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Sample records for mouse hypothalamus pituitary

  1. Hypothalamus-Pituitary-Thyroid Axis.

    PubMed

    Ortiga-Carvalho, Tania M; Chiamolera, Maria I; Pazos-Moura, Carmen C; Wondisford, Fredic E

    2016-01-01

    The hypothalamus-pituitary-thyroid (HPT) axis determines the set point of thyroid hormone (TH) production. Hypothalamic thyrotropin-releasing hormone (TRH) stimulates the synthesis and secretion of pituitary thyrotropin (thyroid-stimulating hormone, TSH), which acts at the thyroid to stimulate all steps of TH biosynthesis and secretion. The THs thyroxine (T4) and triiodothyronine (T3) control the secretion of TRH and TSH by negative feedback to maintain physiological levels of the main hormones of the HPT axis. Reduction of circulating TH levels due to primary thyroid failure results in increased TRH and TSH production, whereas the opposite occurs when circulating THs are in excess. Other neural, humoral, and local factors modulate the HPT axis and, in specific situations, determine alterations in the physiological function of the axis. The roles of THs are vital to nervous system development, linear growth, energetic metabolism, and thermogenesis. THs also regulate the hepatic metabolism of nutrients, fluid balance and the cardiovascular system. In cells, TH actions are mediated mainly by nuclear TH receptors (210), which modify gene expression. T3 is the preferred ligand of THR, whereas T4, the serum concentration of which is 100-fold higher than that of T3, undergoes extra-thyroidal conversion to T3. This conversion is catalyzed by 5'-deiodinases (D1 and D2), which are TH-activating enzymes. T4 can also be inactivated by conversion to reverse T3, which has very low affinity for THR, by 5-deiodinase (D3). The regulation of deiodinases, particularly D2, and TH transporters at the cell membrane control T3 availability, which is fundamental for TH action. © 2016 American Physiological Society. Compr Physiol 6:1387-1428, 2016. PMID:27347897

  2. Changes in oxytocin and vasopressin content in posterior pituitary and hypothalamus following pantethine treatment.

    PubMed

    Ong, G L; Miaskowski, C; Haldar, J

    1990-01-01

    Pantethine, a cysteamine precursor, depletes somatostatin in the cerebral cortex and hypothalamus and prolactin in the anterior pituitary and hypothalamus. This study investigated the effect of pantethine on oxytocin and arginine vasopressin content in the posterior pituitary and hypothalamus. Male Long-Evans rats were injected intraperitoneally with escalating doses of pantethine (i.e., 146.7 mg, 293.4 mg and 586.6 mg/100 gm body weight). Hormone content was determined by radioimmunoassay. Three hours after pantethine treatment, the oxytocin content in the posterior pituitary and the hypothalamus was markedly reduced with all doses of the drug. Vasopressin content in the posterior pituitary and hypothalamus was decreased but to a lesser extent than oxytocin and only with the highest dose of pantethine. Pantethine may act to reduce oxytocin and vasopressin content through intracellular conversion to cysteamine. The exact mechanism of action of pantethine on oxytocin and vasopressin remains to be elucidated. PMID:2402177

  3. MicroRNA expression profiling of the porcine developing hypothalamus and pituitary tissue.

    PubMed

    Zhang, Lifan; Cai, Zhaowei; Wei, Shengjuan; Zhou, Huiyun; Zhou, Hongmei; Jiang, Xiaoling; Xu, Ningying

    2013-01-01

    MicroRNAs (miRNAs), a class of small non-coding RNA molecules, play important roles in gene expressions at transcriptional and post-transcriptional stages in mammalian brain. So far, a growing number of porcine miRNAs and their function have been identified, but little is known regarding the porcine developing hypothalamus and pituitary. In the present study, Solexa sequencing analysis showed 14,129,397 yielded reads, 6,680,678 of which were related to 674 unique miRNAs. After a microarray assay, we detected 175 unique miRNAs in the hypothalamus, including 136 previously known miRNAs and 39 novel candidates, while a total of 140 miRNAs, including 104 known and 36 new candidate miRNAs, were discovered in pituitary. More importantly, 37 and 30 differentially expressed miRNAs from several developmental stages of hypothalamus and pituitary were revealed, respectively. The 37 differentially expressed miRNAs in hypothalamus represented 6 different expression patterns, while the 30 differentially expressed miRNAs in pituitary represented 7 different expression patterns. To clarify potential target genes and specific functions of these differentially expressed miRNAs in hypothalamus and pituitary, TargetScan and Gorilla prediction tools were then applied. The current functional analysis showed that the differentially expressed miRNAs in hypothalamus and pituitary shared many biological processes, with the main differences being found in tissue-specific processes including: CDP-diacylglycerol biosynthetic/metabolic process; phosphatidic acid biosynthetic/metabolic process; energy reserve metabolic process for hypothalamus; adult behavior; sterol transport/homeostasis; and cholesterol/reverse cholesterol transport for pituitary. Overall, this study identified miRNA profiles and differentially expressed miRNAs among various developmental stages in hypothalamus and pituitary and indicated miRNA profiles change with age and brain location, enhancing our knowledge about spatial

  4. Transcriptome-Wide Identification of Preferentially Expressed Genes in the Hypothalamus and Pituitary Gland

    PubMed Central

    St-Amand, Jonny; Yoshioka, Mayumi; Tanaka, Keitaro; Nishida, Yuichiro

    2012-01-01

    To identify preferentially expressed genes in the central endocrine organs of the hypothalamus and pituitary gland, we generated transcriptome-wide mRNA profiles of the hypothalamus, pituitary gland, and parietal cortex in male mice (12–15 weeks old) using serial analysis of gene expression (SAGE). Total counts of SAGE tags for the hypothalamus, pituitary gland, and parietal cortex were 165824, 126688, and 161045 tags, respectively. This represented 59244, 45151, and 55131 distinct tags, respectively. Comparison of these mRNA profiles revealed that 22 mRNA species, including three potential novel transcripts, were preferentially expressed in the hypothalamus. In addition to well-known hypothalamic transcripts, such as hypocretin, several genes involved in hormone function, intracellular transduction, metabolism, protein transport, steroidogenesis, extracellular matrix, and brain disease were identified as preferentially expressed hypothalamic transcripts. In the pituitary gland, 106 mRNA species, including 60 potential novel transcripts, were preferentially expressed. In addition to well-known pituitary genes, such as growth hormone and thyroid stimulating hormone beta, a number of genes classified to function in transport, amino acid metabolism, intracellular transduction, cell adhesion, disulfide bond formation, stress response, transcription, protein synthesis, and turnover, cell differentiation, the cell cycle, and in the cytoskeleton and extracellular matrix were also preferentially expressed. In conclusion, the current study identified not only well-known hypothalamic and pituitary transcripts but also a number of new candidates likely to be involved in endocrine homeostatic systems regulated by the hypothalamus and pituitary gland. PMID:22649398

  5. Progesterone metabolism by the hypothalamus, pituitary, and uterus of the rat during pregnancy

    SciTech Connect

    Marrone, B.L.; Karavolas, H.J.

    1981-07-01

    Metabolites of (/sup 3/H)progesterone were quantitated from incubations of hypothalamus, pituitary, and uterus of rats during different stages of pregnancy. The hypothalamus, anterior pituitary, and a section of uterus from five rats on Days 1, 8, 15, and 21 of pregnancy were incubated individually with (3H)progesterone and analyzed for metabolite formation by reverse isotopic dilution analysis. The radioactive metabolites present were 5 alpha-pregnane-3,20-dione (5 alpha-DHP), 3 alpha-hydroxy-5 alpha-pregnan-20-one, 20 alpha-hydroxy-4-pregnen-3-one, 20 alpha-hydroxy-5 alpha-pregnan-3-one, and 5 alpha-pregnane-3 alpha, 20 alpha-diol. The major metabolite formed by the hypothalamus and pituitary was 5 alpha-DHP. In the pituitary samples, formation of 5 alpha-DHP was decreased on Days 15 and 21 of pregnancy compared to Day 1, and formation of 20 alpha-hydroxy-5 alpha-pregnan-3-one was decreased on Day 21 compared to Day 1. In the uterine samples, 3 alpha-hydroxy-5 alpha-pregnan-20-one was the major metabolite formed at all stages of pregnancy. The formation of all metabolic products of progesterone by the uterus was increased on Day 21 compared to Days 1, 8, and 15 of pregnancy. No changes in the formation of progesterone metabolites were observed in the hypothalamic samples during pregnancy. It is concluded that there are different profiles in the in vitro metabolism of (3H)progesterone by the hypothalamus, pituitary, and uterus of the rat during the course of pregnancy.

  6. Presence and possible site of action of secretin in the rat pituitary and hypothalamus

    SciTech Connect

    Samson, W.K.; Lumpkin, M.D.; McCann, S.M.

    1984-01-09

    Secretin-like immunoreactivity was detected in extracts of several rat brain structures by radioimmunoassay, most notably in the pituitary, hypothalamus, pineal and septum. Its localization to these structures suggested that it might play a role in neuroendocrine events similar to its structural homolog vasoactive intestinal peptide. Dose-related stimulations (MED, 10/sup -7/ M) of prolactin (PRL) release were observed after incubation of synthetic secretin with dispersed, cultured pituitary cells from male and ovariectomized (OVX) female rats. Secretin can now be added to the growing list of putative PRL-releasing agents.

  7. Hypothalamus

    MedlinePlus

    The hypothalamus is an area of the brain that produces hormones that control: Body temperature Hunger Mood Release of ... or inflammation SYMPTOMS OF HYPOTHALAMIC DISEASE Because the hypothalamus controls so many different functions, hypothalamic disease can ...

  8. A Role for Glucocorticoids in Stress-Impaired Reproduction: Beyond the Hypothalamus and Pituitary

    PubMed Central

    Whirledge, Shannon

    2013-01-01

    In addition to the well-characterized role of the sex steroid receptors in regulating fertility and reproduction, reproductive events are also mediated by the hypothalamic-pituitary-adrenal axis in response to an individual's environment. Glucocorticoid secretion in response to stress contributes to the well-characterized suppression of the hypothalamic-pituitary-gonadal axis through central actions in the hypothalamus and pituitary. However, both animal and in vitro studies indicate that other components of the reproductive system are also regulated by glucocorticoids. Furthermore, in the absence of stress, it appears that homeostatic glucocorticoid signaling plays a significant role in reproduction and fertility in all tissues comprising the hypothalamic-pituitary-gonadal axis. Indeed, as central regulators of the immune response, glucocorticoids are uniquely poised to integrate an individual's infectious, inflammatory, stress, nutritional, and metabolic status through glucocorticoid receptor signaling in target tissues. Endocrine signaling between tissues regulating the immune and stress response and those determining reproductive status provides an evolutionary advantage, facilitating the trade-off between reproductive investment and offspring fitness. This review focuses on the actions of glucocorticoids in tissues important for fertility and reproduction, highlighting recent studies that show glucocorticoid signaling plays a significant role throughout the hypothalamic-pituitary-gonadal axis and characterizing these effects as permissive or inhibitory in terms of facilitating reproductive success. PMID:24064362

  9. Constitutive expression of ciliary neurotrophic factor in mouse hypothalamus

    PubMed Central

    Severi, Ilenia; Carradori, Maria Rita; Lorenzi, Teresa; Amici, Adolfo; Cinti, Saverio; Giordano, Antonio

    2012-01-01

    Ciliary neurotrophic factor (CNTF) is a potent survival molecule for a large number of neuronal and glial cells in culture; its expression in glial cells is strongly upregulated after a variety of nerve tissue injuries. Exogenously administered CNTF produces an anorectic effect via activation of hypothalamic neurons and stimulates neurogenesis in mouse hypothalamus. To determine whether CNTF is produced endogenously in the hypothalamus, we sought cellular sources and examined their distribution in adult mouse hypothalamus by immunohistochemistry. CNTF immunoreactivity (IR) was predominantly detected in the ependymal layer throughout the rostrocaudal extension of the third ventricle, where numerous ependymocytes and tanycytes exhibited specific staining. Some astrocytes in the grey matter of the anterior hypothalamus and in the median eminence of the hypothalamic tuberal region were also positive. Stimulation of cells bearing CNTF receptor α (CNTFRα) induces specific activation of the signal transducer and activator of transcription 3 (STAT3) signalling system. Treatment with recombinant CNTF and detection of the nuclear expression of phospho-STAT3 (P-STAT3) showed that CNTF-producing ependymal cells and tanycytes were intermingled with, or very close to, P-STAT3-positive, CNTFRα-bearing cells. A fraction of CNTF-producing ependymal cells and tanycytes and some median eminence astrocytes also exhibited P-STAT3 IR. Thus, in normal adult mice the ependyma of the third ventricle is both a source of and a target for CNTF, which may play hitherto unknown roles in hypothalamic function in physiological conditions. PMID:22458546

