyclin-dependent kinase (Cdk)-2, Cdk4, and Cdk6, and Cdk regulatory proteins p27(Kip1) and p57(Kip2) were not changed by letrozole or letrozole plus estradiol administration. We suggest that estrogen controls the growth of the fetal zone of the fetal adrenal by down-regulating cyclin D1 expression and thus proliferation of progenitor cells within the definitive zone that migrate to the fetal zone. We propose that estrogen restrains growth and function of the fetal zone via cyclin D1 to maintain estrogen levels in a physiological range during primate pregnancy.

  19. Placental Estrogen Suppresses Cyclin D1 Expression in the Nonhuman Primate Fetal Adrenal Cortex*

    PubMed Central

    Dumitrescu, Adina; Aberdeen, Graham W.; Pepe, Gerald J.

    2014-01-01

    We have previously shown that estrogen selectively suppresses growth of the fetal zone of the baboon fetal adrenal cortex, which produces the C19-steroid precursors, eg, dehydroepiandrosterone sulfate, which are aromatized to estrogen within the placenta. In the present study, we determined whether fetal adrenal expression of cell cycle regulators are altered by estrogen and thus provide a mechanism by which estrogen regulates fetal adrenocortical development. Cyclin D1 mRNA levels in the whole fetal adrenal were increased 50% (P < .05), and the number of cells in the fetal adrenal definitive zone expressing cyclin D1 protein was increased 2.5-fold (P < .05), whereas the total number of cells in the fetal zone and fetal serum dehydroepiandrosterone sulfate levels were elevated 2-fold (P < .05) near term in baboons in which fetal serum estradiol levels were decreased by 95% (P < .05) after maternal administration of the aromatase inhibitor letrozole and restored to normal by concomitant administration of letrozole plus estradiol throughout second half of gestation. However, fetal adrenocortical expression of cyclin D2, the cyclin-dependent kinase (Cdk)-2, Cdk4, and Cdk6, and Cdk regulatory proteins p27Kip1 and p57Kip2 were not changed by letrozole or letrozole plus estradiol administration. We suggest that estrogen controls the growth of the fetal zone of the fetal adrenal by down-regulating cyclin D1 expression and thus proliferation of progenitor cells within the definitive zone that migrate to the fetal zone. We propose that estrogen restrains growth and function of the fetal zone via cyclin D1 to maintain estrogen levels in a physiological range during primate pregnancy. PMID:25247468

  20. Adrenal insufficiency: diagnosis and management.

    PubMed

    Munver, Ravi; Volfson, Ilya A

    2006-01-01

    Adrenal insufficiency is a disorder characterized by hypoactive adrenal glands resulting in insufficient production of the hormones cortisol and aldosterone by the adrenal cortex. This disorder may develop as a primary failure of the adrenal cortex or be secondary to an abnormality of the hypothalamic-pituitary axis. Patients with adrenal insufficiency often are asymptomatic or they may present with fatigue, muscle weakness, weight loss, low blood pressure, and sometimes darkening of the skin. The presentation of adrenal insufficiency varies dramatically and poses a major diagnostic dilemma. This review focuses on the diagnosis and treatment of primary and secondary adrenal insufficiency.

  1. The effects of androstenediol and dehydroepiandrosterone on the course and cytokine profile of tuberculosis in BALB/c mice.

    PubMed Central

    Hernandez-Pando, R; De La Luz Streber, M; Orozco, H; Arriaga, K; Pavon, L; Al-Nakhli, S A; Rook, G A

    1998-01-01

    Immunity to Mycobacterium tuberculosis requires a T helper 1 (Th1) cytokine balance accompanied by tumour necrosis factor-alpha (TNF-alpha), and activated macrophages. These facets of the immune response are sensitive to suppression by glucocorticoids (GC), which can reactivate and exacerbate tuberculosis in man and animals. Dehydroepiandrosterone (DHEA) and its derivative, 3beta,17beta androstenediol (AED), are reported to have antiglucocorticoid properties in vivo. We therefore investigated the effects of predetermined optimal doses of these compounds, on the course of pulmonary tuberculosis in an established model in BALB/c mice in which an early phase of Th1-mediated response accompanied by adrenal hyperplasia, is followed by a switch to Th2, progressive loss of TNF-alpha expression and disease progression. Both compounds were protective, particularly AED which caused a fall in bacterial counts and prolonged survival. These effects correlated with the appearance within 3 days of cellular infiltrates rich in cells expressing interleukin-2 (IL-2), IL-1alpha and TNF-alpha, and with partial suppression of the switch to IL-4 producing cells that occurred in controls. AED also caused enhanced development of granulomas at 14 days, and persistence of granuloma formation to 120 days, with a corresponding suppression of areas affected by pneumonia. Much of the therapeutic effect of AED and DHEA was obtained by treating for only the first 3 weeks, which is the phase of adrenal hyperplasia. These results suggest that the ratio of GC to anti-GC steroids may play a role in the pathogenesis of tuberculosis, and further investigation could lead to novel treatment strategies. Images Figure 6 PMID:9824481

  2. The effect of pulsed electromagnetic fields and dehydroepiandrosterone on viability and osteo-induction of human mesenchymal stem cells.

    PubMed

    Kaivosoja, Emilia; Sariola, Veikko; Chen, Yan; Konttinen, Yrjö T

    2015-01-01

    The hypothesis of this work was that human bone marrow-derived mesenchymal stem cells (MSCs) are regulated by pulsed electromagnetic fields (PEMFs) and by intracrine conversion of an adrenal prohormone to dihydrotestosterone. The effect of PEMF and dehydroepiandrosterone (DHEA) on viability and osteogenic differentiation of human MSCs and on the viability of osteoblastic SaOS-2 cells was evaluated. It was found that PEMF promoted the viability rate of both cell types, whereas DHEA decreased the viability rate in a concentration-dependent manner. PEMF did not have major effects on osteo-induction at this low seeding density level (3000 cells/cm(2) ). Instead, DHEA, after MSC-mediated and 5α-reductase-dependent conversion to dihydrotestosterone, clearly promoted the osteo-induction of MSCs induced with β-glyserophosphate, ascorbate and dexamethasone. Alkaline phosphatase (ALP), SMAD1, RUNX2, osteopontin (OP) and osteocalcin (OC) RNA levels were increased and alizarin red S- and hydroxyapatite-specific OsteoImage(TM) stainings disclosed a promoted mineralization process. In addition, DHEA increased OP and OC mRNA levels of non-induced MSCs. A sequential use of mitogenic PEMF early during the fracture healing, followed by later administration of DHEA with osteogenic differentiating effect, might be worth subjecting to a randomized clinical trial.

  3. Elevated serum dehydroepiandrosterone sulfate levels in practitioners of the Transcendental Meditation (TM) and TM-Sidhi programs.

    PubMed

    Glaser, J L; Brind, J L; Vogelman, J H; Eisner, M J; Dillbeck, M C; Wallace, R K; Chopra, D; Orentreich, N

    1992-08-01

    Serum dehydroepiandrosterone sulfate (DHEA-S) levels were measured in 270 men and 153 women who were experienced practitioners of the Transcendental Meditation (TM) and TM-Sidhi programs, mental techniques practiced twice daily, sitting quietly with the eyes closed. These were compared according to sex and 5-year age grouping to 799 male and 453 female nonmeditators. The mean DHEA-S levels in the TM group were higher in all 11 of the age groups measured in women and in 6 of 7 5-year age groups over 40 in men. There were no systematic differences in younger men. Simple regression using TM-group data revealed that this effect was independent of diet, body mass index, and exercise. The mean TM-group levels measured in all women and in the older men were generally comparable to those of nonmeditator groups 5 to 10 years younger. These findings suggest that some characteristics of TM practitioners are modifying the age-related deterioration in DHEA-S secretion by the adrenal cortex.

  4. [Mechanisms of adrenal embryogenesis].

    PubMed

    Barinov, E F; Sulaeva, O N

    2001-01-01

    The aim of this vie is to discuss the general principles of prenatal development of adrenal gland. On the basis of spatial-temporal heterogenity of structural particularites of fetal adrenal cortex, spectrum steroidogenic enzymes and secreting hormones expression in adrenocorticocytes, regulation of proliferation and differentiation processes mechanisms, authors discuss adrenal morphogenesis in three periods of gestation. It was noted the close relationship between placenta development and hypothalamo-pituitary-adrenocortical system formation with specification in each gestation period. Adrenal embryogenesis accompanied by remodeling of structural, functional and biochemical properties of parenchimal-stromal elements of fetal organ. Definitive zonation formation determined by morphogens: ACTH, renal and intraadrenal angiotensin II, estrogens, prostaglandines and other. The action of these factors realization is due to immediately and thought growth factor system (IGF-I, IGF-II, EGF, bFGF), working as paracrine amplificators of morphogenetic signals and activators of transcriptional factors--c-fos and c-jun.

  5. Acute adrenal crisis

    MedlinePlus

    ... condition that occurs when there is not enough cortisol. This is a hormone produced by the adrenal ... parts. The outer portion, called the cortex, produces cortisol. This is an important hormone for controlling blood ...

  6. Alpha-human atrial natriuretic polypeptide (. cap alpha. -hANP) specific binding sites in bovine adrenal gland

    SciTech Connect

    Higuchi, K.; Nawata, H.; Kato, K.I.; Ibayashi, H.; Matsuo, H.

    1986-06-13

    The effects of synthetic ..cap alpha..-human atrial natriuretic polypeptide (..cap alpha..-hANP) on steroidogenesis in bovine adrenocortical cells in primary monolayer culture were investigated. ..cap alpha..-hANP did not inhibit basal aldosterone secretion. ..cap alpha..-hANP induced a significant dose-dependent inhibition of basal levels of cortisol and dehydroepiandrosterone (DHEA) secretion and also of aCTH (10/sup -8/M)-stimulated increases in aldosterone, cortisol and DHEA secretion. Visualization of (/sup 125/I) ..cap alpha..-hANP binding sites in bovine adrenal gland by an in vitro autoradiographic technique demonstrated that these sites were highly localized in the adrenal cortex, especially the zona glomerulosa. These results suggest that the adrenal cortex may be a target organ for direct receptor-mediated actions of ..cap alpha..-hANP.

  7. 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.

  8. Effects of dehydroepiandrosterone and its sulfate on brain tissue in culture and on memory in mice.

    PubMed

    Roberts, E; Bologa, L; Flood, J F; Smith, G E

    1987-03-17

    Low concentrations of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) enhanced neuronal and glial survival and/or differentiation in dissociated cultures of 14-day mouse embryo brain. Posttrial intracisternal injection into the brains of mice undergoing active avoidance training alleviated amnesia and enhanced long-term memory. By minimizing degenerative changes in injured nerve tissue and facilitating plastic changes, DHEA and DHEAS may be of use in treatment of neurodegenerative and memory disorders in man.

  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. [Adrenal pseudocyst; a case report].

    PubMed

    Minagawa, Tomonori; Nishizawa, Shuji; Nakayama, Tsuyoshi; Okaneya, Toshikazu

    2007-02-01

    We report a case of adrenal pseudocyst. A 35-year-old woman presented with palpation of right upper abdominal mass without tenderness. Abdominal computed tomographic scan showed a right retroperitoneal cystic mass 20 cm in diameter. The patient underwent complete resection of the mass, including the normal adrenal gland. The cyst contained 3100 ml of dark brown thrombotic liquid. Histopathological examination revealed adrenal pseudocyst with a thick figrocollagenous wall. The normal adrenal gland was compressed by the wall. Adrenal pseudocyst is a rare disease. The mechanisms of adrenal pseudocyst formation and their expanding nature are discussed.

  11. Androgens and the breast.

    PubMed

    Dimitrakakis, Constantine; Bondy, Carolyn

    2009-01-01

    Androgens have important physiological effects in women while at the same time they may be implicated in breast cancer pathologies. However, data on the effects of androgens on mammary epithelial proliferation and/or breast cancer incidence are not in full agreement. We performed a literature review evaluating current clinical, genetic and epidemiological data regarding the role of androgens in mammary growth and neoplasia. Epidemiological studies appear to have significant methodological limitations and thus provide inconclusive results. The study of molecular defects involving androgenic pathways in breast cancer is still in its infancy. Clinical and nonhuman primate studies suggest that androgens inhibit mammary epithelial proliferation and breast growth while conventional estrogen treatment suppresses endogenous androgens. Abundant clinical evidence suggests that androgens normally inhibit mammary epithelial proliferation and breast growth. Suppression of androgens using conventional estrogen treatment may thus enhance estrogenic breast stimulation and possibly breast cancer risk. Addition of testosterone to the usual hormone therapy regimen may diminish the estrogen/progestin increase in breast cancer risk but the impact of this combined use on mammary gland homeostasis still needs evaluation.

  12. Androgens and the breast

    PubMed Central

    2009-01-01

    Androgens have important physiological effects in women while at the same time they may be implicated in breast cancer pathologies. However, data on the effects of androgens on mammary epithelial proliferation and/or breast cancer incidence are not in full agreement. We performed a literature review evaluating current clinical, genetic and epidemiological data regarding the role of androgens in mammary growth and neoplasia. Epidemiological studies appear to have significant methodological limitations and thus provide inconclusive results. The study of molecular defects involving androgenic pathways in breast cancer is still in its infancy. Clinical and nonhuman primate studies suggest that androgens inhibit mammary epithelial proliferation and breast growth while conventional estrogen treatment suppresses endogenous androgens. Abundant clinical evidence suggests that androgens normally inhibit mammary epithelial proliferation and breast growth. Suppression of androgens using conventional estrogen treatment may thus enhance estrogenic breast stimulation and possibly breast cancer risk. Addition of testosterone to the usual hormone therapy regimen may diminish the estrogen/progestin increase in breast cancer risk but the impact of this combined use on mammary gland homeostasis still needs evaluation. PMID:19889198

  13. Circulating gonadal and adrenal steroids in amyotrophic lateral sclerosis: possible markers of susceptibility and outcome.

    PubMed

    Gargiulo-Monachelli, G M; Sivori, M; Meyer, M; Sica, R E P; De Nicola, A F; Gonzalez-Deniselle, M C

    2014-06-01

    Although changes of circulating steroids have been reported in patients with sporadic amyotrophic lateral sclerosis (ALS), a full comparison of the adrenal and gonadal steroid profile between control subjects and ALS patients is lacking. Considering that respiratory failure is the most frequent cause of death in ALS, we looked into whether a relationship emerged between circulating steroids and respiratory parameters. Serum levels of adrenal and gonadal steroids were measured in 52 age- and gender-matched subjects (28 ALS and 24 controls) using radioimmunoassay techniques. We also evaluated respiratory parameters in ALS patients, including forced vital capacity (FVC), maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP). We found increased levels of testosterone in female ALS patients compared to healthy female subjects. Furthermore, control subjects showed a significant decline of testosterone, dehydroepiandrosterone and its sulfate, and a borderline decline of progesterone with increasing age. Instead, testosterone did not decline with increasing age in ALS patients. We also found that the dehydroepiandrosterone sulfate/cortisol ratio was positively associated with FVC, MIP, and MEP. Moreover, ALS patients showing higher testosterone levels and lower progesterone/free testosterone ratio presented a more rapid worsening of the monthly FVC. In conclusion, first our study revealed a differential steroid profile with age and gender in ALS patients relative to controls. Second, we demonstrated an association between some steroids and their ratios with respiratory function and disease progression. Thus, we hypothesize that the endogenous steroid profile could be a marker of susceptibility and prognosis in ALS patients.

  14. Enhanced cutaneous bioavailability of dehydroepiandrosterone mediated by nano-encapsulation.

    PubMed

    Badihi, Amit; Debotton, Nir; Frušić-Zlotkin, Marina; Soroka, Yoram; Neuman, Rami; Benita, Simon

    2014-09-10

    Polymeric nanocarriers, especially nanospheres (NSs) and nanocapsules (NCs), can promote the penetration of their cargo through the skin barrier, towards improved cutaneous bioavailability. Dehydroepiandrosterone (DHEA), an endogenous hormone exhibiting poor aqueous solubility, was shown to be effective in modulating skin-aging processes following topical application. In this study, we designed adequate DHEA preparations, in an attempt to enable local delivery of the active ingredient to the viable skin layers. In addition, the potential efficiency of DHEA NCs on dermal collagen synthesis was evaluated. Cryo-TEM observations and thermal analysis indicated that DHEA was successfully incorporated within a stable NC-based delivery system. Moreover, higher [(3)H]-DHEA levels were recorded in the viable skin layers following different incubation periods of NCs on excised pig skin specimens as compared to DHEA oil solution (free molecule). Furthermore, significantly higher (4-fold) skin flux values were observed for the DHEA NCs as compared to the values elicited by the oil control solution. Finally, collagen synthesis in human skin organ culture, assessed by the incorporation of [(3)H]-proline, was up to 42% higher for DHEA NCs 48h post-topical application than for the untreated specimens. Overall, these results suggest that poly lactic-co-glycolic acid (PLGA)-based NCs have promising potential to be used topically for various skin disorders. PMID:24956487

  15. Dehydroepiandrosterone Attenuates Cocaine-Seeking Behaviour Independently of Corticosterone Fluctuations.

    PubMed

    Maayan, R; Hirsh, L; Yadid, G; Weizman, A

    2015-11-01

    The neurosteroid dehydroepiandrosterone (DHEA) is involved in the pathophysiology of several psychiatric disorders, including cocaine addiction. We have previously shown that DHEA attenuates cocaine-seeking behaviour, and also that DHEA decreases corticosterone (CORT) levels in plasma and the prefrontal cortex. Previous studies have found that rats demonstrate cocaine-seeking behaviour only when the level of CORT reaches a minimum threshold. In the present study, we investigated whether the attenuating effect of DHEA on cocaine seeking is a result of it reducing CORT levels rather than a result of any unique neurosteroid properties. Rats received either daily DHEA injections (2 mg/kg, i.p.) alone, daily DHEA (2 mg/kg, i.p.) with CORT infusion (to maintain stable basal levels of CORT; 15 mg/kg, s.c.) or vehicle (i.p.) as control, throughout self-administration training and extinction sessions. We found that both DHEA-treated and DHEA + CORT-treated groups showed a significantly lower number of active lever presses compared to controls throughout training and extinction sessions, as well as at cocaine-primed reinstatement. DHEA-treated rats showed lower CORT levels throughout the experimental phases compared to DHEA + CORT-treated and control rats. Additionally, we show that DHEA administered to cocaine-trained rats throughout extinction sessions, or immediately before reinstatement, attenuated cocaine seeking. These findings indicate that DHEA attenuates cocaine-seeking behaviour independently of fluctuations in CORT levels.

  16. Enhanced cutaneous bioavailability of dehydroepiandrosterone mediated by nano-encapsulation.

    PubMed

    Badihi, Amit; Debotton, Nir; Frušić-Zlotkin, Marina; Soroka, Yoram; Neuman, Rami; Benita, Simon

    2014-09-10

    Polymeric nanocarriers, especially nanospheres (NSs) and nanocapsules (NCs), can promote the penetration of their cargo through the skin barrier, towards improved cutaneous bioavailability. Dehydroepiandrosterone (DHEA), an endogenous hormone exhibiting poor aqueous solubility, was shown to be effective in modulating skin-aging processes following topical application. In this study, we designed adequate DHEA preparations, in an attempt to enable local delivery of the active ingredient to the viable skin layers. In addition, the potential efficiency of DHEA NCs on dermal collagen synthesis was evaluated. Cryo-TEM observations and thermal analysis indicated that DHEA was successfully incorporated within a stable NC-based delivery system. Moreover, higher [(3)H]-DHEA levels were recorded in the viable skin layers following different incubation periods of NCs on excised pig skin specimens as compared to DHEA oil solution (free molecule). Furthermore, significantly higher (4-fold) skin flux values were observed for the DHEA NCs as compared to the values elicited by the oil control solution. Finally, collagen synthesis in human skin organ culture, assessed by the incorporation of [(3)H]-proline, was up to 42% higher for DHEA NCs 48h post-topical application than for the untreated specimens. Overall, these results suggest that poly lactic-co-glycolic acid (PLGA)-based NCs have promising potential to be used topically for various skin disorders.

  17. 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 ...

  18. Targeted overexpression of androgen receptor with a liver-specific promoter in transgenic mice.

    PubMed Central

    Chatterjee, B; Song, C S; Jung, M H; Chen, S; Walter, C A; Herbert, D C; Weaker, F J; Mancini, M A; Roy, A K

    1996-01-01

    The rodent liver displays marked age- and sex-dependent changes in androgen sensitivity due to the sexually dimorphic and temporally programmed expression of the androgen receptor (AR) gene. We have altered this normal phenotype by constitutive overexpression of the rat AR transgene in the mouse liver by targeting it via the human phenylalanine hydroxylase (hPAH) gene promoter. These transgenic animals in their heterozygous state produce an approximately 30-fold higher level of the AR in the liver as compared with the nontransgenic control. Androgen inactivation via sulfonation of the hormone by dehydroepiandrosterone sulfotransferase (DST), an androgen-repressible enzyme, also contributes to the age- and sex-dependent regulation of hepatic androgen sensitivity. DST has a broad range of substrate specificity and is responsible for the age- and sex-specific activation of certain polycyclic aromatic hepatocarcinogens as well, by converting them to electrophilic sulfonated derivatives. In the transgenic female, the hepatic expression of DST was approximately 4-fold lower than in normal females, a level comparable to that in normal males. The hPAH-AR mice will serve as a valuable model for studying the sex- and age-invariant expression of liver-specific genes, particularly those involved in the activation of environmental hepatocarcinogens such as the aromatic hydrocarbons. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:8570624

  19. [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.

  20. Genetics of adrenal tumors.

    PubMed

    Opocher, G; Schiavi, F; Cicala, M V; Patalano, A; Mariniello, B; Boaretto, F; Zovato, S; Pignataro, V; Macino, B; Negro, I; Mantero, F

    2009-06-01

    The impact of genetics and genomics on clinical medicine is becoming more and more important. Endocrinology pioneered the development of molecular medicine, but also the study of adrenal tumors had a great impact in this field. Particularly important was the detection of genetics of tumors derived from the adrenal medulla, as well as that of those derived from the sympathetic and parasympathetic paraganglia. The identification of mutations in one of the several pheochromocytoma/paraganglioma susceptibility genes may indicate a specific clinical management drive. Less well understood is the genetics of adrenal cortex tumors, in particular adrenocortical carcinoma, a rare and particularly aggressive disease. There are only a few examples of hereditary transmission of adrenocortical carcinoma, but the analysis of low penetrance genes by genome wide association study may enable us to discover new genetic mechanisms responsible for adrenocortical-derived tumors. PMID:19471236

  1. 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

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

    PubMed

    Builes-Montaño, Carlos Esteban; 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.

  3. 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

  4. Micropenis and congenital adrenal hypoplasia.

    PubMed

    Bourgeois, M J; Jones, B; Waagner, D C; Dunn, D

    1989-01-01

    Micropenis is often an early sign of congenital hypopituitarism. It has also been associated with congenital adrenal hypoplasia in infants with anencephaly and pituitary agenesis. This report is on two infants with micropenis and congenital adrenal hypoplasia. One presented with a similar clinical course and postmortem findings to previously reported cases of adrenal hypoplasia and pituitary agenesis. The other patient represents the first reported case of an infant with micropenis and congenital adrenal hypoplasia in the absence of pituitary agenesis. The histologic patterns of adrenal hypoplasia, as well as the etiologic and clinical implications of its association with micropenis, are discussed.

  5. 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 ...

  6. Low Levels of Dehydroepiandrosterone Sulfate in Younger Burnout Patients

    PubMed Central

    Lennartsson, Anna-Karin; Theorell, Töres; Kushnir, Mark M.; Jonsdottir, Ingibjörg H.

    2015-01-01

    Objective Dehydroepiandrosterone sulphate (DHEA-s) is an anabolic protective hormone of importance for maintenance of health. DHEA-s levels peak in young adults and decline thereafter with age. DHEA-s has previously been shown to be lower in individuals reporting prolonged stress. This study investigates DHEA-s levels in patients with clinical burnout, a disorder caused by long-term psychosocial stress. Methods 122 patients (51% men) and 47 controls (51% men) in the age 25–54 years were included in the study. DHEA-s levels were compared between patients and controls in the whole sample and within each of the three 10-year-interval age groups. Results In the youngest age group (25–34 years), DHEA-s levels were on average 25% lower in the patients (p = 0.006). The differences in DHEA-s levels between patients and controls were more pronounced among female than male participants (on average 32% and 13% lower, respectively). There were no differences in DHEA-s levels between patients and controls in the age group 35–44 years (p = 0.927) or 45–54 years (p = 0.897) or when analyzing all age groups together (p = 0.187). Conclusion The study indicates that levels of the health promoting “youth” hormone DHEA-s are low in younger burnout patients. The fact that younger adults have much higher DHEA-s levels and more pronounced inter-subject variability in DHEA-s levels than older individuals might explain why burnout status differentiates patients from controls only among the youngest patients included in this study. PMID:26441131

  7. 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.

  8. Sources of variation in plasma corticosterone and dehydroepiandrosterone in the male northern cardinal (Cardinalis cardinalis): II. Effects of urbanization, food supplementation and social stress.

    PubMed

    Wright, Sarah; Fokidis, H Bobby

    2016-09-01

    Perturbations in an organism's environment can induce significant shifts in hormone secretory patterns. In this context, the glucocorticoid (GC) steroids secreted by the adrenal cortex have received much attention from ecologists and behaviorists due to their role in the vertebrate stress response. Adrenal GCs, such as corticosterone (CORT), are highly responsive to instability in environmental and social conditions. However, little is understood about how adrenal dehydroepiandrosterone (DHEA) is influenced by changing conditions. We conducted field experiments to determine how circulating CORT and DHEA vary during restraint stress in the male northern cardinals (Cardinalis cardinalis). Specifically, we examined how four different changes in the physical (urbanization and food availability) and social (territorial conflict, distress of a mate) environment affect CORT and DHEA levels. The majority of cardinals responded to restraint stress by increasing and decreasing CORT and DHEA, respectively, however this depended on sampling context. Cardinals sampled from urban habitats had both lower initial and restraint stress CORT concentrations, but a comparable DHEA pattern to those sampled from a forest. Supplementing food to territorial males did not alter circulating initial DHEA or CORT concentrations nor did it change the response to restraint stress when compared to unsupplemented controls. Exposing cardinals to varying durations of song playback, which mimics a territorial intrusion, did not affect CORT levels, but did attenuate the DHEA response to restraint stress. Examining a larger dataset of males captured before, after or at the same time as their female mate, allowed us to address how the stress of a captured mate affected the male's CORT and DHEA response. Males showed elevated initial and restraint CORT and DHEA when their female mate was captured first. Taken together, these data demonstrate that both CORT and DHEA secretion patterns depends on

  9. Immunological Studies on Adrenal Glands

    PubMed Central

    Milgrom, Felix; Witebsky, Ernest

    1962-01-01

    Rabbits injected with a bovine adrenal suspension incorporated into Freund adjuvants produced antibodies reacting in a variety of serological tests with extracts of bovine adrenals as well as with extracts of other bovine organs. The double diffusion gel precipitation procedure and absorption experiments revealed that part of these antibodies were specific for adrenal only. In immunoelectrophoretic analysis the adrenal-specific reaction appeared as a line on the anodal part of the electrophoretic field. When extraction was performed at 100° and the extracts autoclaved at 120°, the adrenal-specific antigen remained unaltered, whereas all but one of the non-adrenal-specific antigens (i.e. antigens shared by other bovine organs) were destroyed. The adrenal-specific antigen was localized predominantly, if not exclusively, in the medulla. A similar or identical antigen was found in the adrenals of sheep but not in those of any other species tested. The adrenal-specific antigen was precipitated by ethanol at 72 per cent concentration; it was not destroyed by 90 per cent phenol extraction. Re-dissolved ethanol precipitate of boiled bovine adrenal extract incorporated into Freund adjuvants elicited production of adrenal-specific antibodies when injected into rabbits. ImagesFIG. 2FIG. 3FIG. 4FIG. 5FIG. 8 PMID:14473880

  10. Congenital Adrenal Hyperplasia and Schmid Metaphyseal Chondrodysplasia in a Child

    PubMed Central

    Khorasani, Efat; Vakili, Rahim

    2016-01-01

    Congenital adrenal hyperplasia (CAH) is a group of hereditary diseases, which are autosomal recessive. CAH occurs due to defect in one of the cortisol coding genes and often clinically presents itself with signs of androgen overproduction. In this article, we report a case of CAH and Schmid metaphyseal dysplasia. Our literature review indicated that this report is the first attempt on CYP11B1 and Schmid dysplasia in a child. The specific diagnosis of 11-β-hydroxylase deficiency can be determined using high basal levels of deoxycorticosterone and/or 11-deoxycortisol serums. PMID:26722148

  11. Perspectives on the relationship of adrenal steroids to rheumatoid arthritis.

    PubMed

    Masi, Alfonse T; Chatterton, Robert T; Aldag, Jean C; Malamet, Raymond L

    2002-06-01

    An expanded model of RA is presented that incorporates cumulative multifactorial processes operating over a prolonged physiological phase prior to initial clinical manifestations. During this phase, progressive imbalances in the homeostasis of core neuroendocrine, immunological, and microvascular systems are believed to occur. Normal adrenal function plays an essential role in helping to maintain homeostasis of core systems in health. In RA, chronic adrenal hypocompetence is suspected to occur in a minority subset of females who have younger clinical onset and males who have associated low serum testosterone levels. Chronic, relative glucocorticoid insufficiency is believed to contribute to development of inflammatory manifestations in RA patients. Androgenic deficiencies, particularly of gonadal origin in males, may also contribute to RA, particularly its decreased anabolic features. Precise influences of hypocompetent adrenal steroid function on long-term modeling of the immunological compartment and control of microvascular activation processes are not well understood. These complex mechanisms need to be elucidated for better understanding of the physiopathogenesis of RA. Nevertheless, at a clinical level, sufficient data are currently available to endorse further controlled studies of early clinical onset patients and prospective investigations to determine more definitively the roles of adrenal (and gonadal) steroids in subsets of RA patients and unaffected susceptible persons in the population.

  12. Synthesis of 16 alpha-3H androgen and estrogen substrates for 16 alpha-hydroxylase.

    PubMed

    Cantineau, R; Kremers, P; De Graeve, J; Cornelis, A; Laszlo, P; Gielen, J E; Lambotte, R

    1981-02-01

    The synthesis of 16 alpha-3H androgens and estrogens is described. 1-(3H)-Acetic acid in the presence of zinc dust reacts with 16 alpha-bromo-17-ketosteroids to produce 16 alpha-3H-17-ketosteroids. This chemical reaction was used to prepare 16 alpha-3H-dehydroepiandrosterone (I) and 16 alpha-3H-estrone acetate (XI) from 16 alpha-bromo-dehydroepiandrosterone (X) and from 16 alpha-bromo-estrone acetate (XII), respectively. Using appropriate microbiological techniques, it was possible to convert these radiolabelled substrates into 16 alpha-3H-androstenedione (II) and 16 alpha-3H-estradiol-17 beta (VII). 16 alpha-3H-Estrone (VI) was obtained by the chemical hydrolysis of 16 alpha-3H-estrone acetate. The label distribution as determined by microbiological 16 alpha-hydroxylations indicated a specific labelling of 77% for androgens and 65% for estrogens in the 16 alpha position. These substrates can be used for measuring the 16 alpha hydroxylase activity, an important step in the biosynthesis of estriol (VIII) and estetrol (IX). PMID:7013160

  13. 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

  14. Ovarian overproduction of androgens

    MedlinePlus

    ... the body's testosterone. Tumors of the ovaries and polycystic ovary syndrome (PCOS) can both cause too much androgen production. ... come back after they have been removed. In polycystic ovary syndrome, these things can reduce symptoms caused by high ...

  15. Effects of long-term simvastatin treatment on testicular and adrenal steroidogenesis in hypercholesterolemic patients.

    PubMed

    Bernini, G P; Argenio, G F; Gasperi, M; Vivaldi, M S; Franchi, F; Salvetti, A

    1994-04-01

    Simvastatin is an inhibitor of 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase, the key enzyme in the synthesis of cholesterol, recently introduced in the therapy of hypercholesterolemic patients. Cholesterol is the precursor of the biosynthesis of steroid hormones; thus, a reduction of the availability of cholesterol in the adrenal and testicular cells may reduce the synthesis of corticosteroids and androgens. To establish whether chronic therapy with simvastatin interferes with the integrity of the hypothalamic-pituitary-adrenal axis and with the adrenal and testicular reserve, we administered simvastatin orally in a single-day 10 mg dose for 6 months in 8 mildly hypercholesterolemic male patients. At weeks 0, 6 and 24 of treatment we evaluated the lipids, the activity of the hypothalamic-pituitary-adrenal axis by means of the Corticotropin-Releasing Hormone (CRH) test, the adrenal reserve by means of the Corticotropin rapid test and, finally, the testicular reserve by means of the Human Chorionic Gonadotropin (HCG) test. Total cholesterol and LDL-cholesterol were significantly reduced by Simvastatin, while the HDL-cholesterol and triglycerides did not change significantly. The hormonal responses to CRH, ACTH and HCG tests at weeks 6 and 24 of treatment were comparable to those obtained in basal conditions. We conclude that Simvastatin, while effective in reducing total and LDL-cholesterol in hypercholesterolemic male patients, did not interfere with hypothalamic-pituitary-adrenal axis activity or with basal and stimulated adrenal and testicular steroidogenesis.

  16. Modulation of Receptor Phosphorylation Contributes to Activation of Peroxisome Proliferator Activated Receptor α by Dehydroepiandrosterone and Other Peroxisome Proliferators

    PubMed Central

    Tamasi, Viola; Miller, Kristy K. Michael; Ripp, Sharon L.; Vila, Ermin; Geoghagen, Thomas E.; Prough, Russell A.

    2008-01-01

    Dehydroepiandrosterone (DHEA), a C19 human adrenal steroid, activates peroxisome proliferator-activated receptor α (PPARα) in vivo but does not ligand-activate PPARα in transient transfection experiments. We demonstrate that DHEA regulates PPARα action by altering both the levels and phosphorylation status of the receptor. Human hepatoma cells (HepG2) were transiently transfected with the expression plasmid encoding PPARα and a plasmid containing two copies of fatty acyl coenzyme oxidase (FACO) peroxisome-proliferator activated receptor responsive element consensus oligonucleotide in a luciferase reporter gene. Nafenopin treatment increased reporter gene activity in this system, whereas DHEA treatment did not. Okadaic acid significantly decreased nafenopin-induced reporter activity in a concentration-dependent manner. Okadaic acid treatment of primary rat hepatocytes decreased both DHEA- and nafenopin-induced FACO activity in primary rat hepatocytes. DHEA induced both PPARα mRNA and protein levels, as well as PP2A message in primary rat hepatocytes. Western blot analysis showed that the serines at positions 12 and 21 were rapidly dephosphorylated upon treatment with DHEA and nafenopin. Results using specific protein phosphatase inhibitors suggested that protein phosphatase 2A (PP2A) is responsible for DHEA action, and protein phosphatase 1 might be involved in nafenopin induction. Mutation of serines at position 6, 12, and 21 to an uncharged alanine residue significantly increased transcriptional activity, whereas mutation to negative charged aspartate residues (mimicking receptor phosphorylation) decreased transcriptional activity. DHEA action involves induction of PPARα mRNA and protein levels as well as increased PPARα transcriptional activity through decreasing receptor phosphorylation at serines in the AF1 region. PMID:18079279

  17. Genetic disorders involving adrenal development.

    PubMed

    Lin, Lin; Ferraz-de-Souza, Bruno; Achermann, John C

    2007-01-01

    The past decade has seen significant advances in our understanding of the genetic aetiology of several forms of adrenal failure that present in infancy or childhood. Several of these disorders affect adrenal development and are termed 'adrenal hypoplasia'. These conditions can be broadly divided into: (1) secondary forms of adrenal hypoplasia due to panhypopituitarism (e.g. HESX1, LHX4, SOX3) or abnormalities in ACTH synthesis (TPIT) or processing (e.g. POMC or PC1); (2) adrenal hypoplasia as part of an ACTH resistance syndrome [MC2R/ACTH receptor, MRAP, AAAS (triple A syndrome)], and (3) primary defects in the development of the adrenal gland itself (primary adrenal hypoplasia). Primary adrenal hypoplasia most commonly occurs in an X-linked form due to mutations in the nuclear receptor DAX1 (NR0B1) but can occur in a poorly understood recessive form or as part of the IMAGe (intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia, genitourinary anomalies) syndrome. Defining the molecular basis of these conditions can have significant clinical implications for management, counselling and presymptomatic diagnosis, as well as providing fascinating insight into normal and abnormal mechanisms of adrenal development in humans.

  18. Development and Function of the Human Fetal Adrenal Cortex: A Key Component in the Feto-Placental Unit

    PubMed Central

    Ishimoto, Hitoshi

    2011-01-01

    Continuous efforts have been devoted to unraveling the biophysiology and development of the human fetal adrenal cortex, which is structurally and functionally unique from other species. It plays a pivotal role, mainly through steroidogenesis, in the regulation of intrauterine homeostasis and in fetal development and maturation. The steroidogenic activity is characterized by early transient cortisol biosynthesis, followed by its suppressed synthesis until late gestation, and extensive production of dehydroepiandrosterone and its sulfate, precursors of placental estrogen, during most of gestation. The gland rapidly grows through processes including cell proliferation and angiogenesis at the gland periphery, cellular migration, hypertrophy, and apoptosis. Recent studies employing modern technologies such as gene expression profiling and laser capture microdissection have revealed that development and/or function of the fetal adrenal cortex may be regulated by a panoply of molecules, including transcription factors, extracellular matrix components, locally produced growth factors, and placenta-derived CRH, in addition to the primary regulator, fetal pituitary ACTH. The role of the fetal adrenal cortex in human pregnancy and parturition appears highly complex, probably due to redundant and compensatory mechanisms regulating these events. Mounting evidence indicates that actions of hormones operating in the human feto-placental unit are likely mediated by mechanisms including target tissue responsiveness, local metabolism, and bioavailability, rather than changes only in circulating levels. Comprehensive study of such molecular mechanisms and the newly identified factors implicated in adrenal development should help crystallize our understanding of the development and physiology of the human fetal adrenal cortex. PMID:21051591

  19. 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.

  20. SAH pituitary adrenal dysfunction.

    PubMed

    Vespa, P

    2011-09-01

    Disruption of the hypothalamic-pituitary-adrenal axis may occur after aneurysmal subarachnoid hemorrhage, resulting in hypopituitarism. An electronic literature search was conducted to identify articles with English-language abstracts published between 1980 and March 2011 that addressed hypothalamic-pituitary-adrenal axis insufficiency and hormone replacement. A total of 18 observational and prospective, randomized studies were selected for this review. Limited data are available evaluating pituitary effects during the acute stage after subarachnoid hemorrhage, with inconsistent results reported. Overall, acutely after subarachnoid hemorrhage, cortisol levels may initially be supranormal, decreasing toward normal levels over time. During the months to years after subarachnoid hemorrhage, pituitary deficiency may occur in up to one in three patients. Limited data suggest modest outcome benefits with fludrocortisone and no benefit or harm from corticosteroids. PMID:21800209

  1. Thyroid and adrenal relationships

    PubMed Central

    Parsons, Victor; Ramsay, Ian

    1968-01-01

    A brief review of the actions of adrenal medullary and thyroid hormones is presented and the ways in which they interact are examined. It is concluded that thyroid hormone produces the necessary intracellular environment without which the steady state and emergency actions of cathecholamines would be vitiated. In hyperthyroidism the increased concentration of thyroid hormones results in a lowering of the threshold for catecholamine action. For this reason it is possible to alleviate many of the symptoms of thyrotoxicosis by means of drugs which block β-adrenergic receptors. Attention is also drawn to the simultaneous occurrence of thyroid and adrenal disease, in the hope that this will encourage the search for further links in this field of endocrinology. PMID:5655216

  2. No Postoperative Adrenal Insufficiency in a Patient with Unilateral Cortisol-Secreting Adenomas Treated with Mifepristone Before Surgery

    PubMed Central

    Saroka, Rachel M.; Kane, Michael P.; Robinson, Lawrence; Busch, Robert S.