  10. Molecular codes defining rostrocaudal domains in the embryonic mouse hypothalamus.

    PubMed

    Ferran, José L; Puelles, Luis; Rubenstein, John L R

    2015-01-01

    The prosomeric model proposes that the hypothalamus is a rostral forebrain entity, placed ventral to the telencephalon and rostral to the diencephalon. Gene expression markers differentially label molecularly distinct dorsoventral progenitor domains, which represent continuous longitudinal bands across the hypothalamic alar and basal regions. There is also circumstantial support for a rostrocaudal subdivision of the hypothalamus into transverse peduncular (caudal) and terminal (rostral) territories (PHy, THy). In addition, there is evidence for a specialized acroterminal domain at the rostral midline of the terminal hypothalamus (ATD). The PHy and THy transverse structural units are presently held to form part of two hypothalamo-telencephalic prosomeres (hp1 and hp2, respectively), which end dorsally at the telencephalic septocommissural roof. PHy and THy have distinct adult nuclei, at all dorsoventral levels. Here we report the results of data mining from the Allen Developing Mouse Brain Atlas database, looking for genes expressed differentially in the PHy, Thy, and ATD regions of the hypothalamus at several developmental stages. This search allowed us to identify additional molecular evidence supporting the postulated fundamental rostrocaudal bipartition of the mouse hypothalamus into the PHy and THy, and also corroborated molecularly the singularity of the ATD. A number of markers were expressed in Thy (Fgf15, Gsc, Nkx6.2, Otx1, Zic1/5), but were absent in PHy, while other genes showed the converse pattern (Erbb4, Irx1/3/5, Lmo4, Mfap4, Plagl1, Pmch). We also identified markers that selectively label the ATD (Fgf8/10/18, Otx2, Pomc, Rax, Six6). On the whole, these data help to explain why, irrespective of the observed continuity of all dorsoventral molecular hypothalamic subdivisions across PHy and THy, different nuclear structures originate within each of these two domains, and also why singular structures arise at the ATD, e.g., the suprachiasmatic nuclei, the

  11. Molecular codes defining rostrocaudal domains in the embryonic mouse hypothalamus

    PubMed Central

    Ferran, José L.; Puelles, Luis; Rubenstein, John L. R.

    2015-01-01

    The prosomeric model proposes that the hypothalamus is a rostral forebrain entity, placed ventral to the telencephalon and rostral to the diencephalon. Gene expression markers differentially label molecularly distinct dorsoventral progenitor domains, which represent continuous longitudinal bands across the hypothalamic alar and basal regions. There is also circumstantial support for a rostrocaudal subdivision of the hypothalamus into transverse peduncular (caudal) and terminal (rostral) territories (PHy, THy). In addition, there is evidence for a specialized acroterminal domain at the rostral midline of the terminal hypothalamus (ATD). The PHy and THy transverse structural units are presently held to form part of two hypothalamo-telencephalic prosomeres (hp1 and hp2, respectively), which end dorsally at the telencephalic septocommissural roof. PHy and THy have distinct adult nuclei, at all dorsoventral levels. Here we report the results of data mining from the Allen Developing Mouse Brain Atlas database, looking for genes expressed differentially in the PHy, Thy, and ATD regions of the hypothalamus at several developmental stages. This search allowed us to identify additional molecular evidence supporting the postulated fundamental rostrocaudal bipartition of the mouse hypothalamus into the PHy and THy, and also corroborated molecularly the singularity of the ATD. A number of markers were expressed in Thy (Fgf15, Gsc, Nkx6.2, Otx1, Zic1/5), but were absent in PHy, while other genes showed the converse pattern (Erbb4, Irx1/3/5, Lmo4, Mfap4, Plagl1, Pmch). We also identified markers that selectively label the ATD (Fgf8/10/18, Otx2, Pomc, Rax, Six6). On the whole, these data help to explain why, irrespective of the observed continuity of all dorsoventral molecular hypothalamic subdivisions across PHy and THy, different nuclear structures originate within each of these two domains, and also why singular structures arise at the ATD, e.g., the suprachiasmatic nuclei, the

  12. Pituitary gland

    MedlinePlus Videos and Cool Tools

    ... gland is the hypothalamus. The hypothalamus decides which hormones the pituitary should release by sending it either ... the hypothalamus, the pituitary gland releases the following hormones: GH (growth hormone) – increases size of muscle and ...

  13. A comparison between the equine and bovine hypothalamus-pituitary-adrenocortical axis.

    PubMed

    van der Kolk, J H; Fouché, N; Gross, J J; Gerber, V; Bruckmaier, R M

    2016-07-01

    In this review, we address the function of the hypothalamus-pituitary-adrenocortical (HPA) axis with special emphasis on the comparison between the bovine and equine species. The pars intermedia of the pituitary gland is particularly well developed in horses and cattle. However, its function is not well appreciated in cattle yet. The Wulzen's cone of the adenohypophysis is a special feature of ruminants. Total basal cortisol concentration is much higher in horses than that in cows with similar free cortisol fractions. Corticotropin-releasing factor (CRF) concentrations in equine pituitary venous blood are lower compared with other species, whereas plasma ACTH concentrations in cows are higher than those in horses. A CRF challenge test induced a more pronounced cortisol response in horses compared with cattle, whereas regarding ACTH challenge testing, the opposite seems true. Based on data from literature, the bovine species is characterized by relatively high basal blood CRF and ACTH and low cortisol and glucose concentrations. Obviously, further lowering of blood cortisol in cattle is easily prevented by the high sensitivity to ACTH, and as a consequence, subsequent increased gluconeogenesis prevents imminent hypoglycemia. Hypoglycemia is less likely in horses given their high muscle glycogen content and their relatively high cortisol concentration. When assessing HPA axis reactivity, response patterns to exogenous ACTH or CRH might be used as a reliable indicator of animal welfare status in cows and horses, respectively, although it is emphasized that considerable caution should be exercised in using measures of HPA activity solely to assess animal welfare. PMID:27345307

  14. Differential requirements for Gli2 and Gli3 in the regional specification of the mouse hypothalamus

    PubMed Central

    Haddad-Tóvolli, Roberta; Paul, Fabian A.; Zhang, Yuanfeng; Zhou, Xunlei; Theil, Thomas; Puelles, Luis; Blaess, Sandra; Alvarez-Bolado, Gonzalo

    2015-01-01

    Secreted protein Sonic hedgehog (Shh) ventralizes the neural tube by modulating the crucial balance between activating and repressing functions (GliA, GliR) of transcription factors Gli2 and Gli3. This balance—the Shh-Gli code—is species- and context-dependent and has been elucidated for the mouse spinal cord. The hypothalamus, a forebrain region regulating vital functions like homeostasis and hormone secretion, shows dynamic and intricate Shh expression as well as complex regional differentiation. Here we asked if particular combinations of Gli2 and Gli3 and of GliA and GliR functions contribute to the variety of hypothalamic regions, i.e., we wanted to approach the question of a possible hypothalamic version of the Shh-Gli code. Based on mouse mutant analysis, we show that: (1) hypothalamic regional heterogeneity is based in part on differentially stringent requirements for Gli2 or Gli3; (2) another source of diversity are differential requirements for Shh of neural vs. non-neural origin; (3) the medial progenitor domain known to depend on Gli2 for its development generates several essential hypothalamic nuclei plus the pituitary and median eminence; (4) the suppression of Gli3R by neural and non-neural Shh is essential for hypothalamic specification. Finally, we have mapped our results on a recent model which considers the hypothalamus as a transverse region with alar and basal portions. Our data confirm the model and are explained by it. PMID:25859185

  15. DEVELOPMENT OF A GENE-EXPRESSION ARRAY FOCUSING ON THE HYPOTHALAMUS-PITUITARY-THYROID AXIS IN XENOPUS LAEVIS

    EPA Science Inventory

    As recommended by the Endocrine Disruptor Screening and Testing Program Advisory Committee (EDSTAC), the USEPA has been developing a screening test capable of detecting effects of Endocrine Disrupting Chemicals (EDCs) on the hypothalamus-pituitary-thyroid (HPT) axis in Xenopus la...

  16. Distinct Types of Feeding Related Neurons in Mouse Hypothalamus

    PubMed Central

    Tang, Yan; Benusiglio, Diego; Grinevich, Valery; Lin, Longnian

    2016-01-01

    The last two decades of research provided evidence for a substantial heterogeneity among feeding-related neurons (FRNs) in the hypothalamus. However, it remains unclear how FRNs differ in their firing patterns during food intake. Here, we investigated the relationship between the activity of neurons in mouse hypothalamus and their feeding behavior. Using tetrode-based in vivo recording technique, we identified various firing patterns of hypothalamic FRNs, which, after the initiation of food intake, can be sorted into four types: sharp increase (type I), slow increase (type II), sharp decrease (type III), and sustained decrease (type IV) of firing rates. The feeding-related firing response of FRNs was rigidly related to the duration of food intake and, to a less extent, associated with the type of food. The majority of these FRNs responded to glucose and leptin and exhibited electrophysiological characteristics of putative GABAergic neurons. In conclusion, our study demonstrated the diversity of neurons in the complex hypothalamic network coordinating food intake. PMID:27242460

  17. A Computational Model of the Rainbow Trout Hypothalamus-Pituitary-Ovary-Liver Axis.

    PubMed

    Gillies, Kendall; Krone, Stephen M; Nagler, James J; Schultz, Irvin R

    2016-04-01

    Reproduction in fishes and other vertebrates represents the timely coordination of many endocrine factors that culminate in the production of mature, viable gametes. In recent years there has been rapid growth in understanding fish reproductive biology, which has been motivated in part by recognition of the potential effects that climate change, habitat destruction and contaminant exposure can have on natural and cultured fish populations. New approaches to understanding the impacts of these stressors are being developed that require a systems biology approach with more biologically accurate and detailed mathematical models. We have developed a multi-scale mathematical model of the female rainbow trout hypothalamus-pituitary-ovary-liver axis to use as a tool to help understand the functioning of the system and for extrapolation of laboratory findings of stressor impacts on specific components of the axis. The model describes the essential endocrine components of the female rainbow trout reproductive axis. The model also describes the stage specific growth of maturing oocytes within the ovary and permits the presence of sub-populations of oocytes at different stages of development. Model formulation and parametrization was largely based on previously published in vivo and in vitro data in rainbow trout and new data on the synthesis of gonadotropins in the pituitary. Model predictions were validated against several previously published data sets for annual changes in gonadotropins and estradiol in rainbow trout. Estimates of select model parameters can be obtained from in vitro assays using either quantitative (direct estimation of rate constants) or qualitative (relative change from control values) approaches. This is an important aspect of mathematical models as in vitro, cell-based assays are expected to provide the bulk of experimental data for future risk assessments and will require quantitative physiological models to extrapolate across biological scales. PMID

  18. A Computational Model of the Rainbow Trout Hypothalamus-Pituitary-Ovary-Liver Axis

    PubMed Central

    Gillies, Kendall; Krone, Stephen M.; Nagler, James J.; Schultz, Irvin R.

    2016-01-01

    Reproduction in fishes and other vertebrates represents the timely coordination of many endocrine factors that culminate in the production of mature, viable gametes. In recent years there has been rapid growth in understanding fish reproductive biology, which has been motivated in part by recognition of the potential effects that climate change, habitat destruction and contaminant exposure can have on natural and cultured fish populations. New approaches to understanding the impacts of these stressors are being developed that require a systems biology approach with more biologically accurate and detailed mathematical models. We have developed a multi-scale mathematical model of the female rainbow trout hypothalamus-pituitary-ovary-liver axis to use as a tool to help understand the functioning of the system and for extrapolation of laboratory findings of stressor impacts on specific components of the axis. The model describes the essential endocrine components of the female rainbow trout reproductive axis. The model also describes the stage specific growth of maturing oocytes within the ovary and permits the presence of sub-populations of oocytes at different stages of development. Model formulation and parametrization was largely based on previously published in vivo and in vitro data in rainbow trout and new data on the synthesis of gonadotropins in the pituitary. Model predictions were validated against several previously published data sets for annual changes in gonadotropins and estradiol in rainbow trout. Estimates of select model parameters can be obtained from in vitro assays using either quantitative (direct estimation of rate constants) or qualitative (relative change from control values) approaches. This is an important aspect of mathematical models as in vitro, cell-based assays are expected to provide the bulk of experimental data for future risk assessments and will require quantitative physiological models to extrapolate across biological scales. PMID

  19. The critical importance of the fetal hypothalamus-pituitary-adrenal axis

    PubMed Central

    Wood, Charles E.; Keller-Wood, Maureen

    2016-01-01

    The fetal hypothalamus-pituitary-adrenal (HPA) axis is at the center of mechanisms controlling fetal readiness for birth, survival after birth and, in several species, determination of the timing of birth. Stereotypical increases in fetal HPA axis activity at the end of gestation are critical for preparing the fetus for successful transition to postnatal life. The fundamental importance in fetal development of the endogenous activation of this endocrine axis at the end of gestation has led to the use of glucocorticoids for reducing neonatal morbidity in premature infants. However, the choice of dose and repetition of treatments has been controversial, raising the possibility that excess glucocorticoid might program an increased incidence of adult disease (e.g., coronary artery disease and diabetes). We make the argument that because of the critical importance of the fetal HPA axis and its interaction with the maternal HPA axis, dysregulation of cortisol plasma concentrations or inappropriate manipulation pharmacologically can have negative consequences at the beginning of extrauterine life and for decades thereafter. PMID:26918188

  20. Maternal Cortisol Mediates Hypothalamus-Pituitary-Interrenal Axis Development in Zebrafish

    PubMed Central

    Nesan, Dinushan; Vijayan, Mathilakath M.

    2016-01-01

    In zebrafish (Danio rerio), de novo synthesis of cortisol in response to stressor exposure commences only after hatch. Maternally deposited cortisol is present during embryogenesis, but a role for this steroid in early development is unclear. We tested the hypothesis that maternal cortisol is essential for the proper development of hypothalamus-pituitary-interrenal (HPI) axis activity and the onset of the stressor-induced cortisol response in larval zebrafish. In this study, zygotic cortisol content was manipulated by microinjecting antibody to sequester this steroid, thereby making it unavailable during embryogenesis. This was compared with embryos containing excess cortisol by microinjection of exogenous steroid. The resulting larval phenotypes revealed distinct treatment effects, including deformed mesoderm structures when maternal cortisol was unavailable and cardiac edema after excess cortisol. Maternal cortisol unavailability heightened the cortisol stress response in post-hatch larvae, whereas excess cortisol abolished the stressor-mediated cortisol elevation. This contrasting hormonal response corresponded with altered expression of key HPI axis genes, including crf, 11B hydroxylase, pomca, and star, which were upregulated in response to reduced cortisol availability and downregulated when embryos had excess cortisol. These findings for the first time underscore a critical role for maternally deposited cortisol in programming HPI axis development and function in zebrafish. PMID:26940285

  1. A Review of the Phenomenon of Hysteresis in the Hypothalamus-Pituitary-Thyroid Axis.

    PubMed

    Leow, Melvin Khee-Shing

    2016-01-01

    The existence of a phase of prolonged suppression of TSH despite normalization of serum thyroid hormones over a variable period of time during the recovery of thyrotoxicosis has been documented in literature. Conversely, a temporary elevation of TSH despite attainment of euthyroid levels of serum thyroid hormones following extreme hypothyroidism has also been observed. This rate-independent lag time in TSH recovery is an evidence of a "persistent memory" of the history of dysthyroid states the hypothalamus-pituitary-thyroid (HPT) axis has encountered after the thyroid hormone perturbations have faded out, a phenomenon termed "hysteresis." Notwithstanding its perplexing nature, hysteresis impacts upon the interpretation of thyroid function tests with sufficient regularity that clinicians risk misdiagnosing and implementing erroneous treatment out of ignorance of this aspect of thyrotropic biology. Mathematical modeling of this phenomenon is complicated but may allow the euthyroid set point to be predicted from thyroid function data exhibiting strong hysteresis effects. Such model predictions are potentially useful for clinical management. Although the molecular mechanisms mediating hysteresis remain elusive, epigenetics, such as histone modifications, are probably involved. However, attempts to reverse the process to hasten the resolution of the hysteretic process may not necessarily translate into improved physiology or optimal health benefits. This is not unexpected from teleological considerations, since hysteresis probably represents an adaptive endocrinological response with survival advantages evolutionarily conserved among vertebrates with a HPT system. PMID:27379016

  2. Hypothalamus-Pituitary-Adrenal Axis Hypersuppression Is Associated with Gastrointestinal Symptoms in Major Depression

    PubMed Central

    Karling, Pontus; Wikgren, Mikael; Adolfsson, Rolf; Norrback, Karl-Fredrik

    2016-01-01

    Background/Aims Gastrointestinal symptoms and hypothalamus-pituitary-adrenal (HPA) axis dysfunction are frequently observed in patients with major depression. The primary aim of the study was to investigate the relationship between HPA-axis function and self-perceived functional gastrointestinal symptoms in major depression. Methods Patients with major depression (n = 73) and controls representative of the general population (n = 146) underwent a weight-adjusted very low dose dexamethasone suppression test (DST). Patients and controls completed the gastrointestinal symptom rating scale-iritable bowel syndrome (GSRS-IBS) and the hospital anxiety depression scale. Medical records of the patients were screened over a ten year period for functional gastrointestinal disorder and pain conditions. Results Patients with high GSRS-IBS scores (above median) exhibited HPA-axis hypersuppression more often than controls (defined by the lowest 10% cutoff of the post-DST cortisol values among controls, adjusted OR 7.25, CI 1.97–26.7) whereas patients with low GSRS-IBS scores did not differ from controls concerning their post-DST cortisol values. Patients who had consulted primary care for functional gastrointestinal disorder (P = 0.039), lumbago (P = 0.006) and chronic multifocal pain (P = 0.057) also exhibited an increased frequency of hypersuppression. Conclusions HPA-axis hypersuppression is associated with functional gastrointestinal symptoms in patients with major depression. PMID:26507800

  3. Influence of triphenyltin exposure on the hypothalamus-pituitary-gonad axis in male Sebastiscus marmoratus.

    PubMed

    Sun, Lingbin; Zhang, Jiliang; Zuo, Zhenghong; Chen, Yixin; Wang, Xinhong; Huang, Xin; Wang, Chonggang

    2011-08-01

    Both triphenyltin (TPT) and tributyltin (TBT) have been used as ingredients of antifouling biocides. However, far fewer studies addressing the reproductive toxicity of TPT on fishes are available than for TBT. The present study was conducted to investigate the effects of TPT at environmentally relevant concentrations on testicular development in male rockfish Sebastiscus marmoratus and to gain insight into its mechanism of action. After exposure for 48 days, the gonadosomatic index had decreased, and there was a reduced number of mature sperm and an abundance of the late stages of spermatocysts in the testes. Although the testosterone levels in the testes were elevated and the 17β-estradiol levels were decreased, spermatogenesis was suppressed. The activity of γ-glutamyl transpeptidase (which is used as a Sertoli cell marker) was decreased after TPT exposure, and serious interstitial fibrosis was observed in the interlobular septa of the testes exposed to TPT. The increased expression of cGnRH-II (chicken-II type gonadotropin-releasing hormone) and sGnRH (salmon-type GnRH), and the decreased expression of LHβ (luteinizing hormone) in the fish brains were detected. The expression of FSHβ (follicle-stimulating hormone) was decreased at day 21, while was increased slightly at day 48. The changes of cGnRH-II, sGnRH, FSHβ and LHβ mRNA levels might have mainly resulted from the alteration of the sex steroids via feedback mechanisms. The decrease of the FSHβ mRNA might have been one of the reasons causing the dysfunction of Sertoli cells, which play a critical role during spermatogenesis. The results suggested that TPT could perturb the function of hypothalamus-pituitary-gonad axis, and inhibiting the spermatogenesis. PMID:21641294

  4. The role of hypothalamus-pituitary-adrenal genes and childhood trauma in borderline personality disorder.

    PubMed

    Martín-Blanco, Ana; Ferrer, Marc; Soler, Joaquim; Arranz, Maria Jesús; Vega, Daniel; Calvo, Natalia; Elices, Matilde; Sanchez-Mora, Cristina; García-Martinez, Iris; Salazar, Juliana; Carmona, Cristina; Bauzà, Joana; Prat, Mónica; Pérez, Víctor; Pascual, Juan C

    2016-06-01

    Current knowledge suggests that borderline personality disorder (BPD) results from the interaction between genetic and environmental factors. Research has mainly focused on monoaminergic genetic variants and their modulation by traumatic events, especially those occurring during childhood. However, to the best of our knowledge, there are no studies on the genetics of hypothalamus-pituitary-adrenal (HPA) axis, despite its vulnerability to early stress and its involvement in BPD pathogenesis. The aim of this study was to investigate the contribution of genetic variants in the HPA axis and to explore the modulating effect of childhood trauma in a large sample of BPD patients and controls. DNA was obtained from a sample of 481 subjects with BPD and 442 controls. Case-control differences in allelic frequencies of 47 polymorphisms in 10 HPA axis genes were analysed. Modulation of genetic associations by the presence of childhood trauma was also investigated by dividing the sample into three groups: BPD with trauma, BPD without trauma and controls. Two FKBP5 polymorphisms (rs4713902-C and rs9470079-A) showed significant associations with BPD. There were also associations between BPD and haplotype combinations of the genes FKBP5 and CRHR1. Two FKBP5 alleles (rs3798347-T and rs10947563-A) were more frequent in BPD subjects with history of physical abuse and emotional neglect and two CRHR2 variants (rs4722999-C and rs12701020-C) in BPD subjects with sexual and physical abuse. Our findings suggest a contribution of HPA axis genetic variants to BPD pathogenesis and reinforce the hypothesis of the modulating effect of childhood trauma in the development of this disorder. PMID:26182893

  5. Views on the co-evolution of the melanocortin-2 receptor, MRAPs, and the hypothalamus/pituitary/adrenal-interrenal axis.

    PubMed

    Dores, Robert M; Garcia, Yesenia

    2015-06-15

    A critical regulatory component of the hypothalamus/pituitary/adrenal axis (HPA) in mammals, reptiles and birds, and in the hypothalamus/pituitary/interrenal (HPI) axis of amphibians and teleosts (modern bony fishes) is the strict ligand selectivity of the melanocortin-2 receptor (MC2R). Tetrapod and teleost MC2R orthologs can only be activated by the anterior pituitary hormone, ACTH, but not by any of the MSH-sized ligands coded in POMC. In addition, both tetrapod and teleost MC2R orthologs require co-expression with the accessory protein, MRAP. However, the MC2R ortholog of the elephant shark, a cartilaginous fish, can be activated by either ACTH or the MSH-sized ligands, and the elephant shark MC2R ortholog does not require co-expression with an MRAP for activation. Given these observations, this review will provide a scenario for the co-evolution of MC2R and MRAP, based on the assumption that the obligate interaction between MC2R and MRAP evolved during the early radiation of the ancestral bony fishes. PMID:25573240

  6. Development of the hypothalamus and pituitary in platypus (Ornithorhynchus anatinus) and short-beaked echidna (Tachyglossus aculeatus).

    PubMed

    Ashwell, Ken W S

    2012-07-01

    The living monotremes (platypus and echidnas) are distinguished by the development of their young in a leathery-shelled egg, a low and variable body temperature and a primitive teat-less mammary gland. Their young are hatched in an immature state and must deal with the external environment, with all its challenges of hypothermia and stress, as well as sourcing nutrients from the maternal mammary gland. The Hill and Hubrecht embryological collections have been used to follow the structural development of the monotreme hypothalamus and its connections with the pituitary gland both in the period leading up to hatching and during the lactational phase of development, and to relate this structural maturation to behavioural development. In the incubation phase, development of the hypothalamus proceeds from closure of the anterior neuropore to formation of the lateral hypothalamic zone and putative medial forebrain bundle. Some medial zone hypothalamic nuclei are emerging at the time of hatching, but these are poorly differentiated and periventricular zone nuclei do not appear until the first week of post-hatching life. Differentiation of the pituitary is also incomplete at hatching, epithelial cords do not develop in the pars anterior until the first week, and the hypothalamo-neurohypophyseal tract does not appear until the second week of post-hatching life. In many respects, the structure of the hypothalamus and pituitary of the newly hatched monotreme is similar to that seen in newborn marsupials, suggesting that both groups rely solely on lateral hypothalamic zone nuclei for whatever homeostatic mechanisms they are capable of at birth/hatching. PMID:22512474

  7. Nutrient restriction induces failure of reproductive function and molecular changes in hypothalamus-pituitary-gonadal axis in postpubertal gilts.