    2016-01-01

    BACKGROUND Glucocorticoid replacement is commonly required to treat secondary adrenal insufficiency after surgical resection of unilateral cortisol-secreting adrenocortical adenomas. Here, we describe a patient with unilateral cortisol-secreting adenomas in which the preoperative use of mifepristone therapy was associated with recovery of the hypothalamic–pituitary–adrenal (HPA) axis, eliminating the need for postoperative glucocorticoid replacement. CASE PRESENTATION A 66-year-old Caucasian man with type 2 diabetes mellitus, hyperlipidemia, hypertension, and obesity was hospitalized for Fournier’s gangrene and methicillin-resistant Staphylococcus aureus sepsis. Abdominal computed tomography scan revealed three left adrenal adenomas measuring 1.4, 2.1, and 1.2 cm and an atrophic right adrenal gland. Twenty-four-hour urinary free cortisol level was elevated (237 µg/24 hours, reference range 0–50 µg/24 hours). Hormonal evaluation after resolution of the infection showed an abnormal 8 mg overnight dexamethasone suppression test (cortisol postdexamethasone 14.5 µg/dL), suppressed adrenocorticotropic hormone (ACTH; <5 pg/mL, reference range 7.2–63.3 pg/mL), and low-normal dehydroepiandrosterone sulfate (50.5 µg/dL, male reference range 30.9–295.6 µg/dL). Because of his poor medical condition and uncontrolled diabetes, his Cushing’s syndrome was treated with medical therapy before surgery. Mifepristone therapy was started and, within five months, his diabetes was controlled and insulin discontinued. The previously suppressed ACTH increased to above normal range accompanied by an increase in dehydroepiandrosterone sulfate levels, indicating recovery of the HPA axis and atrophic contralateral adrenal gland. The patient received one precautionary intraoperative dose of hydrocortisone and none thereafter. Two days postoperatively, ACTH (843 pg/mL) and cortisol levels (44.8 µg/dL) were significantly elevated, reflecting an appropriate HPA axis response to

  3. 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

  4. Adrenal Schwannoma: A Rare Incidentaloma.

    PubMed

    Kumar, Sumit; Karthikeyan, Vilvapathy S; Manohar, Chikkamoga S; Sreelakshmi, K; Shivalingaiah, Maregowda

    2016-08-01

    Adrenal schwannomas are very rare tumours that are difficult to diagnose preoperatively. A 42-year-old male presented with epigastric pain and indigestion. He had history of repeated operations for recurrent facial swelling on both sides of face diagnosed as Angiolymphoid Hyperplasia with Eosinophilia (ALHE). Physical examination revealed right facial swelling. Laboratory tests showed no evidence of hormonal hypersecretion. CECT abdomen showed a well-defined heterogenously enhancing right adrenal mass (5x4cm). Patient underwent right adrenalectomy. Histopathology revealed adrenal schwannoma, confirmed by immunohistochemistry (IHC) showing diffuse expression of S-100. Fine-needle aspiration biopsy of facial lesion confirmed ALHE recurrence. Less than 35 cases have been reported. Diagnosis of adrenal schwannoma on imaging studies is very difficult and surgical resection when performed for non-functioning adrenal masses >4cm clinches the diagnosis. Adrenal schwannoma is highly uncommon and was incidentally associated with recurrent ALHE. PMID:27656499

  5. 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

  6. 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

  7. 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

  8. Etiopathogeny of Primary Adrenal Hypercortisolism.

    PubMed

    Vélayoudom-Céphise, Fritz-Line; Haissaguerre, Magali; Tabarin, Antoine

    2016-01-01

    Primary adrenal hypercortisolism is mainly due to cortisol-producing adrenocortical adenomas, bilateral micronodular or macronodular disease, and adrenal carcinomas. Important advances in the pathophysiology of primary adrenal hypercortisolism have been made in the last few years, partly through the use of new molecular biology tools. Most adrenal abnormalities leading to increased cortisol production involve somatic or germinal mutations of genes encoding elements of the cyclic AMP/protein kinase A signaling pathway, as shown in adrenal adenomas in 2014. One peculiar condition is primary macronodular adrenal hyperplasia (PMAH), which has given rise to new pathophysiological concepts such as regulation of cortisol secretion by illegitimate ligands through aberrant expression of G protein-coupled transmembrane receptors in adrenal nodules and stimulation of cortisol production by local adrenocorticotropic hormone production through autocrine/paracrine mechanisms. These findings provide a basis for the development of targeted therapies as an alternative to surgery. The recent identification of germinal mutations of ARMC5 in PMAH raises the possibility that this is much more frequently an inherited disease than previously suspected. It also offers the possibility of earlier diagnosis of PMAH by genetic screening and, hopefully, of earlier intervention to prevent the onset of hypercortisolism and its complications. The pathophysiology of Cushing's syndrome associated with a subset of adrenal adenomas, including subclinical cortisol-secreting incidentalomas and adrenal carcinomas, remains to be determined. PMID:27212135

  9. Adrenal crisis secondary to bilateral adrenal haemorrhage after hemicolectomy

    PubMed Central

    Tsang, Venessa H M; Kabir, Shahrir; Ip, Julian C Y

    2016-01-01

    Summary Adrenal haemorrhage is a rare cause of adrenal crisis, which requires rapid diagnosis, prompt initiation of parenteral hydrocortisone and haemodynamic monitoring to avoid hypotensive crises. We herein describe a case of bilateral adrenal haemorrhage after hemicolectomy in a 93-year-old female with high-grade colonic adenocarcinoma. This patient’s post-operative recovery was complicated by an acute hypotensive episode, hypoglycaemia and syncope, and subsequent computed tomography (CT) scan of the abdomen revealed bilateral adrenal haemorrhage. Given her labile blood pressure, intravenous hydrocortisone was commenced with rapid improvement of blood pressure, which had incompletely responded with fluids. A provisional diagnosis of hypocortisolism was made. Initial heparin-induced thrombocytopenic screen (HITTS) was positive, but platelet count and coagulation profile were both normal. The patient suffered a concurrent transient ischaemic attack with no neurological deficits. She was discharged on a reducing dose of oral steroids with normal serum cortisol levels at the time of discharge. She and her family were educated about lifelong steroids and the use of parenteral steroids should a hypoadrenal crisis eventuate. Learning points: Adrenal haemorrhage is a rare cause of hypoadrenalism, and thus requires prompt diagnosis and management to prevent death from primary adrenocortical insufficiency. Mechanisms of adrenal haemorrhage include reduced adrenal vascular bed capillary resistance, adrenal vein thrombosis, catecholamine-related increased adrenal blood flow and adrenal vein spasm. Standard diagnostic assessment is a non-contrast CT abdomen. Intravenous hydrocortisone and intravenous substitution of fluids are the initial management. A formal diagnosis of primary adrenal insufficiency should never delay treatment, but should be made afterwards.

  10. Traumatic and non-traumatic adrenal emergencies.

    PubMed

    Chernyak, Victoria; Patlas, Michael N; Menias, Christine O; Soto, Jorge A; Kielar, Ania Z; Rozenblit, Alla M; Romano, Luigia; Katz, Douglas S

    2015-12-01

    Multiple traumatic and non-traumatic adrenal emergencies are occasionally encountered during the cross-sectional imaging of emergency department patients. Traumatic adrenal hematomas are markers of severe polytrauma, and can be easily overlooked due to multiple concomitant injuries. Patients with non-traumatic adrenal emergencies usually present to an emergency department with a non-specific clinical picture. The detection and management of adrenal emergencies is based on cross-sectional imaging. Adrenal hemorrhage, adrenal infection, or rupture of adrenal neoplasm require immediate detection to avoid dire consequences. More often however, adrenal emergencies are detected incidentally in patients being investigated for non-specific acute abdominal pain. A high index of suspicion is required for the establishment of timely diagnosis and to avert potentially life-threatening complications. We describe cross-sectional imaging findings in patients with traumatic and non-traumatic adrenal hemorrhage, adrenal infarctions, adrenal infections, and complications of adrenal masses.

  11. Reinforcing aspects of androgens.

    PubMed

    Wood, Ruth I

    2004-11-15

    Are androgens reinforcing? Androgenic-anabolic steroids (AAS) are drugs of abuse. They are taken in large quantities by athletes and others to increase performance, often with negative long-term health consequences. As a result, in 1991, testosterone was declared a controlled substance. Recently, Brower [K.J. Brower, Anabolic steroid abuse and dependence. Curr. Psychiatry Rep. 4 (2002) 377-387.] proposed a two-stage model of AAS dependence. Users initiate steroid use for their anabolic effects on muscle growth. With continued exposure, dependence on the psychoactive effects of AAS develops. However, it is difficult in humans to separate direct psychoactive effects of AAS from the user's psychological dependence on the anabolic effects of AAS. Thus, studies in laboratory animals are useful to explore androgen reinforcement. Testosterone induces a conditioned place preference in rats and mice, and is voluntarily consumed through oral, intravenous, and intracerebroventricular self-administration in hamsters. Active, gonad-intact male and female hamsters will deliver 1 microg/microl testosterone into the lateral ventricles. Indeed, some individuals self-administer testosterone intracerebroventricularly to the point of death. Male rats develop a conditioned place preference to testosterone injections into the nucleus accumbens, an effect blocked by dopamine receptor antagonists. These data suggest that androgen reinforcement is mediated by the brain. Moreover, testosterone appears to act through the mesolimbic dopamine system, a common substrate for drugs of abuse. Nonetheless, androgen reinforcement is not comparable to that of cocaine or heroin. Instead, testosterone resembles other mild reinforcers, such as caffeine, nicotine, or benzodiazepines. The potential for androgen addiction remains to be determined.

  12. The role of bilateral adrenalectomy in the treatment of congenital adrenal hyperplasia.

    PubMed

    Van Wyk, Judson J; Ritzen, E Martin

    2003-07-01

    This report summarizes follow-up studies in 18 patients who underwent bilateral adrenalectomy for congenital adrenal hyperplasia. Three of these patients were young children with null/null mutations of CYP21, and the other 15 were adrenalectomized because of difficulties in their management on conventional therapy. The average duration of follow-up was 59 months and represents an aggregate of 90 postoperative years. The adrenals were removed laparoscopically in 13 patients and by open flank incisions in five. Adrenal crises associated with severe illnesses occurred in five patients at times when their glucocorticoid substitution was suboptimal. All were responsive to appropriate therapy. Two of these patients were young children who had hypoglycemia during gastroenteritis or febrile illness associated with poor food intake or vomiting. Significant elevations of adrenal steroid precursors, presumably from ectopic adrenal rests, were observed postoperatively in eight of the patients. Patients and parents were nearly unanimous in their enthusiasm for adrenalectomy. In most, signs of androgen excess have decreased, and obesity has become less of a problem with lowering the dose of glucocorticoid. We conclude that adrenalectomy is a safe and efficacious method of managing congenital adrenal hyperplasia in selected patients. Prophylactic adrenalectomy in young children with double null mutations remains experimental. PMID:12843131

  13. Functional zonation of the rat adrenal cortex: the development and maintenance

    PubMed Central

    MITANI, Fumiko

    2014-01-01

    The adrenal cortex of mammals consists of three concentric zones, i.e., the zona glomerulosa (zG), the zona fasciculata (zF), and the zona reticularis (zR), which secrete mineralocorticoids, glucocorticoids, and adrenal androgens, respectively. In 1994, we identified immunohistochemically a new zone between zG and zF of the rat adrenal gland. The zone appeared to be devoid of any significant endocrine functions specific to adrenocortical zones, therefore, we designated the zone as “undifferentiated cell zone (zU)”. Further, BrdU (5-bromo-2′-deoxyuridine)-incorporating cells (cells in S-phase) were concentrated at the outer region and the inner region of zU, and these cells proliferated and migrated bidirectionally: toward zG centrifugally and toward zF centripetally. We proposed that cells in and around zU are stem/progenitor cells of the rat adrenal cortex, maintaining functional zonation of the adrenal cortex. The view is consistent with observations reported recently that Sonic hedgehog (Shh), an important factor in embryonic development and adult stem cell maintenance, exists in zU of the rat adrenal gland and the Shh-containing cells seem to migrate bidirectionally. PMID:24814991

  14. [Morphometry of the adrenals].

    PubMed

    Chumachenko, P A

    1977-05-01

    The authors report on the method of determination of the weight indices of the adrenyl gland glomerular, testicular-reticular and medullar zones with a spheroid shape; it is substantiated by mathematical analysis of a plasticine model of the adrenal gland, whose characteristics approached the actual ones. The method was particularly accurate in determination of the weight of the fascicular-reticular and glomerular zones, and less--in determination of the weight of the medullary layer, the method's error being 0.6-0.9% in the first case, 2.7-3.5% in the second and 5.3-6.4 in the last. PMID:884280

  15. 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

  16. Leiomyosarcoma of the adrenal vein.

    PubMed

    Shao, I-Hung; Lee, Wei-Chen; Chen, Tai-Di; Chiang, Yang-Jen

    2012-01-01

    Leiomyosarcoma of the adrenal gland is extremely rare in the literature. We present a patient with an adrenal leiomyosarcoma originating from the adrenal vein, the pathologic findings and management. A 66-year-old man who was a hepatitis B virus carrier was found to have a huge left suprarenal mass on sonography and computed axial tomography. A huge tumor in the left suprarenal area with a markedly engorged adrenal vein was found during an adrenalectomy. The tumor thrombus extended into the renal vein, close to the inferior vena cava. The left adrenal gland with the whole tumor thrombus was removed completely. Microscopically, the adrenal gland was compressed but not invaded by the spindle cell tumor, which was composed of interlacing fascicles of neoplastic smooth muscle cells. The tumor was localized within the adrenal vein and arose from the venous wall. The patient had no local recurrence for 18 months after en bloc excision of the tumor. We suggest that en bloc excision with a clear and adequate surgical margin is the most important cure procedure for adrenal leiomyosarcoma.

  17. Primary bilateral adrenal non-Hodgkin's lymphoma associated with normal adrenal function.

    PubMed

    Gu, Bin; Ding, Qiang; Xia, Guowei; Fang, Zujun; Fang, Jie; Jiang, Haowen; Yao, Mengshu

    2009-04-01

    Primary bilateral adrenal non-Hodgkin's lymphoma is rare. Adrenal insufficiency or adrenal failure as a result of tumor destruction is the main pathophysiological change of most cases. Normal adrenal function despite bulky bilateral adrenal masses is extremely rare. We present a case of primary bilateral adrenal non-Hodgkin's lymphoma associated with normal adrenal function. Positron emission tomography-computed tomography is helpful to the diagnosis.

  18. No aggression in a 4-year-old boy with an androgen-producing tumour: Case Report

    PubMed Central

    De la Marche, Wouter; Prinsen, Karin; Boot, Annemieke M; Ferdinand, Robert F

    2005-01-01

    Background The androgen testosterone plays a critical role in many aspects of sexual differentiation. Also, it is thought to induce aggressive behaviours or to play a role in social dominance. Case presentation In this case report a 4-year-old boy is described whose testosterone and dehydroepiandrosterone sulphate (DHEA-S) levels were raised to pubertal levels due to a testosterone producing testis tumour. This provided the unique opportunity to examine the effects of elevated levels of androgens on levels of aggression or on social dominance before the onset of puberty. Conclusion The present case report does not support the hypothesis of a causal relationship between testosterone and aggression or between testosterone and social dominance in young children. PMID:16202122

  19. Domestication Effects on Stress Induced Steroid Secretion and Adrenal Gene Expression in Chickens

    PubMed Central

    Fallahsharoudi, Amir; de Kock, Neil; Johnsson, Martin; Ubhayasekera, S. J. Kumari A.; Bergquist, Jonas; Wright, Dominic; Jensen, Per

    2015-01-01

    Understanding the genetic basis of phenotypic diversity is a challenge in contemporary biology. Domestication provides a model for unravelling aspects of the genetic basis of stress sensitivity. The ancestral Red Junglefowl (RJF) exhibits greater fear-related behaviour and a more pronounced HPA-axis reactivity than its domesticated counterpart, the White Leghorn (WL). By comparing hormones (plasmatic) and adrenal global gene transcription profiles between WL and RJF in response to an acute stress event, we investigated the molecular basis for the altered physiological stress responsiveness in domesticated chickens. Basal levels of pregnenolone and dehydroepiandrosterone as well as corticosterone response were lower in WL. Microarray analysis of gene expression in adrenal glands showed a significant breed effect in a large number of transcripts with over-representation of genes in the channel activity pathway. The expression of the best-known steroidogenesis genes were similar across the breeds used. Transcription levels of acute stress response genes such as StAR, CH25 and POMC were upregulated in response to acute stress. Dampened HPA reactivity in domesticated chickens was associated with changes in the expression of several genes that presents potentially minor regulatory effects rather than by means of change in expression of critical steroidogenic genes in the adrenal. PMID:26471470

  20. Domestication Effects on Stress Induced Steroid Secretion and Adrenal Gene Expression in Chickens.

    PubMed

    Fallahsharoudi, Amir; de Kock, Neil; Johnsson, Martin; Ubhayasekera, S J Kumari A; Bergquist, Jonas; Wright, Dominic; Jensen, Per

    2015-01-01

    Understanding the genetic basis of phenotypic diversity is a challenge in contemporary biology. Domestication provides a model for unravelling aspects of the genetic basis of stress sensitivity. The ancestral Red Junglefowl (RJF) exhibits greater fear-related behaviour and a more pronounced HPA-axis reactivity than its domesticated counterpart, the White Leghorn (WL). By comparing hormones (plasmatic) and adrenal global gene transcription profiles between WL and RJF in response to an acute stress event, we investigated the molecular basis for the altered physiological stress responsiveness in domesticated chickens. Basal levels of pregnenolone and dehydroepiandrosterone as well as corticosterone response were lower in WL. Microarray analysis of gene expression in adrenal glands showed a significant breed effect in a large number of transcripts with over-representation of genes in the channel activity pathway. The expression of the best-known steroidogenesis genes were similar across the breeds used. Transcription levels of acute stress response genes such as StAR, CH25 and POMC were upregulated in response to acute stress. Dampened HPA reactivity in domesticated chickens was associated with changes in the expression of several genes that presents potentially minor regulatory effects rather than by means of change in expression of critical steroidogenic genes in the adrenal. PMID:26471470

  1. Domestication Effects on Stress Induced Steroid Secretion and Adrenal Gene Expression in Chickens.

    PubMed

    Fallahsharoudi, Amir; de Kock, Neil; Johnsson, Martin; Ubhayasekera, S J Kumari A; Bergquist, Jonas; Wright, Dominic; Jensen, Per

    2015-10-16

    Understanding the genetic basis of phenotypic diversity is a challenge in contemporary biology. Domestication provides a model for unravelling aspects of the genetic basis of stress sensitivity. The ancestral Red Junglefowl (RJF) exhibits greater fear-related behaviour and a more pronounced HPA-axis reactivity than its domesticated counterpart, the White Leghorn (WL). By comparing hormones (plasmatic) and adrenal global gene transcription profiles between WL and RJF in response to an acute stress event, we investigated the molecular basis for the altered physiological stress responsiveness in domesticated chickens. Basal levels of pregnenolone and dehydroepiandrosterone as well as corticosterone response were lower in WL. Microarray analysis of gene expression in adrenal glands showed a significant breed effect in a large number of transcripts with over-representation of genes in the channel activity pathway. The expression of the best-known steroidogenesis genes were similar across the breeds used. Transcription levels of acute stress response genes such as StAR, CH25 and POMC were upregulated in response to acute stress. Dampened HPA reactivity in domesticated chickens was associated with changes in the expression of several genes that presents potentially minor regulatory effects rather than by means of change in expression of critical steroidogenic genes in the adrenal.

  2. Effect of placental factors on growth and function of the human fetal adrenal in vitro

    SciTech Connect

    Riopel, L.; Branchaud, C.L.; Goodyer, C.G.; Zweig, M.; Lipowski, L.; Adkar, V.; Lefebvre, Y. )

    1989-11-01

    Conditioned medium from human placental monolayer cultures (PM) had a marked stimulatory effect on proliferation (3H-thymidine uptake) of human fetal zone adrenal cells in primary monolayer culture, even in the absence of serum. Epidermal growth factor (EGF) and fibroblast growth factor (FGF) also significantly stimulated fetal adrenal cell growth. However, the effects of PM differed from those of EGF and FGF in several respects: (1) maximal response to PM was 2-5 times greater; (2) mitogenic effects of EGF and FGF were suppressed by adrenocorticotropic hormone (ACTH), whereas that of 50% PM was not; (3) PM inhibited ACTH-stimulated steroidogenesis (dehydroepiandrosterone sulfate and cortisol), but EGF and FGF did not. Preliminary characterization studies have indicated that approximately half of the placental growth-promoting activity is heat resistant and sensitive to bacterial proteases, and that 50-60% of the activity is lost after dialysis with membranes having a molecular weight cutoff of 3500. These findings suggest a role for the placenta in the growth and differentiated function of the human fetal adrenal gland.

  3. Giant adrenal cyst: case study

    PubMed Central

    Carsote, M; Chirita, P; Terzea, D; Paun, S; Beuran, M

    2010-01-01

    One of the rarest situations regarding an adrenal incidentaloma is an adrenal cyst. We present the case of a 61Z–year old male patient diagnosed with peritonitis. During surgery, a right adrenal tumor of 2 cm is discovered. The patient was referred to endocrinology. 6 months later the diameter of the tumor is 7 times bigger than the initial stage. It has no secretory phenotype, except for the small increase of serum aldosterone and the 24–h 17–ketosteroids. Open right adrenalectomy is performed and a cyst of 15 cm is removed. The evolution after surgery is good. The pathological exam reveals an adrenal cyst with calcifications and osteoid metaplasia. The immunohistochemistry showed a positive reaction for CD34 and ACT in the vessels and VIM in the stroma. The adrenal cysts are not frequent and represent a challenge regarding the preoperative diagnostic and surgical procedure of resection. The pathological exam highlights the major aspects. PMID:20945822

  4. Dehydroepiandrosterone Activation of G-protein-coupled Estrogen Receptor Rapidly Stimulates MicroRNA-21 Transcription in Human Hepatocellular Carcinoma Cells.

    PubMed

    Teng, Yun; Radde, Brandie N; Litchfield, Lacey M; Ivanova, Margarita M; Prough, Russell A; Clark, Barbara J; Doll, Mark A; Hein, David W; Klinge, Carolyn M

    2015-06-19

    Little is known about the regulation of the oncomiR miR-21 in liver. Dehydroepiandrosterone (DHEA) regulates gene expression as a ligand for a G-protein-coupled receptor and as a precursor for steroids that activate nuclear receptor signaling. We report that 10 nm DHEA increases primary miR-21 (pri-miR-21) transcription and mature miR-21 expression in HepG2 cells in a biphasic manner with an initial peak at 1 h followed by a second, sustained response from 3-12 h. DHEA also increased miR-21 in primary human hepatocytes and Hep3B cells. siRNA, antibody, and inhibitor studies suggest that the rapid DHEA-mediated increase in miR-21 involves a G-protein-coupled estrogen receptor (GPER/GPR30), estrogen receptor α-36 (ERα36), epidermal growth factor receptor-dependent, pertussis toxin-sensitive pathway requiring activation of c-Src, ERK1/2, and PI3K. GPER antagonist G-15 attenuated DHEA- and BSA-conjugated DHEA-stimulated pri-miR-21 transcription. Like DHEA, GPER agonists G-1 and fulvestrant increased pri-miR-21 in a GPER- and ERα36-dependent manner. DHEA, like G-1, increased GPER and ERα36 mRNA and protein levels. DHEA increased ERK1/2 and c-Src phosphorylation in a GPER-responsive manner. DHEA increased c-Jun, but not c-Fos, protein expression after 2 h. DHEA increased androgen receptor, c-Fos, and c-Jun recruitment to the miR-21 promoter. These results suggest that physiological concentrations of DHEA activate a GPER intracellular signaling cascade that increases pri-miR-21 transcription mediated at least in part by AP-1 and androgen receptor miR-21 promoter interaction.

  5. [SF-1, a key player in adrenal and gonadal differentiation: implications in gonadal dysgenesis and primary ovarian insufficiency].

    PubMed

    Martinerie, L; Bouvattier, C; Lombes, M

    2009-09-01

    Steroidogenic factor 1 (SF-1) gene, identified by Keith Parker in 1992, encodes for an orphan nuclear receptor, NR5A1, whose expression is detected during fetal life in adrenal and gonadal steroidogenic tissues, but also in the developing hypothalamus and in pituitary gonadotropic cells. SF-1 knock-out mouse models exhibit complete adrenal and gonadal agenesis. Human mutations of this transcription factor, were initially associated with primary adrenal failure and male gonadal dysgenesis with various degrees of under androgenization. More recently, identification of novel SF-1 mutations responsible for isolated 46, XY gonadal dysgenesis or 46, XX primary ovarian insufficiency, underscores its central role in the control and maintenance of adrenal and reproductive functions. A better understanding in the regulatory mechanisms of SF-1 signaling pathway, will open new avenues for diagnostic and therapeutic managements of sex differentiation disorders and infertilities.

  6. Reduction of dehydroepiandrosterone sulfate synthesis in women with polycystic ovary syndrome by human menopausal gonadotropin but not purified urinary follicle stimulating hormone: a comparative pilot study.

    PubMed

    Turkmen, S; Backstrom, T; Idil, M

    2004-08-01

    We aimed to compare the effects of two different gonadotropins on steroid production in patients with polycystic ovary syndrome (PCOS). The study group comprised 20 infertile patients diagnosed with PCOS who were accepted into in vitro fertilization-embryo transfer and gamete intra-Fallopian transfer programs. Ten patients were consecutively allocated to a purified urinary follicle stimulating hormone (FSH) administration group while the other ten received human menopausal gonadotropin (hMG). All patients were pretreated with a gonadotropin releasing hormone-agonist. The patients were followed by daily vaginal ultrasonography until at least two follicles reached a diameter of 17 mm or an estradiol value of at least 100 pg/ml per follicle. To induce ovulation, human chorionic gonadotropin was given. On the 3rd day of menstruation, serum estradiol, luteinizing hormone (LH), FSH, total testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS), insulin-like growth factor-I and insulin were measured. These same parameters were measured again on the day of follicle aspiration in both serum and follicular fluid. In both groups, the serum levels of estradiol and androstenedione were raised significantly, and on aspiration day the serum level of DHEAS was significantly raised in the FSH group but not in the hMG group. Our findings suggest that in PCOS patients exogenous hMG induces a different steroid synthesis pattern compared to pure FSH, hypothetically by reduction of the delta-5 steroid synthesis pathway in the adrenals and/or in the ovary. PMID:15624268

  7. Plasma adrenal and gonadal sex steroids in human pubertal development.

    PubMed

    Ducharme, J R; Forest, M G; De Peretti, E; Sempé, M; Collu, R; Bertrand, J

    1976-03-01

    Plasma free dehydroepiandrosterone (DHA), androstenedione (delta), testosterone (T), dihydrotestosterone (DHT), estrone (E1), and estradiol (E2) were measured by radioimmunoassay in 55 boys and 54 girls 3.5 to 16.3 years of age. Plasma DHA increased significantly between 6 and 8 years of age in girls and between 8 and 10 years of age in boys. A further significant increase was noted between 10 and 12 years of age in both sexes. Delta rose significantly between 8 and 10 years of age in girls and between 10 and 12 years in boys. In contrast, no significant increase in T, DHT, or E1, was noted prior to 12 years of age in both sexes. However, E2 showed a significant increase between 10 and 12 years of age in girls. This early rise in the course of pubertal development of the two sex steroids predominantly of adrenal origin, DHA and delta, and its occurence 1 to 2 years earlier in girls than in boys, as does puberty itself, suggest a possible role for these steroids in the mechanisms involved in triggering the hypothalamic-pituitary-gonadal axis at puberty.

  8. The influence of trilostane on steroid hormone metabolism in canine adrenal glands and corpora lutea-an in vitro study.

    PubMed

    Ouschan, C; Lepschy, M; Zeugswetter, F; Möstl, E

    2012-03-01

    Trilostane is widely used to treat hyperadrenocorticism in dogs. Trilostane competitively inhibits the enzyme 3-beta hydroxysteroid dehydrogenase (3β-HSD), which converts pregnenolone (P5) to progesterone (P4) and dehydroepiandrosterone (DHEA) to androstendione (A4). Although trilostane is frequently used in dogs, the molecular mechanism underlying its effect on canine steroid hormone biosynthesis is still an enigma. Multiple enzymes of 3β-HSD have been found in humans, rats and mice and their presence might explain the contradictory results of studies on the effectiveness of trilostane. We therefore investigated the influence of trilostane on steroid hormone metabolism in dogs by means of an in vitro model. Canine adrenal glands from freshly euthanized dogs and corpora lutea (CL) were incubated with increasing doses of trilostane. Tritiated P5 or DHEA were used as substrates. The resulting radioactive metabolites were extracted, separated by thin layer chromatography and visualized by autoradiography. A wide variety of radioactive metabolites were formed in the adrenal glands and in the CL, indicating high metabolic activity in both tissues. In the adrenal cortex, trilostane influences the P5 metabolism in a dose- and time-dependent manner, while DHEA metabolism and metabolism of both hormones in the CL were unaffected. The results indicate for the first time that there might be more than one enzyme of 3β-HSD present in dogs and that trilostane selectively inhibits P5 conversion to P4 only in the adrenal gland.

  9. The influence of trilostane on steroid hormone metabolism in canine adrenal glands and corpora lutea-an in vitro study.

    PubMed

    Ouschan, C; Lepschy, M; Zeugswetter, F; Möstl, E

    2012-03-01

    Trilostane is widely used to treat hyperadrenocorticism in dogs. Trilostane competitively inhibits the enzyme 3-beta hydroxysteroid dehydrogenase (3β-HSD), which converts pregnenolone (P5) to progesterone (P4) and dehydroepiandrosterone (DHEA) to androstendione (A4). Although trilostane is frequently used in dogs, the molecular mechanism underlying its effect on canine steroid hormone biosynthesis is still an enigma. Multiple enzymes of 3β-HSD have been found in humans, rats and mice and their presence might explain the contradictory results of studies on the effectiveness of trilostane. We therefore investigated the influence of trilostane on steroid hormone metabolism in dogs by means of an in vitro model. Canine adrenal glands from freshly euthanized dogs and corpora lutea (CL) were incubated with increasing doses of trilostane. Tritiated P5 or DHEA were used as substrates. The resulting radioactive metabolites were extracted, separated by thin layer chromatography and visualized by autoradiography. A wide variety of radioactive metabolites were formed in the adrenal glands and in the CL, indicating high metabolic activity in both tissues. In the adrenal cortex, trilostane influences the P5 metabolism in a dose- and time-dependent manner, while DHEA metabolism and metabolism of both hormones in the CL were unaffected. The results indicate for the first time that there might be more than one enzyme of 3β-HSD present in dogs and that trilostane selectively inhibits P5 conversion to P4 only in the adrenal gland. PMID:22113849

  10. 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

  11. Synthesis of 16 alpha-/sub 3/H androgen and estrogen substrates for 16 alpha-hydroxylase

    SciTech Connect

    Cantineau, R.; Kremers, P.; De Graeve, J.; Cornelis, A.; Laszlo, P.; Gielen, J.E.; Lambotte, R.

    1981-02-01

    The synthesis of 16 alpha-/sup 3/H androgens and estrogens is described. 1-(/sup 3/H)-Acetic acid in the presence of zinc dust reacts with 16 alpha-bromo-17-ketosteroids to produce 16 alpha-/sup 3/H-17-ketosteroids. This chemical reaction was used to prepare 16 alpha-/sup 3/H-dehydroepiandrosterone (I) and 16 alpha-/sub 4/H-estrone acetate (XI) from 16 alpha-bromo-dehydroepiandrosterone (X) and from 16 alpha-bromo-estrone acetate (XII), respectively. Using appropriate microbiological techniques, it was possible to convert these radiolabelled substrates into 16 alpha-/sup 3/H-androstenedione (II) and 16 alpha-/sup 3/H-estradiol-17 beta (VII). 16 alpha-/sup 3/H-Estrone (VI) was obtained by the chemical hydrolysis of 16 alpha-/sup 3/H-estrone acetate. The label distribution as determined by microbiological 16 alpha-hydroxylations indicated a specific labelling of 77% for androgens and 65% for estrogens in the 16 alpha position. These substrates can be used for measuring the 16 alpha hydroxylase activity, an important step in the biosynthesis of estriol (VIII) and estetrol (IX).

  12. 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.

  13. A connection between extracellular matrix and hormonal signals during the development of the human fetal adrenal gland.

    PubMed

    Chamoux, E; Otis, M; Gallo-Payet, N

    2005-10-01

    The human adrenal cortex, involved in adaptive responses to stress, body homeostasis and secondary sexual characters, emerges from a tightly regulated development of a zone-specific secretion pattern during fetal life. Its development during fetal life is critical for the well being of pregnancy, the initiation of delivery, and even for an adequate adaptation to extra-uterine life. As early as from the sixth week of pregnancy, the fetal adrenal gland is characterized by a highly proliferative zone at the periphery, a concentric migration accompanied by cell differentiation (cortisol secretion) and apoptosis in the central androgen-secreting fetal zone. After birth, a strong reorganization occurs in the adrenal gland so that it better fulfills the newborn's needs, with aldosterone production in the external zona glomerulosa, cortisol secretion in the zona fasciculata and androgens in the central zona reticularis. In addition to the major hormonal stimuli provided by angiotensin II and adrenocorticotropin, we have tested for some years the hypotheses that such plasticity may be under the control of the extracellular matrix. A growing number of data have been harvested during the last years, in particular about extracellular matrix expression and its putative role in the development of the human adrenal cortex. Laminin, collagen and fibronectin have been shown to play important roles not only in the plasticity of the adrenal cortex, but also in cell responsiveness to hormones, thus clarifying some of the unexplained observations that used to feed controversies. PMID:16172742

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

    PubMed

    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

  16. Preliminary results suggesting exaggerated ovarian androgen production early in the course of polycystic ovary syndrome.

    PubMed

    Francis, G L; Getts, A; McPherson, J C

    1990-11-01

    Excess ovarian androgen production might be a cause of the polycystic ovary syndrome (PCO). Previous studies have evaluated adult women with long-standing abnormality of the hypothalamic-pituitary gonadal axis. Abnormal ovarian function in such patients could be a primary or even a secondary finding. For that reason, this study was designed to evaluate ovarian androgen production in symptomatic adolescent females. Simultaneous adrenal suppression, by using dexamethasone, and ovarian stimulation, by using gonadotropin-releasing hormone (GnRH), were achieved in 12 patients. Following stimulation, blood was serially obtained over 8 hr to measure gonadotropin, estrogen, and androgen responses. Based on the androgen response, patients could be divided into two groups. Group A (five) had a significant increase (p less than 0.01) in free testosterone, whereas group B (seven) had no increase in any androgen, including free testosterone (significantly different from group A, p = 0.01). All patients in group A had enlarged or cystic ovaries, whereas only one-quarter patients in group B had enlarged ovaries (significantly different from group A, p less than 0.03). The pituitary and estrogenic response was similar in both groups. These preliminary data suggest that some patients with PCO (group A) have a primary abnormality in ovarian androgen production early in the course of their disease.

  17. Metabolic Syndrome, Androgens, and Hypertension

    PubMed Central

    Moulana, Mohadetheh; Lima, Roberta; Reckelhoff, Jane F.

    2013-01-01

    Obesity is one of the constellation of factors that make up the definition of the metabolic syndrome. Metabolic syndrome is also associated with insulin resistance, dyslipidemia, hypertriglyceridemia, and type 2 diabetes mellitus. The presence of obesity and metabolic syndrome in men and women is also associated with increased risk of cardiovascular disease and hypertension. In men, obesity and metabolic syndrome are associated with reductions in testosterone levels. In women, obesity and metabolic syndrome is associated with increases in androgen levels. In men reductions in androgen levels is associated with inflammation. Androgen supplements reduce inflammation in men. In women, increases in androgens are associated with increases in inflammatory cytokines, and reducing androgens reduces inflammation. In this review the possibility that androgens may have different effects on metabolic syndrome and its sequelae in males and females will be discussed. PMID:21274756

  18. Dehydroepiandrosterone intra vaginal administration for the management of postmenopausal vulvovaginal atrophy.

    PubMed

    Archer, David F

    2015-01-01

    The effects of intravaginal administration of dehydroepiandrosterone (DHEA) for the management of symptomatic vulvovaginal atrophy are reviewed. A literature search related to vulvovaginal atrophy, vaginal atrophy, atrophic vaginitis, estrogen, dehydroepiandrosterone, vulvar itching, burning, dryness, dyspareunia, and libido was performed. Relevant articles addressing the incidence, management, and outcome of DHEA therapy were identified and used for this Expert Opinion. DHEA compared to a placebo is an effective treatment improving symptoms of vaginal atrophy: dyspareunia, burning, itching, and dryness. Objective parameters of vaginal atrophy, specifically pH, vaginal maturation index (VMI), and investigator-evaluated changes in the vagina: moisture, epithelia integrity and color were improved compared to baseline and placebo. There were significant improvements in libido and dyspareunia with the intravaginal use of DHEA that contribute to improved quality of life for postmenopausal women. Dehydroepiandrosterone administered intravaginally on a daily basis is an effective treatment for symptoms, and signs of vulvovaginal atrophy along with libido in postmenopausal women. This article is part of a Special Issue entitled 'Essential role of DHEA'.

  19. Dehydroepiandrosterone intra vaginal administration for the management of postmenopausal vulvovaginal atrophy.

    PubMed

    Archer, David F

    2015-01-01

    The effects of intravaginal administration of dehydroepiandrosterone (DHEA) for the management of symptomatic vulvovaginal atrophy are reviewed. A literature search related to vulvovaginal atrophy, vaginal atrophy, atrophic vaginitis, estrogen, dehydroepiandrosterone, vulvar itching, burning, dryness, dyspareunia, and libido was performed. Relevant articles addressing the incidence, management, and outcome of DHEA therapy were identified and used for this Expert Opinion. DHEA compared to a placebo is an effective treatment improving symptoms of vaginal atrophy: dyspareunia, burning, itching, and dryness. Objective parameters of vaginal atrophy, specifically pH, vaginal maturation index (VMI), and investigator-evaluated changes in the vagina: moisture, epithelia integrity and color were improved compared to baseline and placebo. There were significant improvements in libido and dyspareunia with the intravaginal use of DHEA that contribute to improved quality of life for postmenopausal women. Dehydroepiandrosterone administered intravaginally on a daily basis is an effective treatment for symptoms, and signs of vulvovaginal atrophy along with libido in postmenopausal women. This article is part of a Special Issue entitled 'Essential role of DHEA'. PMID:25201455

  20. 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

  1. Threat perception and familiarity moderate the androgen response to competition in women

    PubMed Central

    Oliveira, Gonçalo A.; Uceda, Sara; Oliveira, Tânia; Fernandes, Alexandre; Garcia-Marques, Teresa; Oliveira, Rui F.

    2013-01-01

    Social interactions elicit androgen responses whose function has been posited to be the adjustment of androgen-dependent behaviors to social context. The activation of this androgen response is known to be mediated and moderated by psychological factors. In this study we tested the hypothesis that the testosterone (T) changes after a competition are not simply related to its outcome, but rather to the way the subject evaluates the event. In particular we tested two evaluative dimensions of a social interaction: familiarity with the opponent and the subjective evaluation of the outcome as threat or challenge. Challenge/threat occurs in goal relevant situations and represent different motivational states arising from the individuals’ subjective evaluation of the interplay between the task demands and coping resources possessed. For challenge the coping resources exceed the task demands, while threat represents a state where coping resources are insufficient to meet the task demands. In this experiment women competed in pairs, against a same sex opponent using the number tracking test as a competitive task. Losers appraised the competition outcome as more threatening than winners, and displayed higher post-competition T levels than winners. No differences were found either for cortisol (C) or for dehydroepiandrosterone. Threat, familiarity with the opponent and T response were associated only in the loser condition. Moderation analysis suggests that for the women that lost the competition the effect of threat on T is moderated by familiarity with the opponent. PMID:23847564

  2. Threat perception and familiarity moderate the androgen response to competition in women.

    PubMed

    Oliveira, Gonçalo A; Uceda, Sara; Oliveira, Tânia; Fernandes, Alexandre; Garcia-Marques, Teresa; Oliveira, Rui F

    2013-01-01

    Social interactions elicit androgen responses whose function has been posited to be the adjustment of androgen-dependent behaviors to social context. The activation of this androgen response is known to be mediated and moderated by psychological factors. In this study we tested the hypothesis that the testosterone (T) changes after a competition are not simply related to its outcome, but rather to the way the subject evaluates the event. In particular we tested two evaluative dimensions of a social interaction: familiarity with the opponent and the subjective evaluation of the outcome as threat or challenge. Challenge/threat occurs in goal relevant situations and represent different motivational states arising from the individuals' subjective evaluation of the interplay between the task demands and coping resources possessed. For challenge the coping resources exceed the task demands, while threat represents a state where coping resources are insufficient to meet the task demands. In this experiment women competed in pairs, against a same sex opponent using the number tracking test as a competitive task. Losers appraised the competition outcome as more threatening than winners, and displayed higher post-competition T levels than winners. No differences were found either for cortisol (C) or for dehydroepiandrosterone. Threat, familiarity with the opponent and T response were associated only in the loser condition. Moderation analysis suggests that for the women that lost the competition the effect of threat on T is moderated by familiarity with the opponent.

  3. Threat perception and familiarity moderate the androgen response to competition in women.

    PubMed

    Oliveira, Gonçalo A; Uceda, Sara; Oliveira, Tânia; Fernandes, Alexandre; Garcia-Marques, Teresa; Oliveira, Rui F

    2013-01-01

    Social interactions elicit androgen responses whose function has been posited to be the adjustment of androgen-dependent behaviors to social context. The activation of this androgen response is known to be mediated and moderated by psychological factors. In this study we tested the hypothesis that the testosterone (T) changes after a competition are not simply related to its outcome, but rather to the way the subject evaluates the event. In particular we tested two evaluative dimensions of a social interaction: familiarity with the opponent and the subjective evaluation of the outcome as threat or challenge. Challenge/threat occurs in goal relevant situations and represent different motivational states arising from the individuals' subjective evaluation of the interplay between the task demands and coping resources possessed. For challenge the coping resources exceed the task demands, while threat represents a state where coping resources are insufficient to meet the task demands. In this experiment women competed in pairs, against a same sex opponent using the number tracking test as a competitive task. Losers appraised the competition outcome as more threatening than winners, and displayed higher post-competition T levels than winners. No differences were found either for cortisol (C) or for dehydroepiandrosterone. Threat, familiarity with the opponent and T response were associated only in the loser condition. Moderation analysis suggests that for the women that lost the competition the effect of threat on T is moderated by familiarity with the opponent. PMID:23847564

  4. Dehydroepiandrosterone Supplementation Combined with Whole-Body Vibration Training Affects Testosterone Level and Body Composition in Mice

    PubMed Central

    Chen, Wen-Chyuan; Chen, Yi-Ming; Huang, Chi-Chang; Tzeng, Yen-Dun

    2016-01-01

    Dehydroepiandrosterone (DHEA), the most abundant sex steroid, is primarily secreted by the adrenal gland and a precursor hormone used by athletes for performance enhancement. Whole-body vibration (WBV) is a well-known light-resistance exercise by automatic adaptations to rapid and repeated oscillations from a vibrating platform, which is also a simple and convenient exercise for older adults. However, the potential effects of DHEA supplementation combined with WBV training on to body composition, exercise performance, and hormone regulation are currently unclear. The objective of the study is to investigate the effects of DHEA supplementation combined with WBV training on body composition, exercise performance, and physical fatigue-related biochemical responses and testosterone content in young-adult C57BL/6 mice. In this study, male C57BL/6 mice were divided into four groups (n = 8 per group) for 6-weeks treatment: sedentary controls with vehicle (SC), DHEA supplementation (DHEA, 10.2 mg/kg), WBV training (WBV; 5.6 Hz, 2 mm, 0.13 g), and WBV training with DHEA supplementation (WBV+DHEA; WBV: 5.6 Hz, 2 mm, 0.13 g and DHEA: 10.2 mg/kg). Exercise performance was evaluated by forelimb grip strength and exhaustive swimming time, as well as changes in body composition and anti-fatigue levels of serum lactate, ammonia, glucose, creatine kinase (CK), and blood urea nitrogen (BUN) after a 15-min swimming exercise. In addition, the biochemical parameters and the testosterone content were measured at the end of the experiment. Six-week DHEA supplementation alone significantly increased mice body weight (BW), muscle weight, testosterone level, and glycogen contents (liver and muscle) when compared with SC group. DHEA supplementation alone had no negative impact on all tissue and biochemical profiles, but could not improve exercise performance. However, WBV+DHEA supplementation also significantly decreased BW, testosterone level and glycogen content of liver, as well as serum

  5. 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. ...