    PubMed

    Zhou, Dongsheng; Zhuo, Yong; Che, Lianqiang; Lin, Yan; Fang, Zhengfeng; Wu, De

    2014-07-01

    People on a diet to lose weight may be at risk of reproductive failure. To investigate the effects of nutrient restriction on reproductive function and the underlying mechanism, changes of reproductive traits, hormone secretions and gene expressions in hypothalamus-pituitary-gonadal axis were examined in postpubertal gilts at anestrus induced by nutrient restriction. Gilts having experienced two estrus cycles were fed a normal (CON, 2.86 kg/d) or nutrient restricted (NR, 1 kg/d) food regimens to expect anestrus. NR gilts experienced another three estrus cycles, but did not express estrus symptoms at the anticipated fourth estrus. Blood samples were collected at 5 days' interval for consecutive three times for measurement of hormone concentrations at the 23th day of the fourth estrus cycle. Individual progesterone concentrations of NR gilts from three consecutive blood samples were below 1.0 ng/mL versus 2.0 ng/mL in CON gilts, which was considered anestrus. NR gilts had impaired development of reproductive tract characterized by absence of large follicles (diameter ≥ 6 mm), decreased number of corepus lutea and atrophy of uterus and ovary tissues. Circulating concentrations of IGF-I, kisspeptin, estradiol, progesterone and leptin were significantly lower in NR gilts than that in CON gilts. Nutrient restriction down-regulated gene expressions of kiss-1, G-protein coupled protein 54, gonadotropin-releasing hormone, estrogen receptor α, progesterone receptor, leptin receptor, follicle-stimulating hormone and luteinizing hormone and insulin-like growth factor I in hypothalamus-pituitary-gonadal axis of gilts. Collectively, nutrient restriction resulted in impairment of reproductive function and changes of hormone secretions and gene expressions in hypothalamus-pituitary-gonadal axis, which shed light on the underlying mechanism by which nutrient restriction influenced reproductive function. PMID:24728609

  8. Distribution of histaminergic neuronal cluster in the rat and mouse hypothalamus.

    PubMed

    Moriwaki, Chinatsu; Chiba, Seiichi; Wei, Huixing; Aosa, Taishi; Kitamura, Hirokazu; Ina, Keisuke; Shibata, Hirotaka; Fujikura, Yoshihisa

    2015-10-01

    Histidine decarboxylase (HDC) catalyzes the biosynthesis of histamine from L-histidine and is expressed throughout the mammalian nervous system by histaminergic neurons. Histaminergic neurons arise in the posterior mesencephalon during the early embryonic period and gradually develop into two histaminergic substreams around the lateral area of the posterior hypothalamus and the more anterior peri-cerebral aqueduct area before finally forming an adult-like pattern comprising five neuronal clusters, E1, E2, E3, E4, and E5, at the postnatal stage. This distribution of histaminergic neuronal clusters in the rat hypothalamus appears to be a consequence of neuronal development and reflects the functional differentiation within each neuronal cluster. However, the close linkage between the locations of histaminergic neuronal clusters and their physiological functions has yet to be fully elucidated because of the sparse information regarding the location and orientation of each histaminergic neuronal clusters in the hypothalamus of rats and mice. To clarify the distribution of the five-histaminergic neuronal clusters more clearly, we performed an immunohistochemical study using the anti-HDC antibody on serial sections of the rat hypothalamus according to the brain maps of rat and mouse. Our results confirmed that the HDC-immunoreactive (HDCi) neuronal clusters in the hypothalamus of rats and mice are observed in the ventrolateral part of the most posterior hypothalamus (E1), ventrolateral part of the posterior hypothalamus (E2), ventromedial part from the medial to the posterior hypothalamus (E3), periventricular part from the anterior to the medial hypothalamus (E4), and diffusely extended part of the more dorsal and almost entire hypothalamus (E5). The stereological estimation of the total number of HDCi neurons of each clusters revealed the larger amount of the rat than the mouse. The characterization of histaminergic neuronal clusters in the hypothalamus of rats and

  9. Recovery of the hypothalamus-pituitary-adrenal axis after short term high dose corticosteroid treatment in neurosurgical practice.

    PubMed

    Hedner, P; Kullberg, G; Bostedt, I

    1984-01-01

    The recovery of the hypothalamus-pituitary-adrenal axis after high-dose short-term steroid treatment was investigated in 18 patients undergoing stereotactic thalamotomy during local anaesthesia, in whom perioperative betamethasone was given in a high dose for 4-5 days and withdrawn without tapering. There were no untoward clinical effects of the abrupt withdrawal of the steroid. Seven patients undergoing the same operation without steroid treatment served as controls. The recovery of the hypothalamus-pituitary-adrenal axis after steroid treatment was studied by basal plasma cortisol levels. In 12 patients the reserve capacity of the system was investigated by the cortisol response to insulin induced hypoglycemia as well. It was found that the basal plasma cortisol levels had normalized 2 days after the abrupt withdrawal of betamethasone. In spite of normalized basal cortisol levels the capacity to respond to stress was reduced for a further 3 days. Six to seven days after the steroid withdrawal the stress response was, however, completely restored. It is concluded that high dose, short term steroid treatment can be withdrawn abruptly, omitting the usual tapering of the dose. During the first week after steroid withdrawal the cortisol response to stress is reduced even in the presence of normal basal cortisol levels. During this period extra corticosteroids must be supplied in case of an emergency situation or an operation. PMID:6393724

  10. Hypothyroidism reduces ObRb-STAT3 leptin signalling in the hypothalamus and pituitary of rats associated with resistance to leptin acute anorectic action.

    PubMed

    Calvino, Camila; Souza, Luana L; Costa-e-Sousa, Ricardo H; Almeida, Norma A S; Trevenzoli, Isis H; Pazos-Moura, Carmen C

    2012-10-01

    Leptin has been shown to regulate the hypothalamus-pituitary-thyroid axis, acting primarily through the STAT3 pathway triggered through the binding of leptin to the long-chain isoform of the leptin receptor, ObRb. We previously demonstrated that although hyperthyroid rats presented leptin effects on TSH secretion, those effects were abolished in hypothyroid rats. We addressed the hypothesis that changes in the STAT3 pathway might explain the lack of TSH response to leptin in hypothyroidism by evaluating the protein content of components of leptin signalling via the STAT3 pathway in the hypothalamus and pituitary of hypothyroid (0·03% methimazole in the drinking water/21 days) and hyperthyroid (thyroxine 5 μg/100 g body weight /5 days) rats. Hypothyroid rats exhibited decreased ObRb and phosphorylated STAT3 (pSTAT3) protein in the hypothalamus, and in the pituitary gland they exhibited decreased ObRb, total STAT3, pSTAT3 and SOCS3 (P<0·05). Except for a modest decrease in pituitary STAT3, no other alterations were observed in hyperthyroid rats. Moreover, unlike euthyroid rats, the hypothyroid rats did not exhibit a reduction in food ingestion after a single injection of leptin (0·5 mg/kg body weight). Therefore, hypothyroidism decreased ObRb-STAT3 signalling in the hypothalamus and pituitary gland, which likely contributes to the loss of leptin action on food intake and TSH secretion, as previously observed in hypothyroid rats. PMID:22875962

  11. Clocks for all seasons: unwinding the roles and mechanisms of circadian and interval timers in the hypothalamus and pituitary

    PubMed Central

    Wood, Shona; Loudon, Andrew

    2014-01-01

    Adaptation to the environment is essential for survival, in all wild animal species seasonal variation in temperature and food availability needs to be anticipated. This has led to the evolution of deep-rooted physiological cycles, driven by internal clocks, which can track seasonal time with remarkable precision. Evidence has now accumulated that a seasonal change in thyroid hormone (TH) availability within the brain is a crucial element. This is mediated by local control of TH-metabolising enzymes within specialised ependymal cells lining the third ventricle of the hypothalamus. Within these cells, deiodinase type 2 enzyme is activated in response to summer day lengths, converting metabolically inactive thyroxine (T4) to tri-iodothyronine (T3). The availability of TH in the hypothalamus appears to be an important factor in driving the physiological changes that occur with season. Remarkably, in both birds and mammals, the pars tuberalis (PT) of the pituitary gland plays an essential role. A specialised endocrine thyrotroph cell (TSH-expressing) is regulated by the changing day-length signal, leading to activation of TSH by long days. This acts on adjacent TSH-receptors expressed in the hypothalamic ependymal cells, causing local regulation of deiodinase enzymes and conversion of TH to the metabolically active T3. In mammals, the PT is regulated by the nocturnal melatonin signal. Summer-like melatonin signals activate a PT-expressed clock-regulated transcription regulator (EYA3), which in turn drives the expression of the TSHβ sub-unit, leading to a sustained increase in TSH expression. In this manner, a local pituitary timer, driven by melatonin, initiates a cascade of molecular events, led by EYA3, which translates to seasonal changes of neuroendocrine activity in the hypothalamus. There are remarkable parallels between this PT circuit and the photoperiodic timing system used in plants, and while plants use different molecular signals (constans vs EYA3) it

  12. Changes in the processing of beta-endorphin in the hypothalamus and pituitary gland of female rats during sexual maturation.

    PubMed

    Martensz, N D

    1985-11-01

    Puberty in the female rat is accompanied by a marked attenuation of the opioid inhibition of luteinizing hormone secretion. One factor which may contribute to this altered role is a change in the metabolism of opioid peptides during sexual maturation. beta-Endorphin undergoes a considerable degree of metabolism through both C-terminal proteolysis and N-acetylation, and these metabolites do not possess opioid activity. The processing of beta-endorphin in the hypothalamus and in the anterior and neurointermediate lobes of the pituitary gland in prepubertal and adult female rats was studied using gel filtration and high performance liquid chromatography coupled with radioimmunoassay. In the anterior lobe, high molecular weight precursors of beta-endorphin (pro-opiomelanocortin and beta-lipotropin) were present in prepubertal (28 days old) rats, but little authentic beta-endorphin was detected. In contrast, only beta-lipotropin and beta-endorphin were present in mature (70 days old) animals. Only beta-endorphin-sized peptides were present in the neurointermediate lobes of both prepubertal and adult rats. However, the proportion of N-acetylated metabolites was higher in sexually mature animals. In the hypothalamus, only beta-endorphin-sized peptides were present in both juvenile and adult animals. However, C-terminal proteolysis increased with age (no acetylated metabolites were detectable in this tissue). The proportion of the total beta-endorphin-like immunoreactivity attributable to beta-endorphin was lower in young adult (first dioestrus after vaginal opening) (55%) and mature (dioestrus, 61-64 days old) rats (56%) compared to prepubertal (30 days old) animals (75%) and the proportions of non-acetylated metabolites [beta-endorphin-(1-27) in young adults and beta-endorphin-(1-26) in adults] were increased concomitantly. These changes were correlated with a reduced luteinizing hormone response to the opiate antagonist naloxone in adult compared to prepubertal rats

  13. Prenatal Stress Induces Long-Term Effects in Cell Turnover in the Hippocampus-Hypothalamus-Pituitary Axis in Adult Male Rats

    PubMed Central

    Baquedano, Eva; García-Cáceres, Cristina; Diz-Chaves, Yolanda; Lagunas, Natalia; Calmarza-Font, Isabel; Azcoitia, Iñigo; Garcia-Segura, Luis M.; Argente, Jesús; Chowen, Julie A.; Frago, Laura M.

    2011-01-01

    Subchronic gestational stress leads to permanent modifications in the hippocampus-hypothalamus-pituitary-adrenal axis of offspring probably due to the increase in circulating glucocorticoids known to affect prenatal programming. The aim of this study was to investigate whether cell turnover is affected in the hippocampus-hypothalamus-pituitary axis by subchronic prenatal stress and the intracellular mechanisms involved. Restraint stress was performed in pregnant rats during the last week of gestation (45 minutes; 3 times/day). Only male offspring were used for this study and were sacrificed at 6 months of age. In prenatally stressed adults a decrease in markers of cell death and proliferation was observed in the hippocampus, hypothalamus and pituitary. This was associated with an increase in insulin-like growth factor-I mRNA levels, phosphorylation of CREB and calpastatin levels and inhibition of calpain -2 and caspase -8 activation. Levels of the anti-apoptotic protein Bcl-2 were increased and levels of the pro-apoptotic factor p53 were reduced. In conclusion, prenatal restraint stress induces a long-term decrease in cell turnover in the hippocampus-hypothalamus-pituitary axis that might be at least partly mediated by an autocrine-paracrine IGF-I effect. These changes could condition the response of this axis to future physiological and pathophysiological situations. PMID:22096592

  14. The effect of trans-resveratrol on post-stroke depression via regulation of hypothalamus-pituitary-adrenal axis.

    PubMed

    Pang, Cong; Cao, Liang; Wu, Fan; Wang, Li; Wang, Gang; Yu, Yingcong; Zhang, Meixi; Chen, Lichao; Wang, Weijie; Lv, Weihong; Chen, Ling; Zhu, Jiejin; Pan, Jianchun; Zhang, Hanting; Xu, Ying; Ding, Lianshu

    2015-10-01

    Post-stroke depression (PSD) occurs about 40% among all stroke survivors, but the effective pharmacotherapy is inadequately understood. The present study investigated the effects of a natural polyphenol trans-resveratrol (RES) on behavioral changes after middle cerebral artery occlusion (MCAO) and examined what its molecular targets may be. RES was shown to decrease the infarct size and neurological scores after MCAO, suggesting the amelioration of brain damage and motor activity. RES also reversed the depressive-like behaviors 13 days after MCAO, both in the forced swimming and sucrose consumption tests. Moreover, MCAO-induced series abnormalities related to depressive-like behaviors, such as an abnormal adrenal gland weight to body weight ratio, an increased expression of the corticotropin-releasing factor (CRF) in the frontal cortex, hippocampus and hypothalamus, the differential expression of glucocorticoid receptor (GR) in these three brain regions, and a decreased brain-derived neurotrophic factor (BDNF) level, were ameliorated after treatment with increasing doses of RES at 10, 20 and 40 mg/kg via gavage. These findings provide compelling evidence that RES protects the brain against focal cerebral ischemia-induced injury, but most of all is its antidepressant-like effect on PSD, which might at least in part be mediated by regulation of hypothalamus-pituitary-adrenal axis function. PMID:25937213

  15. Developmental changes in the expression of somatostatin receptors (1-5) in the brain, hypothalamus, pituitary and spinal cord of the human fetus.

    PubMed

    Goodyer, C G; Grigorakis, S I; Patel, Y C; Kumar, U

    2004-01-01

    The actions of somatostatin (SST) in the nervous system are mediated by specific high affinity SST receptors (SSTR1-5). However, the role of this hormone and the distribution of its receptor subtypes have not yet been defined in neural structures of the human fetus. We have analyzed four neural tissues (CNS, hypothalamus, pituitary and spinal cord) from early to midgestation for the expression of five human SSTR mRNAs, using a reverse transcription-polymerase chain reaction and Southern blot approach. These fetal neural tissues all express mRNA for multiple SSTR subtypes from as early as 16 weeks of fetal life but the developmental patterns of expression vary considerably. Transcripts for SSTR1 and SSTR2A are the most widely distributed, being expressed in all four neural tissues. SSTR2A is often the earliest transcript to be detected (7.5 weeks in CNS). SSTR3 mRNA is confined to the pituitary, hypothalamus, and spinal cord. SSTR4 is expressed in fetal brain, hypothalamus and spinal cord but not pituitary. SSTR5 mRNA is detectable in the pituitary and spinal cord by 14-16 weeks of fetal life. This mapping of SSTR mRNA expression patterns in human fetal neural tissues is an important first step toward our goal of determining the role of SST in the nervous system during early stages in human development. PMID:15062986

  16. Cell Death Atlas of the Postnatal Mouse Ventral Forebrain and Hypothalamus: Effects of Age and Sex

    PubMed Central

    Ahern, Todd H.; Krug, Stefanie; Carr, Audrey V.; Murray, Elaine K.; Fitzpatrick, Emmett; Bengston, Lynn; McCutcheon, Jill; De Vries, Geert J.; Forger, Nancy G.

    2016-01-01

    Naturally occurring cell death is essential to the development of the mammalian nervous system. Although the importance of developmental cell death has been appreciated for decades, there is no comprehensive account of cell death across brain areas in the mouse. Moreover, several regional sex differences in cell death have been described for the ventral forebrain and hypothalamus, but it is not known how widespread the phenomenon is. We used immunohistochemical detection of activated caspase-3 to identify dying cells in the brains of male and female mice from postnatal day (P) 1 to P11. Cell death density, total number of dying cells, and regional volume were determined in 16 regions of the hypothalamus and ventral forebrain (the anterior hypothalamus, arcuate nucleus, anteroventral periventricular nucleus, medial preoptic nucleus, paraventricular nucleus, suprachiasmatic nucleus, and ventromedial nucleus of the hypothalamus; the basolateral, central, and medial amygdala; the lateral and principal nuclei of the bed nuclei of the stria terminalis; the caudate-putamen; the globus pallidus; the lateral septum; and the islands of Calleja). All regions showed a significant effect of age on cell death. The timing of peak cell death varied between P1 to P7, and the average rate of cell death varied tenfold among regions. Several significant sex differences in cell death and/or regional volume were detected. These data address large gaps in the developmental literature and suggest interesting region-specific differences in the prevalence and timing of cell death in the hypothalamus and ventral forebrain. PMID:23296992

  17. Role of the Orexin System on the Hypothalamus-Pituitary-Thyroid Axis

    PubMed Central

    Messina, Antonietta; De Fusco, Carolina; Monda, Vincenzo; Esposito, Maria; Moscatelli, Fiorenzo; Valenzano, Anna; Carotenuto, Marco; Viggiano, Emanuela; Chieffi, Sergio; De Luca, Vincenzo; Cibelli, Giuseppe; Monda, Marcellino; Messina, Giovanni

    2016-01-01

    Hypocretin/orexin (ORX) are two hypothalamic neuropeptides discovered in 1998. Since their discovery, they have been one of the most studied neuropeptide systems because of their projecting fields innervating various brain areas. The orexinergic system is tied to sleep-wakefulness cycle, and narcolepsy is a consequence of their system hypofunction. Orexinergic system is also involved in many other autonomic functions such as feeding, thermoregulation, cardiovascular and neuroendocrine regulation. The main aim of this mini review article is to investigate the relationship between ORX and thyroid system regulation. Although knowledge about the ORX system is evolving, its putative effects on hypothalamic-pituitary-thyroid (HPT) axis still appear unclear. We analyzed some studies about ORX control of HPT axis to know better the relationship between them. The studies that were analyzed suggest Hypocretin/ORX to modulate the thyroid regulation, but the nature (excitatory or inhibitory) of this possible interaction remains actually unclear and needs to be confirmed. PMID:27610076

  18. Role of the Orexin System on the Hypothalamus-Pituitary-Thyroid Axis.

    PubMed

    Messina, Antonietta; De Fusco, Carolina; Monda, Vincenzo; Esposito, Maria; Moscatelli, Fiorenzo; Valenzano, Anna; Carotenuto, Marco; Viggiano, Emanuela; Chieffi, Sergio; De Luca, Vincenzo; Cibelli, Giuseppe; Monda, Marcellino; Messina, Giovanni

    2016-01-01

    Hypocretin/orexin (ORX) are two hypothalamic neuropeptides discovered in 1998. Since their discovery, they have been one of the most studied neuropeptide systems because of their projecting fields innervating various brain areas. The orexinergic system is tied to sleep-wakefulness cycle, and narcolepsy is a consequence of their system hypofunction. Orexinergic system is also involved in many other autonomic functions such as feeding, thermoregulation, cardiovascular and neuroendocrine regulation. The main aim of this mini review article is to investigate the relationship between ORX and thyroid system regulation. Although knowledge about the ORX system is evolving, its putative effects on hypothalamic-pituitary-thyroid (HPT) axis still appear unclear. We analyzed some studies about ORX control of HPT axis to know better the relationship between them. The studies that were analyzed suggest Hypocretin/ORX to modulate the thyroid regulation, but the nature (excitatory or inhibitory) of this possible interaction remains actually unclear and needs to be confirmed. PMID:27610076

  19. Relevance of perceived childhood neglect, 5-HTT gene variants and hypothalamus-pituitary-adrenal axis dysregulation to substance abuse susceptibility.

    PubMed

    Gerra, G; Zaimovic, A; Castaldini, L; Garofano, L; Manfredini, M; Somaini, L; Leonardi, C; Gerra, M L; Donnini, C

    2010-04-01

    The hypotheses of (1) gene x environment interaction in the susceptibility to experiment with drugs and (2) hypothalamus-pituitary-adrenal (HPA) axis involvement in mediating the effects of early adverse experiences and gene variants affecting serotonin function on substance abuse vulnerability were tested by investigating in 187 healthy adolescents the possible relevance of 5-HTT "S" polymorphism, childhood parental neglect reported retrospectively and HPA axis function to the susceptibility to experiment with illicit drugs. Higher frequency of the 5-HTT SS genotype seems to be associated with an increased susceptibility to use illegal psychotropic drugs among the adolescents. At the same time, reduced maternal care perception was found to represent a key intermediate factor of the association between SS polymorphism and drug use, suggesting that genetic factors and parental behavior concur to drug use susceptibility. Our results also confirm the relationship between basal plasma levels of cortisol and adrenocorticotropic hormone (ACTH) on the one hand, and retrospective measures of neglect during childhood: the higher the mother and father neglect CECA-Q scores, the higher the plasma levels of the two HPA hormones. Such positive relationship has been proved to be particularly effective and important when associated to the S-allele, both in homozygote and heterozygote individuals. However, when tested together with genotype and parental neglect, the effect of HPA hormones such as cortisol and ACTH was not found to improve significantly the explanatory power of the risk model. PMID:19824018

  20. PCB disruption of the hypothalamus-pituitary-interrenal axis involves brain glucocorticoid receptor downregulation in anadromous Arctic charr

    USGS Publications Warehouse

    Aluru, N.; Jorgensen, E.H.; Maule, A.G.; Vijayan, M.M.

    2004-01-01

    We examined whether brain glucocorticoid receptor (GR) modulation by polychlorinated biphenyls (PCBs) was involved in the abnormal cortisol response to stress seen in anadromous Arctic charr (Salvelinus alpinus). Fish treated with Aroclor 1254 (0, 1, 10, and 100 mg/kg body mass) were maintained for 5 mo without feeding in the winter to mimic their seasonal fasting cycle, whereas a fed group with 0 and 100 mg/kg Aroclor was maintained for comparison. Fasting elevated plasma cortisol levels and brain GR content but depressed heat shock protein 90 (hsp90) and interrenal cortisol production capacity. Exposure of fasted fish to Aroclor 1254 resulted in a dose-dependent increase in brain total PCB content. This accumulation in fish with high PCB dose was threefold higher in fasted fish compared with fed fish. PCBs depressed plasma cortisol levels but did not affect in vitro interrenal cortisol production capacity in fasted charr. At high PCB dose, the brain GR content was significantly lower in the fasted fish and this corresponded with a lower brain hsp70 and hsp90 content. The elevation of plasma cortisol levels and upregulation of brain GR content may be an important adaptation to extended fasting in anadromous Arctic charr, and this response was disrupted by PCBs. Taken together, the hypothalamus-pituitary- interrenal axis is a target for PCB impact during winter emaciation in anadromous Arctic charr.

  1. A naturally hypersensitive glucocorticoid receptor elicits a compensatory reduction of hypothalamus-pituitary-adrenal axis activity early in ontogeny.

    PubMed

    Muráni, Eduard; Ponsuksili, Siriluck; Jaeger, Alexandra; Görres, Andreas; Tuchscherer, Armin; Wimmers, Klaus

    2016-07-01

    We comprehensively characterized the effects of a unique natural gain-of-function mutation in the glucocorticoid receptor (GR), GRAla610Val, in domestic pigs to expand current knowledge of the phenotypic consequences of GR hypersensitivity. Cortisol levels were consistently reduced in one-week-old piglets, at weaning and in peripubertal age, probably due to a reduced adrenal capacity to produce glucocorticoids (GC), which was indicated by an adrenocortical thinning in GRAla610Val carriers. Adrenocorticotrophic hormone (ACTH) levels were significantly reduced in one-week-old piglets only. Expression analyses in peripubertal age revealed significant downregulation of hypothalamic expression of CRH and AVP, the latter only in females, and upregulation of hepatic expression of SERPINA6, by GRAla610Val Transcriptional repression of proinflammatory genes in peripheral blood mononuclear cells (PBMCs) from GRAla610Val carriers was more sensitive to dexamethasone treatment ex vivo However, no significant effects on growth, body composition, blood chemistry or cell counts were observed under baseline conditions. These results suggest that GRAla610Val-induced GR hypersensitivity elicits a compensatory reduction in endogenous, bioactive glucocorticoid levels via readjustment of the hypothalamus-pituitary-adrenal (HPA) axis early in ontogeny to maintain an adequate response, but carriers are more sensitive to exogenous GC. Therefore, GRAla610Val pigs represent a valuable animal model to explore GR-mediated mechanisms of HPA axis regulation and responses to glucocorticoid-based drugs. PMID:27440422

  2. The hypothalamus-pituitary-thyroid axis in teleosts and amphibians: Endocrine disruption and its consequences to natural populations

    USGS Publications Warehouse

    Carr, J.A.; Patino, R.