  6. 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

  7. 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

  8. Glucocorticoid metabolism in the developing lung: adrenal-like synthesis pathway.

    PubMed

    Provost, Pierre R; Boucher, Eric; Tremblay, Yves

    2013-11-01

    Glucocorticoids (GCs) are essential to normal lung development. They participate in the regulation of important developmental events including morphological changes, and lung maturation leading to the surge of surfactant synthesis by type II epithelial cells. Antenatal GC is administered to mothers at risk of premature delivery to reduce the risk of respiratory distress syndrome (RDS). Sex differences were reported in RDS, in the efficiency of antenatal GC treatment independently of surfactant levels, and in surfactant lipid synthesis. Type II epithelial cell maturation is regulated by epithelial-fibroblast cell-cell communication and involves paracrine factors secreted by fibroblasts under the stimulatory effect of GC. This positive action of GC can be inhibited by androgens through the androgen receptor (AR) present in fibroblasts. In fact, lung development is regulated not only by GC and androgens but also by GC and androgen metabolisms within the developing lung. We recently reviewed the metabolism of androgens in the fetal lung [45]. Here, we review multiple aspects of GC metabolism in the developing lung including inactivation and re-activation by 11β-HSDs, synthesis from the adrenal-like synthesis pathway expressed within the lung and the putative role of CRH and ACTH originating from lung in the regulation of this pathway. This article is part of a Special Issue entitled 'Pregnancy and Steroids'.

  9. Differential metabolism of dehydroepiandrosterone sulfate and estrogen conjugates by normal or malignant AXC/SSh rat prostate cells and effects of these steroid conjugates on cancer cell proliferation in vitro.

    PubMed

    Huot, R I; Shain, S A

    1988-06-01

    Normal AXC/SSh rat ventral prostate and clonally derived AXC/SSh rat prostate cancer cells were evaluated for ability to metabolize estrone sulfate (E1S), estrone glucuronide (E1G), or dehydroepiandrosterone sulfate (DHEAS). Both normal and malignant prostate cells converted E1S to estrone. Neither normal nor malignant prostate cells had significant ability to metabolize DHEAS to DHEA, indicating differential specificity of prostate sulfatases(s) for estrogen and androgen sulfates. Both normal and neoplastic prostate cells possess beta-glucuronidase which hydrolyzed E1G to estrone. To assess potential physiologic consequences of these enzymatic activities, we determined the effect of steroid conjugates on in vitro proliferation of selected clonal lines of AXC/SSh rat prostate cancer cells. DHEAS, 10(-6) to 10(-9) M in decade intervals, did not affect in vitro proliferation of AXC/SSh prostate cancer cells; however, 10(-5) M DHEAS decreased in vitro proliferation of these cells. Neither E1S nor E1G, 10(-5) to 10(-9) M in decade intervals, affected in vitro proliferation of AXC/SSh prostate cancer cells. These findings suggest that low residual levels of steroid conjugates, which are not removed by charcoal stripping of serum, do not affect demonstrated in vitro androgen modulation of AXC/SSh rat prostate cancer cell proliferation (Cancer Res. 46, 3775-3781, 1986).

  10. Accumulation of 5 alpha-reduced androgen glucosiduronates associated with impaired removal in young male hemodialysis patients.

    PubMed

    Boudou, P; Naret, C; Fiet, J; Bonete, R; Tritto, G; Le Duc, A; Poignet, J L; Man, N K

    1995-12-01

    Hypothalamic-pituitary gonadal function is commonly altered in dialysis patients. Even though an improvement in general status and well-being has been noted after recombinant human erythropoietin supplementation, no significant changes were observed in the sex hormone profile. Pituitary gonadal axis as well as 5 alpha-reduced androgen glucosiduronates (i.e. 5 alpha-androstane,3 alpha,17 beta-diol and androsterone) profiles were studied in 23 young male stable dialyzed patients and compared to an age-matched group of healthy subjects. 5 alpha-Reduced androgen glucosiduronates are products of peripheral testosterone (T) metabolism and seem to be a useful tool in assessment of the male androgen status. Their polarity facilitates their urinary excretion, and their clearance is similar to the glomerular filtration rate in healthy men. We observed 1) a pituitary-Leydig cell dysfunction supported by normal serum estradiol and T levels, low free T, and increased LH levels; 2) an alteration of the dehydroepiandrosterone (DHEA) sulfate-DHEA interconversion, reflected by a dramatic decrease in DHEA while DHEA sulfate levels remained in the normal range; 3) an accumulation of 5 alpha-reduced androgen glucosiduronates, whose removal was impaired as shown by their very low sieving coefficients (< 0.012). Taken together, the above observations are consistent with alteration of spermatogenesis with respect to dialysis duration in which earlier elevated baseline serum LH levels indicate a primary defect in Leydig cell function.

  11. Steroidogenesis inhibitors alter but do not eliminate androgen synthesis mechanisms during progression to castration-resistance in LNCaP prostate xenografts.

    PubMed

    Locke, Jennifer A; Nelson, Colleen C; Adomat, Hans H; Hendy, Stephen C; Gleave, Martin E; Guns, Emma S Tomlinson

    2009-07-01

    In castration-resistant prostate cancer (CRPC) many androgen-regulated genes become re-expressed and tissue androgen levels increase despite low serum levels. We and others have recently reported that CRPC tumor cells can de novo synthesize androgens from adrenal steroid precursors or cholesterol and that high levels of progesterone exist in LNCaP tumors after castration serving perhaps as an intermediate in androgen synthesis. Herein, we compare androgen synthesis from [(3)H-progesterone] in the presence of specific steroidogenesis inhibitors and anti-androgens in steroid starved LNCaP cells and CRPC tumors. Similarly, we compare steroid profiles in LNCaP tumors at different stages of CRPC progression. Steroidogenesis inhibitors targeting CYP17A1 and SRD5A2 significantly altered but did not eliminate androgen synthesis from progesterone in steroid starved LNCaP cells and CRPC tumors. Upon exposure to inhibitors of steroidogenesis prostate cancer cells adapt gradually during CRPC progression to synthesize DHT in a compensatory manner through alternative feed-forward mechanisms. Furthermore, tumors obtained immediately after castration are significantly less efficient at metabolizing progesterone ( approximately 36%) and produce a different steroid profile to CRPC tumors. Optimal targeting of the androgen axis may be most effective when tumors are least efficient at synthesizing androgens. Confirmatory studies in humans are required to validate these findings.

  12. 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 ...

  13. Secretion of Unconjugated Androgens and Estrogens by the Normal and Abnormal Human Testis before and after Human Chorionic Gonadotropin

    PubMed Central

    Weinstein, R. L.; Kelch, R. P.; Jenner, M. R.; Kaplan, S. L.; Grumbach, M. M.

    1974-01-01

    The secretion of androgens and estrogens by normal and abnormal testes was compared by determining the concentrations of dehydroepiandrosterone (DHEA), androstenedione (Δ4A), testosterone (T), estrone (E1), and 17β-estradiol (E2) in peripheral and spermatic venous plasma samples from 14 normal men and 5 men with unilateral testicular atrophy. Four normal men and one patient with unilateral atrophy of the testis were given human chorionic gonadotropin (HCG) before surgery. Plasma estrogens were determined by radioimmunoassay; plasma androgens were measured by the double-isotope dilution derivative technique. Peripheral concentrations of these steroids before and after HCG were similar in both the normal men and the patients with unilateral testicular atrophy. In normal men, the mean ±SE spermatic venous concentrations were DHEA, 73.1±11.7 ng/ml; Δ4A, 30.7±7.9 ng/ml; T, 751±114 ng/ml; E1, 306±55 pg/ml; and E2, 1298±216 pg/ml. Three of four subjects with unilateral testicular atrophy had greatly diminished spermatic venous levels of androgens and estrogens. HCG treatment increased the testicular secretion of DHEA and T fivefold, Δ4A threefold, E1 sixfold, and E2 eightfold in normal men. In the single subject with an atrophic testis who received HCG, the spermatic venous concentrations of androgens and estrogens were much less than in normal men similarly treated. We conclude that: (a) E1 is secreted by the human testis, but testicular secretion of E1 accounts for less than 5% of E1 production in normal men; (b) HCG stimulation produces increases in spermatic venous estrogens equal to or greater than the changes in androgens, including testosterone; and (c) strikingly decreased secretion of androgen and estrogen by unilateral atrophic human tests cannot be appreciated by analyses of peripheral steroid concentrations. PMID:4271572

  14. Androgenic Biomarker Profiling in Human Matrices and Cell Culture Samples Using High Through put, Electrospray Tandem Mass Spectrometry

    PubMed Central

    Wilton, John H.; Titus, Mark A.; Efstathiou, Eleni; Fetterly, Gerald J.; Mohler, James L.

    2015-01-01

    BACKGROUND A high throughput, high pressure liquid chromatographic (HPLC) method with triple quadrupole mass spectral detection (LC/MS/MS) was validated for the measurement of 5 endogenous androgens in human plasma and serum and applied to various in vivo and in vitro study samples to pursue a better understanding of the interrelationship of the androgen axis, intracrine metabolism, and castration-recurrent prostate cancer (CaP). METHODS A Shimadzu HPLC system interfaced with a Sciex QTRAP 5500 mass spectrometer with electrospray ionization was used with inline column-switching. Samples were liquid/liquid extracted and chromatographed on a Luna C18(2) column at 60°C with a biphasic gradient using a 15-min run time. RESULTS The method was validated for five androgens in human plasma and serum, and applied to four sets of samples. Plasma (n = 188) and bone marrow aspirate (n = 129) samples from patients with CaP, who received abiraterone acetate plus prednisone for up to 945 days (135 weeks), had undetectable androgens after 8 weeks of treatment. Plasma dehydroepiandrosterone (DHEA) concentrations were higher in African Americans than Caucasian Americans with newly diagnosed CaP. Analysis of prostate tumor tissue homogenates demonstrated reproducible testosterone (T) and dihydrotestosterone (DHT) concentrations with a minimal sample size of ~1.0–2.0 mg of tissue. Finally, cell pellet and media samples from the LNCaP C4-2 cell line showed conversion of T to DHT. CONCLUSION The proposed LC/MS/MS method was validated for quantitation of five endogenous androgens in human plasma and serum, and effectively profiles androgens in clinical specimens and cell culture samples. PMID:24847527

  15. 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.

  16. 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

  17. Autonomic control of adrenal function.

    PubMed Central

    Edwards, A V; Jones, C T

    1993-01-01

    Recent studies of adrenal function in conscious calves are reviewed. These have involved collecting the whole of the adrenal effluent blood from the right adrenal gland at intervals and, where necessary, prior functional hypophysectomy by destruction of the pituitary stalk under general halothane anaesthesia 3 d previously. The adrenal medulla was found to release numerous neuropeptides, in addition to catecholamines, in response to stimulation of the peripheral end of the right splanchnic nerve, which was carried out below behavioural threshold. Many of these responses were enhanced by stimulating intermittently at a relatively high frequency. Intra-aortic infusions of a relatively low dose of acetylcholine (4.5 nmol min-1 kg-1) elicited similar responses. In the adrenal cortex, agonists which either potentiated the steroidogenic response to ACTH or exerted a direct steroidogenic action included VIP, CGRP, CRF and ACh acting via muscarinic receptors. Stimulation of the peripheral end of the right splanchnic nerve strongly potentiated the steroidogenic response to ACTH and there is compelling evidence that the innervation normally plays an important part in cortisol secretion. PMID:8300417

  18. Rare association of adrenal tumors.

    PubMed

    Tica, Irjna; Tica, V I; Mihailov, Claudia

    2007-01-01

    Adrenal incidentalomas represent a true problem both in the clinical diagnosis and in their treatment. A great variety of pathologies may be found under the umbrella of this concept: benign adenomas - functioning or not, myelolipomas, hamartomas, or granulomatous infiltrations of the adrenal. The possibility of malignancy should be considered in each case, especially in patients with a known extra-adrenal primary. In true incidentalomas, size appears to be predictive of malignancy. We present an interesting case because of the surprising association of two adrenal tumors, with a long time lapse between them, with ascites and pleurisy and because of the difficulty of treatment in a patient refusing surgery. We did not find such an association in the medical literature. Miss MR, 61 years old, was treated surgically for pheochromocytoma 28 years ago (left adrenalectomy). She was diagnosed in the past with peritoneal carcinomatosis; paraneoplastic left pleurisy, chronic hepatitis of unknown etiology. She presented at admission cashexia, pallor, signs of left pleural effusion and of ascites, hearts beats and blood pressure within normal limits. Investigations were performed including hormonal tests, ultrasound investigation, hepatic tests, and CT scan but no specific tumour markers. A right adrenal incidentaloma of 21/15 mm - in association with ascites and pleurisy - was found at CT scan. Diagnostic problems are discussed because the patient refused surgery, so no pathological examination was available.

  19. 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

  20. Giant adrenal cyst displacing the right kidney.

    PubMed

    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.

  1. Cushing syndrome due to adrenal tumor

    MedlinePlus

    Adrenal tumor - Cushing syndrome ... Cushing syndrome is a disorder that occurs when your body has a higher than normal level of the ... or cancerous (malignant). Noncancerous tumors that can cause ... Adrenal adenomas Micronodular hyperplasia Cancerous tumors that ...

  2. Dehydroepiandrosterone sulfotransferase is a target for transcriptional induction by the vitamin D receptor.

    PubMed

    Echchgadda, Ibtissam; Song, Chung S; Roy, Arun K; Chatterjee, Bandana

    2004-03-01

    Dehydroepiandrosterone sulfotransferase (SULT2A1) is a cytosolic enzyme that mediates sulfo-conjugation of endogenous hydroxysteroids (dehydroepiandrosterone, testosterone, bile acids), and diverse xenobiotic compounds. Upon sulfonation, SULT2A1 substrates become polar and water-soluble and thus suitable for rapid excretion. SULT2A1 is abundantly expressed in the liver and intestine. Recent evidence has shown that the ligand-activated vitamin D receptor (VDR) can transcriptionally induce the xenobiotic-metabolizing cytochrome P450 enzymes. Herein, we report that VDR also targets SULT2A1 for transcriptional activation. Vitamin D stimulated endogenous SULT2A1 expression and induced transfected human, mouse, and rat SULT2A1 promoters in liver and intestinal cells upon cotransfection with VDR. An inverted repeat DNA element (IR0), located within -191 to -168 positions of mouse and rat Sult2A1, mediates VDR induction of Sult2A1. DNase1 footprinting, competition EMSA, and antibody supershift assay showed that the IR0 is a binding site for the RXR-alpha/VDR heterodimer. Point mutations within the IR0 prevented RXR/VDR binding and abolished VDR-mediated Sult2A1 induction. The IR0 element conferred VDR responsiveness on a thymidine kinase promoter. Thus, VDR-mediated nuclear signaling may be important in the phase II metabolism involving Sult2A1. The rodent Sult2A1 gene is also induced by the farnesoid X receptor (FXR) and pregnane X receptor (PXR) through the same IR0. In competition transfections, FXR or PXR inhibited VDR induction of the IR0. Competitive functional interactions among VDR, PXR, and FXR suggest that the intracellular hormonal and metabolic milieu may determine the extent to which a specific nuclear receptor pathway would influence steroid/xenobiotic metabolism using dehydroepiandrosterone sulfotransferase.

  3. Maternal melatonin selectively inhibits cortisol production in the primate fetal adrenal gland

    PubMed Central

    Torres-Farfan, Claudia; Richter, Hans G; Germain, Alfredo M; Valenzuela, Guillermo J; Campino, Carmen; Rojas-García, Pedro; Forcelledo, María Luisa; Torrealba, Fernando; Serón-Ferré, María

    2004-01-01

    We tested the hypothesis that in primates, maternal melatonin restrains fetal and newborn adrenal cortisol production. A functional G-protein-coupled MT1 membrane-bound melatonin receptor was detected in 90% gestation capuchin monkey fetal adrenals by (a) 2-[125I] iodomelatonin binding (Kd, 75.7 ± 6.9 pm; Bmax, 2.6 ± 0.4 fmol (mg protein)−1), (b) cDNA identification, and (c) melatonin inhibition of adrenocorticotrophic hormone (ACTH)- and corticotrophin-releasing hormone (CRH)-stimulated cortisol but not of dehydroepiandrosterone sulphate (DHAS) production in vitro. Melatonin also inhibited ACTH-induced 3β-hydroxysteroid dehydrogenase mRNA expression. To assess the physiological relevance of these findings, we next studied the effect of chronic maternal melatonin suppression (induced by exposure to constant light during the last third of gestation) on maternal plasma oestradiol during gestation and on plasma cortisol concentration in the 4- to 6-day-old newborn. Constant light suppressed maternal melatonin without affecting maternal plasma oestradiol concentration, consistent with no effect on fetal DHAS, the precursor of maternal oestradiol. However, newborns from mothers under constant light condition had twice as much plasma cortisol as newborns from mothers maintained under a normal light–dark schedule. Newborns from mothers exposed to chronic constant light and daily melatonin replacement had normal plasma cortisol concentration. Our results support a role of maternal melatonin in fetal and neonatal primate cortisol regulation. PMID:14673186

  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. Spontaneous adrenal haemorrhage in pregnancy

    PubMed Central

    A, Anagnostopoulos; S, Sharma

    2011-01-01

    The authors present a case of spontaneous adrenal haemorrhage, in a 28-year-old woman at 36 weeks of a twin pregnancy. Initial symptom was sudden onset chest pain which soon migrated to abdomen, accompanied by hypovolaemic shock and fetal bradycardia. Subsequent caesarean section for suspected placental abruption and resuscitation with nine units of blood, 10 of cryoprecipitate, four of fresh frozen plasma and two of platelets, in order to treat anaemia of Hgb of 3.6 g/dl and disseminated intravascular coagulation, failed to stabilise the woman. A CT scan of abdomen and pelvis then revealed a 15×17×17 cm retroperitoneal haematoma, secondary to right adrenal haemorrhage. Management was with laparotomy drainage and packing of the retroperitoneal haematoma along with the use of activated factor VII. Adrenal haemorrhage in pregnancy is an extremely rare, acute, life-threatening condition, presenting with non-specific symptoms. PMID:22679231

  6. A Case of Bilateral Testicular Tumors Subsequently Diagnosed as Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency

    PubMed Central

    Sha, Yan-Kun; Sha, Yan-Wei; Ding, Lu; Liu, Wei-Wu; Song, Yue-Qiang; Lin, Jin; He, Xue-Mei; Qiu, Ping-Ping; Zhang, Ling; Li, Ping

    2016-01-01

    21-hydroxylase deficiency (21-OHD) caused congenital adrenal hyperplasia (CAH) is a group of autosomal recessive genetic disorders resulting from mutations in genes involved with cortisol (CO) synthesis in the adrenal glands. Testicular adrenal rest tumors (TARTs) are rarely the presenting symptoms of CAH. Here, we describe a case of simple virilizing CAH with TARTs, in a 15-year-old boy. The patient showed physical signs of precocious puberty. The levels of blood adrenocorticotropic hormone (ACTH), urinary 17-ketone steroids (17-KS), dehydroepiandrosterone sulfate (DHEA-S), and serum progesterone (PRGE) were elevated, whereas those of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and CO were reduced. Computed tomography (CT) of the adrenal glands and magnetic resonance imaging (MRI) of the testes showed a soft tissue density (more pronounced on the right side) and an irregularly swollen mass (more pronounced on the left side), respectively. Pathological examination of a specimen of the mass indicated polygonal/circular eosinophilic cytoplasm, cord-like arrangement of interstitial cells, and lipid pigment in the cytoplasm. Immunohistochemistry results precluded a diagnosis of Leydig cell tumors. DNA sequencing revealed a hackneyed homozygous mutation, I2g, on intron 2 of the CYP21A2 gene. The patient’s symptoms improved after a three-month of dexamethasone therapy. Recent radiographic data showed reduced hyperplastic adrenal nodules and testicular tumors. A diagnosis of TART should be considered and prioritized in CAH patients with testicular tumors. Replacement therapy using a sufficient amount of dexamethasone in this case helps combat TART. PMID:26985347

  7. Congenital Adrenal Hyperplasia: Classification of Studies Employing Psychological Endpoints

    PubMed Central

    Stout, Stephanie A.; Litvak, Margarita; Robbins, Natashia M.; Sandberg, David E.

    2010-01-01

    Psychological outcomes in persons with congenital adrenal hyperplasia (CAH) have received substantial attention. The objectives of this paper were to (1) catalog psychological endpoints assessed in CAH outcome studies and (2) classify the conceptual/theoretical model shaping the research design and interpretation of CAH-related psychological effects. A total of 98 original research studies, published between 1955 and 2009, were categorized based on psychological endpoints examined as well as the research design and conceptual model guiding analysis and interpretation of data. The majority of studies (68%) investigated endpoints related to psychosexual differentiation. The preponderance of studies (76%) examined a direct relationship (i.e., inferring causality) between prenatal androgen exposure and psychological outcomes. Findings are discussed in relation to the observed imbalance between theoretical interest in the role of prenatal androgens in shaping psychosexual differentiation and a broader conceptual model that examines the role of other potential factors in mediating or moderating the influence of CAH pathophysiology on psychological outcomes in both affected females and males. The latter approach offers to identify factors amenable to clinical intervention that enhance both health and quality of life outcomes in CAH as well as other disorders of sex development. PMID:20976294

  8. Androgen actions and the ovary.

    PubMed

    Walters, K A; Allan, C M; Handelsman, D J

    2008-03-01

    Although androgens and the androgen receptor (AR) have defining roles in male reproductive development and function, previously no role in female reproductive physiology beyond testosterone (T) as the precursor in estradiol (E(2)) biosynthesis was firmly established. Understanding the role and specific mechanisms of androgen action via the AR in the ovary has been limited by confusion on how to interpret results from pharmacological studies, because many androgens can be metabolized in vivo and in vitro to steroids that can also exert actions via the estrogen receptor (ESR). Recent genetic studies using mouse models with specific disruption of the Ar gene have highlighted the role that AR-mediated actions play in maintaining female fertility through key roles in the regulation of follicle health, development, and ovulation. Furthermore, these genetic studies have revealed that AR-mediated effects influence age-related female fertility, possibly via mechanisms acting predominantly at the hypothalamic-pituitary axis in a dose-dependent manner. This review focuses on combining the findings from pharmacological studies and novel genetic mouse models to unravel the roles of ovarian androgen actions in relation to female fertility and ovarian aging, as well as creating new insights into the role of androgens in androgen-associated reproductive disorders such as polycystic ovarian syndrome.

  9. 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

  10. Androstenedione rhythms in saliva in congenital adrenal hyperplasia.

    PubMed Central

    Young, M C; Walker, R F; Riad-Fahmy, D; Hughes, I A

    1988-01-01

    Serial samples of saliva were collected at home by 17 patients being treated for congenital adrenal hyperplasia to determine the circadian rhythm of androstenedione as an index of therapeutic control. Single samples of blood for measurement of plasma testosterone, 170H-progesterone, and androstenedione concentrations were collected from these and a further seven patients for comparison. Plasma androstenedione concentrations showed a close correlation with plasma concentrations of 170H-progesterone and testosterone. There was a strong correlation between the salivary androstenedione profiles and plasma testosterone concentrations in pubertal girls. Concentrations of androstenedione in saliva decreased during the day but remained raised at each sampling time in relation to plasma testosterone concentrations. Salivary androstenedione profiles are shown as nomograms to distinguish the degree of therapeutic control. The concentration of androstenedione, measured in plasma or saliva, is an alternative marker to monitor control of treatment in congenital adrenal hyperplasia. The measurement in saliva is a useful index of androgen production when blood sampling is difficult. PMID:3389892

  11. Changes in androgens during treatment with four low-dose contraceptives.

    PubMed

    Coenen, C M; Thomas, C M; Borm, G F; Hollanders, J M; Rolland, R

    1996-03-01

    The aim of the present study was to compare changes in the endogenous androgen environment in healthy women while on low-dose oral contraceptives (OCs). One-hundred healthy women were randomized to receive one of four OCs during six months: 21 tablets of Cilest, Femodeen, Marvelon, or Mercilon. During the luteal phase of the pretreatment cycle, body weight and blood pressure were recorded and the following parameters were measured: sex hormone-binding globulin (SHBG), corticosteroid-binding globulin (CBG), testosterone (T), free testosterone (FT), 5 alpha-dihydrotestosterone (DHT), androstenedione (A), dehydroepiandrosterone-sulphate (DHEA-S) and 17 alpha-hydroxyprogesterone (170HP) while also the free androgen index (FAI) was calculated. Measurements were repeated during the 3rd week of pill intake in the 4th and the 6th pill month. There were no differences on body mass and blood pressure with the use of the four OCs. The mean serum DHEA-S decreased significantly in all groups though less in the Mercilon group when compared to Cilest and Marvelon (approximately 20% vs 45%). Mean serum SHBG and CBG increased significantly in all four groups approximately 250% and 100%, respectively. In each group CBG also increased significantly but less in women taking Mercilon (-75%) as compared to the others (-100%). Current low-dose OCs were found to have similar impact on the endogenous androgen metabolism with significant decreases of serum testosterone, DHT, A, and DHEA-S. They may be equally beneficial in women with androgen related syndromes such as acne and hirsutism. PMID:8689882

  12. [Immunoendocrine associations in adrenal glands].

    PubMed

    Sterzl, I; Hrdá, P

    2010-12-01

    Immune and endocrine systems are basic regulatory mechanisms of organism and, including the nervous system, maintain the organism's homeostasis. The main immune system representatives are mononuclear cells, T- and B-cells and their products, in the endocrine system the main representatives are cells of the glands with inner secretion and their products. One of the most important glands for maintaining homeostasis are adrenal glands. It has been proven that either cells of the immune system, either endocrine cells can, although in trace amounts, produce mutually mediators of both systems (hormones, cytokines). Disorders in one system can lead to pathological symptoms in the other system. Also here represent adrenals an important model.

  13. [Adrenal cystic masses. Our experience].

    PubMed

    Costantino, V; Petrin, P; Da Lio, C; Zaramella, D; Pedrazzoli, S

    1993-10-01

    Cystic masses of the adrenal gland are clinically and pathologically rare findings and few cases have been reported up to now in the medical literature. In the present work 5 new cases are reported: 3 adrenal pseudocysts, 1 lymphangioma, 1 cystic pheochromocytoma. In 3 cases there were clinical symptoms of retroperitoneal mass (lumbar pain, palpable mass, digestive symptoms); in 3 cases conventional radiology was helpful; ultrasonography was used for diagnosis in 1, CT scan in 2. In the pheochromocytoma case the real nature of the mass was determined through fluid hormone determination after fine needle puncture. All cases were treated by surgery.

  14. Two case reports of bilateral adrenal myelolipomas

    PubMed Central

    Yang, Yu; Ye, Lin-Yang; Yu, Bo; Guo, Jia-Xiang; Liu, Qian; Chen, Yun

    2015-01-01

    Primary adrenal myelolipoma is a rare, non-functioning adrenal benign tumor that is composed of mature adipose tissue and a variable amount of haemopoietic elements. Clinically, it is difficult to get diagnosed with adrenal myelolipoma because the patient usually doesn’t have obvious symptoms and signs in early stage. In the present study, two cases of primary bilateral adrenal myelolipomas are reported. Clinical presentation, imaging diagnostic features, histopathological changes and surgical treatments of the two patients are discussed. Preoperative diagnostic imaging examinations (B-mode ultrasonography, computed tomography and magnetic resonance imaging sans) assisted getting a prediction diagnosis of bilateral adrenal myelolipomas. A two-stage surgery was used to successfully excise bilateral adrenal myelolipomas in the two patients. Conventional open adrenalectomy was applied to remove the adrenal myelolipomas greater than 6 cm, and laparoscopic adrenalectomy was performed to excise the adrenal tumors smaller than 6 cm. Bilateral adrenal myelolipomas of the two patients were finally confirmed by postoperative histopathological examinations. Understanding clinical, imaging diagnostic and histopathological features of bilateral adrenal myelolipomas will facilitate timely diagnosis and treatment of this condition. Surgical removal of bilateral adrenal myelolipomas is safe, curative and beneficial. The two-stage surgery appears to be the best treatment option for the patients with bilateral adrenal myelolipomas because it achieves optimal treatment effectiveness with minimized sequelae. PMID:26380835

  15. 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.

  16. Adrenal insufficiency and adrenal replacement therapy. Current status in Spain.

    PubMed

    Aulinas, Anna; Casanueva, Felipe; Goñi, Fernando; Monereo, Susana; Moreno, Basilio; Picó, Antonio; Puig-Domingo, Manel; Salvador, Javier; Tinahones, Francisco J; Webb, Susan M

    2013-03-01

    Adrenal insufficiency (AI) is a rare endocrine disease, associated to increased mortality if left untreated. It can be due to a primary failure of the adrenal glands (primary AI) or malfunctioning of the hypothalamic-pituitary-adrenal axis (HPA) (secondary AI). The lack of data on incidence/prevalence of adrenal insufficiency in Spain complicates any evaluation of the magnitude of the problem in our country. Initial symptoms are non-specific, so often there is a delay in diagnosis. Current therapy with available glucocorticoids is associated with decreased quality of life in patients with treated AI, as well as with increased mortality and morbidity, probably related to both over-treatment and lack of hydrocortisone, associated with non-physiological peaks and troughs of the drug over the 24 hours. The availability of a new drug with a modified dual release (immediate and retarded), that requires one only daily dose, improves and simplifies the treatment, increases compliance as well as quality of life, morbidity and possibly mortality. This revision deals with the knowledge on the situation both globally and in Spain, prior to the availability of this new drug.

  17. Dihydrotestosterone synthesis pathways from inactive androgen 5α-androstane-3β,17β-diol in prostate cancer cells: Inhibition of intratumoural 3β-hydroxysteroid dehydrogenase activities by abiraterone

    PubMed Central

    Ando, Takashi; Nishiyama, Tsutomu; Takizawa, Itsuhiro; Ishizaki, Fumio; Miyashiro, Yoshimichi; Takeda, Keisuke; Hara, Noboru; Tomita, Yoshihiko

    2016-01-01

    Intratumoural dihydrotestosterone (DHT) synthesis could be an explanation for castration resistance in prostate cancer (PC). By using liquid chromatography-mass spectrometry, we evaluated the intratumoral DHT synthesis from 5α-androstane-3β,17β-diol (3β-diol), which is inactive androgen metabolized from DHT. 3β-diol had biochemical potential to be converted to DHT via three metabolic pathways and could stimulate PC cell growth. Especially, 3β-diol was not only converted back to upstream androgens such as dehydroepiandrosterone (DHEA) or Δ5-androstenediol but also converted directly to DHT which is the main pathway from 3β-diol to DHT. Abiraterone had a significant influence on the metabolism of DHEA, epiandrosterone and 3β-diol, by the inhibition of the intratumoural 3β-hydroxysteroid dehydrogenase (3β-HSD) activities which is one of key catalysts in androgen metabolic pathway. The direct-conversion of 3β-diol to DHT was catalysed by 3β-HSD and abiraterone could inhibit this activity of 3β-HSD. These results suggest that PC had a mechanism of intratumoural androgen metabolism to return inactive androgen to active androgen and intratumoural DHT synthesis from 3β-diol is important as one of the mechanisms of castration resistance in PC. Additionally, the inhibition of intratumoural 3β-HSD activity could be a new approach to castration-resistant prostate cancer treatment. PMID:27561382

  18. Hypothalamic-pituitary-adrenal axis function in ankylosing spondylitis

    PubMed Central

    Imrich, R; Rovensky, J; Zlnay, M; Radikova, Z; Macho, L; Vigas, M; Koska, J

    2004-01-01

    Objective: To assess basal function and responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis in patients with ankylosing spondylitis during dynamic testing. Methods: Insulin induced hypoglycaemia (IIH) (Actrapid HM 0.1 IU/kg, as intravenous bolus) was induced in 17 patients and 11 healthy controls matched for age, sex, and body mass index. Concentrations of glucose, adrenocorticotrophic hormone (ACTH), cortisol, insulin, dehydroepiandrosterone sulphate (DHEAS), 17α-hydroxyprogesterone, interleukin 6 (IL-6), and tumour necrosis factor α (TNFα) were determined in plasma. Results: Comparable basal cortisol levels were found in the two groups, with a trend to be lower in ankylosing spondylitis. In the ankylosing spondylitis group, there were higher concentrations of IL-6 (mean (SEM): 16.6 (2.8) pg/ml v 1.41 (0.66) pg/ml in controls; p<0.001) and TNFα (8.5 (1.74) pg/ml v 4.08 (0.42) pg/ml in controls; p<0.01). Glucose, insulin, ACTH, DHEAS, and 17α-hydroxyprogesterone did not differ significantly from control. The IIH test was carried out successfully in 11 of the 17 patients with ankylosing spondylitis, and the ACTH and cortisol responses were comparable with control. General linear modelling showed a different course of glycaemia (p = 0.041) in the ankylosing spondylitis patients who met the criteria for a successful IIH test compared with the controls. Conclusions: The results suggest there is no difference in basal HPA axis activity and completely preserved responsiveness of the HPA axis in patients with ankylosing spondylitis. The interpretation of the different course of glycaemia during IIH in ankylosing spondylitis requires further investigation. PMID:15140773

  19. Anesthetic considerations on adrenal gland surgery.

    PubMed

    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

  20. Adrenal lymphangioma removed by a retroperitoneoscopic procedure.

    PubMed

    Liu, Ben; Li, Yanyuan; Wang, Shuo

    2013-02-01

    We report a case of an adrenal lymphangioma removed by retroperitoneal laparoscopy. A 45-year-old female was referred to the urological ward for an adrenal mass that was incidentally detected by ultrasound examination one month earlier. An abdominal ultrasonography (US) scan revealed a 3.0 cm anechoic cystic mass, while a computed tomography (CT) scan revealed a 3.0×2.7 cm left adrenal cystic mass, which was suspected to be an adrenal cyst. The patient underwent retroperitoneoscopic removal of the tumor. Pathological evaluation revealed a cystic lymphangioma in the left adrenal gland.

  1. 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

  2. The Relationship between Dehydroepiandrosterone (DHEA), Working Memory and Distraction – A Behavioral and Electrophysiological Approach

    PubMed Central

    do Vale, Sónia; Selinger, Lenka; Martins, João Martin; Gomes, Ana Coelho; Bicho, Manuel; do Carmo, Isabel; Escera, Carles

    2014-01-01

    Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulphate (DHEAS) have been reported to have memory enhancement effects in humans. A neuro-stimulatory action and an anti-cortisol mechanism of action may contribute to that relation. In order to study DHEA, DHEAS and cortisol relations to working memory and distraction, we recorded the electroencephalogram of 23 young women performing a discrimination (no working memory load) or 1-back (working memory load) task in an audio-visual oddball paradigm. We measured salivary DHEA, DHEAS and cortisol both before each task and at 30 and 60 min. Under working memory load, a higher baseline cortisol/DHEA ratio was related to higher distraction as indexed by an enhanced novelty P3. This suggests that cortisol may lead to increased distraction whereas DHEA may hinder distraction by leading to less processing of the distractor. An increased DHEA production with consecutive cognitive tasks was found and higher DHEA responses attributed to working memory load were related to enhanced working memory processing as indexed by an enhanced visual P300. Overall, the results suggest that in women DHEA may oppose cortisol effects reducing distraction and that a higher DHEA response may enhance working memory at the electrophysiological level. PMID:25105970

  3. Adrenal gland and nonrenal retroperitoneum.

    PubMed

    Yeh, H C

    1987-01-01

    Ultrasound, as the initial cross-sectional imaging technique, confirmed the value of axial records. Although computerized tomography and possibly magnetic resonance offers better resolution, ultrasonography has the advantage of being less expensive, convenient, and highly portable. With these specific indications and reservations, ultrasonography of the adrenal and retroperitoneum has an accepted role in imaging.

  4. PAPSS2 Deficiency Causes Androgen Excess via Impaired DHEA Sulfation—In Vitro and in Vivo Studies in a Family Harboring Two Novel PAPSS2 Mutations

    PubMed Central

    Oostdijk, Wilma; Idkowiak, Jan; Mueller, Jonathan W.; House, Philip J.; Taylor, Angela E.; O'Reilly, Michael W.; Hughes, Beverly A.; de Vries, Martine C.; Kant, Sarina G.; Santen, Gijs W. E.; Verkerk, Annemieke J. M. H.; Uitterlinden, André G.; Wit, Jan M.; Losekoot, Monique

    2015-01-01

    Context: PAPSS2 (PAPS synthase 2) provides the universal sulfate donor PAPS (3′-phospho-adenosine-5′-phosphosulfate) to all human sulfotransferases, including SULT2A1, responsible for sulfation of the crucial androgen precursor dehydroepiandrosterone (DHEA). Impaired DHEA sulfation is thought to increase the conversion of DHEA toward active androgens, a proposition supported by the previous report of a girl with inactivating PAPSS2 mutations who presented with low serum DHEA sulfate and androgen excess, clinically manifesting with premature pubarche and early-onset polycystic ovary syndrome. Patients and Methods: We investigated a family harboring two novel PAPSS2 mutations, including two compound heterozygous brothers presenting with disproportionate short stature, low serum DHEA sulfate, but normal serum androgens. Patients and parents underwent a DHEA challenge test comprising frequent blood sampling and urine collection before and after 100 mg DHEA orally, with subsequent analysis of DHEA sulfation and androgen metabolism by mass spectrometry. The functional impact of the mutations was investigated in silico and in vitro. Results: We identified a novel PAPSS2 frameshift mutation, c.1371del, p.W462Cfs*3, resulting in complete disruption, and a novel missense mutation, c.809G>A, p.G270D, causing partial disruption of DHEA sulfation. Both patients and their mother, who was heterozygous for p.W462Cfs*3, showed increased 5α-reductase activity at baseline and significantly increased production of active androgens after DHEA intake. The mother had a history of oligomenorrhea and chronic anovulation that required clomiphene for ovulation induction. Conclusions: We provide direct in vivo evidence for the significant functional impact of mutant PAPSS2 on DHEA sulfation and androgen activation. Heterozygosity for PAPSS2 mutations can be associated with a phenotype resembling polycystic ovary syndrome. PMID:25594860

  5. High prevalence of abnormal adrenal response in girls with central precocious puberty at early pubertal stages.

    PubMed

    Lazar, L; Kauli, R; Bruchis, C; Nordenberg, J; Galatzer, A; Pertzelan, A

    1995-10-01

    Abnormal adrenal response is often observed in girls with precocious adrenarche (1). We studied the adrenal response in 112 girls with idiopathic true central precocious puberty (CPP) at early stages of puberty compared to that in 21 girls with normal puberty (controls). The aims of this study were to determine the prevalence of abnormal adrenal response at early stages of puberty, the possible correlation of abnormal adrenal response with pubertal signs at onset of puberty and with plasma androgen levels, and a possible association with the activity of the hypothalamic-pituitary-gonadal (HPG) axis. All participants underwent a combined i.v. adrenocorticotropic hormone (ACTH)-gonadotropin-releasing hormone (GnRH) test at Tanner stage 2-3: 62 of the CPP girls before and 50 during treatment with GnRH analog. The stimulated levels of 17-hydroxypregnenolone (17OHPreg) and the stimulated 17OHPreg/17-hydroxyprogesterone ratio were analyzed and compared to previously reported norms. The result revealed three patterns of adrenal response: normal (17OHPreg < or = 24 nmol/l and 17OHPreg/17OHP ratio < or = 7) in 50/112 (44.6%) CPP patients and 17/21 (80.9%) controls; exaggerated (17OHPreg > 24 nmol/l, 17OHPreg/17OHP ratio < or = 7) in 50/112 (44.6%) CPP patients and 3/21 (14.3%) controls; and non-classical 3 beta-hydroxysteroid dehydrogenase deficiency (17OHPreg > 24 nmol/l and 17OHPreg/17OHP ratio > 7) in 12/112 (10.8%) CPP patients and 1/21 (4.8%) controls. The clinical features at onset of puberty were comparable in all girls with the CPP in spite of the different adrenal response patterns.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. [Clinical features and StAR gene mutations in children with congenital lipoid adrenal hyperplasia].

    PubMed

    Xie, Ting; Zheng, Ji-Peng; Huang, Yong-Lan; Fan, Chun; Wu, Dong-Yan; Tan, Min-Yi; Li, Xiu-Zhen; Cheng, Jing; Liu, Li

    2015-05-01

    This article reported the clinical manifestations, steroid profiles and adrenal ultrasound findings in two unrelated Chinese girls with lipoid congenital adrenal hyperplasia (LCAH). Direct DNA sequencing and restriction fragment length polymorphism (RFLP) analysis were used to identify the mutations of steroidogenic acute regulatory protein (StAR) gene. The two patients with 46,XX karyotype, presented hyperpigmentation, growth retardation, and hyponatremia. Steroid profiles analysis revealed elevated plasma adrenocorticotrophic hormone levels, decreased or normal serum cortisol levels and low levels of androgens. Ultrasound examinations revealed that enlarged adrenals in patient 1 and normal adrenals in patient 2. Direct DNA sequencing of StAR gene showed a reported homozygous for c.772C>T(p.Q258X) in patient 1. Compound heterozygous for c.367G>A(p.E123K) and IVS4+2T>A (both novel mutations) were found in patient 2, inherited from her mother and father respectively. The amino acid of mutant position of the novel p.E123K was highly conserved in ten different species and was predicted to have impacts on the structure and function of StAR protein by the PolyPhen-2 prediction software. RFLP analysis revealed three bands (670, 423 and 247 bp) in patient 2 and her father and two bands (423 and 247 bp) in her mother and 50 controls. It is concluded that LCAH should be considered in girls with early onset of adrenal insufficiency and that steroid profiles, karyotype analysis, adrenal ultrasound and StAR gene analysis may be helpful for the definite diagnosis of LCAH.