    2011-01-01

    Teleosts and pond-breeding amphibians may be exposed to a wide variety of anthropogenic, waterborne contaminants that affect the hypothalamus-pituitary-thyroid (HPT) axis. Because thyroid hormone is required for their normal development and reproduction, the potential impact of HPT-disrupting contaminants on natural teleost and amphibian populations raises special concern. There is laboratory evidence indicating that persistent organic pollutants, heavy metals, pharmaceutical and personal care products, agricultural chemicals, and aerospace products may alter HPT activity, development, and reproduction in teleosts and amphibians. However, at present there is no evidence to clearly link contaminant-induced HPT alterations to impairments in teleost or amphibian population health in the field. Also, with the exception of perchlorate for which laboratory studies have shown a direct link between HPT disruption and adverse impacts on development and reproductive physiology, little is known about if or how other HPT-disrupting contaminants affect organismal performance. Future field studies should focus on establishing temporal associations between the presence of HPT-disrupting chemicals, the occurrence of HPT alterations, and adverse effects on development and reproduction in natural populations; as well as determining how complex mixtures of HPT contaminants affect organismal and population health. ?? 2010 Elsevier Inc.

  3. Fluoride Exposure, Follicle Stimulating Hormone Receptor Gene Polymorphism and Hypothalamus-pituitary-ovarian Axis Hormones in Chinese Women.

    PubMed

    Zhao, Ming Xu; Zhou, Guo Yu; Zhu, Jing Yuan; Gong, Biao; Hou, Jia Xiang; Zhou, Tong; Duan, Li Ju; Ding, Zhong; Cui, Liu Xin; Ba, Yue

    2015-09-01

    The effects of fluoride exposure on the functions of reproductive and endocrine systems have attracted widespread attention in academic circle nowadays. However, it is unclear whether the gene-environment interaction may modify the secretion and activity of hypothalamus-pituitary- ovarian (HPO) axis hormones. Thus, the aim of this study was to explore the influence of fluoride exposure and follicle stimulating hormone receptor (FSHR) gene polymorphism on reproductive hormones in Chinese women. A cross sectional study was conducted in seven villages of Henan Province, China during 2010-2011. A total of 679 women aged 18-48 years were recruited through cluster sampling and divided into three groups, i.e. endemic fluorosis group (EFG), defluoridation project group (DFPG), and control group (CG) based on the local fluoride concentration in drinking water. The serum levels of gonadotropin releasing hormone (GnRH), follicle stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) were determined respectively and the FSHR polymorphism was detected by real time PCR assay. The results provided the preliminary evidence indicating the gene-environment interaction on HPO axis hormones in women. PMID:26464260

  4. Hypothalamus-Pituitary-Adrenal cell-mediated immunity regulation in the Immune Restoration Inflammatory Syndrome

    PubMed Central

    Khakshooy, Allen; Chiappelli, Francesco

    2016-01-01

    Over one third of the patients sero-positive for the human immunodeficiency virus (HIV) with signs of the acquired immune deficiency syndrome (AIDS), and under treatment with anti-retroviral therapy (ART), develop the immune reconstitution inflammatory syndrome (IRIS). It is not clear what variables are that determine whether a patient with HIV/AIDS will develop ART-related IRIS, but the best evidence base thus far indicates that HIV/AIDS patients with low CD4 cell count, and HIV/AIDS patients whose CD4 count recovery shows a sharp slope, suggesting a particularly fast "immune reconstitution", are at greater risk of developing IRIS. Here, we propose the hypothesis that one important variable that can contribute to low CD4 cell count number and function in ART-treated HIV/AIDS patients is altered hypothalamic-pituitary-adrenal (HPA) cell-mediated immune (CMI) regulation. We discuss HPA-CMI deregulation in IRIS as the new frontier in comparative effectiveness research (CRE) for obtaining and utilizing the best evidence base for treatment of patients with HIV/AIDS in specific clinical settings. We propose that our hypothesis about altered HPA-CMI may extend to the pathologies observed in related viral infection, including Zika PMID:27212842

  5. Hypothalamus-Pituitary-Adrenal cell-mediated immunity regulation in the Immune Restoration Inflammatory Syndrome.

    PubMed

    Khakshooy, Allen; Chiappelli, Francesco

    2016-01-01

    Over one third of the patients sero-positive for the human immunodeficiency virus (HIV) with signs of the acquired immune deficiency syndrome (AIDS), and under treatment with anti-retroviral therapy (ART), develop the immune reconstitution inflammatory syndrome (IRIS). It is not clear what variables are that determine whether a patient with HIV/AIDS will develop ART-related IRIS, but the best evidence base thus far indicates that HIV/AIDS patients with low CD4 cell count, and HIV/AIDS patients whose CD4 count recovery shows a sharp slope, suggesting a particularly fast "immune reconstitution", are at greater risk of developing IRIS. Here, we propose the hypothesis that one important variable that can contribute to low CD4 cell count number and function in ART-treated HIV/AIDS patients is altered hypothalamic-pituitary-adrenal (HPA) cell-mediated immune (CMI) regulation. We discuss HPA-CMI deregulation in IRIS as the new frontier in comparative effectiveness research (CRE) for obtaining and utilizing the best evidence base for treatment of patients with HIV/AIDS in specific clinical settings. We propose that our hypothesis about altered HPA-CMI may extend to the pathologies observed in related viral infection, including Zika. PMID:27212842

  6. The effects of subchronic acrylamide exposure on gene expression, neurochemistry, hormones, and histopathology in the hypothalamus-pituitary-thyroid axis of male Fischer 344 rats

    SciTech Connect

    Bowyer, J.F.; Latendresse, J.R.; Delongchamp, R.R.; Muskhelishvili, L.; Warbritton, A.R.; Thomas, M.; Tareke, E.; McDaniel, L.P.; Doerge, D.R.

    2008-07-15

    Acrylamide (AA) is an important industrial chemical that is neurotoxic in rodents and humans and carcinogenic in rodents. The observation of cancer in endocrine-responsive tissues in Fischer 344 rats has prompted hypotheses of hormonal dysregulation, as opposed to DNA damage, as the mechanism for tumor induction by AA. The current investigation examines possible evidence for disruption of the hypothalamic-pituitary-thyroid axis from 14 days of repeated exposure of male Fischer 344 rats to doses of AA that range from one that is carcinogenic after lifetime exposure (2.5 mg/kg/d), an intermediate dose (10 mg/kg/d), and a high dose (50 mg/kg/d) that is neurotoxic for this exposure time. The endpoints selected include: serum levels of thyroid and pituitary hormones; target tissue expression of genes involved in hormone synthesis, release, and receptors; neurotransmitters in the CNS that affect hormone homeostasis; and histopathological evaluation of target tissues. These studies showed virtually no evidence for systematic alteration of the hypothalamic-pituitary-thyroid axis and do not support hormone dysregulation as a plausible mechanism for AA-induced thyroid cancer in the Fischer 344 rat. Specifically, there were no significant changes in: 1) mRNA levels in hypothalamus or pituitary for TRH, TSH, thyroid hormone receptor {alpha} and {beta}, as well 10 other hormones or releasing factors; 2) mRNA levels in thyroid for thyroglobulin, thyroid peroxidase, sodium iodide symporter, or type I deiodinases; 3) serum TSH or T3 levels (T4 was decreased at high dose only); 4) dopaminergic tone in the hypothalamus and pituitary or importantly 5) increased cell proliferation (Mki67 mRNA and Ki-67 protein levels were not increased) in thyroid or pituitary. These negative findings are consistent with a genotoxic mechanism of AA carcinogenicity based on metabolism to glycidamide and DNA adduct formation. Clarification of this mechanistic dichotomy may be useful in human cancer risk

  7. Interface between metabolic balance and reproduction in ruminants: focus on the hypothalamus and pituitary.

    PubMed

    Clarke, Iain J

    2014-06-01

    This article is part of a Special Issue "Energy Balance". The interface between metabolic regulators and the reproductive system is reviewed with special reference to the sheep. Even though sheep are ruminants with particular metabolic characteristics, there is a broad consensus across species in the way that the reproductive system is influenced by metabolic state. An update on the neuroendocrinology of reproduction indicates the need to account for the way that kisspeptin provides major drive to gonadotropin releasing hormone (GnRH) neurons and also mediates the feedback effects of gonadal steroids. The way that kisspeptin function is influenced by appetite regulating peptides (ARP) is considered. Another newly recognised factor is gonadotropin inhibitory hormone (GnIH), which has a dual function in that it suppresses reproductive function whilst also acting as an orexigen. Our understanding of the regulation of food intake and energy expenditure has expanded exponentially in the last 3 decades and historical perspective is provided. The function of the regulatory factors and the hypothalamic cellular systems involved is reviewed with special reference to the sheep. Less is known of these systems in the cow, especially the dairy cow, in which a major fertility issue has emerged in parallel with selection for increased milk production. Other endocrine systems--the hypothalamo-pituitary-adrenal axis, the growth hormone (GH) axis and the thyroid hormones--are influenced by metabolic state and are relevant to the interface between metabolic function and reproduction. Special consideration is given to issues such as season and lactation, where the relationship between metabolic hormones and reproductive function is altered. PMID:24568750

  8. The Effects of Disturbance on Hypothalamus-Pituitary-Thyroid (HPT) Axis in Zebrafish Larvae after Exposure to DEHP

    PubMed Central

    Lu, Chun-Jiao; Mirza, Zakaria; Zhang, Wei; Jia, Yong-Fang; Li, Wei-Guo

    2016-01-01

    Di-(2-ethylhexyl) phthalate (DEHP) has the potential to disrupt the thyroid endocrine system, but the underlying mechanism is unknown. In this study, zebrafish (Danio rerio) embryos were exposed to different concentrations of DEHP (0, 40, 100, 200, 400 μg/L) from 2 to 168 hours post fertilization (hpf). Thyroid hormones (THs) levels and transcriptional profiling of key genes related to hypothalamus-pituitary-thyroid (HPT) axis were examined. The result of whole-body thyroxine (T4) and triiodothyronine (T3) indicated that the thyroid hormone homeostasis was disrupted by DEHP in the zebrafish larvae. After exposure to DEHP, the mRNA expressions of thyroid stimulating hormone (tshβ) and corticotrophin releasing hormone (crh) genes were increased in a concentration dependent manner, respectively. The expression level of genes involved in thyroid development (nkx2.1 and pax8) and thyroid synthesis (sodium/iodide symporter, nis, thyroglobulin, tg) were also measured. The transcripts of nkx2.1 and tg were significantly increased after DEHP exposure, while those of nis and pax8 had no significant change. Down-regulation of uridinediphosphate-glucuronosyl-transferase (ugt1ab) and up-regulation of thyronine deiodinase (dio2) might change the THs levels. In addition, the transcript of transthyretin (ttr) was up-regulated, while the mRNA levels of thyroid hormone receptors (trα and trβ) remained unchanged. All the results demonstrated that exposure to DEHP altered the whole-body thyroid hormones in the zebrafish larvae and changed the expression profiling of key genes related to HPT axis, proving that DEHP induced the thyroid endocrine toxicity and potentially affected the synthesis, regulation and action of thyroid hormones. PMID:27223697

  9. Role of the dorsomedial hypothalamus in glucocorticoid-mediated feedback inhibition of the hypothalamic-pituitary-adrenal axis.