  7. Adrenal adrenoceptors in heart failure

    PubMed Central

    de Lucia, Claudio; Femminella, Grazia D.; Gambino, Giuseppina; Pagano, Gennaro; Allocca, Elena; Rengo, Carlo; Silvestri, Candida; Leosco, Dario; Ferrara, Nicola; Rengo, Giuseppe

    2014-01-01

    Heart failure (HF) is a chronic clinical syndrome characterized by the reduction in left ventricular (LV) function and it represents one of the most important causes of morbidity and mortality worldwide. Despite considerable advances in pharmacological treatment, HF represents a severe clinical and social burden. Sympathetic outflow, characterized by increased circulating catecholamines (CA) biosynthesis and secretion, is peculiar in HF and sympatholytic treatments (as β-blockers) are presently being used for the treatment of this disease. Adrenal gland secretes Epinephrine (80%) and Norepinephrine (20%) in response to acetylcholine stimulation of nicotinic cholinergic receptors on the chromaffin cell membranes. This process is regulated by adrenergic receptors (ARs): α2ARs inhibit CA release through coupling to inhibitory Gi-proteins, and β ARs (mainly β2ARs) stimulate CA release through coupling to stimulatory Gs-proteins. All ARs are G-protein-coupled receptors (GPCRs) and GPCR kinases (GRKs) regulate their signaling and function. Adrenal GRK2-mediated α2AR desensitization and downregulation are increased in HF and seem to be a fundamental regulator of CA secretion from the adrenal gland. Consequently, restoration of adrenal α2AR signaling through the inhibition of GRK2 is a fascinating sympatholytic therapeutic strategy for chronic HF. This strategy could have several significant advantages over existing HF pharmacotherapies minimizing side-effects on extra-cardiac tissues and reducing the chronic activation of the renin–angiotensin–aldosterone and endothelin systems. The role of adrenal ARs in regulation of sympathetic hyperactivity opens interesting perspectives in understanding HF pathophysiology and in the identification of new therapeutic targets. PMID:25071591

  8. Intraoperative identification of adrenal-renal fusion

    PubMed Central

    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

  9. [Adrenal injury in blunt abdominal trauma].

    PubMed

    Abakumov, M M; Smoliar, A N; Barmina, T G; Boĭko, A V; Shalimova, I G

    2009-01-01

    10 patients with adrenal damage were observed during 2.5 years. It amounted 0.93% of all patients with closed abdominal injuries. The right adrenal gland was traumatized in all cases evidently due to it's compression between right lobe of liver and vertebral column. Adrenal damage is observed quite often in combination with injuries of right liver lobe, right kidney and retroperitoneal hematoma formation. 5 patients underwent laparotomy on account of intra-abdominal bleeding, but adrenal damage was never revealed. Ultrasound and tomographic semiotics of adrenal damage was worked out, which allowed ascertaining diagnosis in 80% on application of ultrasound study and in 100% at computer tomography. Injury of one adrenal gland was not accompanied by adrenal failure and did not require hormonal replacement therapy.

  10. Limited Diagnostic Utility of Plasma Adrenocorticotropic Hormone for Differentiation between Adrenal Cushing Syndrome and Cushing Disease

    PubMed Central

    Hong, A Ram; Kim, Jung Hee; Hong, Eun Shil; Kim, I Kyeong; Park, Kyeong Seon; Ahn, Chang Ho; Kim, Sang Wan; Shin, Chan Soo

    2015-01-01

    Background Measurement of the plasma adrenocorticotropic hormone (ACTH) level has been recommended as the first diagnostic test for differentiating between ACTH-independent Cushing syndrome (CS) and ACTH-dependent CS. When plasma ACTH values are inconclusive, a differential diagnosis of CS can be made based upon measurement of the serum dehydroepiandrosterone sulfate (DHEA-S) level and results of the high-dose dexamethasone suppression test (HDST). The aim of this study was to assess the utility of plasma ACTH to differentiate adrenal CS from Cushing' disease (CD) and compare it with that of the HDST results and serum DHEA-S level. Methods We performed a retrospective, multicenter study from January 2000 to May 2012 involving 92 patients with endogenous CS. The levels of plasma ACTH, serum cortisol, 24-hour urine free cortisol (UFC) after the HDST, and serum DHEA-S were measured. Results Fifty-seven patients had adrenal CS and 35 patients had CD. The area under the curve of plasma ACTH, serum DHEA-S, percentage suppression of serum cortisol, and UFC after HDST were 0.954, 0.841, 0.950, and 0.997, respectively (all P<0.001). The cut-off values for plasma ACTH, percentage suppression of serum cortisol, and UFC after HDST were 5.3 pmol/L, 33.3%, and 61.6%, respectively. The sensitivity and specificity of plasma ACTH measurement were 84.2% and 94.3%, those of serum cortisol were 95.8% and 90.6%, and those of UFC after the HDST were 97.9% and 96.7%, respectively. Conclusion Significant overlap in plasma ACTH levels was seen between patients with adrenal CS and those with CD. The HDST may be useful in differentiating between these forms of the disease, especially when the plasma ACTH level alone is not conclusive. PMID:26248856

  11. Dehydroepiandrosterone Sulfate Stimulates Expression of Blood-Testis-Barrier Proteins Claudin-3 and -5 and Tight Junction Formation via a Gnα11-Coupled Receptor in Sertoli Cells

    PubMed Central

    Papadopoulos, Dimitrios; Dietze, Raimund; Shihan, Mazen; Kirch, Ulrike; Scheiner-Bobis, Georgios

    2016-01-01

    Dehydroepiandrosterone sulfate (DHEAS) is a circulating sulfated steroid considered to be a pro-androgen in mammalian physiology. Here we show that at a physiological concentration (1 μM), DHEAS induces the phosphorylation of the kinase Erk1/2 and of the transcription factors CREB and ATF-1 in the murine Sertoli cell line TM4. This signaling cascade stimulates the expression of the tight junction (TJ) proteins claudin-3 and claudin-5. As a consequence of the increased expression, tight junction connections between neighboring Sertoli cells are augmented, as demonstrated by measurements of transepithelial resistance. Phosphorylation of Erk1/2, CREB, or ATF-1 is not affected by the presence of the steroid sulfatase inhibitor STX64. Erk1/2 phosphorylation was not observed when dehydroepiandrosterone (DHEA) was used instead of DHEAS. Abrogation of androgen receptor (AR) expression by siRNA did not affect DHEAS-stimulated Erk1/2 phosphorylation, nor did it change DHEAS-induced stimulation of claudin-3 and claudin-5 expression. All of the above indicate that desulfation and conversion of DHEAS into a different steroid hormone is not required to trigger the DHEAS-induced signaling cascade. All activating effects of DHEAS, however, are abolished when the expression of the G-protein Gnα11 is suppressed by siRNA, including claudin-3 and -5 expression and TJ formation between neighboring Sertoli cells as indicated by reduced transepithelial resistance. Taken together, these results are consistent with the effects of DHEAS being mediated through a membrane-bound G-protein-coupled receptor interacting with Gnα11 in a signaling pathway that resembles the non-classical signaling pathways of steroid hormones. Considering the fact that DHEAS is produced in reproductive organs, these findings also suggest that DHEAS, by acting as an autonomous steroid hormone and influencing the formation and dynamics of the TJ at the blood-testis barrier, might play a crucial role for the

  12. Silent intravascular lymphoma initially manifesting as a unilateral adrenal incidentaloma.

    PubMed

    Takahashi, Yoshiko; Iida, Keiji; Hino, Yasuhisa; Ohara, Takeshi; Kurahashi, Toshifumi; Tashiro, Takashi; Chihara, Kazuo

    2012-01-01

    Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of malignant lymphoma. Although the involvement of adrenal glands in IVLBCL is often observed, primary adrenal IVLBCL is rare. Most reported cases of adrenal IVLBCL showed bilateral lesions resulting in rapidly progressive adrenal failure and poor prognosis. Here, we report a case of slowly progressive primary adrenal IVLBCL manifesting initially with unilateral adrenal incidentaloma. This case is a silent IVLBCL and shows that the enlargement of both adrenal glands can be followed.

  13. Primary bilateral adrenal intravascular large B-cell lymphoma associated with adrenal failure.

    PubMed

    Fukushima, Ayumi; Okada, Yosuke; Tanikawa, Takahisa; Onaka, Takashi; Tanaka, Aya; Higashi, Takehiro; Tsukada, Junichi; Tanaka, Yoshiya

    2003-07-01

    We report a rare case of bilateral primary adrenal non-Hodgkin's lymphoma with adrenal failure. A 66-year-old woman developed symptoms of adrenal failure. The cause of adrenal failure was suspected to be malignant lymphoma based on the high levels of serum soluble interleukin-2 receptor and LDH. Bilateral adrenalectomy was performed and pathological examination showed intravascular large B-cell lymphoma (IVL). Although complete remission was achieved, recurrence occurred three months later with brain metastases. IVL should be suspected in patients with bilateral adrenal tumors who present with rapidly progressive adrenal failure.

  14. Changes in the fecal concentrations of cortisol and androgen metabolites in captive male jaguars (Panthera onca) in response to stress.

    PubMed

    Morato, R G; Bueno, M G; Malmheister, P; Verreschi, I T N; Barnabe, R C

    2004-12-01

    In the present study we determined the efficacy of the measurement of fecal cortisol and androgen metabolite concentrations to monitor adrenal and testicular activity in the jaguar (Panthera onca). Three captive male jaguars were chemically restrained and electroejaculated once or twice within a period of two months. Fecal samples were collected daily for 5 days before and 5 days after the procedure and stored at -20 degrees C until extraction. Variations in the concentrations of cortisol and androgen metabolites before and after the procedure were determined by solid phase cortisol and testosterone radioimmunoassay and feces dry weight was determined by drying at 37 degrees C for 24 h under vacuum. On four occasions, fecal cortisol metabolite levels were elevated above baseline (307.8 +/- 17.5 ng/g dry feces) in the first fecal sample collected after the procedure (100 to 350% above baseline). On one occasion, we did not detect any variation. Mean (+/- SEM) fecal androgen concentration did not change after chemical restraint and electroejaculation (before: 131.1 +/- 26.7, after: 213.7 +/- 43.6 ng/g dry feces). These data show that determination of fecal cortisol and androgen metabolites can be very useful for a noninvasive assessment of animal well-being and as a complement to behavioral, physiological, and pathological studies. It can also be useful for the study of the relationship between adrenal activity and reproductive performance in the jaguar.

  15. Changes in the fecal concentrations of cortisol and androgen metabolites in captive male jaguars (Panthera onca) in response to stress.

    PubMed

    Morato, R G; Bueno, M G; Malmheister, P; Verreschi, I T N; Barnabe, R C

    2004-12-01

    In the present study we determined the efficacy of the measurement of fecal cortisol and androgen metabolite concentrations to monitor adrenal and testicular activity in the jaguar (Panthera onca). Three captive male jaguars were chemically restrained and electroejaculated once or twice within a period of two months. Fecal samples were collected daily for 5 days before and 5 days after the procedure and stored at -20 degrees C until extraction. Variations in the concentrations of cortisol and androgen metabolites before and after the procedure were determined by solid phase cortisol and testosterone radioimmunoassay and feces dry weight was determined by drying at 37 degrees C for 24 h under vacuum. On four occasions, fecal cortisol metabolite levels were elevated above baseline (307.8 +/- 17.5 ng/g dry feces) in the first fecal sample collected after the procedure (100 to 350% above baseline). On one occasion, we did not detect any variation. Mean (+/- SEM) fecal androgen concentration did not change after chemical restraint and electroejaculation (before: 131.1 +/- 26.7, after: 213.7 +/- 43.6 ng/g dry feces). These data show that determination of fecal cortisol and androgen metabolites can be very useful for a noninvasive assessment of animal well-being and as a complement to behavioral, physiological, and pathological studies. It can also be useful for the study of the relationship between adrenal activity and reproductive performance in the jaguar. PMID:15558198

  16. Androgen receptor (AR) in cardiovascular diseases.

    PubMed

    Huang, Chiung-Kuei; Lee, Soo Ok; Chang, Eugene; Pang, Haiyan; Chang, Chawnshang

    2016-04-01

    Cardiovascular diseases (CVDs) are still the highest leading cause of death worldwide. Several risk factors have been linked to CVDs, including smoking, diabetes, hyperlipidemia, and gender among others. Sex hormones, especially the androgen and its receptor, androgen receptor (AR), have been linked to many diseases with a clear gender difference. Here, we summarize the effects of androgen/AR on CVDs, including hypertension, stroke, atherosclerosis, abdominal aortic aneurysm (AAA), myocardial hypertrophy, and heart failure, as well as the metabolic syndrome/diabetes and their impacts on CVDs. Androgen/AR signaling exacerbates hypertension, and anti-androgens may suppress hypertension. Androgen/AR signaling plays dual roles in strokes, depending on different kinds of factors; however, generally males have a higher incidence of strokes than females. Androgen and AR differentially modulate atherosclerosis. Androgen deficiency causes elevated lipid accumulation to enhance atherosclerosis; however, targeting AR in selective cells without altering serum androgen levels would suppress atherosclerosis progression. Androgen/AR signaling is crucial in AAA development and progression, and targeting androgen/AR profoundly restricts AAA progression. Men have increased cardiac hypertrophy compared with age-matched women that may be due to androgens. Finally, androgen/AR plays important roles in contributing to obesity and insulin/leptin resistance to increase the metabolic syndrome.

  17. Adrenal imaging (Part 1): Imaging techniques and primary cortical lesions

    PubMed Central

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

    2015-01-01

    Adrenal glands can be affected by a variety of lesions. Adrenal lesions can either be primary, of adrenal origin, or secondary to other pathologies. Primary adrenal lesions can further be either of cortical or medullary origin. Functioning adrenal lesions can also give clues to the histologic diagnosis and direct workup. Over the years, various imaging techniques have been developed that have increased diagnostic accuracy and helped in better characterization of adrenal lesions non-invasively. In the first part of the two part series, we review adrenal imaging techniques and adrenal cortical tumors such as adenomas, adrenocortical tumors, adrenal hyperplasia and oncocytomas. PMID:25593820

  18. Replacement therapy with DHEA plus corticosteroids in patients with chronic inflammatory diseases--substitutes of adrenal and sex hormones.

    PubMed

    Straub, R H; Schölmerich, J; Zietz, B

    2000-01-01

    A dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis was found in animal models of chronic inflammatory diseases, and the defect was located in more central portions of the HPA axis. This defect of neuroendocrine regulatory mechanisms contributes to the onset of the model disease. Since these first observations in animal models were made, evidence has accumulated that the possible defect in the HPA axis in humans is more distal to the hypothalamus or pituitary gland: In chronic inflammatory diseases, such as rheumatoid arthritis, an alteration of the HPA stress response results in inappropriately low cortisol secretion in relation to adrenocorticotropic hormone (ACTH) secretion. Furthermore, it has recently been shown that the serum levels of another adrenal hormone, dehydroepiandrosterone (DHEA), were significantly lower after ACTH stimulation in patients with rheumatoid arthritis without prior corticosteroids than in healthy controls. These studies clearly indicate that chronic inflammation alters, particularly, the adrenal response. However, at this point, the reason for the specific alteration of adrenal function in relation to pituitary function remains to be determined. Since one of the down-regulated adrenal hormones, DHEA, is an inhibitor of cytokines due to an inhibition of nuclear factor-kappa B (NF-kappa B) activation, low levels of this hormone may be deleterious in chronic inflammatory diseases. We have recently demonstrated that DHEA is a potent inhibitor of IL-6, which confirmed an earlier study in mice. Since IL-6 is an important factor for B lymphocyte differentiation, the missing down-regulation of this cytokine, and others such as TNF, may be a significant risk factor in rheumatic diseases. Since in these patients, administration of prednisolone or the chronic inflammatory process itself alters adrenal function, endogenous adrenal hormones in relation to proinflammatory cytokines change. Furthermore, these mechanisms may also lead to

  19. Cardiovascular risk factors and events in women with androgen excess.

    PubMed

    Macut, D; Antić, I B; Bjekić-Macut, J

    2015-03-01

    Androgen excess (AE) was approximated to be present in 7% of the adult population of women. Polycystic ovary syndrome (PCOS) is the most prevalent among them, followed by idiopathic hirsutism (IH), congenital adrenal hyperplasia (CAH), hyperandrogenic insulin-resistant acanthosis nigricans (HAIRAN) syndrome, and androgen-secreting neoplasms (ASNs). Increased cardiovascular risk was implicated in women with AE. Serum testosterone independently increases risk for cardiovascular disease (CVD), and correlates even with indices of subclinical atherosclerosis in various populations of postmenopausal women. Hyperandrogenism in PCOS is closely related to the aggravation of abdominal obesity, and together with insulin resistance forming the metabolic core for the development of CVD. However, phenotypic variability of PCOS generates significant influence on the cardiometabolic risks. Numerous risk factors in PCOS lead to 5-7 times higher risk for CVD and over 2-fold higher risk for coronary heart disease and stroke. However, issue on the cardiometabolic risk in postmenopausal women with hyperandrogenic history is still challenging. There is a significant overlapping in the CVD characteristics of women with PCOS and variants of CAH. Relevant clinical data on the prevalence and cardiometabolic risk and events in women with IH, HAIRAN syndrome or ASNs are scarce. The effects of various oral contraceptives (OCs) and antiandrogenic compounds on metabolic profile are varying, and could be related to the selected populations and different therapy regiments mainly conducted in women with PCOS. It is assumed relation of OCs containing antiandrogenic progestins to the increased risk of cardiovascular and thromboembolic events.

  20. Androgenic influence on serotonergic activation of the HPA stress axis.

    PubMed

    Goel, Nirupa; Plyler, Kimberly S; Daniels, Derek; Bale, Tracy L

    2011-05-01

    The higher incidence of stress-mediated affective disorders in women may be a function of gonadal hormone influence on complex interactions between serotonin and neural circuits that mediate the hypothalamic-pituitary-adrenal (HPA) stress axis. The paraventricular nucleus of the hypothalamus (PVN) receives serotonergic innervation, and selective serotonin reuptake inhibitors such as citalopram activate the HPA axis independent of stress. We have previously demonstrated that the magnitude of this serotonergic activation was greater in females and was attenuated by testosterone administration; however, the potential central sites of action where androgens reduce these serotonergic effects have not been determined. Therefore, we examined a time course of corticosterone production and used central c-Fos protein levels to assay neuronal activation in stress-related brain regions in female, male, and gonadectomized male mice after an acute citalopram injection (15 mg/kg). In the hippocampus, c-Fos-immunoreactivity was greater in males than in females or gonadectomized males. This same pattern emerged in the lateral septum after vehicle and gonadectomy reversed the effect of citalopram. These regions are important for inhibitory influences on the PVN, and accordingly, hippocampal c-Fos levels were negatively correlated with corticosterone production. No sex differences in c-Fos were detected in the PVN, cingulate cortex, or paraventricular thalamus in response to vehicle or citalopram. These data support brain region-specific regulation of the HPA axis where sex differences may be mediated partly through androgen enhancement of signaling in inhibitory regions.

  1. 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...

  2. Robotic renal and adrenal surgery.

    PubMed

    Sung, Gyung Tak; Gill, Inderbir S

    2003-12-01

    Technology today is evolving at a dramatic rate. Quantum development has occurred in the area of robotic enhancement technology (RET) in the last decade. Incorporation of RET with advanced telecommunication technologies is a recent integration in medicine, with growth potential and application in the delivery of modern health care. There remain, however, many areas which need to be further improved and evaluated before clinical applications of the robot become accepted in adrenal and renal minimally invasive surgery. PMID:14712880

  3. Effects of dehydroepiandrosterone sulfate and progesterone on spatial learning and memory in young and aged mice.

    PubMed

    Bodensteiner, Karin J; Stone, Ivan J; Ghiraldi, Loraina L

    2008-07-01

    Young (2-4 months) and aged (14-16 months) male Swiss-Webster albino mice (n = 7 per group) were subcutaneously injected with 20 mg/kg/day dehydroepiandrosterone sulfate (DHEAS), progesterone (P), DHEAS + P, or vehicle control and trained over a 5-day period in a Morris water maze. The subjects were tested 48 hr after training for memory recall as measured by latencies to locate the hidden platform, and trunk blood was collected immediately thereafter. As expected, latency to platform decreased for all groups over the 6 testing days, with aged mice taking longer to reach platform than did young mice. However, results did not support the hypotheses that DHEAS-treated mice would exhibit shorter latencies and that P-treated mice would show longer latencies to platform in comparison with age-matched controls. These results raise doubts about the effectiveness of commercially available supplements claiming to promote enhanced memory in humans.

  4. Peptidomimetics Based On Dehydroepiandrosterone Scaffold: Synthesis, Antiproliferation Activity, Structure-Activity Relationship, and Mechanisms

    NASA Astrophysics Data System (ADS)

    Wang, Xiaohui; Su, Haihuan; Wang, Wenda; Chen, Changshui; Cao, Xiufang

    2016-09-01

    A series of novel peptidomimetics bearing dehydroepiandrosterone moiety were designed, synthesized, and evaluated for their inhibition activities against cell proliferation. According to the preliminary studies on inhibitory activities, some of the newly prepared compounds indicated significantly inhibition activities against human hepatoma cancer (HepG2), human lung cancer (A549), human melanoma (A875) cell lines compared with the control 5-fluorouracil. Especially, compounds Ii (IC50 < 14 μM) and Ik (IC50 < 13 μM) exhibited obvious inhibition activities against all tested cell lines. The highly potential compound Ik induced apoptosis in HepG2 cells were analyzed by flow cytometry, and the apoptotic effects of compound Ik were further evaluated using Annexin V-FITC/propidium iodide dual staining assay, which revealed these highly potential compounds induced cell death in HepG2 cells at least partly by apoptosis.

  5. Peptidomimetics Based On Dehydroepiandrosterone Scaffold: Synthesis, Antiproliferation Activity, Structure-Activity Relationship, and Mechanisms

    PubMed Central

    Wang, Xiaohui; Su, Haihuan; Wang, Wenda; Chen, Changshui; Cao, Xiufang

    2016-01-01

    A series of novel peptidomimetics bearing dehydroepiandrosterone moiety were designed, synthesized, and evaluated for their inhibition activities against cell proliferation. According to the preliminary studies on inhibitory activities, some of the newly prepared compounds indicated significantly inhibition activities against human hepatoma cancer (HepG2), human lung cancer (A549), human melanoma (A875) cell lines compared with the control 5-fluorouracil. Especially, compounds Ii (IC50 < 14 μM) and Ik (IC50 < 13 μM) exhibited obvious inhibition activities against all tested cell lines. The highly potential compound Ik induced apoptosis in HepG2 cells were analyzed by flow cytometry, and the apoptotic effects of compound Ik were further evaluated using Annexin V-FITC/propidium iodide dual staining assay, which revealed these highly potential compounds induced cell death in HepG2 cells at least partly by apoptosis. PMID:27585479

  6. Dehydroepiandrosterone sulphate loading test and determination of plasma oestetrol concentration in late pregnancy.

    PubMed

    Schollberg, K; Seiler, E; Wagner, S

    1985-04-01

    Intravenous application of dehydroepiandrosterone sulphate (DHEA-S) was performed in 6 women with normal progress of pregnancy, 3 pregnant women with multiple pregnancy and 4 pregnants with intrauterine death of the foetus (32nd to 38th week). The oestetrol concentrations in blood serum were estimated during 5 h after the injection. In most cases an increase could be observed, but this was inhomogenous. The oestetrol concentration even rises in cases of intrauterine death of the foetus. In 7 cases of uncomplicated pregnancies the DHEA-S loading test was done within 2 to 6 h before delivery. The oestetrol concentration in the cord serum of the newborns was not higher than in controls without DHEA-S application, whereas oestradiol in maternal serum showed the expected rise. We conclude that the determination of oestetrol after DHEA-S loading can not be used for the judgement of the foetal situation. PMID:3160598

  7. Peptidomimetics Based On Dehydroepiandrosterone Scaffold: Synthesis, Antiproliferation Activity, Structure-Activity Relationship, and Mechanisms.

    PubMed

    Wang, Xiaohui; Su, Haihuan; Wang, Wenda; Chen, Changshui; Cao, Xiufang

    2016-01-01

    A series of novel peptidomimetics bearing dehydroepiandrosterone moiety were designed, synthesized, and evaluated for their inhibition activities against cell proliferation. According to the preliminary studies on inhibitory activities, some of the newly prepared compounds indicated significantly inhibition activities against human hepatoma cancer (HepG2), human lung cancer (A549), human melanoma (A875) cell lines compared with the control 5-fluorouracil. Especially, compounds Ii (IC50 < 14 μM) and Ik (IC50 < 13 μM) exhibited obvious inhibition activities against all tested cell lines. The highly potential compound Ik induced apoptosis in HepG2 cells were analyzed by flow cytometry, and the apoptotic effects of compound Ik were further evaluated using Annexin V-FITC/propidium iodide dual staining assay, which revealed these highly potential compounds induced cell death in HepG2 cells at least partly by apoptosis. PMID:27585479

  8. Laparoscopic Resection of an Adrenal Schwannoma

    PubMed Central

    Konstantinos, Toutouzas G.; Panagiotis, Kekis B.; Nikolaos, Michalopoulos V.; Ioannis, Flessas; Andreas, Manouras; Geogrios, Zografos

    2012-01-01

    Background and Objectives: Schwannomas are tumors originating from Schwann cells of the peripheral nerve sheath (neurilemma) of the neuroectoderm. Rarely, schwannomas can arise from the retroperitoneum and adrenal medulla. We describe a case of a 71-y-old woman who presented with an incidentally discovered adrenal tumor. Methods: Ultrasound and computed tomography scans revealed a lesion with solid and cystic areas originating from the left adrenal gland. The patient underwent complete laparoscopic resection of the tumor and the left adrenal gland. Results: Histopathological examination and immunohistochemical staining of the excised specimen revealed a benign schwannoma measuring 5.5×5×3.7 cm. To our knowledge, few other cases of laparoscopic resection of adrenal schwannomas have been reported. Conclusion: Because preoperative diagnosis of adrenal tumors is inconclusive, complete laparoscopic excision allows for definitive diagnosis with histological evaluation and represents the treatment of choice. PMID:23484583

  9. Adrenal cyst--a case report.

    PubMed

    Huang, S P; Chen, C C; Li, C C; Wu, W J; Chou, Y H; Huang, C H

    2001-03-01

    Adrenal cysts are rare and mostly silent clinically. Herein we report a case of adrenal cyst. A 55-year-old female was incidentally found to have a left suprarenal cystic lesion with a calcified wall by abdominal sonography during a work-up for her epigastralgia and left flank pain. Then, computed tomography (CT) revealed a left adrenal cystic mass with wall calcification, magnetic resonance imaging (MRI) showed left retroperitoneal cystic mass with fluid content, and angiography demonstrated an avascular lesion. Surgical exploration was performed via a flank incision and a calcified cystic adrenal mass was excised. The pathologic diagnosis was adrenal pseudocyst with calcified wall. We discuss the diagnosis and management of adrenal cyst and briefly review the literature.

  10. Androgen insensitive male rats display increased anxiety-like behavior on the elevated plus maze.

    PubMed

    Hamson, Dwayne K; Jones, Bryan A; Csupity, Attila S; Ali, Faezah M; Watson, Neil V

    2014-02-01

    Male rats carrying the testicular feminization mutation (Tfm-affected males) are insensitive to androgens, resulting in a female-typical peripheral phenotype despite possession of inguinal testes that are androgen secretory. Androgen-dependent neural and behavioral processes may likewise show atypical sexual differentiation. Interestingly, these mutant rats display elevated serum corticosterone, suggesting a chronic anxiety phenotype and dysregulated hypothalamic-pituitary-adrenal axis. In order to understand if elevated anxiety-like behavior is a possible mediating variable affecting the display of certain androgen-dependent behaviors, we compared the performance of Tfm-affected males to wild type males and females in the elevated plus maze (EPM). Two well-established indicators of anxiety-like behavior in the EPM were analyzed: total percentage of time spent on the open arms, and the percentage of open arm entries. We also analyzed the total number of open arm entries. Interestingly, Tfm-affected males spent less percentage of time on the open arms than both males and females, suggesting increased anxiety-like behavior. Percentage of open arm entries and the total number of arm entries was comparable between the groups, indicating that the observed decrease in the percentage of time spent on the open arms was not due to a global reduction in exploratory behavior. These data, in contrast to earlier reports, thus implicate androgen receptor-mediated functions in the expression of anxiety behaviors in male rats. Given that anxiety is widely reported as a precipitating factor in depression, studying the role of the androgen receptor in anxiety may give insights into the pathogenesis of major depressive disorder.

  11. Dehydroepiandrosterone-sulfate is associated with cardiovascular reactivity to stress in women.

    PubMed

    Hirokawa, Kumi; Ohira, Tetsuya; Nagayoshi, Mako; Kajiura, Mitsugu; Imano, Hironori; Kitamura, Akihiko; Kiyama, Masahiko; Okada, Takeo; Iso, Hiroyasu

    2016-07-01

    Cardiovascular stress reactivity is a predictor of atherosclerosis and cardiac events. Dehydroepiandrosterone (DHEA) protects against cardiovascular diseases, but results among previous studies have been inconsistent. We investigated the association between dehydroepiandrosterone-sulfate (DHEA-s) and cardiovascular stress reactivity in Japanese women and men. Among 979 healthy Japanese subjects (641 women and 338 men), serum levels of DHEA-s, systolic blood pressure (SBP) and diastolic blood pressure (DBP), heart rate, heart rate variability, and peripheral blood flow were measured under rest and two types of task. Mean differences in measured variables during tasks and a post-task period were calculated as changes in stress reactivity. Variables of stress reactivity were adjusted for multiple potential confounding factors. In women, DHEA-s levels showed positive associations with changes in SBP and DBP (standardized beta=0.12, p=0.020; 0.17, 0.002, respectively). Stratification by menopausal status and other lifestyle factors (e.g., smoking status, alcohol consumption) were conducted. Significant positive associations remained in pre-menopausal (standardized beta=0.13, p=0.037; 0.18, 0.005), non-smoking (0.12, 0.010; 0.18, <0.001), and non-drinking women (0.14, 0.021; 0.21, 0.001), and women without a medical history (0.15, 0.020; 0.20, 0.001). In men, there was no significant association between DHEA-s levels and changes in stress reactivity. DHEA-s levels were positively associated with high blood-pressure reactivity to stress in women, and being menopausal, smoking, and alcohol consumption modified this association. PMID:27104812

  12. The transcriptional programme of the androgen receptor (AR) in prostate cancer.

    PubMed

    Lamb, Alastair D; Massie, Charlie E; Neal, David E

    2014-03-01

    The androgen receptor (AR) is essential for normal prostate and prostate cancer cell growth. AR transcriptional activity is almost always maintained even in hormone relapsed prostate cancer (HRPC) in the absence of normal levels of circulating testosterone. Current molecular techniques, such as chromatin-immunoprecipitation sequencing (ChIP-seq), have permitted identification of direct AR-binding sites in cell lines and human tissue with a distinct coordinate network evident in HRPC. The effectiveness of novel agents, such as abiraterone acetate (suppresses adrenal androgens) or enzalutamide (MDV3100, potent AR antagonist), in treating advanced prostate cancer underlines the on-going critical role of the AR throughout all stages of the disease. Persistent AR activity in advanced disease regulates cell cycle activity, steroid biosynthesis and anabolic metabolism in conjunction with regulatory co-factors, such as the E2F family, c-Myc and signal transducer and activator of transcription (STAT) transcription factors. Further treatment approaches must target these other factors.

  13. Operative approaches to the adrenal gland.

    PubMed

    Guz, B V; Straffon, R A; Novick, A C

    1989-08-01

    Various adrenal disorders necessitate surgical intervention, and familiarity with adrenal pathophysiology and surgical anatomy is crucial to the success of these procedures. A number of operative approaches--anterior, posterior, flank, and thoracoabdominal--are available; the choice must be made on the basis of the patient's adrenal pathology, body habitus, and surgical history as well as the surgeon's experience and familiarity with the different options. PMID:2665278

  14. Adrenal Failure due to Adrenal Metastasis of Lung Cancer: A Case Report

    PubMed Central

    Faulhaber, Gustavo Adolpho Moreira; Borges, Flavia Kessler; Ascoli, Aline Maria; Seligman, Renato; Furlanetto, Tania Weber

    2011-01-01

    We report a case of a patient with adrenal failure due to bilateral adrenal metastasis of lung cancer. This is a rare presentation of lung cancer. We review the differential diagnosis of weight loss and how to make diagnosis of adrenal insufficiency. PMID:22606443

  15. 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.

  16. 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.

  17. The association of dehydroepiandrosterone and dehydroepiandrosterone sulfate with anxiety sensitivity and electronic diary negative affect among smokers with and without posttraumatic stress disorder.

    PubMed

    Van Voorhees, Elizabeth E; Dennis, Michelle F; McClernon, F Joseph; Calhoun, Patrick S; Buse, Natalie A; Beckham, Jean C

    2013-08-01

    Posttraumatic stress disorder (PTSD) is associated with increased smoking initiation, maintenance, and relapse. Dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) are neurosteroids that have been associated with mood measures as well as smoking status, and nicotine is associated with increased DHEA and DHEAS levels. Given the difficulties with mood experienced by smokers with PTSD, the purpose of the current study was to evaluate the association between negative affect and anxiety sensitivity with DHEA and DHEAS levels. Ninety-six smokers with and without PTSD provided blood samples for neurosteroid analyses and completed self-report measures of anxiety sensitivity and electronic diary ratings of negative affect. As expected, PTSD smokers reported higher levels of anxiety sensitivity (F(1,94) = 20.67, partial η2 = 0.18, P < 0.0001) and negative affect (F(1,91) = 7.98, partial η2 = 0.08, P = 0.006). After accounting for age and sex, DHEAS was significantly inversely associated with both anxiety sensitivity (F(3,92) = 6.97, partial η2 = 0.07, P = 0.01) and negative affect (F(3,87) = 10.52, partial η2 = 0.11, P = 0.002) across groups. Effect sizes indicated that these effects are moderate to high. No significant interactions of diagnosis and DHEA(S) levels with mood measures were detected. Given that nicotine is known to elevate DHEA(S) levels, these results suggest that DHEAS may serve as a biomarker of the association between mood and nicotine among smokers. Implications for the results include (1) the use of DHEAS measurement across time and across quit attempts and (2) the potential for careful use of DHEA supplementation to facilitate abstinence during smoking cessation.

  18. Investigation of patients with atypical or severe hyperandrogenaemia including androgen-secreting ovarian teratoma.

    PubMed

    Dennedy, Michael Conall; Smith, Diarmuid; O'Shea, Donal; McKenna, T Joseph

    2010-02-01

    Approximately 7% of women of reproductive age manifest polycystic ovary syndrome (PCOS) and <0.5% have other causes of hyperandrogenism including congenital adrenal hyperplasia (CAH), androgen-secreting tumour of an ovary or an adrenal gland, Cushing's syndrome or hyperthecosis. The presence of features atypical of PCOS should prompt more extensive evaluation than that usually undertaken. Features atypical of PCOS include the onset of symptoms outside the decade of 15-25 years, rapid progression of symptoms, the development of virilization and a serum testosterone concentration in excess of twice the upper limit of the reference range. Ethnic background, family history and specific clinical findings, e.g. Cushingoid appearance, may inform a focused investigation. Otherwise, patients should have measurement of 17-hydroxyprogesterone (17-OHP) under basal conditions ideally in the early morning, and if abnormal, they should have measurement of 17-OHP one hour after the administration of synthetic ACTH, 250 microg i.v., to screen for CAH, which is present in approximately 2% of hyperandrogenic patients. The overnight cortisol suppression test employing 1 mg dexamethasone at midnight is a sensitive test for Cushing's syndrome. Coronal tomographic (CT) scanning of the adrenals and transvaginal ultrasonography of the ovaries are the investigations of choice when screening for tumours in these organs. Less frequently required is catheterization and sampling from both adrenal and ovarian veins, which is a technically demanding procedure with potential complications which may provide definitive diagnostic information not available from other investigations. Illustrative case reports highlight some complexities in the investigation of hyperandrogenic patients presenting with features atypical of PCOS and include only the ninth case report of an androgen-secreting ovarian teratoma.

  19. 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

  20. Serum androgen-anabolic hormones and the risk of rheumatoid arthritis

    PubMed Central

    Heikkila, R; Aho, K; Heliovaara, M; Knekt, P; Reunanen, A; Aromaa, A; Leino, A; Palosuo, T

    1998-01-01

    OBJECTIVE—It has been hypothesised, mainly on the basis of indirect evidence, that low serum concentrations of androgen-anabolic hormones would play a causal part in the aetiology of rheumatoid arthritis (RA).
METHODS—A case-control study was nested with a Finnish cohort of 19 072 adults who had neither arthritis nor a history of it at the baseline examination during 1973-1977. Pre-illness serum specimens for the assay of testosterone and dehydroepiandrosterone sulphate (DHEAS) were available from 116 cases who had developed RA by late 1989. Three controls per each incident case were individually matched for sex, age, and municipality.
RESULTS—The mean testosterone concentration was 1.4 nmol/l in those 84 women who developed RA and 1.4 nmol/l in their controls; the corresponding figures for DHEAS were 5.2 µmol/l and 5.5 µmol/l, respectively. Mean testosterone concentration in the 32 male cases was 26.1 nmol/l and 26.4 nmol/l in their controls; the corresponding figures for DHEAS were 11.2 µmol/l and 10.1 µmol/l, respectively. Analysis by subgroups (rheumatoid factor positive and negative disease, premenopausal and postmenopausal women) and by hormone distributions showed no differences.
CONCLUSION—The findings are not in line with the contention that low concentrations of testosterone and DHEAS play a part in the aetiology of RA.

 Keywords: rheumatoid arthritis; epidemiology; testosterone; dehydroepiandrosterone sulphate PMID:9741311

  1. 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

  2. Targeting intratumoral androgens: statins and beyond

    PubMed Central

    Schweizer, Michael T.; Yu, Evan Y.

    2016-01-01

    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

  3. Adrenal haemorrhage with cholestasis and adrenal crisis in a newborn of a diabetic mother.

    PubMed

    Koklu, Esad; Kurtoglu, Selim; Akcakus, Mustafa; Koklu, Selmin

    2007-03-01

    The large hyperaemic foetal adrenal gland is vulnerable to vascular damage. This may occur in the neonatal period as a consequence of difficult labour, or its aetiology may not be apparent. The spectrum of presentation is considerable, ranging from asymptomatic to severe life-threatening intra-abdominal haemorrhage. The presentation of adrenal insufficiency may be delayed but the regenerative capacity of the adrenal is great, and most adrenal haemorrhage is not associated with significantly impaired function. Some reports showed that cholestatic hepatopathy with congenital hypopituitarism reversed by hydrocortisone treatment is considered in the context of the endocrine syndrome, probably as a consequence of the adrenal failure. We describe a case of bilateral adrenal haemorrhage with hepatitis syndrome and persistent hypoglycaemia in a newborn male with striking features of neonatal cholestasis and adrenal crisis.

  4. 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.

  5. Yolk androgens reduce offspring survival.

    PubMed

    Sockman, K W; Schwabl, H

    2000-07-22

    Females may favour some offspring over others by differential deposition of yolk hormones. In American kestrels (Falco sparverius), we found that yolks of eggs laid late in the sequence of a clutch had more testosterone (T) and androstenedione (A4) than yolks of first-laid eggs. To investigate the effects of these yolk androgens on nestling 'fitness', we injected both T and A4 into the yolks of first-laid eggs and compared their hatching time, nestling growth and nestling survival with those of first-laid eggs in which we injected vehicle as a control. Compared to controls, injection of T and A4 at a dose intended to increase their levels to those of later-laid eggs delayed hatching and reduced nestling growth and survival rates. Yolk androgen treatment of egg 1 had no effect on survival of siblings hatching from subsequently laid eggs. The adverse actions of yolk androgen treatment in the kestrel are in contrast to the favourable actions of yolk T treatment found previously in canaries (Serinus canaria). Additional studies are necessary in order to determine whether the deposition of yolk androgens is an adaptive form of parental favouritism or an adverse by-product of endocrine processes during egg formation. Despite its adaptive significance, such 'transgenerational' effects of steroid hormones may have helped to evolutionarily shape the hormonal mechanisms regulating reproduction. PMID:10983830

  6. Yolk androgens reduce offspring survival.

    PubMed Central

    Sockman, K W; Schwabl, H

    2000-01-01

    Females may favour some offspring over others by differential deposition of yolk hormones. In American kestrels (Falco sparverius), we found that yolks of eggs laid late in the sequence of a clutch had more testosterone (T) and androstenedione (A4) than yolks of first-laid eggs. To investigate the effects of these yolk androgens on nestling 'fitness', we injected both T and A4 into the yolks of first-laid eggs and compared their hatching time, nestling growth and nestling survival with those of first-laid eggs in which we injected vehicle as a control. Compared to controls, injection of T and A4 at a dose intended to increase their levels to those of later-laid eggs delayed hatching and reduced nestling growth and survival rates. Yolk androgen treatment of egg 1 had no effect on survival of siblings hatching from subsequently laid eggs. The adverse actions of yolk androgen treatment in the kestrel are in contrast to the favourable actions of yolk T treatment found previously in canaries (Serinus canaria). Additional studies are necessary in order to determine whether the deposition of yolk androgens is an adaptive form of parental favouritism or an adverse by-product of endocrine processes during egg formation. Despite its adaptive significance, such 'transgenerational' effects of steroid hormones may have helped to evolutionarily shape the hormonal mechanisms regulating reproduction. PMID:10983830

  7. 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

  8. Unilateral adrenal hemorrhagic infarction in essential thrombocythemia.

    PubMed

    Burnet, G; Lambert, M; Annet, L; Lefebvre, C

    2015-12-01

    Adrenal hemorrhage is a rare disease associated with various conditions. We report a case of a 68-year-old woman with abdominal and back pain. The diagnostic work-up showed a left adrenal gland infarction associated with essential thrombocythemia. Treatment consisted in painkillers and treating the underlying condition in order to prevent further thrombotic events.

  9. Images of pheochromocytoma in adrenal glands.

    PubMed

    McDermott, Shaunagh; McCarthy, Colin J; Blake, Michael A

    2015-08-01

    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.

  10. 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.

  11. [Two cystic retroperitoneal lesions mimicking adrenal cysts].

    PubMed

    Grabellus, F; Dereskewitz, C; Schmitz, K J; Kaiser, G M; Kühl, H; Kersting, C; Frilling, A; Metz, K A; Baba, H A

    2005-05-01

    Adrenal cysts are uncommon lesions and most of them are found incidentally during abdominal imaging. We report on two benign extraadrenal lesions mimicking adrenal tumors in abdominal imaging. The histopathological investigation of the lesions revealed a foregut duplication cyst of the lesser gastric curvature and an epithelial inclusion cyst (epidermoid cyst) in an intrapancreatic accessory spleen respectively.

  12. Laparoscopic extirpation of giant adrenal ganglioneuroma

    PubMed Central

    Abraham, George P; Siddaiah, Avinash T; Das, Krishanu; Krishnamohan, Ramaswami; George, Datson P; Abraham, Jisha J; Chandramathy, Sreerenjini K

    2014-01-01

    Laparoscopic adrenalectomy is the standard of care for management of adrenal neoplasms. However, large sized adrenal lesions are considered as relative contraindication for laparoscopic extirpation. We report laparoscopic excision of giant ganglioneuroma of adrenal gland in a 33-year-old female patient. Patient was presented with left loin pain of 2 months duration. Computed tomography (CT) scan was suggestive of non-enhancing left suprarenal mass measuring 17 × 10 cm. Preoperative endocrine evaluation ruled out functional adrenal tumor. Patient underwent transperitoneal excision of suprarenal mass. The lesion could be completely extirpated laparoscopically. Duration of surgery was 250 minutes. Estimated blood loss was 230 milliliters. Specimen was extracted through pfannenstiel incision. No significant intraoperative or postoperative happenings were recorded. Microscopic features were suggestive of ganglioneuroma of adrenal gland. PMID:24501511

  13. Diagnosis and management of adrenal insufficiency.

    PubMed

    Bancos, Irina; Hahner, Stefanie; Tomlinson, Jeremy; Arlt, Wiebke

    2015-03-01

    Adrenal insufficiency continues to be a challenge for patients, their physicians, and researchers. During the past decade, long-term studies have shown increased mortality and morbidity and impaired quality of life in patients with adrenal insufficiency. These findings might, at least partially, be due to the failure of glucocorticoid replacement therapy to closely resemble physiological diurnal secretion of cortisol. The potential effect of newly developed glucocorticoid drugs is a focus of research, as are the mechanisms potentially underlying increased morbidity and mortality. Adrenal crisis remains a threat to lives, and awareness and preventative measures now receive increasing attention. Awareness should be raised in medical teams and patients about adrenal insufficiency and management of adrenal crisis to improve clinical outcome.

  14. Guidelines for the diagnosis and treatment of adrenal insufficiency in the adult.

    PubMed

    de Miguel Novoa, Paz; Vela, Elena Torres; García, Nuria Palacios; Rodríguez, Manuela Moreira; Guerras, Icíar Solache; Martínez de Salinas Santamaría, María de Los Ángeles; Masó, Anna Aulinas

    2014-09-01

    Adrenal insufficiency (AI) is a disease characterized by a deficient production or action of glucocorticoids, with or without deficiency in mineral corticoids and/or adrenal androgens. It can result from disease intrinsic to the adrenal cortex (primary AI), from pituitary diseases that hamper the release of corticotropin (secondary AI) or from hypothalamic disorders that impair the secretion of the corticotropin-releasing hormone (tertiary AI). It is a disease with a low prevalence but its impact on the affected individual is very high as it can be life-threathening if not treated or lead to health problems if inadequately treated. However, currently there are no specific guidelines for the management of this disease. Therefore, at the proposal of the Spanish Society of Endocrinology and Nutrition (SEEN) board, a task-force under the Neuroendocrinology Knowledge Area of the SEEN was established, with the mandate of updating the diagnosis and treatment of AI. In fulfilment of this mandate the task-force has elaborated the present guide that, based on a comprehensive review of literature, is intended to provide an answer to questions related to the management of this disease. It is, therefore, an essentially practical document, mainly aimed at guiding the health professionals involved in the care of IA patients.

  15. Extensive expertise in endocrinology. Adrenal crisis.

    PubMed

    Allolio, Bruno

    2015-03-01

    Adrenal crisis is a life-threatening emergency contributing to the excess mortality of patients with adrenal insufficiency. Studies in patients on chronic replacement therapy for adrenal insufficiency have revealed an incidence of 5-10 adrenal crises/100 patient years and suggested a mortality rate from adrenal crisis of 0.5/100 patient years. Patients with adrenal crisis typically present with profoundly impaired well-being, hypotension, nausea and vomiting, and fever responding well to parenteral hydrocortisone administration. Infections are the major precipitating causes of adrenal crisis. Lack of increased cortisol concentrations during infection enhances pro-inflammatory cytokine release and sensitivity to the toxic effects of these cytokines (e.g. tumour necrosis factor alpha). Furthermore, pro-inflammatory cytokines may impair glucocorticoid receptor function aggravating glucocorticoid deficiency. Treatment of adrenal crisis is simple and highly effective consisting of i.v. hydrocortisone (initial bolus of 100  mg followed by 200  mg over 24  h as continuous infusion) and 0.9% saline (1000  ml within the first hour). Prevention of adrenal crisis requires appropriate hydrocortisone dose adjustments to stressful medical procedures (e.g. major surgery) and other stressful events (e.g. infection). Patient education is a key for such dose adjustments but current education concepts are not sufficiently effective. Thus, improved education strategies are needed. Every patient should carry an emergency card and should be provided with an emergency kit for parenteral hydrocortisone self-administration. A hydrocortisone pen would hold a great potential to lower the current barriers to hydrocortisone self-injection. Improved patient education and measures to facilitate parenteral hydrocortisone self-administration in impending crisis are expected to significantly reduce morbidity and mortality from adrenal crisis.

  16. A case of human intramuscular adrenal gland transplantation as a cure for chronic adrenal insufficiency.

    PubMed

    Grodstein, E; Hardy, M A; Goldstein, M J

    2010-02-01

    Intramuscular endocrine gland transplantation has been well described as it pertains to parathyroid autotransplantation; however, transplantation of the adrenal gland is less well characterized. While adrenal autotransplantation in the setting of Cushing's disease has been described, intramuscular adrenal allotransplantation as a cure for adrenal insufficiency to our knowledge has not been previously carried out. Current treatment for adrenal insufficiency leaves patients without diurnal variation in cortisol release and susceptible to the detrimental effects of chronic hypercortisolism. We describe here the case of a 5-year-old girl with renal failure who had adrenal insufficiency following fulminant meningococcemia that led to requirements for both stress-dose steroid and mineralocorticoid replacement. Ten months after the onset of her disease, she received a simultaneous renal and adrenal gland transplant from her mother. The adrenal gland allograft was morselized into 1 mm(3) segments and implanted into three 2 cm pockets created in her rectus abdominis muscle. Three years after surgery, her allograft remains fully functional, responding well to adrenocorticotropin hormone stimulation and the patient does not require any steroid or mineral-corticoid supplementation. We believe this case represents the first description of successful functional intramuscular adrenal allograft transplantation with long-term follow up as a cure for adrenal insufficiency.

  17. Hypothalamic pituitary adrenal axis and prolactin abnormalities in suicidal behavior.

    PubMed

    Pompili, Maurizio; Serafini, Gianluca; Palermo, Mario; Seretti, Maria Elena; Stefani, Henry; Angeletti, Gloria; Lester, David; Amore, Mario; Girardi, Paolo

    2013-11-01

    Hypothalamic-Pituitary-Adrenal (HPA) axis hyperactivity measured with the dexamethasone suppression test and the dexamethesone/CRH test may have some predictive power for suicidal behavior in patients with mood disorders. Increased prolactin (PRL) levels may be related both to physiological and pathological conditions. HPA-axis abnormalities and increased levels of PRL may coexist, and common neuroendocrine changes may activate both HPA axis and PRL release. HPA-axis hyperactivity is presumably present in a large subpopulation of depressed subjects. Suicidal behavior is considered to be a form of inward-directed aggression, and aggressive behavior has been connected to high androgen levels. However, lower plasma total testosterone levels have also been reported in subjects with depression and higher suicidality. Lipid/immune dysregulations, the increased ratio of blood fatty acids, and increased PRL levels may each be associated with the increased production of pro-inflammatory cytokines, which have been reported in patients with major depression and patients engaging in suicidal behavior. Although no studies have been done to determine whether ante-mortem physical stress may be detected by raised post-mortem PRL, this would be of great interest for physicians.

  18. Astrocytes as a target for neuroprotection: Modulation by progesterone and dehydroepiandrosterone.

    PubMed

    Arbo, Bruno Dutra; Bennetti, Fernando; Ribeiro, Maria Flavia

    2016-09-01

    Stroke and traumatic injuries of the brain and spinal cord are major public health issues. In the last few decades, hundreds of clinical trials with patients suffering from these conditions have been done, however, most of them had not succeeded and there is still the need to develop more effective treatments for these conditions. Astrocytes play critical roles in the development, function and survival of neurons in the central nervous system. These cells are implicated in the pathophysiology and in the response to several neuropathological conditions and may represent potential cell targets for neuroprotective strategies. Progesterone and dehydroepiandrosterone (DHEA) are neuroactive steroids that modulate neuronal and astroglial function and have neuroprotective effects in different experimental models, being potential candidates to the development of new therapeutic approaches for brain and spinal cord injuries. The aim of this review is to discuss the role of astrocytes in the pathophysiology of brain and spinal cord injuries and how they could be modulated by progesterone and DHEA for the treatment of these conditions.

  19. Biotransformation of dehydro-epi-androsterone by Aspergillus parasiticus: Metabolic evidences of BVMO activity.

    PubMed

    Mascotti, M Laura; Palazzolo, Martín A; Bisogno, Fabricio R; Kurina-Sanz, Marcela

    2016-05-01

    The research on the synthesis of steroids and its derivatives is of high interest due to their clinical applications. A particular focus is given to molecules bearing a D-ring lactone like testolactone because of its bioactivity. The Aspergillus genus has been used to perform steroid biotransformations since it offers a toolbox of redox enzymes. In this work, the use of growing cells of Aspergillus parasiticus to study the bioconversion of dehydro-epi-androsterone (DHEA) is described, emphasizing the metabolic steps leading to D-ring lactonization products. It was observed that A. parasiticus is not only capable of transforming bicyclo[3.2.0]hept-2-en-6-one, the standard Baeyer-Villiger monooxygenase (BVMO) substrate, but also yielded testololactone and the homo-lactone 3β-hydroxy-17a-oxa-D-homoandrost-5-en-17-one from DHEA. Moreover, the biocatalyst degraded the lateral chain of cortisone by an oxidative route suggesting the action of a BVMO, thus providing enough metabolic evidences denoting the presence of BVMO activity in A. parasiticus. Furthermore, since excellent biotransformation rates were observed, A. parasiticus is a promising candidate for the production of bioactive lactone-based compounds of steroidal origin in larger scales. PMID:27025973

  20. Dehydroepiandrosterone (DHEA) reduces embryo aneuploidy: direct evidence from preimplantation genetic screening (PGS)

    PubMed Central

    2010-01-01

    Background Dehydroepiandrosterone (DHEA) has been reported to improve pregnancy chances in women with diminished ovarian reserve (DOR), and to reduce miscarriage rates by 50-80%. Such an effect is mathematically inconceivable without beneficial effects on embryo ploidy. This study, therefore, assesses effects of DHEA on embryo aneuploidy. Methods In a 1:2, matched case control study 22 consecutive women with DOR, supplemented with DHEA, underwent preimplantation genetic screening (PGS) of embryos during in vitro fertilization (IVF) cycles. Each was matched by patient age and time period of IVF with two control IVF cycles without DHEA supplementation (n = 44). PGS was performed for chromosomes X, Y, 13, 16, 18, 21 and 22, and involved determination of numbers and percentages of aneuploid embryos. Results DHEA supplementation to a significant degree reduced number (P = 0.029) and percentages (P < 0.001) of aneuploid embryos, adjusted for relevant covariates. Short term supplementation (4-12 weeks) resulted in greatest reduction in aneuploidy (21.6%, 95% CI -2.871-46.031). Discussion Beneficial DHEA effects on DOR patients, at least partially, are the likely consequence of lower embryo aneuploidy. DHEA supplementation also deserves investigation in older fertile women, attempting to conceive, where a similar effect, potentially, could positively affect public health. PMID:21067609

  1. Dehydroepiandrosterone protects mice from endotoxin toxicity and reduces tumor necrosis factor production.

    PubMed Central

    Danenberg, H D; Alpert, G; Lustig, S; Ben-Nathan, D

    1992-01-01

    Recent reports have demonstrated an immunomodulating activity of dehydroepiandrosterone (DHEA) different from that described for glucocorticoids. The present study was designed to test DHEA's activity in endotoxic shock and to investigate its effect on endotoxin-induced production of tumor necrosis factor (TNF). Mortality of CD-1 mice exposed to a lethal dose of lipopolysaccharide (LPS; 800 micrograms per mouse) was reduced from 95 to 24% by treatment with a single dose of DHEA, given 5 min before LPS. LPS administration resulted in high levels of TNF, a response that was significantly blocked by DHEA, both in vivo and in vitro. DHEA treatment also reduced LPS-induced increments in serum corticosterone levels, a parameter considered not to be mediated by TNF. In another experimental model, mice sensitized with D-galactosamine, followed by administration of recombinant human TNF, were subjected to 89% mortality rate, which was reduced to 55% in DHEA-treated mice. These data show that DHEA protects mice from endotoxin lethality. The protective effect is probably mediated by reduction of TNF production as well as by effecting both TNF-induced and non-TNF-induced phenomena. PMID:1444309

  2. Diurnal and stress-reactive dehydroepiandrosterone levels and telomere length in youth.

    PubMed

    Dismukes, Andrew R; Meyer, Vanessa J; Shirtcliff, Elizabeth A; Theall, Katherine P; Esteves, Kyle C; Drury, Stacy S

    2016-05-01

    The current investigation examined the association between the aging-related biomarkers dehydroepiandrosterone (DHEA) and telomere length (TL) in community-recruited African-American youth. The examination of DHEA included stress reactive, basal and diurnal sampling, in order to elucidate the underlying physiological process that may overlap with TL. One hundred and two participants completed the Trier Social Stressor Test for children (TSST-C). TL was obtained from all youth from buccal swabs on the same day as the TSST-C. Saliva samples from 83 participants were obtained over the course of two additional days to measure waking and diurnal levels of DHEA. DHEA diurnal slope was a robust predictor of TL (B=0.516, P<0.05), while other DHEA values were not significantly associated with TL. This study is one of the first studies to examine basal, diurnal and reactivity measurements of DHEA in youth. Furthermore, this is the first study, to our knowledge, to demonstrate a positive association between DHEA, a putative anti-aging hormone, and TL, an indicator of cellular aging. PMID:27221260

  3. Ergosteroids: induction of thermogenic enzymes in liver of rats treated with steroids derived from dehydroepiandrosterone.

    PubMed Central

    Lardy, H; Partridge, B; Kneer, N; Wei, Y

    1995-01-01

    Dehydroepiandrosterone (DHEA), an intermediate in the biosynthesis of testosterone and estrogens, exerts several physiological effects not involving the sex hormones. When fed to rats it induces the thermogenic enzymes mitochondrial sn-glycerol-3-phosphate dehydrogenase and cytosolic malic enzyme in their livers. Animals and humans, and their excised tissues, are known to hydroxylate DHEA at several positions and to interconvert 7 alpha-hydroxy-DHEA, 7 beta-hydroxy-DHEA, 7-oxo-DHEA, and the corresponding derivatives of androst-5-enediol. We report here that these 7-oxygenated derivatives are active inducers of these thermogenic enzymes in rats and that the 7-oxo derivatives are more active than the parent steroids. We postulate that the 7 alpha-hydroxy and 7-oxo derivatives are on a metabolic pathway from DHEA to more active steroid hormones. These 7-oxo steroids have potential as therapeutic agents because of their increased activity and because they are not convertible to either testosterone or estrogens. PMID:7604042

  4. Diurnal and stress-reactive dehydroepiandrosterone levels and telomere length in youth

    PubMed Central

    Dismukes, Andrew R; Meyer, Vanessa J; Shirtcliff, Elizabeth A; Theall, Katherine P; Esteves, Kyle C

    2016-01-01

    The current investigation examined the association between the aging-related biomarkers dehydroepiandrosterone (DHEA) and telomere length (TL) in community-recruited African-American youth. The examination of DHEA included stress reactive, basal and diurnal sampling, in order to elucidate the underlying physiological process that may overlap with TL. One hundred and two participants completed the Trier Social Stressor Test for children (TSST-C). TL was obtained from all youth from buccal swabs on the same day as the TSST-C. Saliva samples from 83 participants were obtained over the course of two additional days to measure waking and diurnal levels of DHEA. DHEA diurnal slope was a robust predictor of TL (B=0.516, P<0.05), while other DHEA values were not significantly associated with TL. This study is one of the first studies to examine basal, diurnal and reactivity measurements of DHEA in youth. Furthermore, this is the first study, to our knowledge, to demonstrate a positive association between DHEA, a putative anti-aging hormone, and TL, an indicator of cellular aging. PMID:27221260

  5. Dehydroepiandrosterone reverses chronic hypoxia/reoxygenation-induced right ventricular dysfunction in rats.

    PubMed

    Dumas de La Roque, Eric; Bellance, Nadège; Rossignol, Rodrigue; Begueret, Hugues; Billaud, Marie; dos Santos, Pierre; Ducret, Thomas; Marthan, Roger; Dahan, Diana; Ramos-Barbón, David; Amor-Carro, Óscar; Savineau, Jean-Pierre; Fayon, Michael

    2012-12-01

    Dehydroepiandrosterone (DHEA) prevents chronic hypoxia-induced pulmonary hypertension and associated right ventricle dysfunction in rats. In this animal model, reoxygenation following hypoxia reverses pulmonary hypertension but not right ventricle dysfunction. We thus studied the effect of DHEA on the right ventricle after reoxygenation, i.e. after a normoxic recovery phase secondary to chronic hypoxia in rats. Right ventricle function was assessed in vivo by Doppler echocardiography and in vitro by the isolated perfused heart technique in three groups of animals: control, recovery (21 days of hypoxia followed by 21 days of normoxia) and recovery DHEA (30 mg · kg(-1) every 2 days during the recovery phase). Right ventricle tissue was assessed by optical and electron microscopy. DHEA abolished right ventricle diastolic dysfunction, as the echographic E wave remained close to that of controls (mean ± SD 76.5 ± 2.4 and 79.7 ± 1.7 cm · s(-1), respectively), whereas it was diminished to 40.3 ± 3.7 in the recovery group. DHEA also abolished right ventricle systolic dysfunction, as shown by the inhibition of the increase in the slope of the pressure-volume curve in isolated heart. The DHEA effect was related to cardiac myocytes proliferation. In conclusion, DHEA prevents right ventricle dysfunction in this animal model by preventing cardiomyocyte alteration.

  6. Dehydroepiandrosterone-enhanced dual specificity protein phosphatase (DDSP) prevents diet-induced and genetic obesity.

    PubMed

    Watanabe, Tetsuhiro; Ashida, Kenji; Goto, Kiminobu; Nawata, Hajime; Takayanagi, Ryoichi; Yanase, Toshihiko; Nomura, Masatoshi

    Dehydroepiandrosterone (DHEA) exerts a wide variety of therapeutic effects against medical disorders, such as diabetes and obesity. However, the molecular basis of DHEA action remains to be clarified. Previously, we reported that DHEA-enhanced dual specificity protein phosphatase, designated DDSP, is one of the target molecules of DHEA. To examine the role of DDSP in DHEA signaling, we generated mice that carry a DDSP transgene in which expression is driven by the CAG promoter (DDSP-Tg). DDSP-Tg mice weighed significantly less than wild-type (WT) control mice when a high fat diet was supplied (p < 0.01). No difference in food-intake or locomotor activity was found between DDSP-Tg and WT mice. Oxygen consumption of DDSP-Tg mice was higher than that of WT mice (p < 0.01), which suggested an increase in basal metabolism in DDSP-Tg mice. To further investigate the role of DDSP in genetic obese mice, DDSP-Tg mice with a db/db background were generated (DDSP-Tg db/db). We observed cancellation of obesity by the db/db mutation and development of a cachexic phenotype in DDSP-Tg db/db mice. In conclusion, our study shows that expression of DDSP leads to prevention of diet-induced and genetic (db/db) obesity. Anti-obese effects of DHEA might be mediated through DDSP, which might be a therapeutic target for intervention of obesity.

  7. Sonography of the adrenal glands in the adult.

    PubMed

    Kim, Kyoung Won; Kim, Jeong Kon; Choi, Hyuck Jae; Kim, Mi-hyun; Lee, Jeongjin; Cho, Kyoung-Sik

    2012-01-01

    Although its capability has been overlooked, sonography can be a useful screening tool for adrenal lesion in adults. In this article, we discuss scan technique, patient positioning, and anatomic consideration for adrenal sonography in adults and illustrate sonographic appearance of normal adrenal gland as well as adrenal tumors and tumor-like lesions.

  8. 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

  9. 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

  10. Modulation of adrenal gap junction expression.

    PubMed

    Murray, S A; Shah, U S

    1998-01-01

    To increase our knowledge of the role of peptide hormone stimulation in gap junction protein expression and adrenal cortical cell function, primary rat adrenal cortical cells were treated with adrenocorticotropin, and gap junction proteins were measured. Immunocytochemistry and western blot analysis were used to detect and characterize gap junction type and distribution. The gap junction protein, connexin 43 (alpha 1), was detected. Analysis of six connexin protein types did not reveal gap junction species other than alpha 1. Cells of the inner adrenal cortical zones, zonae fasciculata and reticularis, were demonstrated to have the highest number of gap junctions per cell in the adrenal gland. Adrenal cell cultures enriched for the two inner cortical adrenal zones were established and demonstrated also to express alpha 1 gap junction protein. Adrenocorticotropin (40 mUnits/ml) and dibutyryl cyclic adenosine monophosphate (1 mM) treatments increased alpha 1 gap junction protein levels and decreased cell proliferation rates in the cell cultures. The results are consistent with the hypothesis that gap junction expression can be regulated by adrenocorticotropin acting through the second messenger cyclic adenosine monophosphate. It can be suggested that gap junction expression in the adrenal gland may be under hormonal influence, and that gap junctions serve as passage for movement of molecules involved in control of cell proliferation. PMID:9694574

  11. 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.

  12. 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.

  13. A novel cell layer without corticosteroid-synthesizing enzymes in rat adrenal cortex: histochemical detection and possible physiological role.

    PubMed

    Mitani, F; Suzuki, H; Hata, J; Ogishima, T; Shimada, H; Ishimura, Y

    1994-07-01

    A stratum of cells that did not contain both aldosterone synthase cytochrome P450 (cytochrome P450aldo) and cytochrome P45011 beta was found immunohistochemically between the zona glomerulosa and the zona fasciculata of the rat adrenal cortex. As cytochromes P450aldo and P45011 beta are the enzymes responsible for the biosynthesis of aldosterone and corticosterone, respectively, the cells there are considered to be incapable of synthesizing both aldosterone and corticosterone. Furthermore, the cells are regarded as inert in producing adrenal androgens, because rat adrenal cortex is known to lack steroid 17 alpha-hydroxylase. Thus, the stratum is composed of cells that do not synthesize any of the major corticosteroids in significant quantities. It was 5-10 cells thick under normal feeding conditions, but diminished to 4-5 cells thick when animals were maintained under Na restriction, which is known to stimulate the secretion of angiotensin-II. When the distribution of 5-bromo-2'-deoxyuridine-labeled nuclei in the adrenocortex from BrdU-administered rats was examined, the stained nuclei were concentrated in and around the cell stratum. The pulse-chase experiments showed that the labeled cells migrated out of this layer and into the zonae fasciculata-reticularis. On the basis of these findings, we suggest that the newly discovered cell layer is the progenitor cell zone of the rat adrenal cortex.

  14. Neuroprotective actions of androgens on motoneurons.

    PubMed

    Fargo, Keith N; Foecking, Eileen M; Jones, Kathryn J; Sengelaub, Dale R

    2009-07-01

    Androgens have a variety of protective and therapeutic effects in both the central and peripheral nervous systems. Here we review these effects as they related specifically to spinal and cranial motoneurons. Early in development, androgens are critical for the formation of important neuromuscular sex differences, decreasing the magnitude of normally occurring cell death in select motoneuron populations. Throughout the lifespan, androgens also protect against motoneuron death caused by axonal injury. Surviving motoneurons also display regressive changes to their neurites as a result of both direct axonal injury and loss of neighboring motoneurons. Androgen treatment enhances the ability of motoneurons to recover from these regressive changes and regenerate both axons and dendrites, restoring normal neuromuscular function. Androgens exert these protective effects by acting through a variety of molecular pathways. Recent work has begun to examine how androgen treatment can interact with other treatment strategies in promoting recovery from motoneuron injury.

  15. Next-generation steroidogenesis inhibitors, dutasteride and abiraterone, attenuate but still do not eliminate androgen biosynthesis in 22RV1 cells in vitro.

    PubMed

    Pham, Steven; Deb, Subrata; Ming, Dong Sheng; Adomat, Hans; Hosseini-Beheshti, Elham; Zoubeidi, Amina; Gleave, Martin; Guns, Emma S Tomlinson

    2014-10-01

    Castration resistant prostate cancer (CRPC) is often lethal and inevitably develops after androgen ablation therapy. However, in the majority of cases it remains androgen dependent. CRPC tumors have the ability to synthesize their own androgens from cholesterol by engaging in de novo steroidogenesis. We investigated the potential of 22RV1 prostate cancer cells to convert the supplemented steroid precursors within this pathway under the effects of current clinical steroidogenesis inhibitors such as abiraterone and dutasteride, either alone or in combination. Under steroid starved conditions, enzymes responsible for de novo steroidogenesis were upregulated. Testosterone and dihydrotestosterone (DHT) were formed by using both dehydroepiandrosterone (DHEA) and progesterone as substrates. Formation of testosterone and DHT was higher following incubation with DHEA compared to progesterone. Progesterone decreased the mRNA expression of enzymes responsible for steroidogenesis. Abiraterone treatment decreased testosterone production but increased several precursor steroids in both classical and backdoor pathways in the presence of progesterone. In contrast, the DHT levels were elevated following treatment with abiraterone when progesterone was absent. Dutasteride decreased the formation of testosterone, DHT and precursor steroids in the backdoor pathway but increased steroid precursors in the classical steroidogenesis pathway. The combination of abiraterone and dutasteride decreased testosterone and DHT in the presence of progesterone but increased DHT in the absence of progesterone. Abiraterone inhibited androgen receptor (AR) activation but not to the same extent as MDV3100. However, abiraterone and dutasteride treatment, either alone or in combination, were more effective in decreasing prostate specific antigen secretion into the media than MDV3100. Thus, while interventions with these drugs alone or in combination fail to completely inhibit steroidogenesis in the 22RV1

  16. Atorvastatin treatment does not affect gonadal and adrenal hormones in type 2 diabetes patients with mild to moderate hypercholesterolemia.

    PubMed

    Santini, Stefano A; Carrozza, Cinzia; Lulli, Paola; Zuppi, Cecilia; CarloTonolo, Gian; Musumeci, Salvatore

    2003-01-01

    Atorvastatin, a second generation synthetic 3-hydroxy 3-methylglutaryl-coenzyme-A (HMG-CoA) reductase inhibitor used in the treatment of hypercholesterolemia, reduces both intracellular cholesterol synthesis and serum cholesterol levels, and this could have a potential negative impact on gonadal and adrenal steroidogenesis. Hypercholesterolemia in type 2 diabetes, even when mild, must be treated in an aggressive way, due to the more strict therapeutic goals than in the non diabetic population. Since the wide use of 3-hydroxy 3-methylglutaryl-coenzyme-A (HMG-CoA) reductase inhibitor (statins) in type 2 diabetes, the main aim of our study was to evaluate the effects of "therapeutic" doses of atorvastatin on gonadal and adrenal hormones in 24 type 2 diabetic patients (16 males and 8 postmenopausal females), with mild to moderate hypercholesterolemia (LDL-cholesterol = 150.1 +/- 32.0 and 189.9 +/- 32.9 mg/dl, respectively) studied before and after a 3 months treatment with atorvastatin (20 mg/day). In all patients, lipids and serum cortisol, dehydroepiandrosterone sulphate (DHEA-S), androstendione and sex hormone binding globulin (SHBG) were measured, with the addition, only in males, of testosterone and free testosterone index. After atorvastatin treatment a significant decrease in total and LDL cholesterol was observed (p < 0.05), while HDL-cholesterol did not significantly change ( p = N.S.), as no significant difference was found between steroid hormones measured before and after atorvastatin either in male and females. In conclusion, our data suggest that, in type 2 diabetic patients, the use of atorvastatin has no clinically important effects on either gonadal or adrenal steroid hormones.

  17. Adrenomyeloneuropathy Presenting With Adrenal Insufficiency

    PubMed Central

    Park, Hee Dong; Choi, Yong Min; Kang, Jin Ho

    2013-01-01

    Adrenomyeloneuropathy (AMN), one of the variants of X-linked adrenoleukodystrophy (ALD), is inherited peroxisomal disorder associated with the accumulation of very long chain fatty acids (VLCFA). AMN is characterized primarily by involvements of long ascending and descending tracts of the spinal cord and peripheral neuropathy, which leads to spastic paraparesis and urinary and erectile dysfunction. We experienced the AMN case of a 33-year-old man presenting bilateral progressive spastic paraparesis, impotence and urge incontinence with primary adrenal failures, as confirmed by increased serum of VLCFA concentrations. Considering that somatosensory evoked potentials in posterior tibial nerve was the only abnormal finding in electrophysiologic findings when compared with the severe spastic gait pattern shown, it is necessary to follow up with electrophysiologic studies. PMID:24020038

  18. Recognition and management of adrenal emergencies.

    PubMed

    Torrey, Susan P

    2005-08-01

    Although clinical conditions associated with dysfunction of the ad-renal gland are often subtle, even insidious, in their presentation,and diagnosis and treatment usually are confined to outpatient clinics and offices, there are several situations that warrant the attention of emergency physicians. Recognition of the spectrum of presentations of pheochromocytoma, adrenal insufficiency, and pituitary apoplexy, and the sequelae of corticosteroid therapy and withdrawal, are critically important areas to emergency medicine. Prompt diagnosis with appropriate treatment and referral will reduce morbidity and mortality in many patients each year. A related topic pertinent to emergency physicians is the management of incidental adrenal masses that are discovered on abdominal radio-logic imaging.

  19. 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

  20. Antiproliferative effect of a synthetic aptamer mimicking androgen response elements in the LNCaP cell line.

    PubMed

    Kouhpayeh, S; Einizadeh, A R; Hejazi, Z; Boshtam, M; Shariati, L; Mirian, M; Darzi, L; Sojoudi, M; Khanahmad, H; Rezaei, A

    2016-08-01

    Prostate cancer usually develops to a hormone-refractory state that is irresponsive to conventional therapeutic approaches. Therefore, new methods for treating aggressive prostate cancer are under development. Because of the importance of androgen receptors (ARs) in the development of the hormone-refractory state and AR mechanism of action, this study was designed. A single-stranded DNA as an aptamer was designed that could mimic the hormone response element (HRE). The LNCaP cells as an AR-rich model were divided into three sets of triplicate groups: the test group was transfected with Aptamer Mimicking HRE (AMH), Mock received only transfection reagents (mock) and a negative control. All three sets received 0, 10 and 100 nM of dehydroepiandrosterone (DHEA) separately. Data analysis showed hormone dependency of LNCaP cells in the negative control group upon treatment with 10 and 100 nM DHEA (compared with cells left untreated (P=0.001)). Transfection of AMH resulted in significant reduction of proliferation in the test group when compared with the negative control group with 10 (P=0.001) or 100 nM DHEA (P=0.02). AMH can form a hairpin structure at 37 °C and mimic the genomic HRE. Hence, it is capable of effectively competing with genomic HRE and interrupting the androgen signaling pathway in a prostate cancer cell line (LNCaP). PMID:27364573

  1. Race differentials in partnering patterns among older U.S. men: influence of androgens or religious participation?

    PubMed

    Das, Aniruddha; Nairn, Stephanie

    2013-10-01

    Using nationally representative data from the 2005-2006 U.S. National Social Life, Health, and Aging Project, this study queried race differences in older men's polyamorous and casual sex, as well as stratification of these patterns by endogenous androgens (testosterone and dehydroepiandrosterone) and by regular religious participation. Results suggested that despite their respective prominence in the biomedical and sociological literatures on sex, neither "bottom up" hormonal influences nor "top down" religious social control were major structuring factors for greater lifetime as well as current likelihood of these behaviors among older Black than White men. Androgens were higher among the former, but did not seem to drive these race patterns. Regular church attendance--while negatively associated with non-monogamous and prolific partnering, and hence possibly a social control mechanism among all men--played only a weak role in moderating ethnic variations in these behaviors. It is speculated that these differences may instead be driven by unexamined current or early factors, including, perhaps, Black men's greater exposure to sexualizing processes in adolescence that, even in late life, may outweigh more temporally-proximal influences. PMID:23605573

  2. The biosynthesis of some androst-16-enes from C21 and C19 steroids in boar testicular and adrenal tissue

    PubMed Central

    Ahmad, N.; Gower, D. B.

    1968-01-01

    1. The formation of androst-16-enes from [4-14C]progesterone has been investigated with long-term incubations and short-term kinetic studies. After 4hr., 1·7 and 10·3% respectively of 3α- and 3β-hydroxy-5α-androst-16-enes were formed in boar testis minces, but much smaller yields were obtained in boar adrenal. Both tissues formed small quantities of androsta-4,16-dien-3-one. 2. The amounts of androst-4-ene-3,17-dione and testosterone isolated were small, suggesting that androst-16-ene formation may occur preferentially in the boar testis. 3. In the absence of tissue no radioactive androst-16-enes were formed. 4. Incubation of both [4-14C]pregnenolone and [7α-3H]progesterone resulted in 3α- and 3β-hydroxy-5α-androst-16-enes containing 3H/14C ratios of near unity and confirmed that both C21 steroids were precursors. A similar incubation with 17α-hydroxy[4-14C]-progesterone and [7α-3H]progesterone gave the same Δ16-alcohols, but they contained only 3H, indicating that side-chain cleavage of pregnenolone and progesterone occurred before 17α-hydroxylation. 5. Dehydroepiandrosterone, testosterone, testosterone acetate and 16-dehydroprogesterone were not found to be precursors of Δ16-steroids. 6. A pathway is proposed for the biosynthesis of 3α- and 3β-hydroxy-5α-androst-16-enes from pregnenolone and progesterone; this may involve androsta-4,16-dien-3-one as an intermediate, but excludes 17α-hydroxyprogesterone, testosterone and dehydroepiandrosterone. ImagesPLATE 1 PMID:4233122

  3. 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

  4. Presence of kisspeptin-like immunoreactivity in human adrenal glands and adrenal tumors.

    PubMed

    Takahashi, Kazuhiro; Shoji, Itaru; Shibasaki, Akiko; Kato, Ichiro; Hiraishi, Keisuke; Yamamoto, Hajime; Kaneko, Kiriko; Murakami, Osamu; Morimoto, Ryo; Satoh, Fumitoshi; Ito, Sadayoshi; Totsune, Kazuhito

    2010-05-01

    Kisspeptins are neuropeptides which activate the hypothalamo-pituitary gonadal axis and are considered to play important physiological roles in the reproduction. Kisspeptins have also been reported to stimulate the aldosterone secretion from the adrenal cortex. However, the expression of kisspeptins in human adrenal glands and adrenal tumors has not been clarified yet. We, therefore, studied the presence of kisspeptin-like immunoreactivity (LI) in human adrenal glands and adrenal tumors (adrenocortical adenomas, adrenocortical carcinomas, and pheochromocytomas) by radioimmunoassay and immunocytochemistry. Kisspeptin-LI was detected in all the tissues examined; normal portions of adrenal glands (3.0 +/- 2.3 pmol/g wet weight, n = 21, mean +/- SD), aldosterone-producing adenomas (4.6 +/- 3.3 pmol/g wet weight, n = 10), cortisol-producing adenomas (2.7 +/- 1.4 pmol/g wet weight, n = 14), adrenocortical carcinomas (1.7 +/- 0.2 pmol/g wet weight, n = 4), and pheochromocytomas (1.8 +/- 0.8 pmol/g wet weight, n = 6). There was no significant difference in kisspeptin-LI levels among them. Immunocytochemistry showed positive kisspeptin-immunostaining in normal adrenal glands, with stronger immunostaining found in the medulla. Furthermore, positive kisspeptin-immunostaining was found in all types of adrenal tumors examined; adrenocortical adenomas, adrenocortical carcinomas, and pheochromocytomas. The intensity of kisspeptin-immunostaining in these adrenal tumors was, however, not so strong as that in normal adrenal medulla. The present study has shown for the first time the presence of kisspeptin-LI in adrenal glands and adrenal tumors.

  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. Sex-specific prenatal stress effects on the rat reproductive axis and adrenal gland structure

    PubMed Central

    George, Susan O; Hogg, Charis O; Lai, Yu-Ting; Brunton, Paula J

    2016-01-01

    Abstract 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

  7. Adrenal incidentalomas: A collection of six interesting cases and brief review of literature

    PubMed Central

    Panchani, Roopal; Goyal, Ashutosh; Varma, Tarun; Gupta, Nitinranjan; Tripathi, Sudhir; Kumar, Surender

    2012-01-01

    Introduction: Adrenal incidentalomas (AI) are detected in approximately 4-7% of patients in imaging studies. Majority are benign, but careful evaluation is warranted to rule out carcinoma and functional adenomas. Aim: The purpose of presenting these cases is to highlight the approach to management of AI in terms of diagnosis, follow-up, and treatment. Materials and Methods: Seven patients presenting in the endocrine clinic with AI were evaluated for their presenting clinical features and investigated. Results: Case 1 was a 49-year-old female, with adrenal androgen secreting adrenocortical carcinoma with amenorrhoea which was mistaken as menopause. She had minimal hirsutism, which was mistaken as postmenopausal hirsutism. Case 2 was a 39-year-old male, presenting with hyperglycemia found to have Conns’ syndrome with aldosterone producing adenoma on routine ultrasound. Case 3 was a 32-year-old male, presenting with gastritis and bloating, where ultrasound showed bilateral large adrenal masses revealed as diffuse large B cell lymphoma on biopsy. Case 4 was a 21-year-old boy, who had pheochromocytoma misdiagnosed as benign intracranial hypertension (HTN). Case 5 was a 59-year-old hypertensive male, presenting with fever had pheochromocytoma with catecholamine excess, producing fever. Case 6 was isolated adrenal tuberculosis who presented with chronic diarrhea. Conclusion: AI are common, though prevalence varies depending on the reason for scanning, the characteristics of the population studied, and the radiological techniques used. Most are non-secreting cortical adenomas. AI should be evaluated both biochemically and radiologically. When a hormonal disorder is suspected clinically, targeted, diagnostic testing for autonomous cortisol secretion, pheochromocytoma, and hyperaldosteronism is indicated. PMID:23565436

  8. [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.

  9. Bilateral adrenal myelolipoma in Cushing's disease: a relook into the role of corticotropin in adrenal tumourigenesis.

    PubMed

    Chakraborty, Partha Pratim; Bhattacharjee, Rana; Mukhopadhyay, Pradip; Chowdhury, Subhankar

    2016-01-01

    Adrenal myelolipomas are infrequently encountered benign tumours of unknown aetiology. In the majority of cases they are unilateral, and clinically and hormonally silent, only requiring periodic follow-up. However, bilateral adrenal myelolipomas are sometimes associated with endocrine disorders and warrant appropriate evaluation. Though the understanding of the pathophysiology of adrenal myelolipomas has long been elusive, adrenocorticotropic hormone (ACTH) has been proposed as the main tropic factor in a number of studies. Cushing's disease is rarely associated with bilateral and sometimes giant myelolipomas. In this article, the association of bilateral adrenal myelolipomas with Cushing's disease has been discussed and the role of ACTH in the tumourigenesis has been reviewed. PMID:27307426

  10. Bilateral adrenal myelolipoma in Cushing's disease: a relook into the role of corticotropin in adrenal tumourigenesis.

    PubMed

    Chakraborty, Partha Pratim; Bhattacharjee, Rana; Mukhopadhyay, Pradip; Chowdhury, Subhankar

    2016-01-01

    Adrenal myelolipomas are infrequently encountered benign tumours of unknown aetiology. In the majority of cases they are unilateral, and clinically and hormonally silent, only requiring periodic follow-up. However, bilateral adrenal myelolipomas are sometimes associated with endocrine disorders and warrant appropriate evaluation. Though the understanding of the pathophysiology of adrenal myelolipomas has long been elusive, adrenocorticotropic hormone (ACTH) has been proposed as the main tropic factor in a number of studies. Cushing's disease is rarely associated with bilateral and sometimes giant myelolipomas. In this article, the association of bilateral adrenal myelolipomas with Cushing's disease has been discussed and the role of ACTH in the tumourigenesis has been reviewed.