    PubMed

    Stamper, Christopher E; Hennessey, Patrick A; Hale, Matthew W; Lukkes, Jodi L; Donner, Nina C; Lowe, Kenneth R; Paul, Evan D; Spencer, Robert L; Renner, Kenneth J; Orchinik, Miles; Lowry, Christopher A

    2015-01-01

    Previous studies suggest that multiple corticolimbic and hypothalamic structures are involved in glucocorticoid-mediated feedback inhibition of the hypothalamic-pituitary-adrenal (HPA) axis, including the dorsomedial hypothalamus (DMH), but a potential role of the DMH has not been directly tested. To investigate the role of the DMH in glucocorticoid-mediated negative feedback, adult male Sprague Dawley rats were implanted with jugular cannulae and bilateral guide cannulae directed at the DMH, and finally were either adrenalectomized (ADX) or were subjected to sham-ADX. ADX rats received corticosterone (CORT) replacement in the drinking water (25 μg/mL), which, based on initial studies, restored a rhythm of plasma CORT concentrations in ADX rats that was similar in period and amplitude to the diurnal rhythm of plasma CORT concentrations in sham-ADX rats, but with a significant phase delay. Following recovery from surgery, rats received microinjections of either CORT (10 ng, 0.5 μL, 0.25 μL/min, per side) or vehicle (aCSF containing 0.2% EtOH), bilaterally, directly into the DMH, prior to a 40-min period of restraint stress. In sham-ADX rats, bilateral intra-DMH microinjections of CORT, relative to bilateral intra-DMH microinjections of vehicle, decreased restraint stress-induced elevation of endogenous plasma CORT concentrations 60 min after the onset of intra-DMH injections. Intra-DMH CORT decreased the overall area under the curve for plasma CORT concentrations during the intermediate time frame of glucocorticoid negative feedback, from 0.5 to 2 h following injection. These data are consistent with the hypothesis that the DMH is involved in feedback inhibition of HPA axis activity at the intermediate time frame. PMID:25556980

  10. The role of the hypothalamus-pituitary-adrenal/interrenal axis in mediating predator-avoidance trade-offs.

    PubMed

    Harris, Breanna N; Carr, James A

    2016-05-01

    Maintaining energy balance and reproducing are important for fitness, yet animals have evolved mechanisms by which the hypothalamus-pituitary-adrenal/interrenal (HPA/HPI) axis can shut these activities off. While HPA/HPI axis inhibition of feeding and reproduction may have evolved as a predator defense, to date there has been no review across taxa of the causal evidence for such a relationship. Here we review the literature on this topic by addressing evidence for three predictions: that exposure to predators decreases reproduction and feeding, that exposure to predators activates the HPA/HPI axis, and that predator-induced activation of the HPA/HPI axis inhibits foraging and reproduction. Weight of evidence indicates that exposure to predator cues inhibits several aspects of foraging and reproduction. While the evidence from fish and mammals supports the hypothesis that predator cues activate the HPA/HPI axis, the existing data in other vertebrate taxa are equivocal. A causal role for the HPA axis in predator-induced suppression of feeding and reproduction has not been demonstrated to date, although many studies report correlative relationships between HPA activity and reproduction and/or feeding. Manipulation of HPA/HPI axis signaling will be required in future studies to demonstrate direct mediation of predator-induced inhibition of feeding and reproduction. Understanding the circuitry linking sensory pathways to their control of the HPA/HPI axis also is needed. Finally, the role that fear and anxiety pathways play in the response of the HPA axis to predator cues is needed to better understand the role that predators have played in shaping anxiety related behaviors in all species, including humans. PMID:27080550

  11. Role of the dorsomedial hypothalamus in glucocorticoid-mediated feedback inhibition of the hypothalamic-pituitary-adrenal axis

    PubMed Central

    Stamper, Christopher E.; Hennessey, Patrick A.; Hale, Matthew W.; Lukkes, Jodi L.; Donner, Nina C.; Lowe, Kenneth R.; Paul, Evan D.; Spencer, Robert L.; Renner, Kenneth J.; Orchinik, Miles; Lowry, Christopher A.

    2015-01-01

    Previous studies suggest that multiple corticolimbic and hypothalamic structures are involved in glucocorticoid-mediated feedback inhibition of the hypothalamic-pituitary-adrenal (HPA) axis, including the dorsomedial hypothalamus (DMH), but a potential role of the DMH has not been directly tested. To investigate the role of the DMH in glucocorticoid-mediated negative feedback, adult male Sprague Dawley rats were implanted with jugular cannulae and bilateral guide cannulae directed at the DMH, and finally were either adrenalectomized (ADX) or were subjected to sham-ADX. Adrenalectomized rats received CORT replacement in the drinking water (25 µg/ml), which, based on initial studies, restored a rhythm of plasma CORT concentrations in ADX rats that was similar in period and amplitude to the diurnal rhythm of plasma CORT concentrations in sham-ADX rats, but with a significant phase delay. Following recovery from surgery, rats received microinjections of either CORT (10 ng, 0.5 µL, 0.25 µL/min, per side) or vehicle (aCSF containing 0.2% EtOH), bilaterally, directly into the DMH, prior to a 40 min period of restraint stress. In sham-ADX rats, bilateral intra-DMH microinjections of CORT, relative to bilateral intra-DMH microinjections of vehicle, decreased restraint stress-induced elevation of endogenous plasma CORT concentrations 60 minutes after the onset of intra-DMH injections. Intra-DMH CORT decreased the overall area under the curve for plasma CORT concentrations during the intermediate time frame of glucocorticoid negative feedback, from 0.5–2 h following injection. These data are consistent with the hypothesis that the DMH is involved in feedback inhibition of HPA axis activity at the intermediate time frame. PMID:25556980

  12. Hypothalamus-pituitary-adrenal axis activity and the subsequent response to chronic stress differ depending upon life history stage.

    PubMed

    Lattin, Christine R; Bauer, Carolyn M; de Bruijn, Robert; Michael Romero, L

    2012-09-15

    The hypothalamus-pituitary-adrenal (HPA) axis is modulated seasonally in many species, and chronic stress can alter HPA functioning. However, it is not known how these two factors interact - are there particular life history stages when animals are more or less vulnerable to chronic stress? We captured wild house sparrows (Passer domesticus) in Massachusetts during six different life history stages: early and late winter, pre-laying, breeding, late breeding, and molt. At each time point, we tested HPA function by measuring baseline and stress-induced corticosterone (CORT), negative feedback in response to an injection of dexamethasone, and maximum adrenal response through an injection of adrenocorticotropic hormone. We then brought birds into captivity as a model for chronic stress, and repeated the four tests 5 days later. At capture, all HPA variables varied seasonally. Birds showed increased negative feedback during breeding and late winter compared to pre-laying. Furthermore, birds during the late breeding period had down-regulated their HPA axis, perhaps in preparation for molt. After 5 days of captivity, house sparrows lost ∼11% of initial body mass, although birds lost more weight during molt and early winter. Overall, captive sparrows showed elevated baseline CORT and increased negative feedback, although negative feedback did not show a significant increase during any individual life history stage. During most of the year, adrenal sensitivity was unaffected by captivity. However, during late breeding and molt, adrenal sensitivity increased during captivity. Taken together, these data provide further support that HPA function naturally varies throughout the year, with the interesting consequence that molting birds may potentially be more vulnerable to a chronic stressor such as captivity. PMID:22841762

  13. Ontogenesis of peptidergic neurons within the genoarchitectonic map of the mouse hypothalamus

    PubMed Central

    Díaz, Carmen; Morales-Delgado, Nicanor; Puelles, Luis

    2015-01-01

    During early development, the hypothalamic primordium undergoes anteroposterior and dorsoventral regionalization into diverse progenitor domains, each characterized by a differential gene expression code. The types of neurons produced selectively in each of these distinct progenitor domains are still poorly understood. Recent analysis of the ontogeny of peptidergic neuronal populations expressing Sst, Ghrh, Crh and Trh mRNAs in the mouse hypothalamus showed that these cell types originate from particular dorsoventral domains, characterized by specific combinations of gene markers. Such analysis implies that the differentiation of diverse peptidergic cell populations depends on the molecular environment where they are born. Moreover, a number of these peptidergic neurons were observed to migrate radially and/or tangentially, invading different adult locations, often intermingled with other cell types. This suggests that a developmental approach is absolutely necessary for the understanding of their adult distribution. In this essay, we examine comparatively the ontogenetic hypothalamic topography of twelve additional peptidergic populations documented in the Allen Developmental Mouse Brain Atlas, and discuss shared vs. variant aspects in their apparent origins, migrations and final distribution, in the context of the respective genoarchitectonic backgrounds. This analysis should aid ulterior attempts to explain causally the development of neuronal diversity in the hypothalamus, and contribute to our understanding of its topographic complexity in the adult. PMID:25628541

  14. Estrogen impairs glucocorticoid dependent negative feedback on the hypothalamic-pituitary-adrenal axis via estrogen receptor alpha within the hypothalamus.

    PubMed

    Weiser, M J; Handa, R J

    2009-03-17

    Numerous studies have established a link between individuals with affective disorders and a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, most notably characterized by a reduced sensitivity to glucocorticoid negative (-) feedback. Furthermore there is a sex difference in the etiology of mood disorders with incidence in females being two to three times that of males, an association that may be a result of the influence of estradiol (E2) on HPA axis function. In these studies, we have examined the effect of E2 on glucocorticoid-mediated HPA axis (-) feedback during both the diurnal peak and the stress-induced rise in corticosterone (CORT). Young adult female Sprague-Dawley (SD) rats were ovariectomized (OVX) and 1 week later treated subcutaneous (s.c.) with oil or estradiol benzoate (EB) for 4 days. On the 4th day of treatment, animals were injected with a single dose of dexamethasone (DEX), or vehicle. EB treatment significantly increased the evening elevation in CORT and the stress-induced rise in CORT. In contrast, DEX treatment reduced the diurnal and stress induced rise in CORT and adrenocorticotropic hormone (ACTH), and this reduction was not apparent following co-treatment with EB. To determine a potential site of E2's action, female SD rats were OVX and 1 week later, wax pellets containing E2, the estrogen receptor beta (ERbeta) agonist diarylpropionitrile (DPN), or the estrogen receptor alpha (ERalpha) agonist propylpyrazoletriol (PPT), was implanted bilaterally and dorsal to the paraventricular nucleus of the hypothalamus (PVN). Seven days later, animals were injected s.c. with a single dose of DEX, or vehicle to test for glucocorticoid-dependent (-) feedback. Results show that E2 and PPT increased, while DPN decreased the diurnal peak and stress-induced CORT and ACTH levels as compared to controls. Furthermore, E2 and PPT impaired the ability of DEX to inhibit both the diurnal and the stress-induced rise in CORT and ACTH, whereas DPN had

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

    PubMed

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

    2003-02-28

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

  16. Hypothalamus-pituitary-thyroid feedback control: implications of mathematical modeling and consequences for thyrotropin (TSH) and free thyroxine (FT4) reference ranges.

    PubMed

    Goede, Simon L; Leow, Melvin Khee-Shing; Smit, Jan W A; Klein, Harald H; Dietrich, Johannes W

    2014-06-01

    The components of thyrotropic feedback control are well established in mainstream physiology and endocrinology, but their relation to the whole system's integrated behavior remains only partly understood. Most modeling research seeks to derive a generalized model for universal application across all individuals. We show how parameterizable models, based on the principles of control theory, tailored to the individual, can fill these gaps. We develop a system network describing the closed-loop behavior of the hypothalamus-pituitary (HP)-thyroid interaction and the set point targeted by the control system at equilibrium. The stability of this system is defined by using loop gain conditions. Defined points of homeostasis of the hypothalamus-pituitary-thyroid (HPT) feedback loop found at the intersections of the HP and thyroid transfer functions at the boundaries of normal reference ranges were evaluated by loop gain calculations. At equilibrium, the feedback control approaches a point defined in both dimensions by a [TSH]-[FT4] coordinate for which the loop gain is greater than unity. This model describes the emergence of homeostasis of the HPT axis from characteristic curves of HP and thyroid, thus supporting the validity of the translation between physiological knowledge and clinical reference ranges. PMID:24789568

  17. Pituitary Androgen Receptor Signalling Regulates Prolactin but Not Gonadotrophins in the Male Mouse

    PubMed Central

    O’Hara, Laura; Curley, Michael; Tedim Ferreira, Maria; Cruickshanks, Lyndsey; Milne, Laura; Smith, Lee B.