  11. 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

  12. Image-Guided Ablation of Adrenal Lesions

    PubMed Central

    Yamakado, Koichiro

    2014-01-01

    Although laparoscopic adrenalectomy has remained the standard of care for the treatment for adrenal tumors, percutaneous image-guided ablation therapy, such as chemical ablation, radiofrequency ablation, cryoablation, and microwave ablation, has been shown to be clinically useful in many nonsurgical candidates. Ablation therapy has been used to treat both functioning adenomas and malignant tumors, including primary adrenal carcinoma and metastasis. For patients with functioning adenomas, biochemical and symptomatic improvement is achieved in 96 to 100% after ablation; for patients with malignant adrenal neoplasms, however, the survival benefit from ablation therapy remains unclear, though good initial results have been reported. This article outlines the current role of ablation therapy for adrenal lesions, as well as identifying some of the technical considerations for this procedure. PMID:25049444

  13. 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

  14. 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

  15. Hormonal and metabolic evaluation of adrenal incidentalomas.

    PubMed

    Wagnerova, H; Dudasova, D; Lazurova, I

    2009-01-01

    The biochemical and hormonal data in patients with adrenal incidentalomas were evaluated to compare the differences between adrenal adenomas and other benign lesions and to find the relationship between metabolic parameters and adrenal hormones. Ninety two patients (29men, age 20-90 years) with incidentally discovered unilateral or bilateral adrenal masses detected on CT were included in this study for the reasons others than adrenal pathology. Glycemia, cholesterolemia, triglyceridemia, hormonal evaluation including plasma ACTH, plasma aldosterone, plasma renin acitivity, overnight dexametasone test, ACTH test, free plasma metanephrines, urinary catecholamines were determined. In the group of patients with adrenal masses the prevalence of arterial hypertension was three fold higher, the prevalence of DM was approximately five fold higher and the prevalence of the overweight and obesity two fold higher than is reported in the general population. The most frequent adrenal masses were nonfunctional masses, the occurence of functional lesions was as follows: steroid enzymopathies (an exaggerated response of 17-OHP indicating a possible 21-hydroxylase deficiency), subclinical Cushing syndrome, primary aldosteronism and pheochromocytoma (5%, 2%, 2% and 1% respectively). There were no significant differences in evaluated data between patients with adenomas and hyperplasia and also no significant difference in evaluated data between lesions smaller than 3 cm and lesions greater than 3 cm. We did not find any correlations between plasma cortisol and lipid values. In this study we confirmed a higher prevalence of symptoms characteristic for different metabolic syndromes in these patients with adrenal incidentalomas, which indicate systematic screening for the metabolic syndrome including evaluation of the insuline resistance in this patients. PMID:19728761

  16. Chronic Heroin Dependence Leading to Adrenal Insufficiency

    PubMed Central

    2014-01-01

    Opioids have been the mainstay for pain relief and palliation over a long period of time. They are commonly abused by drug addicts and such dependence usually imparts severe physiologic effects on multiple organ systems. The negative impact of opioids on the endocrine system is poorly understood and often underestimated. We describe a patient who developed severe suppression of the hypothalamic-pituitary adrenal (HPA) axis leading to secondary adrenal insufficiency due to long standing abuse of opioids. PMID:25221675

  17. 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

  18. 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

  19. 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

  20. Effects of 7-keto dehydroepiandrosterone on voluntary ethanol intake in male rats.

    PubMed

    Worrel, Mary E; Gurkovskaya, Olga V; Leonard, Stuart T; Lewis, Peter B; Winsauer, Peter J

    2011-06-01

    Administration of dehydroepiandrosterone (DHEA), a neurosteroid that can negatively modulate the GABA A receptor, has been shown to decrease voluntary intake of ethanol in rats. In vivo, DHEA can be metabolized to a variety of metabolites, including 3β-acetoxyandrost-5-ene-7,17-dione (7-keto DHEA), a metabolite without the prohormonal effects of DHEA. This study compared the effectiveness of 7-keto DHEA with DHEA for reducing ethanol intake in the same group of rats. The subjects, previously trained to drink ethanol using a saccharin-fading procedure, had access to ethanol for 30 min daily and the amount consumed was recorded. Subjects were administered 10 and 56 mg/kg of DHEA or 7-keto DHEA intraperitoneally 15 min before drinking sessions. Subjects received each particular dose daily until one of two criteria was met, that is, either ethanol intake did not differ by more than 20% of the mean for 3 consecutive days or for a maximum of 8 days. Both 10 and 56 mg/kg of 7-keto DHEA significantly reduced the dose of ethanol consumed. Although 10mg/kg of 7-keto DHEA produced decreases similar to those found with DHEA, the 56-mg/kg dose of 7-keto DHEA was significantly more effective at decreasing the dose of ethanol consumed than the same dose of DHEA. These results show that 7-keto DHEA is comparable with, or possibly more effective than, DHEA at decreasing ethanol consumption in rats, and that 7-keto DHEA is a compound deserving further investigation as a possible clinical treatment for alcohol abuse without the prohormonal effects of DHEA.

  1. Unemployment is associated with lower cortisol awakening and blunted dehydroepiandrosterone responses.

    PubMed

    Gallagher, Stephen; Sumner, Rachel C; Muldoon, Orla T; Creaven, Ann-Marie; Hannigan, Ailish

    2016-07-01

    Previous research has investigated the endocrinological consequences of unemployment as a likely pathway behind chronic stress and negative health outcomes. Despite these early attempts at delineating the neuroendocrine consequences of the chronic stress experienced by the unemployed, identifying a consistent and stable effect has remained elusive. Here we sought to strengthen existing knowledge into the effect of the stress of employment status on cortisol by improving on the methodological weaknesses of earlier studies and extend this line of enquiry by measuring the steroid hormone Dehydroepiandrosterone-Sulfate (DHEAS). Saliva samples were collected from unemployed and employed participants at four time points across two days. As expected, unemployed people reported higher stress, lower social support and lower self-esteem. Unexpectedly, the unemployed showed lower overall cortisol output, a likely consequence of a higher cortisol awakening response (CAR) in the employed. However, they also had a higher DHEA output across the day, albeit the diurnal pattern across the day was more dysregulated compared to that seen in those employed with a blunted response evident in the evening; the cortisol:DHEAS ratio was also lower in the unemployed group. Further, these hormone differences were correlated with self-esteem and stress. Taken together these results suggest that the relationship between employment status and endocrine responses is far more complicated than previously thought. We have shown for the first time that unemployed people have a lower CAR, but also show a blunted DHEA response relative to those employed and we suggest that this may be a feature of chronic stress exposure or perhaps dependent on the prevailing socio-economic context.

  2. Dietary dehydroepiandrosterone inhibits bone marrow and leukemia cell transplants: role of food restriction.

    PubMed

    Catalina, Fernando; Milewich, Leon; Kumar, Vinay; Bennett, Michael

    2003-12-01

    Dietary dehydroepiandrosterone (DHEA) inhibits the proliferation of syngeneic bone marrow cells (BMC) infused into lethally irradiated mice. Potential mechanisms for suppression of hematopoiesis were evaluated and the findings were as follows: (i) depletion of NK, T, B or macrophage cells failed to reverse suppression by DHEA; (ii) stem cell stimulation by erythropoietin, growth hormone, interleukin-2, Friend leukemia virus, or cyclophosphamide failed to reverse suppression; (iii) supplementation of fatty acids, mevalonate, or deoxyribonucleotides, which are dependent upon glucose-6-phosphate dehydrogenase function, did not enhance BMC growth in mice fed DHEA; (iv) DHEA downstream metabolites 4-androstenedione and 17beta-estradiol, as well as the synthetic steroid, 16alpha-chloroepiandrosterone (but not testosterone or 5-androstene-3beta,17beta-diol), also inhibited BMC growth. Tamoxifen antagonized the effects of 17beta-estradiol but not DHEA; (v) dietary DHEA causes hypothermia, but housing of DHEA-fed mice at 34 degrees C to maintain normal body temperature did not reverse suppression; (vi) DHEA leads to a decrease in food intake in rodents. Pair-feeding control diet to mice fed DHEA mimicked the effects of dietary DHEA; (vii) adrenalectomy and orchiectomy decrease the levels of stress and sex hormones, respectively. Neither procedure affected the ability of food restriction or DHEA feeding to inhibit hematopoiesis; (viii) growth of GR-3 NM pre-B leukemia cells in unirradiated mice was also suppressed by DHEA or food restriction. We conclude that DHEA, by reducing food intake in mice, inhibits bone marrow and leukemia cell growth. The precise mechanism(s) by which reduced food intake per se inhibits hematopoiesis is not known, but may involve an increased rate of cellular apoptosis.

  3. Dehydroepiandrosterone has strong antifibrotic effects and is decreased in idiopathic pulmonary fibrosis.

    PubMed

    Mendoza-Milla, Criselda; Valero Jiménez, Ana; Rangel, Claudia; Lozano, Alfredo; Morales, Violeta; Becerril, Carina; Chavira, Roberto; Ruiz, Víctor; Barrera, Lourdes; Montaño, Martha; Pardo, Annie; Selman, Moisés

    2013-11-01

    Idiopathic pulmonary fibrosis (IPF) is an ageing-related lung disorder characterised by expansion of the myofibroblast population and aberrant lung remodelling. Dehydroepiandrosterone (DHEA), a steroid pro-hormone, decreases with age but an exaggerated decline has been associated with chronic degenerative diseases. We quantified the plasma levels of DHEA and its sulfated form (DHEA-S) in 137 IPF patients and 58 controls and examined the effects of DHEA on human lung fibroblasts. Plasma DHEA/DHEA-S was significantly decreased in male IPF patients (median (range) DHEA: 4.4 (0.2-29.2) versus 6.7 (2.1-15.2) ng · mL(-1), p<0.01; DHEA-S: 47 (15.0-211) versus 85.2 (37.6-247.0) μg · dL(-1), p<0.001), while in females only DHEA-S was significantly decreased (32.6 (15.0-303.0) versus 68.3 (16.4-171) μg · dL(-1), p<0.001). DHEA caused a decrease in fibroblast proliferation and an approximately two-fold increase in fibroblast apoptosis, probably through the intrinsic pathway with activation of caspase-9. This effect was accompanied by upregulation of several pro-apoptotic proteins (Bax and cyclin-dependent kinase-inhibitor CDNK1A) and downregulation of anti-apoptotic proteins, such as cellular inhibitor of apoptosis (c-IAP)1 and c-IAP2. DHEA also caused a significant decrease of transforming growth factor-β1-induced collagen production and fibroblast to myofibroblast differentiation, and inhibited platelet-derived growth factor-induced fibroblast migration. These findings demonstrate a disproportionate decrease of DHEA/DHEA-S in IPF patients and indicate that this molecule has multiple antifibrotic properties.

  4. Effects of acute and chronic administration of neurosteroid dehydroepiandrosterone sulfate on neuronal excitability in mice

    PubMed Central

    Svob Strac, Dubravka; Vlainic, Josipa; Samardzic, Janko; Erhardt, Julija; Krsnik, Zeljka

    2016-01-01

    Background Neurosteroid dehydroepiandrosterone sulfate (DHEAS) has been associated with important brain functions, including neuronal survival, memory, and behavior, showing therapeutic potential in various neuropsychiatric and cognitive disorders. However, the antagonistic effects of DHEAS on γ-amino-butyric acidA receptors and its facilitatory action on glutamatergic neurotransmission might lead to enhanced brain excitability and seizures and thus limit DHEAS therapeutic applications. The aim of this study was to investigate possible age and sex differences in the neuronal excitability of the mice following acute and chronic DHEAS administration. Methods DHEAS was administered intraperitoneally in male and female adult and old mice either acutely or repeatedly once daily for 4 weeks in a 10 mg/kg dose. To investigate the potential proconvulsant properties of DHEAS, we studied the effects of acute and chronic DHEAS treatment on picrotoxin-, pentylentetrazole-, and N-methyl-D-aspartate-induced seizures in mice. The effects of acute and chronic DHEAS administration on the locomotor activity, motor coordination, and body weight of the mice were also studied. We also investigated the effects of DHEAS treatment on [3H]flunitrazepam binding to the mouse brain membranes. Results DHEAS did not modify the locomotor activity, motor coordination, body weight, and brain [3H]flunitrazepam binding of male and female mice. The results failed to demonstrate significant effects of single- and long-term DHEAS treatment on the convulsive susceptibility in both adult and aged mice of both sexes. However, small but significant changes regarding sex differences in the susceptibility to seizures were observed following DHEAS administration to mice. Conclusion Although our findings suggest that DHEAS treatment might be safe for various potential therapeutic applications in adult as well as in old age, they also support subtle interaction of DHEAS with male and female hormonal status

  5. Unemployment is associated with lower cortisol awakening and blunted dehydroepiandrosterone responses.

    PubMed

    Gallagher, Stephen; Sumner, Rachel C; Muldoon, Orla T; Creaven, Ann-Marie; Hannigan, Ailish

    2016-07-01

    Previous research has investigated the endocrinological consequences of unemployment as a likely pathway behind chronic stress and negative health outcomes. Despite these early attempts at delineating the neuroendocrine consequences of the chronic stress experienced by the unemployed, identifying a consistent and stable effect has remained elusive. Here we sought to strengthen existing knowledge into the effect of the stress of employment status on cortisol by improving on the methodological weaknesses of earlier studies and extend this line of enquiry by measuring the steroid hormone Dehydroepiandrosterone-Sulfate (DHEAS). Saliva samples were collected from unemployed and employed participants at four time points across two days. As expected, unemployed people reported higher stress, lower social support and lower self-esteem. Unexpectedly, the unemployed showed lower overall cortisol output, a likely consequence of a higher cortisol awakening response (CAR) in the employed. However, they also had a higher DHEA output across the day, albeit the diurnal pattern across the day was more dysregulated compared to that seen in those employed with a blunted response evident in the evening; the cortisol:DHEAS ratio was also lower in the unemployed group. Further, these hormone differences were correlated with self-esteem and stress. Taken together these results suggest that the relationship between employment status and endocrine responses is far more complicated than previously thought. We have shown for the first time that unemployed people have a lower CAR, but also show a blunted DHEA response relative to those employed and we suggest that this may be a feature of chronic stress exposure or perhaps dependent on the prevailing socio-economic context. PMID:27018925

  6. Effects of dehydroepiandrosterone (DHEA) on cardiovascular risk factors in older women with frailty characteristics

    PubMed Central

    Boxer, R. S.; Kleppinger, A.; Brindisi, J.; Feinn, R.; Burleson, J. A.; Kenny, A. M.

    2010-01-01

    Objective: this analysis was to investigate the effects of dehydroepiandrosterone (DHEA) on cardiovascular risk factors in older women with frailty characteristics. Design, setting and participants: the study was a double-blind, randomised, placebo-controlled trial of 99 women (mean 76.6 ± 6.0 year) with the low DHEA-S level and frailty. Intervention: participants received 50 mg/day DHEA or placebo for 6 months; all received calcium (1,000–1,200 mg/day diet) and supplement (combined) and cholecalciferol (1,000 IU/day). Women participated in 90-min twice weekly exercise regimens, either chair aerobics or yoga. Main outcome measures: assessment of outcome variables included hormone levels (DHEA-S, oestradiol, oestrone, testosterone and sex hormone-binding globulin (SHBG)), lipid profiles (total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol and triglycerides), body composition measured by dual energy absorptiometry, glucose levels and blood pressure (BP). Results: eighty-seven women (88%) completed 6 months of study; 88% were pre-frail demonstrating 1–2 frailty characteristics and 12% were frail with ≥3 characteristics. There were significant changes in all hormone levels including DHEA-S, oestradiol, oestrone and testosterone and a decline in SHBG levels in those taking DHEA supplements. In spite of changes in hormone levels, there were no significant changes in cardiovascular risk factors including lipid profiles, body or abdominal fat, fasting glucose or BP. Conclusion: research to date has not shown consistent effects of DHEA on cardiovascular risk, and this study adds to the literature that short-term therapy with DHEA is safe for older women in relation to cardiovascular risk factors. This study is novel in that we recruited women with evidence of physical frailty. PMID:20484057

  7. Dehydroepiandrosterone protects male and female hippocampal neurons and neuroblastoma cells from glucose deprivation.

    PubMed

    Vieira-Marques, Claudia; Arbo, Bruno Dutra; Ruiz-Palmero, Isabel; Ortiz-Rodriguez, Ana; Ghorbanpoor, Samar; Kucharski, Luiz Carlos; Arevalo, Maria A; Garcia-Segura, Luis Miguel; Ribeiro, Maria Flávia M

    2016-08-01

    Dehydroepiandrosterone (DHEA) modulates neurogenesis, neuronal function, neuronal survival and metabolism, enhancing mitochondrial oxidative capacity. Glucose deprivation and hypometabolism have been implicated in the mechanisms that mediate neuronal damage in neurological disorders, and some studies have shown that these mechanisms are sexually dimorphic. It was also demonstrated that DHEA is able to attenuate the hypometabolism that is related to some neurodegenerative diseases, eliciting neuroprotective effects in different experimental models of neurodegeneration. The aim of this study was to evaluate the effect of DHEA on the viability of male and female hippocampal neurons and SH-SY5Y neuroblastoma cells exposed to glucose deprivation. It was observed that after 12h of pre-treatment, DHEA was able to protect SH-SY5Y cells from glucose deprivation for 6h (DHEA 10(-12), 10(-8) and 10(-6)M) and 8h (DHEA 10(-8)M). In contrast, DHEA was not neuroprotective against glucose deprivation for 12 or 24h. DHEA (10(-8)M) also protected SH-SY5Y cells when added together or even 1h after the beginning of glucose deprivation (6h). Furthermore, DHEA (10(-8)M) also protected primary neurons from both sexes against glucose deprivation. In summary, our findings indicate that DHEA is neuroprotective against glucose deprivation in human neuroblastoma cells and in male and female mouse hippocampal neurons. These results suggest that DHEA could be a promising candidate to be used in clinical studies aiming to reduce neuronal damage in people from both sexes. PMID:27174000

  8. Dehydroepiandrosterone anti-atherogenesis effect is not via its conversion to estrogen

    PubMed Central

    Cheng, Heng-hui; Hu, Xiao-jing; Ruan, Qiu-rong

    2009-01-01

    Aim: This study was conducted to demonstrate the anti-atherosclerotic effect of dehydroepiandrosterone (DHEA) and to investigate its possible mechanisms and whether this effect is related to its conversion to estrogen. Methods: Forty male New Zealand White rabbits aged 3 months were divided into 5 groups (n=8 per group) and fed different diets for 10 weeks. Serum lipid levels, the area of atherosclerotic lesions and the mRNA levels of monocyte chemoattractant protein-1 (MCP-1) and vascular cell adhesion molecule-1 (VCAM-1) in aortic lesions were measured. Then cultured vascular smooth muscle cells (VSMCs) stimulated by oxidized low density lipoprotein-cholesterol (ox-LDL) were treated by DHEA. The gene and protein expression levels of MCP-1 and VCAM-1 in VSMCs was detected. The plasmid with or without the gene of cytochrome P450 aromatase (CYP19) was transient transfected into cultured VSMCs respectively. Twenty hours later, the cells were stimulated with ox-LDL and DHEA. Results: DHEA could obviously decrease the area of atherosclerotic lesions and the expressions of MCP-1 and VCAM-1 in aortic lesions. But all-trans retinoic acid (atRA) which was reported would limit restenosis after balloon angioplasty had no visible synergistic effect with DHEA. DHEA could also reduce ox-LDL-induced MCP-1 and VCAM-1 expression in untransfected or transfected VSMCs. Conclusion: The anti-atherosclerotic effect of DHEA had nothing to do with the catalysis of cytochrome P450 aromatase (CYP19), or was not related to its conversion to estrogen. PMID:19060916

  9. Serum cortisol and dehydroepiandrosterone-sulfate levels after balneotherapy and physical therapy in patients with fibromyalgia

    PubMed Central

    Semiz, Esra A.; Hizmetli, Sami; Semiz, Murat; Karadağ, Ahmet; Adalı, Merve; Tuncay, Mehmet S.; Alim, Bulent; Hayta, Emrullah; Uslu, Ali U.

    2016-01-01

    Objectives: To investigated serum cortisol and serum dehydroepiandrosterone-sulphate (DHEA-S) levels between fibromyalgia (FMS) patients and a control group, and the effect of balneotherapy (BT) on these hormones. Methods: Seventy-two patients with FMS and 39 healthy volunteers were included in the study. This prospective and cross-sectional study was carried out in the Medical Faculty, Physical Medicine and Rehabilitation Clinic, Cumhuriyet University, Cumhuriyet, Turkey between June 2012 and June 2013. Patients were divided into 2 groups. There were 40 patients in the first group, consisting of BT and physical therapy (PT) administered patients. There were 32 FMS patients in the second group who were only administered PT. Thirty-nine healthy volunteers were enrolled as a control group. Result: Cortisol was observed to be lower in FMS patients compared with the controls (10.10±4.08 μg/dL and 11.78±3.6 μg/dL; p=0.033). Serum DHEA-S level was observed to be lower in FMS patients compared with the controls (89.93±53.96 μg/dL and 143.15±107.92 μg/dL; p=0.015). Average serum cortisol levels of patients receiving BT were determined to be 9.95±3.20 μg/dL before treatment and 9.06±3.77μg/dL after treatment; while average serum DHEA-S levels were 77.60±48.05 μg/dL before treatment, and 76.84±48.71 μg/dL after treatment. No significant changes were determined in serum cortisol and DHEA-S levels when measured again after BT and PT. Conclusion: Low levels of serum cortisol and DHEA-S were suggested to be associated with the physiopathology of FMS. PMID:27146618

  10. Androgens inhibit aromatase expression through DAX-1: insights into the molecular link between hormone balance and Leydig cancer development.

    PubMed

    Maris, Pamela; Campana, Antonella; Barone, Ines; Giordano, Cinzia; Morelli, Catia; Malivindi, Rocco; Sisci, Diego; Aquila, Saveria; Rago, Vittoria; Bonofiglio, Daniela; Catalano, Stefania; Lanzino, Marilena; Andò, Sebastiano

    2015-04-01

    Leydig cell tumors (LCTs) of the testis are steroid-secreting tumors associated with various steroid biosynthetic abnormalities and endocrine dysfunctions. Despite their overall rarity, LCTs are still of substantial interest owing to the paucity of information regarding their exact nature and malignant potential. In the present study, we disclose the ability of androgens to inhibit Leydig tumor cell proliferation by opposing to self-sufficient in situ estrogen production. In rat Leydig tumor cells, R2C, androgen treatment significantly decreases the expression and the enzymatic activity of cytocrome P450 aromatase, responsible for the local conversion of androgens into estrogens. This inhibitory effect relies on androgen receptor (AR) activation and involves negative regulation of the CYP19 gene transcriptional activity through the nuclear orphan receptor DAX-1 (dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1). Ligand-activated AR up-regulates the expression of DAX-1 and promotes its increased recruitment within the steroidogenic factor-1 site-containing region of the aromatase proximal promoter II in association with the nuclear receptor corepressor. The biological relevance in LCTs of the newly highlighted functional interplay between AR, DAX-1, and aromatase is underlined by our in vivo observations, revealing a marked down-regulation of AR and DAX-1 expression and a strong increase in aromatase levels in testes tissues from old Fischer rats with spontaneously developed Leydig cell neoplasia, compared with normal testes tissues from younger animals. In elucidating a mechanism by which androgens modulate the growth of Leydig tumor cells, our finding support the hypothesis that maintaining the adequate balance between androgen and estrogens may represent the key for blocking estrogen-secreting Leydigioma development, opening new prospects for therapeutic intervention. PMID:25603045

  11. Mycobacterium smegmatis synthesizes in vitro androgens and estrogens from different steroid precursors.

    PubMed

    Dlugovitzky, Diana G; Fontela, María Sol; Martinel Lamas, Diego J; Valdez, Ricardo A; Romano, Marta C

    2015-07-01

    Fast-growing mycobacteria such as Mycobacterium sp. and Mycobacterium smegmatis degrade natural sterols. They are a model to study tuberculosis. Interestingly, M. smegmatis has been found in river effluents derived from paper production, and therefore, it would be important to gain further insight into its capacity to synthesize steroids that are potential endocrine disruptors affecting the development and reproduction of fishes. To our knowledge, the capacity of M. smegmatis to synthesize estrogens and even testosterone has not been previously reported. Therefore, the objective of this study was to investigate the capacity of M. smegmatis to synthesize in vitro testosterone and estrogens from tritiated precursors and to investigate the metabolic pathways involved. Results obtained by thin-layer chromatography showed that (3)H-progesterone was transformed to 17OH-progesterone, androstenedione, testosterone, estrone, and estradiol after 6, 12, or 24 h of incubation. (3)H-androstenedione was transformed into testosterone and estrogens, mainly estrone, and (3)H-testosterone was transformed to estrone and androstenedione. Incubation with (3)H-dehydroepiandrosterone rendered androstenediol, testosterone, and estrogens. This ability to transform less potent sex steroids like androstenedione and estrone into other more active steroids like testosterone and estradiol or vice versa suggests that M. smegmatis can influence the amount of self-synthesized strong androgens and estrogens and can transform those found in the environment. PMID:25994226

  12. 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)

  13. Effect of argan and olive oil consumption on the hormonal profile of androgens among healthy adult Moroccan men.

    PubMed

    Derouiche, Abdelfettah; Jafri, Ali; Driouch, Issam; El Khasmi, Mohammed; Adlouni, Ahmed; Benajiba, Nada; Bamou, Youssef; Saile, Rachid; Benouhoud, Mohammed

    2013-01-01

    This study aimed to assess the effect of virgin argan oil (VAO) and extra virgin olive oil (EVO) on the hormonal profile of androgens and anthropometric parameters among healthy adult Moroccan men during a controlled nutritional intervention. The study was carried out on 60 young and healthy male volunteers aged between 23 and 40 years old. During a stabilization period of 2 weeks they consumed butter. The group was then randomized into two categories, the first one consuming VAO and the second EVO for 3 weeks. Testosterone (T), luteinizing hormone (LH) and dehydroepiandrosterone (DHEAS) serum concentrations were measured at the beginning of the study and at the end of each period. The Mann-Whitney test was used to compare the two groups (VAO and EVO) during each step of the study. Differences in androgens and anthropometric parameters between the baseline and after 3 weeks of the diet in the VAO and EVO groups were analyzed using the Wilcoxon test. T and LH serum concentrations significantly increased after the intervention period. T levels increased by 19.9% and 17.4% (p < 0.0001), and LH levels by 18.5% (p < 0.007) and 42.6% (p < 0.0001), respectively, for VAO and EVO (p < 0.0001). However, DHEAS serum concentrations, body weight, body mass index, arterial pressure and daily energetic intake did not show any significant variation after the intervention with either argan or olive oils. The results suggest that consumption of AVO and EVO might be the origin of a positive action on the androgen hormonal profile of men.

  14. Neurobiological and Neuropsychiatric Effects of Dehydroepiandrosterone (DHEA) and DHEA Sulfate (DHEAS)

    PubMed Central

    Maninger, Nicole; Wolkowitz, Owen M.; Reus, Victor I.; Epel, Elissa S.; Mellon, Synthia H.

    2009-01-01

    DHEA and DHEAS are steroids synthesized in human adrenals, but their function is unclear. In addition to adrenal synthesis, evidence also indicates that DHEA and DHEAS are synthesized in the brain, further suggesting a role of these hormones in brain function and development. Despite intensifying research into the biology of DHEA and DHEAS, many questions concerning their mechanisms of action and their potential involvement in neuropsychiatric illnesses remain unanswered. We review and distill the preclinical and clinical data on DHEA and DHEAS, focusing on (i) biological actions and putative mechanisms of action, (ii) differences in endogenous circulating concentrations in normal subjects and patients with neuropsychiatric diseases, and (iii) the therapeutic potential of DHEA in treating these conditions. Biological actions of DHEA and DHEAS include neuroprotection, neurite growth, and antagonistic effects on oxidants and glucocorticoids. Accumulating data suggest abnormal DHEA and/or DHEAS concentrations in several neuropsychiatric conditions. The evidence that DHEA and DHEAS may be fruitful targets for pharmacotherapy in some conditions is reviewed. PMID:19063914

  15. 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.

  16. Androgen receptor gene mutation, rearrangement, polymorphism.

    PubMed

    Eisermann, Kurtis; Wang, Dan; Jing, Yifeng; Pascal, Laura E; Wang, Zhou

    2013-09-01

    Genetic aberrations of the androgen receptor (AR) caused by mutations, rearrangements, and polymorphisms result in a mutant receptor that has varied functions compared to wild type AR. To date, over 1,000 mutations have been reported in the AR with most of these being associated with androgen insensitivity syndrome (AIS). While mutations of AR associated with prostate cancer occur less often in early stage localized disease, mutations in castration-resistant prostate cancer (CRPC) patients treated with anti-androgens occur more frequently with 10-30% of these patients having some form of mutation in the AR. Resistance to anti-androgen therapy usually results from gain-of-function mutations in the LBD such as is seen with bicalutamide and more recently with enzalutamide (MDV3100). Thus, it is crucial to investigate these new AR mutations arising from drug resistance to anti-androgens and other small molecule pharmacological agents.

  17. Hyperinsulinaemic androgen excess in adolescent girls.

    PubMed

    Ibáñez, Lourdes; Ong, Ken K; López-Bermejo, Abel; Dunger, David B; de Zegher, Francis

    2014-08-01

    Hyperinsulinaemic androgen excess is the most common cause of hirsutism, acne and menstrual irregularity in adolescent girls. Here, we propose that the disorder frequently originates from an absolute or relative excess of lipids in adipose tissue, and from associated changes in insulin sensitivity, gonadotropin secretion and ovarian androgen release. Girls from populations with genotypes attuned to nutritionally harsh conditions seem to be particularly vulnerable to the development of hyperinsulinaemic androgen excess in today's obesogenic environment. We propose that hirsutism, hyperandrogenaemia and menstrual irregularity (≥2 years after menarche) is used as a diagnostic triad for the disorder. No pharmacological therapy has been approved for girls with androgen excess; however, lifestyle intervention is essential to reduce adiposity. In girls without obesity who are not sexually active, insulin sensitization has more broadly normalizing effects than estradiol-progestogen combinations. The early recognition of girls at risk of developing hyperinsulinaemic androgen excess might enable prevention in childhood.

  18. [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

  19. 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

  20. 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.

  1. [The imaging diagnosis of adrenal tumors].

    PubMed

    Cózar Olmo, J M; Martínez-Piñeiro, J A; García-Matres, M J; Hervás, C M; Cárcamo, P; Martínez-Piñeiro, L; Avellana, J A; de la Peña, J

    1992-05-01

    From 1967 to 1991 we have diagnosed and treated 73 adrenal tumors in 63 patients: 12 pheochromocytomas, 24 adrenal cortical adenomas, 15 hyperplasias, 16 carcinomas, 3 myelolipomas, 2 cysts and 1 neuroblastoma. We conducted a retrospective study to analyze the preoperative images obtained by different diagnostic techniques and attempted to correlate tumor size and site with the results of the histological analysis of the surgical specimen. Nephrotomography with pneumoretroperitoneum and IV Nephrotomography were useful in detecting the increase of the size of the gland in 10 of 25 cases submitted to these procedures (40%). Arteriography as second or third technique of choice confirmed the presence of an adrenal tumor in 15 of the 21 cases evaluated by this procedure (70%). US and CT detected 94% (31/33) and 100% (33/33) of the cases, respectively. Fourteen cases were incidentally discovered by CT (7) and US (7). A direct relationship between tumor size and degree of malignancy could be established since the carcinomas had a mean diameter of 7 cm (range 5 to 12 cm). Concerning the histologic nature of the disease, specific images were found in 3 cases of adrenal myelolipoma (hyperechoic on US and of low density similar to fat on CT) and 2 cysts (anechoic with posterior band evidenced on us and liquid on CT). Radioisotopes were also utilized for tumor localization and there was positive uptake of I-131-IMBG in 2 cases of adrenal pheochromocytoma; 1 extra-adrenal (left lateral aortic paraganglioma) and 1 case of malignant adrenal pheochromocytoma with metastasis to the lungs.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. 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

  3. Androgens and the aging male.

    PubMed

    Seidman, Stuart N

    2007-01-01

    In contrast to women, men do not experience a sudden cessation of gonadal function comparable to menopause. However, there is a progressive reduction in male hypothalamic-pituitary-gonadal (HPG) axis function: testosterone levels decline through both central (pituitary) and peripheral (testicular) mechanisms, and there is a loss of the circadian rhythm of testosterone secretion. The progressive decline in testosterone levels has been demonstrated in both cross-sectional and longitudinal studies, and overall at least 25% of men over age 70 meet laboratory criteria for hypogonadism (ie, testosterone deficiency). Such age-associated HPG hypofunctioning, which has been termed "andropause," is thought to be responsible for a variety of symptoms experienced by elderly men, including weakness, fatigue, reduced muscle and bone mass, impaired hematopoiesis, sexual dysfunction (including erectile dysfunction and loss of libido), and depression. Although, it has been difficult to establish correlations between these symptoms and plasma testosterone levels, there is some evidence that testosterone replacement leads to symptom relief, particularly with respect to muscle strength, bone mineral density, and erectile dysfunction. There is little evidence of a link between the HPG axis hypofunctioning and depressive illness, and exogenous androgens have not been consistently shown to have antidepressant activity. This article reviews the relationship between androgens, depression, and sexual function in aging men.

  4. [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

  5. 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.

  6. Thymus and adrenal glands in elder abuse.

    PubMed

    Hayashi, Takahito; Bunai, Yasuo; Ago, Kazutoshi; Ago, Mihoko; Ogata, Mamoru

    2011-12-01

    Endogenous glucocorticoid-induced thymic involution is generally considered to be an important finding for determining child abuse. The present study investigated the weight of the thymus and the adrenal glands in elder abuse cases to identify a potential marker for elder abuse. There was no significant difference in the thymus and the adrenal weight between elder abuse and control cases. However, the elder abuse cases in which the duration of abuse was less than 3 months showed a significant increase in the adrenal weight in comparison to control cases. In such cases, histopathological findings showed a loss of intracellular light granules from the zona fasciculata, which might indicate a loss of cholesterol due to the overproduction of glucocorticoid. These results might imply that the elderly, who were maltreated for less than 3 months, were in the early phase of a long-term stress state during which stress-induced overproduction of glucocorticoid was observed in adrenal glands as indicated by Selye. Our results suggest that an increase in adrenal weight may be a potential marker for elder abuse of relatively short periods, especially less than a few months.

  7. Adrenal insufficiency in patients with decompensated cirrhosis

    PubMed Central

    Karagiannis, Apostolos KA; Nakouti, Theodora; Pipili, Chrysoula; Cholongitas, Evangelos

    2015-01-01

    Adrenal reserve depletion and overstimulation of the hypothalamus-pituitary-adrenal (HPA) axis are causes for adrenal insufficiency (AI) in critically ill individuals. Cirrhosis is a predisposing condition for AI in cirrhotics as well. Both stable cirrhotics and liver transplant patients (early and later after transplantation) have been reported to present AI. The mechanisms leading to reduced cortisol production in cirrhotics are the combination of low cholesterol levels (the primary source of cortisol), the increased cytokines production that overstimulate and exhaust HPA axis and the destruction of adrenal glands due to coagulopathy. AI has been recorded in 10%-82% cirrhotics depending on the test used to evaluate adrenal function and in 9%-83% stable cirrhotics. The similarity of those proportions support the assumption that AI is an endogenous characteristic of liver disease. However, the lack of a gold standard method for AI assessment and the limitation of precise thresholds in cirrhotics make difficult the recording of the real prevalence of AI. This review aims to summarize the present data over AI in stable, critically ill cirrhotics and liver transplant recipients. Moreover, it provides information about the current knowledge in the used diagnostic tools and the possible effectiveness of corticosteroids administration in critically ill cirrhotics with AI. PMID:26052400

  8. Effect of age, gender and exercise on salivary dehydroepiandrosterone circadian rhythm profile in human volunteers.

    PubMed

    Al-Turk, Walid; Al-Dujaili, Emad A S

    2016-02-01

    There has been a lot of effort by scientists to elucidate the multi functions of the naturally occurring hormone, dehydroepiandrosterone (DHEA). However, to plan research experiments optimally, it is important first to characterize the diurnal rhythm in healthy individuals. The aim of this research was to investigate the daily circadian rhythms of DHEA among the 2 genders, and the effect of age and exercise on salivary DHEA circadian rhythms. Volunteers (20-39 and 40-60 years) were recruited for 2 studies investigating the salivary DHEA circadian rhythm. The first study looked at the effect of gender and age on DHEA levels on 2 non-consecutive days, and the second study explored the effect of exercise on DHEA circadian rhythm in males. DHEA levels were estimated by a sensitive and specific ELISA method. The results showed a clear daily circadian rhythm in salivary DHEA in all participants groups, however the profile was flatter in the older female group. There was a significant difference between age and gender groups particularly at 8.00 h. In young males DHEA reduced from 541.1 ± 101.3 (mean ± sd) at 8.00 h to 198.9 ± 90.7 pg/mL at 18.00 h; p<0.0001, and young females from 401.6 ± 149.5 to 215.4 ± 95.3 pg/mL; p<0.001. In older males DHEA reduced from 267.5 ± 32.4 to 132.5 ± 46.7 pg/mL; p<0.001, and older females from 147.7 ± 78.1 to 89.5 ± 29.1 pg/mL; p=0.05. DHEA levels on 2 non-consecutive days showed some variations but this was not significant. Aerobic exercise has significantly increased DHEA levels at 2 time points of the day (p=0.05) in male subjects. In conclusion, our study showed a clear daily circadian rhythm in salivary DHEA in all participants was observed, but the profile was flatter in the older groups.

  9. Detection of dehydroepiandrosterone misuse by means of gas chromatography- combustion-isotope ratio mass spectrometry.

    PubMed

    Mareck, Ute; Geyer, Hans; Flenker, Ulrich; Piper, Thomas; Thevis, Mario; Schänzer, Wilhelm

    2007-01-01

    According to World Anti-Doping Agency (WADA) rules (WADA Technical Document-TD2004EAAS) urine samples containing dehydroepiandrosterone (DHEA) concentrations greater than 100 ng ML(-1) shall be submitted to isotope ratio mass spectrometry (IRMS) analysis. The threshold concentration is based on the equivalent to the glucuronide, and the DHEA concentrations have to be adjusted for a specific gravity value of 1.020. In 2006, 11,012 doping control urine samples from national and international federations were analyzed in the Cologne doping control laboratory, 100 (0.9%) of them yielding concentrations of DHEA greater than 100 ng mL(-1). Sixty-eight percent of the specimens showed specific gravity values higher than 1.020, 52% originated from soccer players, 95% were taken in competition, 85% were male urines, 99% of the IRMS results did not indicate an application of testosterone or related prohormones. Only one urine sample was reported as an adverse analytical finding having 319 ng mL(-1) DHEA (screening result), more than 10,000 ng mL(-1) androsterone and depleted carbon isotope ratio values for the testosterone metabolites androsterone and etiocholanolone. Statistical evaluation showed significantly different DHEA concentrations between specimens taken in- and out-of- competition, whereas females showed smaller DHEA values than males for both types of control. Also a strong influence of the DHEA excretion on different sport disciplines was detectable. The highest DHEA values were detected for game sports (soccer, basketball, handball, ice hockey), followed by boxing and wrestling. In 2007, 6622 doping control urine samples were analyzed for 3alpha,5-cyclo-5alpha-androstan-6beta-ol-17-one (3alpha,5-cyclo), a DHEA metabolite which was described as a useful gas chromatography-mass spectrometry (GC-MS) screening marker for DHEA abuse. Nineteen urine specimens showed concentrations higher than the suggested threshold of 140 ng mL(-1), six urine samples yielded

  10. Structural characteristics of anabolic androgenic steroids contributing to binding to the androgen receptor and to their anabolic and androgenic activities. Applied modifications in the steroidal structure.

    PubMed

    Fragkaki, A G; Angelis, Y S; Koupparis, M; Tsantili-Kakoulidou, A; Kokotos, G; Georgakopoulos, C

    2009-02-01

    Anabolic androgenic steroids (AAS) are synthetic derivatives of testosterone introduced for therapeutic purposes providing enhanced anabolic potency with reduced androgenic effects. Androgens mediate their action through their binding to the androgen receptor (AR) which is mainly expressed in androgen target tissues, such as the prostate, skeletal muscle, liver and central nervous system. This paper reviews some of the wide spectrum of testosterone and synthetic AAS structure modifications related to the intended enhancement in anabolic activity. The structural features of steroids necessary for effective binding to the AR and those which contribute to the stipulation of the androgenic and anabolic activities are also presented.

  11. Mechanisms of Androgen-Independent Prostate Cancer

    PubMed Central

    Saraon, Punit; Drabovich, Andrei P.; Jarvi, Keith A.; Diamandis, Eleftherios P.

    2014-01-01

    Abstract Prostate cancer is the second leading cause of cancer-related deaths among men in North America. Almost all prostate cancers begin in an androgen-dependent state, so androgen deprivation therapy is administered and results in improved clinical outcomes. However, over time, some cancerous cells are able to survive and grow during this treatment, resulting in androgen-independent prostate cancer. At this point, the disease is fatal, as there are no effective targeted therapies available. Most prostate cancer tumors require androgen receptor (AR) signalling for survival. During the progression to androgen-independence, this signalling cascade has been found to be altered at many levels within prostate cancers. Mechanisms that enhance AR signalling during androgen deprivation include: AR gene amplifications, AR gene mutations, changes in expression of AR co-regulatory proteins, changes in expression of steroid-generating enzymes, ligand-independent activation of AR via ‘outlaw’ pathways, and AR-independent pathways that become activated, termed ‘bypass’ pathways. One or more of these aforementioned changes can lead to prostate cancer cells to gain androgen-independent properties. Understanding the molecular alterations that occur during this process will allow for improved therapeutic strategies to target key molecules and pathways important for this progression. PMID:27683456

  12. Biochemical and physiological aspects of endogenous androgens.

    PubMed

    Kicman, Andrew T

    2010-01-01

    This review attempts to give a synopsis of the major aspects concerning the biochemistry of endogenous androgens, supplemented with several facets of physiology, particularly with respect to testosterone. Testosterone continues to be the most common adverse finding declared by World Anti-Doping Agency accredited laboratories, such samples having an augmented testosterone to epitestosterone ratio. Knowledge regarding the precursors and metabolism of endogenous testosterone is therefore fundamental to understanding many of the issues concerning doping with testosterone and its prohormones, including the detection of their administration. Further, adverse findings for nandrolone are frequent, but this steroid and 19-norandrostenedione are also produced endogenously, an appealing hypothesis being that they are minor by-products of the aromatization of androgens. At sports tribunals pertaining to adverse analytical findings of natural androgen administration, experts often raise issues that concern some aspect of steroid biochemistry and physiology. Salient topics included within this review are the origins and interconversion of endogenous androgens, the biosynthesis of testosterone and epitestosterone, the mechanism of aromatization, the molecular biology of the androgen receptor, the hypothalamic-pituitary-testicular axis, disturbances to this axis by anabolic steroid administration, the transport (binding) of androgens in blood, and briefly the metabolism and excretion of androgens.

  13. Mechanisms of Androgen-Independent Prostate Cancer

    PubMed Central

    Saraon, Punit; Drabovich, Andrei P.; Jarvi, Keith A.; Diamandis, Eleftherios P.

    2014-01-01

    Abstract Prostate cancer is the second leading cause of cancer-related deaths among men in North America. Almost all prostate cancers begin in an androgen-dependent state, so androgen deprivation therapy is administered and results in improved clinical outcomes. However, over time, some cancerous cells are able to survive and grow during this treatment, resulting in androgen-independent prostate cancer. At this point, the disease is fatal, as there are no effective targeted therapies available. Most prostate cancer tumors require androgen receptor (AR) signalling for survival. During the progression to androgen-independence, this signalling cascade has been found to be altered at many levels within prostate cancers. Mechanisms that enhance AR signalling during androgen deprivation include: AR gene amplifications, AR gene mutations, changes in expression of AR co-regulatory proteins, changes in expression of steroid-generating enzymes, ligand-independent activation of AR via ‘outlaw’ pathways, and AR-independent pathways that become activated, termed ‘bypass’ pathways. One or more of these aforementioned changes can lead to prostate cancer cells to gain androgen-independent properties. Understanding the molecular alterations that occur during this process will allow for improved therapeutic strategies to target key molecules and pathways important for this progression.

  14. Effects of St John's wort (Hypericum perforatum L.) extract on plasma androgen concentrations in healthy men and women: a pilot study.

    PubMed

    Donovan, Jennifer L; DeVane, C Lindsay; Lewis, John G; Wang, Jun-Sheng; Ruan, Ying; Chavin, Kenneth D; Markowitz, John S

    2005-10-01

    St John's wort extract (SJW; Hypericum perforatum L.) is taken extensively as a putative herbal antidepressant. It has been shown to induce the activity of cytochrome P-450 3A4 (CYP3A4) and to increase the clearance of numerous drugs and steroids such as cortisol and ethinyl estradiol. This study was conducted to determine if SJW exposure also alters the concentrations of circulating androgenic steroid hormones. The study was conducted using healthy volunteers (6M, 6F) studied before and after a 14-day treatment period with a SJW preparation previously demonstrated to induce the activity of CYP3A4. Plasma concentrations of testosterone, dihydrotestosterone (DHT), dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG) and the combined concentrations of androsterone sulfate (AoS) and epiandrosterone sulfate (epiAoS) were measured by immunoassay methods. The results of analysis demonstrated that SJW did not significantly alter the majority of the androgens studied (p > 0.05) although the combined concentrations of the 5alpha-reduced steroids, AoS and epiAoS, significantly declined following treatment in all subjects (p = 0.02), and in males (p = 0.04). Furthermore, the testosterone to DHT ratio was increased in both men and women. Although the latter increase did not reach statistical significance, it is also consistent with the possible inhibition of 5alpha-reductase by SJW. It is concluded that despite significant induction of CYP3A4, short term administration of SJW does not significantly alter the concentrations of most circulating androgens in men and women but may produce a dimunition in some of the circulating 5alpha-reduced androgens.

  15. Interactions of androgens, green tea catechins and the antiandrogen flutamide with the external glucose-binding site of the human erythrocyte glucose transporter GLUT1.

    PubMed

    Naftalin, Richard J; Afzal, Iram; Cunningham, Philip; Halai, Mansur; Ross, Clare; Salleh, Naguib; Milligan, Stuart R

    2003-10-01

    This study investigates the effects of androgens, the antiandrogen flutamide and green tea catechins on glucose transport inhibition in human erythrocytes. These effects may relate to the antidiabetogenic effects of green tea. Testosterone, 4-androstene-3,17-dione, dehydroepiandrosterone (DHEA) and DHEA-3-acetate inhibit glucose exit from human erythrocytes with half-maximal inhibitions (Ki) of 39.2+/-8.9, 29.6+/-3.7, 48.1+/-10.2 and 4.8+/-0.98 microM, respectively. The antiandrogen flutamide competitively relieves these inhibitions and of phloretin. Dehydrotestosterone has no effect on glucose transport, indicating the differences between androgen interaction with GLUT1 and human androgen receptor (hAR). Green tea catechins also inhibit glucose exit from erythrocytes. Epicatechin 3-gallate (ECG) has a Ki ECG of 0.14+/-0.01 microM, and epigallocatechin 3-gallate (EGCG) has a Ki EGCG of 0.97+/-0.13 microM. Flutamide reverses these effects. Androgen-screening tests show that the green tea catechins do not act genomically. The high affinities of ECG and EGCG for GLUT1 indicate that this might be their physiological site of action. There are sequence homologies between GLUT1 and the ligand-binding domain (LBD) of hAR containing the amino-acid triads Arg 126, Thr 30 and Asn 288, and Arg 126, Thr 30 and Asn 29, with similar 3D topology to the polar groups binding 3-keto and 17-beta OH steroid groups in hAR LBD. These triads are appropriately sited for competitive inhibition of glucose import at the external opening of the hydrophilic pore traversing GLUT1.

  16. Selective androgen receptor modulators: in pursuit of tissue-selective androgens.

    PubMed

    Omwancha, Josephat; Brown, Terry R

    2006-10-01

    The androgen receptor mediates the androgenic and anabolic activity of the endogenous steroids testosterone and 5alpha-dihydrotestosterone. Current knowledge of the androgen receptor protein structure, and the molecular mechanisms surrounding the binding properties and activities of agonists and antagonists has led to the design and development of novel nonsteroidal ligands with selected tissue-specific androgen receptor agonist and antagonist activities. The activity of these compounds, termed selective androgen receptor modulators (SARMs), is directed toward the maintenance or enhancement of anabolic effects on bone and muscle with minimal androgenic effects on prostate growth. SARMs are of potential therapeutic value in the treatment of male hypogonadism, osteoporosis, frailty and muscle wasting, burn injury and would healing, anemia, mood and depression, benign prostatic hyperplasia and prostate cancer.

  17. 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

  18. 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 ...

  19. 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 ...

  20. Neurologic complications of disorders of the adrenal glands.

    PubMed

    Bertorini, Tulio E; Perez, Angel

    2014-01-01

    Disorders of the adrenal glands frequently have secondary neurological manifestations, while some diseases that involve the central nervous system are accompanied by adrenal gland dysfunction. Excessive corticosteroid secretions in primary or secondary Cushing's syndrome causes muscle weakness and behavioral disturbances, such as emotional lability and sometimes depression, while adrenal insufficiency may cause fatigue, weakness, and depression. Adrenoleukodystrophy and adrenoneuromyelopathy are X-linked recessive disorders of the metabolism of very long chain fatty acids that manifest with white matter abnormalities of the brain, myelopathy and/or neuropathy, as well as adrenal insufficiency. Other disorders of the adrenal glands include hyperaldosteroidism, which may cause weakness from hypokalemia. Dysfunction of the adrenal medulla causes excessive or deficient secretion of catecholamines, primarily causing cardiovascular symptoms. This chapter reviews the clinical manifestations and diagnostic aspects and treatment of the various disorders of the adrenal glands. Some of the congenital adrenal diseases are also discussed.

  1. [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

  2. Adrenal Hypoplasia Congenita: A Rare Cause of Primary Adrenal Insufficiency and Hypogonadotropic Hypogonadism

    PubMed Central

    Loureiro, Marta; Reis, Filipa; Robalo, Brígida; Pereira, Carla; Sampaio, Lurdes

    2015-01-01

    Primary adrenal insufficiency is defined by the impaired synthesis of adrenocortical hormones due to an intrinsic disease of the adrenal cortex. Determining its etiology is crucial to allow adequate long-term management and genetic counseling. We report the case of a male adolescent that presented in the neonatal period with adrenal crisis and received replacement therapy for primary adrenal insufficiency. During follow-up, adrenal hypoplasia congenita (AHC) was suspected given his persistently raised adrenocorticotropic hormone levels, with markedly low 17-OH progesterone and androstenedione levels. DNA sequence analysis revealed a mutation in NR0B1 gene (c.1292delG), confirming the diagnosis. Delayed puberty and persistent low levels of gonadotropins led to testosterone replacement therapy. X-linked AHC is a rare cause of primary adrenal insufficiency and hypogonadotropic hypogonadism, related to mutations in NR0B1 gene. Despite its rarity, AHC should be considered in patients who present with primary adrenal failure, low levels of 17-OH progesterone and hypogonadotropic hypogonadism. PMID:26500747

  3. Adrenal steroids modulate the immune response during Brucella abortus infection by a mechanism that depends on the regulation of cytokine production.

    PubMed

    Gentilini, María Virginia; Velásquez, Lis Noelia; Barrionuevo, Paula; Arriola Benitez, Paula Constanza; Giambartolomei, Guillermo Hernán; Delpino, María Victoria

    2015-05-01

    Human brucellosis is a protean disease with a diversity of clinical signs and symptoms resulting from infection with Brucella species. Recent reports suggest a cross-regulation between adrenal steroids (cortisol and dehydroepiandrosterone [DHEA]) and the immune system. Monocytes and macrophages are the main replication niche for Brucella. Therefore, we investigated the role of adrenal hormones on the modulation of the immune response mediated by macrophages in B. abortus infection. Cortisol treatment during B. abortus infection significantly inhibits cytokine, chemokine, and MMP-9 secretion. In contrast, DHEA treatment had no effect. However, DHEA treatment increases the expression of costimulatory molecules (CD40, CD86), the adhesion molecule CD54, and major histocompatibility complex class I (MHC-I) and MHC-II expression on the surface of B. abortus-infected monocytes. It is known that B. abortus infection inhibits MHC-I and MHC-II expression induced by gamma interferon (IFN-γ) treatment. DHEA reverses B. abortus downmodulation of the MHC-I and -II expression induced by IFN-γ. Taken together, our data indicate that DHEA immune intervention may positively affect monocyte activity during B. abortus infection.

  4. Adrenal Steroids Modulate the Immune Response during Brucella abortus Infection by a Mechanism That Depends on the Regulation of Cytokine Production

    PubMed Central

    Gentilini, María Virginia; Velásquez, Lis Noelia; Barrionuevo, Paula; Arriola Benitez, Paula Constanza; Giambartolomei, Guillermo Hernán

    2015-01-01

    Human brucellosis is a protean disease with a diversity of clinical signs and symptoms resulting from infection with Brucella species. Recent reports suggest a cross-regulation between adrenal steroids (cortisol and dehydroepiandrosterone [DHEA]) and the immune system. Monocytes and macrophages are the main replication niche for Brucella. Therefore, we investigated the role of adrenal hormones on the modulation of the immune response mediated by macrophages in B. abortus infection. Cortisol treatment during B. abortus infection significantly inhibits cytokine, chemokine, and MMP-9 secretion. In contrast, DHEA treatment had no effect. However, DHEA treatment increases the expression of costimulatory molecules (CD40, CD86), the adhesion molecule CD54, and major histocompatibility complex class I (MHC-I) and MHC-II expression on the surface of B. abortus-infected monocytes. It is known that B. abortus infection inhibits MHC-I and MHC-II expression induced by gamma interferon (IFN-γ) treatment. DHEA reverses B. abortus downmodulation of the MHC-I and -II expression induced by IFN-γ. Taken together, our data indicate that DHEA immune intervention may positively affect monocyte activity during B. abortus infection. PMID:25733519

  5. 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

  6. Imaging of the adrenal gland lesions.

    PubMed

    Herr, Keith; Muglia, Valdair F; Koff, Walter José; Westphalen, Antonio Carlos

    2014-01-01

    With the steep increase in the use of cross-sectional imaging in recent years, the incidentally detected adrenal lesion, or "incidentaloma", has become an increasingly common diagnostic problem for the radiologist, and a need for an approach to classifying these lesions as benign, malignant or indeterminate with imaging has spurred an explosion of research. While most incidentalomas represent benign disease, typically an adenoma, the possibility of malignant involvement of the adrenal gland necessitates a reliance on imaging to inform management decisions. In this article, we review the literature on adrenal gland imaging, with particular emphasis on computed tomography, magnetic resonance imaging, and photon-emission tomography, and discuss how these findings relate to clinical practice. Emerging technologies, such as contrast-enhanced ultrasonography, dual-energy computed tomography, and magnetic resonance spectroscopic imaging will also be briefly addressed.

  7. Imaging of the adrenal gland lesions*

    PubMed Central

    Herr, Keith; Muglia, Valdair F.; Koff, Walter José; Westphalen, Antonio Carlos

    2014-01-01

    With the steep increase in the use of cross-sectional imaging in recent years, the incidentally detected adrenal lesion, or "incidentaloma", has become an increasingly common diagnostic problem for the radiologist, and a need for an approach to classifying these lesions as benign, malignant or indeterminate with imaging has spurred an explosion of research. While most incidentalomas represent benign disease, typically an adenoma, the possibility of malignant involvement of the adrenal gland necessitates a reliance on imaging to inform management decisions. In this article, we review the literature on adrenal gland imaging, with particular emphasis on computed tomography, magnetic resonance imaging, and photon-emission tomography, and discuss how these findings relate to clinical practice. Emerging technologies, such as contrast-enhanced ultrasonography, dual-energy computed tomography, and magnetic resonance spectroscopic imaging will also be briefly addressed. PMID:25741090

  8. Gallium-68 PSMA uptake in adrenal adenoma.

    PubMed

    Law, W Phillip; Fiumara, Frank; Fong, William; Miles, Kenneth A

    2016-08-01

    Gallium-68 (Ga-68) labelled prostate-specific membrane antigen (PSMA) imaging by positron emission tomography (PET) has emerged as a promising tool for staging of prostate cancer and restaging of disease in recurrence or biochemical failure after definitive treatment of prostate cancer. Ga-68 PSMA PET produces high target-to-background images of prostate cancer and its metastases which are reflective of the significant overexpression of PSMA in these cells and greatly facilitates tumour detection. However, relatively little is known about the PSMA expression of benign neoplasms and non-prostate epithelial malignancies. This is a case report of PSMA uptake in an adrenal adenoma incidentally discovered on PET performed for restaging of biochemically suspected prostate cancer recurrence. With the increasing use of PSMA PET in the management of prostate cancer - and the not infrequent occurrence of adrenal adenomas - the appearance of low- to moderate-grade PSMA uptake in adrenal adenomas should be one with which reporting clinicians are familiar.

  9. 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

  10. Bilateral adrenal hemorrhage in polycythemia vera

    PubMed Central

    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

  11. A very rare bilateral adrenal tumor.

    PubMed

    Toniato, Antonio; Boschin, Isabella Merante; Pelizzo, Maria Rosa

    2014-04-01

    We report a case of very rare adrenal tumor. A 54-year-old patient was classified as affected by bilateral adrenal incidentaloma that surprisingly, on histology resulted solitary fibrous tumors. Solitary fibrous tumor (SFT) is an uncommon mesenchymal neoplasm. Only five cases of localization of SFT in adrenal gland are reported in the literature, while the frequency of retroperitoneum localization is more frequent, about 30 cases. Immunohistochemically, SFT can be positive for CD34 antigen, vimentin, CD99, and bcl-2 and usually negative for cytokeratins, chromogranin A, NSE, neurofilaments, synoptophysin, and S-100. Surgical excision remains the main treatment in fact the recurrence is locoregional and correlated with positive margins due to incomplete excision, while distant metastases are correlated with atypical or malignant features.

  12. 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.

  13. Spontaneous Idiopathic Unilateral Adrenal Haemorrhage (SIAH).

    PubMed

    Naqvi, Syed Ali; Zaman, Shamas; Ahmed, Irfan

    2015-04-01

    Spontaneous Idiopathic Adrenal Haemorrhage (SIAH) is an unusual surgical emergency which can present with life threatening massive retroperitoneal bleeding. Most of the cases reported in the literature are associated with use of anticoagulation or underlying adrenal pathology such as tumors or cysts. Since this clinical entity is uncommon and clinical presentation is very indistinct, the diagnosis can be easily missed and can be challenging for the treating physicians. Nevertheless a raised clinical suspicion coupled with advances in radiological imaging have considerably improved the detection of SIAH in recent times. We report an unusual case of a 20 years old healthy female student who presented to our hospital with sudden onset of abdominal pain and shock. She was diagnosed as a case of massive spontaneous idiopathic unilateral adrenal haemorrhage, unaccompanied by any hematologic disorder, trauma or underlying pathology. Although patient was hemodynamically unstable at presentation, she was resuscitated promptly, investigated appropriately, hence recovered uneventfully with conservative management alone.

  14. The androgen receptor gene mutations database.

    PubMed

    Patterson, M N; Hughes, I A; Gottlieb, B; Pinsky, L

    1994-09-01

    The androgen receptor gene mutations database is a comprehensive listing of mutations published in journals and meetings proceedings. The majority of mutations are point mutations identified in patients with androgen insensitivity syndrome. Information is included regarding the phenotype, the nature and location of the mutations, as well as the effects of the mutations on the androgen binding activity of the receptor. The current version of the database contains 149 entries, of which 114 are unique mutations. The database is available from EMBL (NetServ@EMBL-Heidelberg.DE) or as a Macintosh Filemaker file (mc33001@musica.mcgill.ca).

  15. Androgens in pregnancy: roles in parturition

    PubMed Central

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

    2014-01-01

    BACKGROUND Understanding the physiology of pregnancy enables effective management of pregnancy complications that could otherwise be life threatening for both mother and fetus. A functional uterus (i) retains the fetus in utero during pregnancy without initiating stretch-induced contractions and (ii) is able to dilate the cervix and contract the myometrium at term to deliver the fetus. The onset of labour is associated with successful cervical remodelling and contraction of myometrium, arising from concomitant activation of uterine immune and endocrine systems. A large body of evidence suggests that actions of local steroid hormones may drive changes occurring in the uterine microenvironment at term. Although there have been a number of studies considering the potential role(s) played by progesterone and estrogen at the time of parturition, the bio-availability and effects of androgens during pregnancy have received less scrutiny. The aim of this review is to highlight potential roles of androgens in the biology of pregnancy and parturition. METHODS A review of published literature was performed to address (i) androgen concentrations, including biosynthesis and clearance, in maternal and fetal compartments throughout gestation, (ii) associations of androgen concentrations with adverse pregnancy outcomes, (iii) the role of androgens in the physiology of cervical remodelling and finally (iv) the role of androgens in the physiology of myometrial function including any impact on contractility. RESULTS Some, but not all, androgens increase throughout gestation in maternal circulation. The effects of this increase are not fully understood; however, evidence suggests that increased androgens might regulate key processes during pregnancy and parturition. For example, androgens are believed to be critical for cervical remodelling at term, in particular cervical ripening, via regulation of cervical collagen fibril organization. Additionally, a number of studies highlight

  16. 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.

  17. 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.

  18. 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.

  19. Crossover of the hypothalamic pituitary-adrenal/interrenal, -thyroid, and -gonadal axes in testicular development.

    PubMed

    Castañeda Cortés, Diana C; Langlois, Valerie S; Fernandino, Juan I

    2014-01-01

    Besides the well-known function of thyroid hormones (THs) for regulating metabolism, it has recently been discovered that THs are also involved in testicular development in mammalian and non-mammalian species. THs, in combination with follicle stimulating hormone, lead to androgen synthesis in Danio rerio, which results in the onset of spermatogenesis in the testis, potentially relating the hypothalamic-pituitary-thyroid (HPT) gland to the hypothalamic-pituitary-gonadal (HPG) axes. Furthermore, studies in non-mammalian species have suggested that by stimulating the thyroid-stimulating hormone (TSH), THs can be induced by corticotropin-releasing hormone. This suggests that the hypothalamic-pituitary-adrenal/interrenal gland (HPA) axis might influence the HPT axis. Additionally, it was shown that hormones pertaining to both HPT and HPA could also influence the HPG endocrine axis. For example, high levels of androgens were observed in the testis in Odonthestes bonariensis during a period of stress-induced sex-determination, which suggests that stress hormones influence the gonadal fate toward masculinization. Thus, this review highlights the hormonal interactions observed between the HPT, HPA, and HPG axes using a comparative approach in order to better understand how these endocrine systems could interact with each other to influence the development of testes.

  20. Involvement of the adrenal glands and testis in gap junction formation via testosterone within the male rat anterior pituitary gland.

    PubMed

    Sakuma, Eisuke; Wada, Ikuo; Otsuka, Takanobu; Wakabayashi, Kenjiro; Ito, Kinya; Soji, Tsuyoshi; Herbert, Damon C

    2012-12-01

    We investigated the influence of testicular and adrenal androgens on the presence of gap junctions between folliculo-stellate cells in the anterior pituitary glands of 60-day-old Wistar-Imamichi strain male rats. The animals were separated into six groups: Group A served as the controls and had free access to a normal diet and water, Group B was given a normal diet and 0.9% NaCl for their drinking water as the controls of adrenalectomized groups, Group C was castrated, Group D was adrenalectomized, Group E was both castrated and adrenalectomized, and Group F was also both castrated and adrenalectomized. In addition, the animals of Group F were administered a dose of testosterone that is known to produce high physiological levels of the hormones in plasma. Five rats from each group were sacrificed 1, 2, 3, 4, 5, 6, and 7 days after their respective operation, and the anterior pituitary glands were removed and prepared for observation by transmission electron microscopy. We quantified the number of follicles and gap junctions and calculated the rate of occurrence as the ratio of the number of gap junctions existing between folliculo-stellate cells per intersected follicle profile. Simultaneous removal of adrenal glands with castration resulted in a significantly decrease in the number of gap junctions, whereas the administration of testosterone to these rats compensated for this change. These observations indicate that the preservation of gap junctions between folliculo-stellate cells is mainly dependent on androgens from both the testes and adrenal glands in adult male rats.

  1. The effect of anabolic steroids on the gastrointestinal system, kidneys, and adrenal glands.

    PubMed

    Modlinski, Ryan; Fields, Karl B

    2006-04-01

    Over the past several decades we have seen an increase in the prevalence of anabolic steroid use by athletes. Because use of anabolic steroids is illicit, much of our knowledge of their side effects is derived from case reports, retrospective studies, or comparisons with studies in other similar patient groups. It has been shown that high-dose anabolic steroids have an effect on lowering high-density lipoprotein, increasing low-density lipoprotein, and increasing the atherogenic-promoting apolipoprotein A. Steroid abuse can also be hepatotoxic, promoting disturbances such as biliary stasis, peliosis hepatis, and even hepatomas, which are all usually reversible upon discontinuation. Suppression of the hypothalamic adrenal axis can also lead to profound adrenal changes that are also reversible with time. Although rare, renal side effects have also been documented, leading to acute renal failure and even Wilms' tumors in isolated cases. Much of our knowledge of these potentially severe but usually limited side effects is confounded by use of combinations of different steroid preparations and by the concomitant use with other substances. Physicians must target their efforts at counseling adolescents and other athletes about the potential harms of androgenic anabolic steroids and the legal options to improve strength and performance.

  2. Expanding the therapeutic use of androgens via selective androgen receptor modulators (SARMs).

    PubMed

    Gao, Wenqing; Dalton, James T

    2007-03-01

    Selective androgen receptor modulators (SARMs) are a novel class of androgen receptor (AR) ligands that might change the future of androgen therapy dramatically. With improved pharmacokinetic characteristics and tissue-selective pharmacological activities, SARMs are expected to greatly extend the clinical applications of androgens to osteoporosis, muscle wasting, male contraception and diseases of the prostate. Mechanistic studies with currently available SARMs will help to define the contributions of differential tissue distribution, tissue-specific expression of 5alpha-reductase, ligand-specific regulation of gene expression and AR interactions with tissue-specific coactivators to their observed tissue selectivity, and lead to even greater expansion of selective anabolic therapies.

  3. Intratumoral de novo steroid synthesis activates androgen receptor in castration-resistant prostate cancer and is upregulated by treatment with CYP17A1 inhibitors.

    PubMed

    Cai, Changmeng; Chen, Sen; Ng, Patrick; Bubley, Glenn J; Nelson, Peter S; Mostaghel, Elahe A; Marck, Brett; Matsumoto, Alvin M; Simon, Nicholas I; Wang, Hongyun; Chen, Shaoyong; Balk, Steven P

    2011-10-15

    Relapse of castration-resistant prostate cancer (CRPC) that occurs after androgen deprivation therapy of primary prostate cancer can be mediated by reactivation of the androgen receptor (AR). One important mechanism mediating this AR reactivation is intratumoral conversion of the weak adrenal androgens DHEA and androstenedione into the AR ligands testosterone and dihydrotestosterone. DHEA and androstenedione are synthesized by the adrenals through the sequential actions of the cytochrome P450 enzymes CYP11A1 and CYP17A1, so that CYP17A1 inhibitors such as abiraterone are effective therapies for CRPC. However, the significance of intratumoral CYP17A1 and de novo androgen synthesis from cholesterol in CRPC, and the mechanisms contributing to CYP17A1 inhibitor resistance/relapse, remain to be determined. We report that AR activity in castration-resistant VCaP tumor xenografts can be restored through CYP17A1-dependent de novo androgen synthesis, and that abiraterone treatment of these xenografts imposes selective pressure for increased intratumoral expression of CYP17A1, thereby generating a mechanism for development of resistance to CYP17A1 inhibitors. Supporting the clinical relevance of this mechanism, we found that intratumoral expression of CYP17A1 was markedly increased in tumor biopsies from CRPC patients after CYP17A1 inhibitor therapy. We further show that CRPC cells expressing a progesterone responsive T877A mutant AR are not CYP17A1 dependent, but that AR activity in these cells is still steroid dependent and mediated by upstream CYP11A1-dependent intraturmoral pregnenolone/progesterone synthesis. Together, our results indicate that CRPCs resistant to CYP17A1 inhibition may remain steroid dependent and therefore responsive to therapies that can further suppress de novo intratumoral steroid synthesis.

  4. A success story in congenital adrenal hyperplasia.

    PubMed

    Kriplani, Alka; Lunkad, Amol; Agarwal, Nutan; Kulshreshtha, Bindu; Ariachery, C Aminni

    2012-12-01

    Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders characterized by enzyme defects in adrenal steroidogenic pathways. CAH due to 21-hydroxylase deficiency accounts for 95 % of cases. This case was diagnosed to have simple virilizing type of CAH and started on dexamethasone, and underwent genitoplasty and clitoroplasty at 25 years of age, then was married 3 years after surgery and conceived spontaneously 2 years after marriage, to deliver a healthy male baby. Thus, proper diagnosis and treatment with steroids and genitoplasty can give females with CAH a normal sexual, normal menstrual, and reproductive function.

  5. 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

  6. 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

  7. 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

  8. 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.

  9. A case of non-Hodgkin's lymphoma primary arising in both adrenal glands associated with adrenal failure.

    PubMed

    Nishiuchi, Takamasa; Imachi, Hitomi; Fujiwara, Mako; Murao, Koji; Onishi, Hiroaki; Kiguchi, Tohru; Takimoto, Hidetaka; Kushida, Yoshio; Haba, Reiji; Ishida, Toshihiko

    2009-02-01

    It is known that adrenal insufficiency is one of the complications in primary adrenal lymphoma, especially those with bilateral adrenal involvement. A 73-year-old man was referred for general fatigue and high fever to the nearest hospital. The patient was transferred to our hospital for evaluation of bilateral adrenal tumors and hyponatremia. He was diagnosed as having non-Hodgkin's lymphoma (NHL) with primaries arising in both adrenal glands. Primary adrenal lymphoma (PAL) is a rare extra-nodal NHL. Although an appropriate treatment of this disease has not been established, our case has demonstrated that the combination of rituximab and THP-COP chemotherapy could be administered, and that it improved clinical manifestations. This case raises the suggestion that malignant lymphoma should be suspected in patients with bilateral adrenal tumors that present with progressive adrenal insufficiency.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Retroperitoneal foregut duplication cyst presenting as an adrenal mass.

    PubMed

    Terry, N Elizabeth; Senkowski, Christopher K; Check, William; Brower, Steven T

    2007-01-01

    A 75 year-old woman presented to the authors' institution with abdominal pain and early satiety. An adrenal mass was found on CT scanning. Laparoscopic adrenalectomy was performed, and the patient was found to have a retroperitoneal bronchogenic cyst adherent to the adrenal gland. The workup of an adrenal mass is discussed as well as the pathophysiology of bronchogenic cysts.

  16. 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.

  17. Adrenal axis activation by chronic social stress fails to inhibit gonadal function in male rats.

    PubMed

    Lemaire, V; Taylor, G T; Mormède, P

    1997-11-01

    Stress in males via the hypothalamic-pituitary-adrenal (HPA) axis may set into motion varied physiological alterations, including dysfunction of the hypothalamic-pituitary-gonadal (HPG) axis. However, the influence of the HPA on the HPG axis may not always be inhibitory. Presence or absence of stimuli of sexual significance that typically activates the HPG axis may alter the influence of the adrenal axis on gonadal axes. In this project, we used male rats and chronic social stimulation that included brief or extended periods with female rats to examine HPA-HPG axes interactions. In experiment 1, we used intact males and a 'chronic social stress' paradigm developed in our previous research that induces social instability by daily changing the membership of group-housed males with females. Thymus weight was reduced and corticosterone levels were marginally increased by chronic social stress, indicating a HPA axis hyperactivity. The HPG axis was also activated as shown by the increased weight of the androgen-sensitive sex structures. These results indicate that when these two axes are stimulated together, neither interferes with nor suppresses activities of the other. Implants of corticosterone pellets to adrenalectomized animals that maintained constant, high corticosterone levels failed to reverse the gonadal hyperactivity induced by sexual stimulation. In a second experiment, we studied the influence of different intensity of sexual stimulations on HPA-HPG axes interactions. Increased corticosterone levels and adrenal weight, indicating a HPA hyperactivity, failed to inhibit HPG hyperactivity as measured by the increased sexual organs weight, whatever the sexual intensity of the stimulation. This work demonstrates that the gonadal axis is freed from suppression when sexual stimulation occurs together with stress. The general conclusion is that the nature of complex social settings is important in determining interactions between the two neuroendocrine axes.

  18. Transcriptome Profiling Reveals Differentially Expressed Transcripts Between the Human Adrenal Zona Fasciculata and Zona Reticularis

    PubMed Central

    Rege, Juilee; Nakamura, Yasuhiro; Wang, Tao; Merchen, Todd D.; Sasano, Hironobu

    2014-01-01

    Context: The human adrenal zona fasciculata (ZF) and zona reticularis (ZR) are responsible for the production of cortisol and 19-carbon steroids (often called adrenal androgens), respectively. However, the gene profiles and exact molecular mechanisms leading to the functional phenotype of the ZF and ZR are still not clearly defined. In the present study, we identified the transcripts that are differentially expressed in the ZF and ZR. Objective: The objective of the study was to compare the transcriptome profiles of ZF and ZR. Design and Methods: ZF and ZR were microdissected from 10 human adrenals. Total RNA was extracted from 10 ZF/ZR pairs and hybridized to Illumina microarray chips. The 10 most differentially expressed transcripts were studied with quantitative RT-PCR (qPCR). Immunohistochemistry was also performed on four zone-specific genes. Results: Microarray results demonstrated that only 347 transcripts of the 47 231 were significantly different by 2-fold or greater in the ZF and ZR. ZF had 195 transcripts with 2-fold or greater increase compared with its paired ZR, whereas ZR was found to have 152 transcripts with 2-fold or greater higher expression than in ZF. Microarray and qPCR analysis of transcripts encoding steroidogenic enzymes (n = 10) demonstrated that only 3β-hydroxysteroid dehydrogenase, steroid sulfotransferase, type 5 17β-hydroxysteroid dehydrogenase, and cytochrome b5 were significantly different. Immunohistochemistry and qPCR studies confirmed that the ZF had an increased expression of lymphoid enhancer-binding factor 1 and nephroblastoma overexpressed, whereas ZR showed an increased expression of solute carrier family 27 (fatty acid transporter) (SLC27A2), member 2 and TSPAN12 (tetraspanin 12) Conclusion: Microarray revealed several novel candidate genes for elucidating the molecular mechanisms governing the ZF and ZR, thereby increasing our understanding of the functional zonation of these two adrenocortical zones. PMID:24423296

  19. 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

  20. 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

  1. 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 ...

  2. The androgen receptor gene mutations database.

    PubMed

    Gottlieb, B; Trifiro, M; Lumbroso, R; Vasiliou, D M; Pinsky, L

    1996-01-01

    The current version of the androgen receptor (AR) gene mutations database is described. We have added (if available) data on the androgen binding phenotype of the mutant AR, the clinical phenotype of the affected persons, the family history and whether the pathogenicity of a mutation has been proven. Exonic mutations are now listed in 5'-->3' sequence regardless of type and single base pair changes are presented in codon context. Splice site and intronic mutations are listed separately. The database has allowed us to substantiate and amplify the observation of mutational hot spots within exons encoding the AR androgen binding domain. The database is available from EML (ftp://www.ebi.ac.uk/pub/databases/androgen) or as a Macintosh Filemaker file (MC33@musica.mcgill.ca).

  3. Androgen deprivation therapy for prostate cancer.

    PubMed

    Singer, Eric A; Golijanin, Dragan J; Miyamoto, Hiroshi; Messing, Edward M

    2008-02-01

    Androgen deprivation continues to play a crucial role in the treatment of advanced and metastatic prostate cancer. In the 65 years since its use was first described, urologists and medical oncologists have developed new and innovative ways to manipulate the hypothalamic-pituitary-gonadal axis with the goal of alleviating symptoms and prolonging the life of men with prostate cancer. Despite the successes that androgen deprivation therapy has brought, each method and regimen possesses unique benefits and burdens, of which the clinician and patient must be cognizant. This review discusses the first-line androgen deprivation methods and regimens presently in use with special attention paid to their side effects and the management of them, as well as the question of when to initiate androgen deprivation therapy.

  4. 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.

  5. 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

  6. Androgen receptor in male breast cancer.

    PubMed

    Sas-Korczynska, Beata; Adamczyk, Aagnieszka; Niemiec, Joanna; Harazin-Lechowska, Agnieszka; Ambicka, Aleksandra; Jakubowicz, Jerzy

    2015-12-01

    We present the androgen receptor (AR) status in 32 breast cancers diagnosed in male patients. Androgen receptor expression was found in 62.5% tumors and it was more frequent (85% of cases) in estrogen-positive tumours. The analyses of its impact on treatment results showed that AR immmunopositivity is a prognostic factor for overall survival, and AR immunonegativity is also correlated with worse prognosis (distant metastases developed more frequently and earlier).

  7. Pilot study of adrenal steroid hormones in hair as an indicator of chronic mental and physical stress.

    PubMed

    Ullmann, E; Barthel, A; Petrowski, K; Stalder, T; Kirschbaum, C; Bornstein, S R

    2016-01-01

    Currently, the quantitative analysis of moderators affecting the function of the hypothalamus-pituitary-adrenal (HPA)-axis in health and sickness is still unreliable. This is, in particular, due to physiological factors such as pulsatile ultradian and circadian glucocorticoid secretion as well as to methodological limitations of the current techniques for steroid hormone determination. Based on this background, the determination of long-term hair steroid concentrations is an important methodological improvement allowing for the quantitative analysis of chronic HPA axis-activation. In order to determine the relationship between chronic mental and physical stress and a chronic activation of the HPA axis, we performed a cross-sectional pilot-study with 40 healthy students and examined the relationships between physical activity, mental burden(s), subjective stress perceptions, depressiveness, anxiety, physical complaints, sense of coherence, resilience, and the long-term integrated steroid hormone levels in hair. The results showed that the concentrations of cortisol, cortisone, and dehydroepiandrosterone in hair were significantly correlated to mental (p = 0.034) and physical stress (p = 0.001) as well as to subjective stress perception (p = 0.006). We conclude that steroid concentrations in hair are decisive predictors for an increase in the long-term-HPA axis activity. Moreover, this biomarker is suitable for capturing the stresslevel after burdening events and physical activity. PMID:27174654

  8. Pilot study of adrenal steroid hormones in hair as an indicator of chronic mental and physical stress

    PubMed Central

    Ullmann, E.; Barthel, A; Petrowski, K.; Stalder, T.; Kirschbaum, C.; Bornstein, S. R.

    2016-01-01

    Currently, the quantitative analysis of moderators affecting the function of the hypothalamus-pituitary-adrenal (HPA)-axis in health and sickness is still unreliable. This is, in particular, due to physiological factors such as pulsatile ultradian and circadian glucocorticoid secretion as well as to methodological limitations of the current techniques for steroid hormone determination. Based on this background, the determination of long-term hair steroid concentrations is an important methodological improvement allowing for the quantitative analysis of chronic HPA axis-activation. In order to determine the relationship between chronic mental and physical stress and a chronic activation of the HPA axis, we performed a cross-sectional pilot-study with 40 healthy students and examined the relationships between physical activity, mental burden(s), subjective stress perceptions, depressiveness, anxiety, physical complaints, sense of coherence, resilience, and the long-term integrated steroid hormone levels in hair. The results showed that the concentrations of cortisol, cortisone, and dehydroepiandrosterone in hair were significantly correlated to mental (p = 0.034) and physical stress (p = 0.001) as well as to subjective stress perception (p = 0.006). We conclude that steroid concentrations in hair are decisive predictors for an increase in the long-term-HPA axis activity. Moreover, this biomarker is suitable for capturing the stresslevel after burdening events and physical activity. PMID:27174654

  9. Androgen receptor expression in gastrointestinal stromal tumor.

    PubMed

    Lopes, Lisandro F; Bacchi, Carlos E

    2009-03-01

    The aim of this study was to evaluate the expression of estrogen, progesterone, and androgen receptors in a large series of gastrointestinal stromal tumors. Clinical and pathologic data were reviewed in 427 cases of gastrointestinal stromal tumor and the expression of such hormone receptors was investigated by immunohistochemistry using tissue microarray technique. All tumors were negative for estrogen receptor expression. Progesterone and androgen receptors expression was observed in 5.4% and 17.6% of tumors, respectively. We found the higher average age at diagnosis, the lower frequency of tumors located in the small intestine, and the higher frequency of extragastrointestinal tumors to be statistically significant in the group of tumors with androgen receptor expression in contrast to the group showing no androgen receptor expression. There was no statistic difference between such groups regarding sex, tumor size, mitotic count, cell morphology, and risk of aggressive behavior. Considering that the expression of androgen receptors in gastrointestinal stromal tumors is not negligible, further studies are encouraged to establish the role of androgen deprivation therapy for gastrointestinal stromal tumors.

  10. 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

  11. Bilateral adrenal [corrected] nodules due to histoplasmosis in an elderly.

    PubMed

    Carvalho, Flávio Pedreira de Freitas de; Curiati, José Antônio Esper; Mauad, Thaís; Incerti, Milena Mendes; Jacob Filho, Wilson

    2007-02-01

    We report a case history of an 84-year-old elderly male patient that presented with a clinical picture suggestive of adrenal failure and bilateral adrenal nodules detected by abdominal computed tomography. A fine needle-guided biopsy was inconclusive for achieving a final diagnosis. The patient died due to septic shock and the autopsy disclosed histoplasmosis with extensive bilateral necrosis of the adrenal glands. Although the adrenal involvement in chronic disseminated histoplasmosis has been described, there have been few reports of the infection being associated with adrenal insufficiency.

  12. Functioning adrenal myelolipoma: A rare cause of hypertension

    PubMed Central

    Jakka, Nagendar; Venkateshwarlu, J.; Satyavani, Naga; Neelaveni, K.; Ramesh, Jayanthy

    2013-01-01

    Co-occurrence of adrenal incidentaloma with hypertension calls for evaluation of endocrine causes including pheochromocytoma, Cushing's disease, and primary aldosteronism. We are reporting 40-years-old man who presented with hypertension and adrenal mass. He had elevated metanephrines, histology of resected adrenal mass revealed adrenal myelolipoma, and immuno-histochemistry was positive for chromogranin A. Both his blood pressure and urinary metanephrines returned to normal after surgery. The association of hypertension and adrenal myelolipoma may not be entirely coincidental, as it may be associated with secreting catecholamine. Literature on such an uncommon association is reviewed briefly as well. PMID:24251175

  13. 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

  14. 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 ...

  15. Imaging features of benign adrenal cysts.

    PubMed

    Sanal, Hatice Tuba; Kocaoglu, Murat; Yildirim, Duzgun; Bulakbasi, Nail; Guvenc, Inanc; Tayfun, Cem; Ucoz, Taner

    2006-12-01

    Benign adrenal gland cysts (BACs) are rare lesions with a variable histological spectrum and may mimic not only each other but also malignant ones. We aimed to review imaging features of BACs which can be helpful in distinguishing each entity and determining the subsequent appropriate management. PMID:16962278

  16. Adrenal Cushing's syndrome may resemble eating disorders.

    PubMed

    Hatakeyama, Makiko; Nakagami, Taku; Yasui-Furukori, Norio

    2014-01-01

    We encountered a patient who presented extreme weight loss and received an eating disorder diagnosis that was later identified as adrenal Cushing's syndrome. A 32-year-old woman with a 2-year history of an eating disorder was admitted to our psychiatric ward due to dehydration, malnutrition and low weight. Her height and body weight were 152.1 cm and 29.8 kg, respectively (body mass index: 12.8). Her other symptoms included a depressed mood, decreased interest, retardation and suicidal ideation. Standard medical cares were prescribed to treat the depressive symptoms and eating disorder, but the depressive episode and low body weight of the patient persisted. Computed tomography of the abdomen revealed an unexpected left adrenal gland tumor. Cushing's syndrome was diagnosed based on several endocrinological examinations. After an enucleation of the left adrenal gland tumor, the patient began eating, and her body weight increased gradually. Her body weight increased to 42.0-47.0 kg (body mass index: 18.2-20.3). Her mental and physical conditions had stabilized. This case suggests that adrenal Cushing's syndrome may resemble eating disorders.

  17. 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.

  18. Haemorrhagic adrenal pseudocyst: a case report.

    PubMed

    Jain, P; Shukla, N K; Das, S K; Kapila, K; Kapur, M

    1988-01-01

    A case of a non-functioning adrenal pseudocyst is reported herein. The key role of sonography and abdominal CT in the diagnosis of this rare retroperitoneal cystic lesion is highlighted. A possible etiological relationship with the trauma of parturition is proposed in our patient.

  19. Adrenal Nodular Hyperplasia in Hereditary Leiomyomatosis and Renal Cell Cancer

    PubMed Central

    Shuch, Brian; Ricketts, Christopher J.; Vocke, Cathy D.; Valera, Vladimir A.; Chen, Clara C.; Gautam, Rabi; Gupta, Gopal N.; Macias, Gabriela S. Gomez; Merino, Maria J.; Bratslavsky, Gennady; Linehan, W Marston

    2015-01-01

    Purpose Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is characterized by cutaneous leiomyomas, uterine fibroids, and aggressive papillary renal cell carcinoma (RCC). A number of our HLRCC patients were found to have atypical adrenal nodules and which were further evaluated to determine if these adrenal nodules were associated with HLRCC. Methods HLRCC patients underwent a comprehensive clinical and genetic evaluation. Clinical presentation, anatomic and functional imaging, endocrine evaluation, pathologic examination and the results from germline mutation testing were reviewed. Results Twenty of 255 HLRCC patients (7.8%) were found to have primary adrenal lesions. Among these, three were found to have bilateral adrenal lesions and four were found to have multiple nodules. Two patients had ACTH-independent hypercortisolism. A total of 27 adrenal lesions were evaluated. The imaging characteristics of five (18.5%) of these lesions were not consistent with adenoma by non-contrast CT criteria. PET imaging was positive in 7 of 10 cases (70%). Twelve nodules were surgically resected from ten adrenal glands. Pathologic examination revealed macronodular adrenal hyperplasia in all specimens. Conclusions Unilateral and bilateral adrenal nodular hyperplasia was detected in a subset of patients affected with HLRCC. A functional endocrine evaluation is recommended when an adrenal lesion is discovered. Imaging frequently demonstrates lesions that are not typical of adenomas and PET imaging may be positive. To date, no patient has been found to have adrenal malignancy and active surveillance of HLRCC adrenal nodules appears justified. PMID:22982371

  20. 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

  1. Cardiovascular physiology of androgens and androgen testosterone therapy in postmenopausal women.

    PubMed

    Ling, Shanhong; Komesaroff, Paul A; Sudhir, Krishnankutty

    2009-03-01

    Women before menopause are at relatively lower risk of cardiovascular disease (CVD) compared with age-matched men and after menopause this gender advantage disappears. Androgen has been known to be an independent factor contributing to the higher male susceptibility to CVD, through adverse effects on lipids, blood pressure, and glucose metabolism. High androgen levels also contribute to CVD development in women with polycystic ovary syndrome as well as androgen abusing athletes and body builders. On the other hand, decline in androgen levels, as a result of ageing in men, is associated with hypertension, diabetes and atherosclerosis. Postmenopausal women, particularly those with oophorectomy are generally in low levels of sex hormones and androgen insufficiency is independently associated with the higher incidence of atherosclerosis in postmenopausal women. Androgen testosterone therapy (ATT) has been commonly used to improve well-being and libido in aging men with low androgen levels. The therapy has been demonstrated also to effectively reduce atherogenesis in these people. The use of ATT in postmenopausal women has increased in recent years and to date, however, the cardiovascular benefits of such therapy in these women remain uncertain. This review focuses on research regarding the impact of endogenous androgens and ATT on the cardiovascular physiology and CVD development in postmenopausal women.

  2. 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.

  3. Selective androgen receptor modulators as improved androgen therapy for advanced breast cancer.

    PubMed

    Coss, Christopher C; Jones, Amanda; Dalton, James T

    2014-11-01

    Androgens were at one time a therapeutic mainstay in the treatment of advanced breast cancer. Despite comparable efficacy, SERMs and aromatase inhibitors eventually became the therapies of choice due to in part to preferred side-effect profiles. Molecular characterization of breast tumors has revealed an abundance of androgen receptor expression but the choice of an appropriate androgen receptor ligand (agonist or antagonist) has been confounded by multiple conflicting reports concerning the role of the receptor in the disease. Modern clinical efforts have almost exclusively utilized antagonists. However, the recent clinical development of selective androgen receptor modulators with greatly improved side-effect profiles has renewed interest in androgen agonist therapy for advanced breast cancer.

  4. Dehydroepiandrosterone activates AMP kinase and regulates GLUT4 and PGC-1α expression in C2C12 myotubes

    SciTech Connect

    Yokokawa, Takumi; Sato, Koji; Iwanaka, Nobumasa; Honda, Hiroki; Higashida, Kazuhiko; Iemitsu, Motoyuki; Hayashi, Tatsuya; Hashimoto, Takeshi

    2015-07-17

    Exercise and caloric restriction (CR) have been reported to have anti-ageing, anti-obesity, and health-promoting effects. Both interventions increase the level of dehydroepiandrosterone (DHEA) in muscle and blood, suggesting that DHEA might partially mediate these effects. In addition, it is thought that either 5′-adenosine monophosphate-activated protein kinase (AMPK) or peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) mediates the beneficial effects of exercise and CR. However, the effects of DHEA on AMPK activity and PGC-1α expression remain unclear. Therefore, we explored whether DHEA in myotubes acts as an activator of AMPK and increases PGC-1α. DHEA exposure increased glucose uptake but not the phosphorylation levels of Akt and PKCζ/λ in C2C12 myotubes. In contrast, the phosphorylation levels of AMPK were elevated by DHEA exposure. Finally, we found that DHEA induced the expression of the genes PGC-1α and GLUT4. Our current results might reveal a previously unrecognized physiological role of DHEA; the activation of AMPK and the induction of PGC-1α by DHEA might mediate its anti-obesity and health-promoting effects in living organisms. - Highlights: • We assessed whether dehydroepiandrosterone (DHEA) activates AMPK and PGC-1α. • DHEA exposure increased glucose uptake in C2C12 myotubes. • The phosphorylation levels of AMPK were elevated by DHEA exposure. • DHEA induced the expression of the genes PGC-1α and GLUT4. • AMPK might mediate the anti-obesity and health-promoting effects of DHEA.

  5. 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.

  6. 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

  7. Menstrual bleeding in a female infant with congenital adrenal hyperplasia: altered maturation of the hypothalamic-pituitary-ovarian axis.

    PubMed

    Uli, N; Chin, D; David, R; Geneiser, N; Roche, K; Marino, F; Shapiro, E; Prasad, K; Oberfield, S

    1997-10-01

    Vaginal bleeding during the neonatal period is commonly related to the withdrawal of maternal estrogens. Vaginal bleeding has also been reported in female infants with congenital adrenal hyperplasia and has been proposed to be due to a treatment-induced activation of the hypothalamic-pituitary-ovarian axis. We report a female infant with the salt-losing form of congenital adrenal hyperplasia due to 21-hydroxylase deficiency, who had the onset of vaginal bleeding at 3 months of life. Adrenal steroid suppression had been achieved by 2.5 weeks of age. At the time of bleeding, imaging studies revealed an enlarged right ovary with a dominant 3-cm cyst and additional small cysts that had not been seen on the newborn sonogram. The uterus was enlarged and stimulated. Three weeks later (1 week after the cessation of bleeding), repeat ultrasound demonstrated a marked decrease in the size of the right ovary, and the dominant cyst was no longer seen. The patient had a heightened FSH response to GnRH and elevated levels of estradiol for age. At 5 months of age, no further episodes of sustained vaginal bleeding were observed. Repeat hormonal levels were prepubertal, and pelvic sonogram demonstrated no evidence of stimulation. The findings in our patient suggest that a decline in adrenal androgens after glucocorticoid treatment resulted in an increase in gonadotropin levels, which then triggered a transient and augmented end-organ response (menses). Further, we suggest that our infant's hormonal findings may reflect a delay in the timely development of the negative restraint by sex steroids on gonadotropins that is normally observed in infancy.

  8. Renin knockout rat: control of adrenal aldosterone and corticosterone synthesis in vitro and adrenal gene expression

    PubMed Central

    Gehrand, Ashley; Bruder, Eric D.; Hoffman, Matthew J.; Engeland, William C.; Moreno, Carol

    2014-01-01

    The classic renin-angiotensin system is partly responsible for controlling aldosterone secretion from the adrenal cortex via the peptide angiotensin II (ANG II). In addition, there is a local adrenocortical renin-angiotensin system that may be involved in the control of aldosterone synthesis in the zona glomerulosa (ZG). To characterize the long-term control of adrenal steroidogenesis, we utilized adrenal glands from renin knockout (KO) rats and compared steroidogenesis in vitro and steroidogenic enzyme expression to wild-type (WT) controls (Dahl S rat). Adrenal capsules (ZG; aldosterone production) and subcapsules [zona reticularis/fasciculata (ZFR); corticosterone production] were separately dispersed and studied in vitro. Plasma renin activity and ANG II concentrations were extremely low in the KO rats. Basal and cAMP-stimulated aldosterone production was significantly reduced in renin KO ZG cells, whereas corticosterone production was not different between WT and KO ZFR cells. As expected, adrenal renin mRNA expression was lower in the renin KO compared with the WT rat. Real-time PCR and immunohistochemical analysis showed a significant decrease in P450aldo (Cyp11b2) mRNA and protein expression in the ZG from the renin KO rat. The reduction in aldosterone synthesis in the ZG of the renin KO adrenal seems to be accounted for by a specific decrease in P450aldo and may be due to the absence of chronic stimulation of the ZG by circulating ANG II or to a reduction in locally released ANG II within the adrenal gland. PMID:25394830

  9. Sex-dependent role of glucocorticoids and androgens in the pathophysiology of human obesity.

    PubMed

    Pasquali, R; Vicennati, V; Gambineri, A; Pagotto, U

    2008-12-01

    Obesity, particularly its abdominal phenotype, a harbinger of the metabolic syndrome, cardiovascular diseases (CVDs) and type 2 diabetes mellitus (T2D), is becoming one of the most significant public health problems worldwide. Among many other potential factors, derangement of multiple hormone systems have increasingly been considered for their potential importance in the pathophysiology of obesity and the metabolic syndrome, with particular reference to glucocorticoids and sex hormones. These systems have a fundamental and coordinating role in the physiology of intermediate metabolism and cardiovascular function, and in the response to acute and chronic stress challenge. Abdominal obesity is associated with a hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and impaired androgen balance, although these alterations differ according to sex. As there is also increasing evidence that there are many differences between the sexes in the susceptibility and development of obesity, T2D and CVDs, we support the hypothesis that alterations of the HPA axis and androgen balance may have an important function in this context. This is further supported by the fact that there are important differences between males and females in their ability to adapt to both internal and particularly to environmental (external) stressors. In addition, there is also evidence that, in both physiological and pathological conditions, a close cross talk exists between sex hormones and glucocorticoids at both neuroendocrine and peripheral level, again with different specificities according to sex.

  10. 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

  11. 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

  12. Spongian diterpenoids inhibit androgen receptor activity

    PubMed Central

    Yang, Yu Chi; Meimetis, Labros G; Tien, Amy H; Mawji, Nasrin R; Carr, Gavin; Wang, Jun; Andersen, Raymond J; Sadar, Marianne D

    2013-01-01

    Androgen receptor (AR) is a ligand-activated transcription factor and a validated drug target for all stages of prostate cancer. Antiandrogens compete with physiological ligands for AR ligand-binding domain (LBD). High-throughput screening of a marine natural product library for small molecules that inhibit AR transcriptional activity yielded the furanoditerpenoid spongia-13(16),-14-dien-19-oic acid, designated terpene 1 (T1). Characterization of T1 and the structurally related semi-synthetic analogues (T2 and T3) revealed that these diterpenoids have antiandrogen properties that include inhibition of both androgen-dependent proliferation and AR transcriptional activity by a mechanism that involved competing with androgen for AR LBD and blocking essential N/C interactions required for androgen-induced AR transcriptional activity. Structure activity relationship analyses revealed some chemical features of T1 that are associated with activity and yielded T3 as the most potent analogue. In vivo, T3 significantly reduced the weight of seminal vesicles, which are an androgen-dependent tissue, thereby confirming T3’s on-target activity. The ability to create analogues of diterpenoids that have varying antiandrogen activity represents a novel class of chemical compounds for the analysis of AR ligand-binding properties and therapeutic development. PMID:23443807

  13. Discovery AND Therapeutic Promise OF Selective Androgen Receptor Modulators

    PubMed Central

    Chen, Jiyun; Kim, Juhyun; Dalton, James T.

    2007-01-01

    Androgens are essential for male development and the maintenance of male secondary characteristics, such as bone mass, muscle mass, body composition, and spermatogenesis. The main disadvantages of steroidal androgens are their undesirable physicochemical and pharmacokinetic properties. The recent discovery of nonsteroidal selective androgen receptor modulators (SARMs) provides a promising alternative for testosterone replacement therapies with advantages including oral bioavailability, flexibility of structural modification, androgen receptor specificity, tissue selectivity, and the lack of steroid-related side effects. PMID:15994457

  14. Discovery and therapeutic promise of selective androgen receptor modulators.

    PubMed

    Chen, Jiyun; Kim, Juhyun; Dalton, James T

    2005-06-01

    Androgens are essential for male development and the maintenance of male secondary characteristics, such as bone mass, muscle mass, body composition, and spermatogenesis. The main disadvantages of steroidal androgens are their undesirable physicochemical and pharmacokinetic properties. The recent discovery of nonsteroidal selective androgen receptor modulators (SARMs) provides a promising alternative for testosterone replacement therapies with advantages including oral bioavailability, flexibility of structural modification, androgen receptor specificity, tissue selectivity, and the lack of steroid-related side effects.

  15. Giant adrenal pseudocyst harbouring adrenocortical cancer

    PubMed Central

    Wilkinson, Michael; Fanning, Deirdre Mary; Moloney, James; Flood, Hugh

    2011-01-01

    The authors report a very rare case of adreno-cortical carcinoma arising in a giant adrenal pseudocyst. A 64-year-old woman presented to the emergency department with a 6 week history of progressively worsening severe left abdominal pain, anorexia, anergia and constipation. On examination, she was cachectic with tenderness over the left abdomen and flank. Medical history was significant for gastritis and anaemia. During her investigation, a well-defined para-renal 12×6 centimetre multi-loculated cyst, of uncertain origin was identified on CT. Ultrasound-guided biopsy was not diagnostic. MRI showed the cyst to be likely adrenal in origin. Serum and urinary catecholamines were unremarkable. At laparotomy an unresectable large, tense, fixed, cystic mass was seen to occupy the left side of the abdomen. The cyst was de-roofed. Pathology showed a high-grade poorly differentiated adreno-cortical carcinoma with a pseudo-capsule. She died 2 months postoperatively. PMID:22679267

  16. Allgrove Syndrome: Adrenal Insufficiency with Hypertensive Encephalopathy.

    PubMed

    Aftab, Sommayya; Manzoor, Jaida; Talat, Nabila; Khan, Hafiz Sajid; Subhanie, Maroof; Khalid, Nauman Abbas

    2016-09-01

    Allgrove syndrome or triple-Asyndrome is a rare familial multisystem autosomal recessive disorder. It is characterised by triad of alacrima, achalasia and adrenal insufficiency due to adrenocorticotropin hormone (ACTH) resistance. If it is associated with autonomic dysfunction, it is termed as 4-Asyndrome. This syndrome is caused by a mutation in the Achalasia - Addisonism - Alacrima (AAAS) gene on chromosome 12q13 encoding the nuclear pore protein ALADIN. A5-year boy presented with history of fits and altered sensorium for one day. He also had increased pigmentation of body and persistent vomiting since six months of age. Laboratory investigations and imaging revealed alacrimia, achalasia and adrenal insufficiency due to ACTH resistance. He had episodes of hypertensive crises, for which he was thoroughly investigated and it was found to be due to autonomic instability. Based on clinical findings and investigations he was diagnosed as case of Allgrove syndrome or 4-Asyndrome with autonomic dysfunction. PMID:27671188

  17. Bilateral adrenal gland haemorrhage: an unusual cause

    PubMed Central

    Shenoy, Vasant; Malabu, Usman; Cameron, Donald; Sangla, Kunwarjit

    2014-01-01

    Summary Our patient had drainage of a large amoebic liver abscess. This got complicated by a severe degree of hypotension, which required aggressive fluid resuscitation and hydrocortisone support. Computerised tomography (CT) of the abdomen revealed bilateral adrenal gland haemorrhage (BAH) resulting in primary adrenal gland failure, which was the cause for hypotension. Patient was on long-term warfarin for provoked deep vein thrombosis of lower limb, which was discontinued before the procedure. Thrombophilia profile indicated the presence of lupus anticoagulant factor with prolonged activated partial thromboplastin time (aPTT). Patient was discharged on lifelong warfarin. This case emphasises the need for strong clinical suspicion for diagnosing BAH, rare but life-threatening condition, and its association with amoebic liver abscess and anti-phospholipid antibody syndrome (APLS). Learning points Recognition of BAH as a rare complication of sepsis.APLS can rarely cause BAH. PMID:25276353

  18. Electrical excitability of cultured adrenal chromaffin cells.

    PubMed Central

    Biales, B; Dichter, M; Tischler, A

    1976-01-01

    1. Adult human and gerbil adrenal medullary cells were maintained in dissociated cell culture and studied by micro-electrode penetration. 2. In the best recordings, chromaffin cell transmembrane potentials exceeded -50mV. 3. Chromaffin cells were capable of generating all-or-nothing over-shooting action potentials, similar to those generated by sympathetic neurones. 4. The action potentials were blocked by tetrodotoxin (TTX, 10(-6)g/ml.) but were not blocked by removal of Ca or by CoCl2 (10 mM). We conclude that the action potentials are probably generated by a Na mechanism. 5. Chromaffin cells are depolarized by the iontophoretic application of acetylcholine (ACh). This depolarization was accompanied by an increased membrane conductance and could trigger action potentials. 6. Action potentials were also found in cells in fresh slices of gerbil adrenal medullae. Images Plate 1 PMID:1034699

  19. Cushing syndrome associated with an adrenal tumour

    PubMed Central

    Vieira, Helena; Brain, Caroline

    2012-01-01

    Cushing syndrome (CS) in children is a rare disorder that is most frequently caused by an adrenal tumour or a pituitary corticotrophin-secreting adenoma. The management is challenging and requires an individualised approach and multidisciplinary care. We present the case of a 23-month-old female child with a history of excessive weight gain, growth failure, hirsutism, acne and behavioural difficulties. Investigations revealed elevated serum midnight cortisol and 24 h urinary free cortisol. Overnight dexamethasone suppression testing showed no suppression of cortisol levels. Abdominal imaging revealed a right-sided suprarenal mass. She underwent right adrenalectomy and the histology showed an adrenal cortical carcinoma. There was clinical improvement with catch-up growth and weight normalisation. Despite being rare in clinical practice, in a child with weight gain, hirsuitism and growth failure the diagnosis must be considered. The overall prognosis of CS in childhood is good, but challenges remain to ensure normal growth and body composition. PMID:22927284

  20. Transcriptional network of androgen receptor in prostate cancer progression.

    PubMed

    Takayama, Ken-ichi; Inoue, Satoshi

    2013-08-01

    The androgen receptor belongs to the nuclear receptor superfamily and functions as a ligand-dependent transcription factor. It binds to the androgen responsive element and recruits coregulatory factors to modulate gene transcription. In addition, the androgen receptor interacts with other transcription factors, such as forkhead box A1, and other oncogenic signaling pathway molecules that bind deoxyribonucleic acid and regulate transcription. Androgen receptor signaling plays an important role in the development of prostate cancer. Prostate cancer cells proliferate in an androgen-dependent manner, and androgen receptor blockade is effective in prostate cancer therapy. However, patients often progress to castration-resistant prostate cancer with elevated androgen receptor expression and hypersensitivity to androgen. Recently, comprehensive analysis tools, such as complementary DNA microarray, chromatin immunoprecipitation-on-chip and chromatin immunoprecipitation-sequence, have described the androgen-mediated diverse transcriptional program and gene networks in prostate cancer. Furthermore, functional and clinical studies have shown that some of the androgen receptor-regulated genes could be prognostic markers and potential therapeutic targets for the treatment of prostate cancer, particularly castration-resistant prostate cancer. Thus, identifying androgen receptor downstream signaling events and investigating the regulation of androgen receptor activity is critical for understanding the mechanism of carcinogenesis and progression to castration-resistant prostate cancer.

  1. Androgens and Male Sexual Function: A Review of Human Studies

    ERIC Educational Resources Information Center

    Schiavi, Raul C.; White, Daniel

    1976-01-01

    The scope of this article is a review and brief discussion of recently gathered information on androgens and sexual behavior in men. Current pharmacological research does not furnish specific evidence that administration of androgens or preprations that stimulate the secretion of endogenous androgens have beneficial effects on functional…

  2. Adrenal Metastasis from Uterine Papillary Serous Carcinoma

    PubMed Central

    Lubana, Sandeep Singh; Singh, Navdeep; Tuli, Sandeep S.; Seligman, Barbara

    2016-01-01

    Patient: Female, 60 Final Diagnosis: UPSC with adrenal metastasis Symptoms: Post menopausal bleeding Medication: — Clinical Procedure: Adrenalectomy Specialty: Oncology Objective: Rare disease Background: Uterine papillary serous carcinoma (UPSC) is a highly malignant form of endometrial cancer with a high propensity for metastases and recurrences even when there is minimal or no myometrial invasion. It usually metastasizes to the pelvis, retroperitoneal lymph nodes, upper abdomen, and peritoneum. However, adrenal metastases from UPSC is extremely rare. Here, we present a case of UPSC with adrenal metastasis that occurred 6 years after the initial diagnosis. Case Report: A 60-year-old woman previously diagnosed with uterine papillary serous carcinoma at an outside facility presented in September of 2006 with postmenopausal bleeding. She underwent comprehensive surgical staging with FIGO (International Federation of Gynecology and Obstetrics) stage 2. Post-operatively, the patient was treated with radiation and chemotherapy. The treatment was completed in April of 2007. The patient had no evidence of disease until July 2009 when she was found to have a mass highly suspicious for malignancy. Subsequently, she underwent right upper lobectomy. The morphology of the carcinoma was consistent with UPSC. She refused chemotherapy due to a previous history of chemotherapy-induced neuropathy. The patient was followed up with regular computed tomography (CT) scans. In October 2012 a new right adrenal nodule was seen on CT, which showed intense metabolic uptake on positron emission tomography (PET)/CT scan. The patient underwent right adrenalectomy. Pathology of the surgical specimen was consistent with UPSC. Conclusions: UPSC is an aggressive variant of endometrial cancer associated with high recurrence rate and poor prognoses. Long-term follow-up is needed because there is a possibility of late metastases, as in this case. PMID:27117594

  3. Renal infarction associated with adrenal pheochromocytoma.

    PubMed

    Thewjitcharoen, Yotsapon; Atikankul, Taywin; Sunthornyothin, Sarat

    2013-09-01

    The coexistence of pheochromocytoma and renal artery stenosis had been reported occasionally from the possible mechanism of catecholoamine-induced vasospasm and extrinsic compression of renal artery in some reported cases. However, renal infarction caused by pheochromocytoma is an uncommon phenomenon. Herein, we report an interesting case of adrenal pheochromocytoma associated with renal artery thrombosis, which should be included in the differential diagnosis of pheochromocytoma patients who present with abdominal pain.

  4. Mineralocorticoid production of adrenal cortical adenomas.

    PubMed

    Gláz, E; Rácz, K; Varga, I; Kiss, R; Tóth, M; Fütö, L

    1993-04-01

    We studied in vitro and in vivo corticosteroid production as well as the presence of symptoms of an increased mineralocorticoid effect in patients with 'silent' adrenal cortical adenomas, and compared these results to those found in patients with classical mineralocorticoid excess syndromes. We found that under in vitro conditions, cells from 'silent' adrenal cortical adenomas (n = 19) produced substantial amounts of both zona glomerulosa and fasciculata steroids, although the production of steroids in these cells was lower compared to that in mineralocorticoid-producing adenoma cells (n = 26). Patients with aldosterone-producing and 'silent' adenomas had significantly increased plasma atrial natriuretic peptide levels, which remained non-suppressible after upright posture and furosemide administration. Of the 25 patients with 'silent' adenomas, 11 had low and non-stimulable plasma renin activity (PRA) before but, in most cases, not after adrenal surgery. When compared to those with normal PRA (n = 14), patients with low PRA 'silent' adenomas (n = 11) had higher blood pressure which was significantly reduced after surgery, and a mild hypokalemia before but not after surgery. Although basal plasma concentrations of aldosterone, 18-hydroxy-corticosterone, corticosterone, deoxycorticosterone, 18-hydroxy-DOC, cortisol,11-deoxycortisol and 17-hydroxy-progesterone (17-OH-P) were not increased in either groups of 'silent' adenomas, ACTH stimulation produced a hyperreactive response for all measured steroids, of which an extremely high 17-OH-P seemed to be one of the most intriguing findings. We consider that these observations in 'silent' adrenal cortical adenomas may justify surgical intervention, irrespective of the size and potential malignancy of these adenomas. PMID:8481352

  5. Effect of inter-cycle interval on oocyte production in humans in the presence of the weak androgen DHEA and follicle stimulating hormone: a case-control study

    PubMed Central

    2014-01-01

    Background In various animal models androgens have been demonstrated to enhance follicle stimulating hormone (FSH) activity on granulosa cells during small growing follicle stages. To assess whether similar synergism may also exist in humans we investigated women on androgen (dehydroepiandrosterone, DHEA) supplementation with varying concomitant FSH exposure. Methods In a case controlled cohort study we determine if time interval between IVF cycles of IVF treatment with FSH had an effect on ovarian response to ovulation induction in women supplemented with DHEA. Among 85 women with known low functional ovarian reserve (LFOR), supplemented with DHEA, and undergoing at least 3 consecutive IVF cycles, 68 demonstrated short (<120 days) intervals between repeated cycles (Group 1) and were, therefore, considered to have consistent FSH exposure. In contrast 17 women (Group 2) demonstrated long (> = 120 days) intervals between repeated cycles and, therefore, were considered to demonstrate inconsistent FSH exposure. Trends in oocyte yields were compared between these groups, utilizing mixed model repeated measures ANOVA, adjusted for initial age and FSH dose. Results Only women in Group I demonstrated a linear increase in oocyte yields across their three cycles of treatments (F = 7.92; df 1, 68.6; p = 0.017). Moreover, the analysis revealed a significant interaction between the two patient groups and cycle number for retrieved oocytes (F = 6.32, df = 2, 85.9, p = 0.003). Conclusions This study offers preliminary confirmatory evidence that repeated short interval exposure to androgens in combination with FSH improves human FOR. A higher level of evidence will require prospectively randomized studies. PMID:25048047

  6. Seasonal changes in courtship behavior, plasma androgen levels and in hypothalamic aromatase immunoreactivity in male free-living European starlings (Sturnus vulgaris).

    PubMed

    Pintér, Ottó; Péczely, Péter; Zsebok, Sándor; Zelena, Dóra

    2011-05-15

    In songbirds from temperate latitudes, singing during spring has an essential role in mate attraction, while during the non-breeding season it is connected to territorial aggression and/or maintaining dominance hierarchies or flock cohesion. Courtship behavior is regulated by plasma testosterone (T) levels. Other androgens, like dehydroepiandrosterone (DHEA) could be responsible for aggression. The aromatization of androgens in the brain is an essential step in mediating their effects on behavior. Our goal was to determine whether the seasonal changes in male courtship behavior (measured by average song bout length and wing-waving/flicking) are related to seasonal changes in androgen activity (measured by plasma T, DHEA levels) and aromatase (ARO) immunoreactivity in the preoptic area/medial preoptic nucleus (POA/POM) of free-living male starlings. DHEA increased during pair formation, decreased at nesting and remained at low levels. The number of ARO cells - in line with the T levels - increased during the courtship and nesting periods, but outside the breeding season it was low. Song bout length showed a similar pattern, namely the peak was reached during the courtship period, and after that males stopped singing when chicks started to hatch. Short and fast wing-flicking and wing-waving behavior was observed only during the breading season. Summarizing, we have found that song bout length of male starlings changes parallel with plasma T levels and ARO immunoreactivity in the POA/POM. Furthermore, DHEA levels were low during the sexually inactive period which suggests that other mechanisms could be involved in the aggressive non-courtship behavior/vocalization in these birds. PMID:21310152

  7. Endoscopic Retroperitoneal Adrenalectomy for Adrenal Metastases

    PubMed Central

    Simutis, Gintaras; Lengvenis, Givi; Beiša, Virgilijus; Strupas, Kęstutis

    2014-01-01

    Objectives. To evaluate whether retroperitoneal approach for adrenalectomy is a safe and effective treatment for adrenal metastases (AM). Methods. From June 2004 to January 2014, nine consecutive patients with AM were treated with endoscopic retroperitoneal adrenalectomy (ERA). A retrospective study was conducted, and clinical data, tumor characteristics, and oncologic outcomes were acquired and analyzed. Results. Renal cancer was the primary site of malignancy in 44.4% of cases. The mean operative time was 132 ± 10.4 min. There were 5 synchronous and 4 metachronous AM. One patient required conversion to transperitoneal laparoscopic procedure. No mortality or perioperative complications were observed. The median overall survival was 11 months (range: 2–42 months). Survival rates of 50% and 25% were identified at 1 and 3 years, respectively. At the end of the study, 4 patients were alive with a mean observed follow-up of 20 months. No patients presented with local tumor relapse or port-site metastases. Conclusions. This study shows that ERA is a safe and effective procedure for resection of AM and advances the surgical treatment of adrenal disease. The use of the retroperitoneal approach for adrenal tumors less than 6 cm can provide very favorable surgical outcomes. PMID:25276132

  8. [Oncocytic tumors of the adrenal gland].

    PubMed

    Capela, Andreia; Martinho, Aurélia; Paixão Duarte, Fernanda; Garcia, Hermano; Rocha Pires, Francisco; Theias Manso, Rita; Aparício, Samuel; Costa, Ana Maria

    2013-01-01

    The oncocytic tumors of the adrenal gland are rare. To date there's only 147 cases published. The authors present a case of a 34 year-old man admitted to the hospital with lumbar pain and fever. At medical examination a mass was found in the left upper quadrant of the abdomen. The hormonal measurements of the adrenal gland were normal and the abdominal angio CT showed a left retroperitoneal lesion measuring 145 x 157 x 128 mm with extensive necrotic and hemorrhagic areas. The patient underwent a complete surgical resection of the lesion. The mass weighted 1495g and the histological exam revealed an oncocytic tumor of the adrenal gland with uncertain potential. Most of the oncocytic tumors are non functioning and must be considered in the differential diagnosis of adrenocortical tumors. The biologic behavior and the prognosis of these tumors are variable and still need a better definition. Due to the rarity of these tumors the authors made a revision on the published bibliography.

  9. The androgen receptor gene mutations database.

    PubMed

    Gottlieb, B; Trifiro, M; Lumbroso, R; Pinsky, L

    1997-01-01

    The current version of the androgen receptor (AR) gene mutations database is described. The total number of reported mutations has risen from 212 to 272. We have expanded the database: (i) by adding a large amount of new data on somatic mutations in prostatic cancer tissue; (ii) by defining a new constitutional phenotype, mild androgen insensitivity (MAI); (iii) by placing additional relevant information on an internet site (http://www.mcgill.ca/androgendb/ ). The database has allowed us to examine the contribution of CpG sites to the multiplicity of reports of the same mutation in different families. The database is also available from EMBL (ftp.ebi.ac.uk/pub/databases/androgen) or as a Macintosh Filemaker Pro or Word file (MC33@musica,mcgill.ca)

  10. Androgen deficiency and metabolic syndrome in men

    PubMed Central

    Winter, Ashley G.; Zhao, Fujun

    2014-01-01

    Metabolic syndrome (MetS) is a growing health concern worldwide. Initially a point of interest in cardiovascular events, the cluster of HTN, obesity, dyslipidemia, and insulin resistance known as MetS has become associated with a variety of other disease processes, including androgen deficiency and late-onset hypogonadism (LOH). Men with MetS are at a higher risk of developing androgen deficiency, and routine screening of testosterone (T) is advised in this population. The pathophysiology of androgen deficiency in MetS is multifactorial, and consists of inflammatory, enzymatic, and endocrine derangements. Many options for the concomitant treatment of both disorders exist. Direct treatment of MetS, whether by diet, exercise, or surgery, may improve T levels. Conversely, testosterone replacement therapy (TRT) has been shown to improve MetS parameters in multiple randomized controlled trials (RTCs). PMID:26816752

  11. Androgen receptor in human endothelial cells

    PubMed Central

    Torres-Estay, Verónica; Carreño, Daniela V; San Francisco, Ignacio F; Sotomayor, Paula; Godoy, Alejandro S; Smith, Gary J

    2015-01-01

    Androgen receptor (AR) is a ligand-inducible transcription factor, and a member of the steroid-thyroid-retinoid receptor superfamily, that mediates the biological effects of androgens in a wide range of physiological and pathological processes. AR expression was identified in vascular cells nearly 20 years ago, and recent research has shown that AR mediates a variety of actions of androgens in endothelial and vascular smooth muscle cells. In this mini-review, we review evidence indicating the importance of AR in human endothelial cell (HUVEC) homeostatic and pathogenic processes. Although a role for AR in the modulation of HUVEC biology is evident, the molecular mechanisms by which AR regulates HUVEC homeostasis and disease processes are not fully understood. Understanding these mechanisms could provide critical insights into the processes of pathogenesis of diseases ranging from cardiovascular disease to cancer that are major causes of human morbidity and mortality. PMID:25563353

  12. Partial Androgen Insensitivity Syndrome Presenting with Gynecomastia

    PubMed Central

    Lee, Sung Won; Kwak, Dong Shin; Jung, In Sub; Kwak, Joo Hee; Park, Jung Hwan; Hong, Sang Mo; Lee, Chang Bum; Park, Yong Soo; Kim, Dong Sun; Choi, Woong Hwan

    2015-01-01

    Gynecomastia is a benign enlargement of the male breast caused by the proliferation of glandular breast tissue. Determining the various causes of gynecomastia such as physiological causes, drugs, systemic diseases, and endocrine disorders is important. Androgen insensitivity syndrome (AIS) is a rare endocrine disorder presenting with gynecomastia and is a disorder of male sexual differentiation caused by mutations within the androgen receptor gene. All individuals with AIS have the 46 XY karyotype, although AIS phenotypes can be classified as mild, partial or complete and can differ among both males and females including ambiguous genitalia or infertility in males. We experienced a case of partial AIS presenting with gynecomastia and identified the androgen receptor gene mutation. PMID:25433660

  13. Pathological changes in anabolic androgenic steroid users.

    PubMed

    Lusetti, Monia; Licata, Manuela; Silingardi, Enrico; Reggiani Bonetti, Luca; Palmiere, Cristian

    2015-07-01

    Several classes of recreational and prescription drugs have additional effects on the heart and vasculature, which may significantly contribute to morbidity and mortality in chronic users. The study presented herein focuses on pathological changes involving the heart possibly due to anabolic androgenic steroid use. The role these hormones may play in their occurrence of sudden cardiac death is also investigated. 98 medico-legal cases including 6 anabolic androgenic steroid users were retrospectively reviewed. Autopsies, histology, immunohistochemistry, biochemistry and toxicology were performed in all cases. Pathological changes consisted of various degrees of interstitial and perivascular fibrosis as well as fibroadipous metaplasia and perineural fibrosis within the myocardium of the left ventricle. Within the limits of the small number of investigated cases, our results appear to confirm former observations on this topic and suggest anabolic androgenic steroid's potential causative role in the pathogenesis of sudden cardiac deaths in chronic users.

  14. Androgen Modulation of Hippocampal Structure and Function

    PubMed Central

    Atwi, Sarah; McMahon, Dallan; Scharfman, Helen; MacLusky, Neil J.

    2016-01-01

    Androgens have profound effects on hippocampal structure and function, including induction of spines and spine synapses on the dendrites of CA1 pyramidal neurons, as well as alterations in long-term synaptic plasticity (LTP) and hippocampally dependent cognitive behaviors. How these effects occur remains largely unknown. Emerging evidence, however, suggests that one of the key elements in the response mechanism may be modulation of brain-derived neurotrophic factor (BDNF) in the mossy fiber (MF) system. In male rats, orchidectomy increases synaptic transmission and excitability in the MF pathway. Testosterone reverses these effects, suggesting that testosterone exerts tonic suppression on MF BDNF levels. These findings suggest that changes in hippocampal function resulting from declining androgen levels may reflect the outcome of responses mediated through normally balanced, but opposing, mechanisms: loss of androgen effects on the hippocampal circuitry may be compensated, at least in part, by an increase in BDNF-dependent MF plasticity. PMID:25416742

  15. [A Case of Synchronous Malignant Pheochromocytomas in Bilateral Adrenal Glands].

    PubMed

    Usui, Kimitsugu; Hirasawa, Terukazu; Kobayashi, Masataka; Shioi, Kouichi; Kobayashi, Kazuki; Sakai, Naoki; Noguchi, Sumio; Tsuura, Yukio

    2016-06-01

    We present a case of synchronous malignant pheochromocytoma in bilateral adrenal glands. A 73- year-old man presented to our hospital with bilateral adrenal masses incidentally found during abdominal ultrasonography examination for an unrelated issue. The patient had a 30-year history of hypertension and paroxysmal atrial fibrillation. Computed tomography and magnetic resonance imaging showed heterogeneous tumors in bilateral adrenal glands and an enlarged para-aortic lymph node. Hormonal examinations revealed a high value of urinary catecholamines. Metaiodobenzylguanidine (MIBG) scintigraphy showed increased uptake in bilateral adrenal glands and the lymph node. Both adrenal tumors and the node were surgically removed. Pathological examination revealed histologically distinct tissue between the two adrenal tumors. The patient received five cycles of adjuvant chemotherapy, consisting of cyclophosphamide, vincristine, and dacarbazine. The patient has been in remission for 32 months following surgical treatment. PMID:27452493

  16. [A Case of Synchronous Malignant Pheochromocytomas in Bilateral Adrenal Glands].

    PubMed

    Usui, Kimitsugu; Hirasawa, Terukazu; Kobayashi, Masataka; Shioi, Kouichi; Kobayashi, Kazuki; Sakai, Naoki; Noguchi, Sumio; Tsuura, Yukio

    2016-06-01

    We present a case of synchronous malignant pheochromocytoma in bilateral adrenal glands. A 73- year-old man presented to our hospital with bilateral adrenal masses incidentally found during abdominal ultrasonography examination for an unrelated issue. The patient had a 30-year history of hypertension and paroxysmal atrial fibrillation. Computed tomography and magnetic resonance imaging showed heterogeneous tumors in bilateral adrenal glands and an enlarged para-aortic lymph node. Hormonal examinations revealed a high value of urinary catecholamines. Metaiodobenzylguanidine (MIBG) scintigraphy showed increased uptake in bilateral adrenal glands and the lymph node. Both adrenal tumors and the node were surgically removed. Pathological examination revealed histologically distinct tissue between the two adrenal tumors. The patient received five cycles of adjuvant chemotherapy, consisting of cyclophosphamide, vincristine, and dacarbazine. The patient has been in remission for 32 months following surgical treatment.

  17. Prolonged adrenal insufficiency after unilateral adrenalectomy for Cushing's Syndrome.

    PubMed

    Kulshreshtha, Bindu; Arora, Arpita; Aggarwal, Anshita; Bhardwaj, Minakshi

    2015-01-01

    The contralateral healthy adrenal in patients undergoing unilateral adrenalectomy for Cushing's is known to be suppressed temporarily and forms the basis of peri and postoperative steroids. We present four cases of Cushing's who had prolonged adrenal insufficiency with continued requirement for steroids for periods ranging 1-4 years after unilateral adrenalectomy for Cushing's. We further review literature regarding the recovery of the hypothalamo pituitary adrenal axis postsurgery in patients with Cushing's syndrome.

  18. [Extreme kidney displacement caused by an adrenal pseudocyst].

    PubMed

    Tragl, K H; Obrowsky, L; Swoboda, G; Langthaler, B; Brezina, K; Machacek, E

    1985-03-01

    Renal displacement is very infrequently associated with a space occupying adrenal disease and sometimes imposes major diagnostic problems. The diagnosis of monstrous, retroperitoneal cysts is of particular difficulty. In a 51-year-old female patient the diagnosis and the association of a cystic formation to the adrenal gland could only be made at surgery, despite the steadily increasing renal displacement. The etiology of adrenal cysts, the diagnostic procedures and the possible concurrence of hypertension are discussed.

  19. [HPLC analysis of dehydroepiandrosterone sulfate in serum with use of solid-phase extraction on hyper cross-linked polystyrene (Purosep-200)].

    PubMed

    Dutov, A A; Nikitin, D A; Luk'ianova, Yu L; Sverkunova, A V; Martynova, A V; Ermolina, A V

    2014-01-01

    We have developed a simple HPLC method for analysis of the dehydroepiandrosterone sulfate (DHEA-sulfate) in serum with use a new procedure of solid-phase extraction (SPE) on hyper cross-linked polystyrene (Purosep-200) and fast chromatographic separation on the monolithic column under isocratic elution and UV detection at 200 nm. Complete SPE procedure lasts for about 7 min, chromatographic separation takes less than 6 min. Simplicity and high reproducibility of this method makes it attractive in routine clinical practice.

  20. The clinical manifestations, diagnosis, and treatment of adrenal emergencies.

    PubMed

    Tucci, Veronica; Sokari, Telematé

    2014-05-01

    Emergency medicine physicians should be able to identify and treat patients whose clinical presentations, including key historical, physical examination, and laboratory findings are consistent with diagnoses of primary, secondary, and tertiary adrenal insufficiency, adrenal crisis, and pheochromocytoma. Failure to make a timely diagnosis leads to increased morbidity and mortality. As great mimickers, adrenal emergencies often present with a constellation of nonspecific signs and symptoms that can lead even the most diligent emergency physician astray. The emergency physician must include adrenal emergencies in the differential diagnosis when encountering such clinical pictures.