    2015-01-01

    Production of the androgen testosterone is controlled by a negative feedback loop within the hypothalamic-pituitary-gonadal (HPG) axis. Stimulation of testicular Leydig cells by pituitary luteinising hormone (LH) is under the control of hypothalamic gonadotrophin releasing hormone (GnRH), while suppression of LH secretion by the pituitary is controlled by circulating testosterone. Exactly how androgens exert their feedback control of gonadotrophin secretion (and whether this is at the level of the pituitary), as well as the role of AR in other pituitary cell types remains unclear. To investigate these questions, we exploited a transgenic mouse line (Foxg1Cre/+; ARfl/y) which lacks androgen receptor in the pituitary gland. Both circulating testosterone and gonadotrophins are unchanged in adulthood, demonstrating that AR signalling is dispensable in the male mouse pituitary for testosterone-dependent regulation of LH secretion. In contrast, Foxg1Cre/+; ARfl/y males have a significant increase in circulating prolactin, suggesting that, rather than controlling gonadotrophins, AR-signalling in the pituitary acts to suppress aberrant prolactin production in males. PMID:25799562

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

    PubMed

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

    1999-11-01

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

  19. The antiovulatory potential of progesterone antagonists correlates with a down-regulation of progesterone receptors in the hypothalamus, pituitary and ovaries.

    PubMed

    Donath, J; Nishino, Y; Schulz, T; Michna, H

    2000-03-01

    These studies analyze the regulation of progesterone receptors (PRs) in central and peripheral tissues with the aim of further understanding mechanistically the inhibition of ovulation by progesterone antagonists (PA). Therefore, it was of interest to investigate the influence of the progesterone receptor antagonist, Onapristone (ON), on PRs in the ovary, pituitary (PT), and hypothalamus (HYP), since ON effectively inhibits ovulation in rats. For this study PMSG/hCG-primed immature and adult female rats were treated with ON. Immunohistochemistry was used for the detection of PRs. Progesterone (P4) and estradiol (E2) levels were determined by RIA. PR expression in the ovaries of immature rats was not detectable until after hCG administration. In these animals, ON caused a reduction in the staining intensity of PR in the tertiary follicles at the time when the preovulatory P4-surge was inhibited (6 h post hCG). Adult rats treated for 15 days with ON showed a decreased PR expression in PT and HYP. At this time (proestrus, 7 p.m.) the P4 and E2 levels are significantly lowered. These results suggest that after treatment with ON the expression of PR is reduced in the ovary, PT and HYP. The regulation of PR in the ovary seems to be less dependent on estrogens than on LH. Thus, it is conceivable that the reduced PR expression after ON treatment may be a result of decreased LH sensitivity in the ovary. In the pituitary and hypothalamus, PR expression is stimulated by estrogens and progesterone, and therefore the fall in the P4 and E2 levels in ON-treated animals may be responsible for the reduced PR expression in PT and HYP, and may contribute to the antiovulatory effect of ON. We therefore conclude that the mechanism of the antiovulatory potency of progesterone antagonists is based on a reduced preovulatory P4-production and PR expression in the ovary and also on the down-regulation of PR in the anterior pituitary and hypothalamus. PMID:10755181

  20. Exposure to a Complex Cocktail of Environmental Endocrine-Disrupting Compounds Disturbs the Kisspeptin/GPR54 System in Ovine Hypothalamus and Pituitary Gland

    PubMed Central

    Bellingham, Michelle; Fowler, Paul A.; Amezaga, Maria R.; Rhind, Stewart M.; Cotinot, Corinne; Mandon-Pepin, Beatrice; Sharpe, Richard M.; Evans, Neil P.

    2009-01-01

    Background Ubiquitous environmental chemicals, including endocrine-disrupting chemicals (EDCs), are associated with declining human reproductive health, as well as an increasing incidence of cancers of the reproductive system. Verifying such links requires animal models exposed to “real-life,” environmentally relevant concentrations/mixtures of EDC, particularly in utero, when sensitivity to EDC exposure is maximal. Objectives We evaluated the effects of maternal exposure to a pollutant cocktail (sewage sludge) on the ovine fetal reproductive neuroendocrine axes, particularly the kisspeptin (KiSS-1)/GPR54 (G-protein–coupled receptor 54) system. Methods KiSS-1, GPR54, and ERα (estrogen receptor α) mRNA expression was quantified in control (C) and treated (T) maternal and fetal (110-day) hypothalami and pituitary glands using semiquantitative reverse transcription polymerase chain reaction, and colocalization of kisspeptin with LHβ (luteinizing hormone β) and ERα in C and T fetal pituitary glands quantified using dual-labeling immunohistochemistry. Results Fetuses exposed in utero to the EDC mixture showed reduced KiSS-1 mRNA expression across three hypothalamic regions examined (rostral, mid, and caudal) and had fewer kisspetin immunopositive cells colocalized with both LHβ and ERα in the pituitary gland. In contrast, treatment had no effect on parameters measured in the adult ewe hypothalamus or pituitary. Conclusions This study demonstrates that the developing fetus is sensitive to real-world mixtures of environmental chemicals, which cause significant neuroendocrine alterations. The important role of kisspeptin/GPR54 in regulating puberty and adult reproduction means that in utero disruption of this system is likely to have long-term consequences in adulthood and represents a novel, additional pathway through which environmental chemicals perturb human reproduction. PMID:20019906

  1. Establishment of Leptin-Responsive Cell Lines from Adult Mouse Hypothalamus

    PubMed Central

    Iwakura, Hiroshi; Dote, Katsuko; Bando, Mika; Koyama, Hiroyuki; Hosoda, Kiminori; Kangawa, Kenji; Nakao, Kazuwa

    2016-01-01

    Leptin resistance is considered to be the primary cause of obesity. However, the cause of leptin resistance remains incompletely understood, and there is currently no cure for the leptin-resistant state. In order to identify novel drug-target molecules that could overcome leptin resistance, it would be useful to develop in vitro assay systems for evaluating leptin resistance. In this study, we established immortalized adult mouse hypothalamus—derived cell lines, termed adult mouse hypothalamus (AMH) cells, by developing transgenic mice in which SV40 Tag was overexpressed in chromogranin A—positive cells in a tamoxifen-dependent manner. In order to obtain leptin-responsive clones, we selected clones based on the phosphorylation levels of STAT3 induced by leptin. The selected clones were fairly responsive to leptin in terms of STAT3, ERK, and Akt phosphorylation and induction of c-Fos mRNA induction. Pretreatment with leptin, insulin, and palmitate attenuated the c-Fos mRNA response to leptin, suggesting that certain aspects of leptin resistance might be reconstituted in this cellular model. These cell lines are useful tools for understanding the molecular nature of the signal disturbance in the leptin-resistant state and for identifying potential target molecules for drugs that relieve leptin resistance, although they have drawbacks including de-differentiated nature and lack of long-time stability. PMID:26849804

  2. Topography of Somatostatin Gene Expression Relative to Molecular Progenitor Domains during Ontogeny of the Mouse Hypothalamus

    PubMed Central

    Morales-Delgado, Nicanor; Merchan, Paloma; Bardet, Sylvia M.; Ferrán, José L.; Puelles, Luis; Díaz, Carmen

    2010-01-01

    The hypothalamus comprises alar, basal, and floor plate developmental compartments. Recent molecular data support a rostrocaudal subdivision into rostral (terminal) and caudal (peduncular) halves. In this context, the distribution of neuronal populations expressing somatostatin (Sst) mRNA was analyzed in the developing mouse hypothalamus, comparing with the expression pattern of the genes Orthopedia (Otp), Distal-less 5 (Dlx5), Sonic Hedgehog (Shh), and Nk2 homeobox 1 (Nkx2.1). At embryonic day 10.5 (E10.5), Sst mRNA was first detectable in the anterobasal nucleus, a Nkx2.1-, Shh-, and Otp-positive basal domain. By E13.5, nascent Sst expression was also related to two additional Otp-positive domains within the alar plate and one in the basal plate. In the alar plate, Sst-positive cells were observed in rostral and caudal ventral subdomains of the Otp-positive paraventricular complex. An additional basal Sst-expressing cell group was found within a longitudinal Otp-positive periretromamillary band that separates the retromamillary area from tuberal areas. Apart of subsequent growth of these initial populations, at E13.5 and E15.5 some Sst-positive derivatives migrate tangentially into neighboring regions. A subset of cells produced at the anterobasal nucleus disperses ventralward into the shell of the ventromedial hypothalamic nucleus and the arcuate nucleus. Cells from the rostroventral paraventricular subdomain reach the suboptic nucleus, whereas a caudal contingent migrates radially into lateral paraventricular, perifornical, and entopeduncular nuclei. Our data provide a topologic map of molecularly defined progenitor areas originating a specific neuron type during early hypothalamic development. Identification of four main separate sources helps to understand causally its complex adult organization. PMID:21441981

  3. PPARγ mRNA in the adult mouse hypothalamus: distribution and regulation in response to dietary challenges

    PubMed Central

    Liu, Yang; Huang, Ying; Lee, Syann; Bookout, Angie L.; Castorena, Carlos M.; Wu, Hua; Gautron, Laurent

    2015-01-01

    Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-activated transcription factor that was originally identified as a regulator of peroxisome proliferation and adipocyte differentiation. Emerging evidence suggests that functional PPARγ signaling also occurs within the hypothalamus. However, the exact distribution and identities of PPARγ-expressing hypothalamic cells remains under debate. The present study systematically mapped PPARγ mRNA expression in the adult mouse brain using in situ hybridization histochemistry. PPARγ mRNA was found to be expressed at high levels outside the hypothalamus including the neocortex, the olfactory bulb, the organ of the vasculosum of the lamina terminalis (VOLT), and the subfornical organ. Within the hypothalamus, PPARγ was present at moderate levels in the suprachiasmatic nucleus (SCh) and the ependymal of the 3rd ventricle. In all examined feeding-related hypothalamic nuclei, PPARγ was expressed at very low levels that were close to the limit of detection. Using qPCR techniques, we demonstrated that PPARγ mRNA expression was upregulated in the SCh in response to fasting. Double in situ hybridization further demonstrated that PPARγ was primarily expressed in neurons rather than glia. Collectively, our observations provide a comprehensive map of PPARγ distribution in the intact adult mouse hypothalamus. PMID:26388745

  4. ROLE OF LEPTIN IN MODULATING THE HYPOTHALAMUS-PITUITARY AXIS AND LUTEINIZING HORMONE SECRETION IN THE PREPUBERAL GILT.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In experiment I (EXP), prepuberal gilts received intracerebroventricular (ICV) leptin (LEP) injections. Blood was collected 4h before and 3h after ICV inj. of .9% saline (S; n=3), 10 ug (n=4), 50 ug (n=4) or 100 ug (n=4) of LEP in S. EXP II, pituitary cells in culture were challenged with 0.1 nM, 1...

  5. The peptide ACTH(1-39), adrenal growth and steroidogenesis in the sheep fetus after disconnection of the hypothalamus and pituitary.

    PubMed

    Phillips, I D; Ross, J T; Owens, J A; Young, I R; McMillen, I C

    1996-03-15

    1. We have investigated the role of the fetal hypothalamo-pituitary axis in the control of adrenocortical growth and steroidogenesis in the sheep fetus during late gestation. Plasma concentrations of ACTH(1-39) increased between 120-125 and 136-142 days (P < 0.05), but did not change after surgical disconnection of the fetal hypothalamus and pituitary (HPD) at 106-120 days gestation. There was no effect of either gestational age or HPD on the circulating concentrations of the ACTH-containing precursors pro-opiomelanocortin (POMC) and pro-ACTH (the 22 kDa N-terminal portion of POMC). 2. In the fetal sheep adrenal, the relative abundance of the mRNAs of the steroidogenic enzymes CYPIIA1 and CYP21A1 increased between 130-135 and 136-140 days gestation (P < 0.05) and remained high after 141 days, whereas that of CYP17 mRNA increased after 141 days gestation (P < 0.05). The abundance of adrenal 3 beta-HSD mRNA did not change between 130 and 145 days. 3. Hypothalamo-pituitary disconnection significantly reduced the abundance of of CYPIIA1 mRNA, 3 beta-HSD mRNA and CYP17 mRNA by 3.4, 3.1 and 3.7 times, respectively, at 140-142 days gestation (P < 0.05). 4. In the intact group of fetal sheep, adrenal weight increased between 130-135 and 141-145 days (P < 0.05), but there was no change in the abundance of adrenal insulin-like growth factor II (IGF-II) mRNA across this gestational age range. Hypothalamo-pituitary disconnection significantly reduced fetal adrenal weight to 66% that of intact sheep (P < 0.01), but did not alter the abundance of IGF-II mRNA in the fetal adrenal at 140-142 days. 5. Our results suggest that the prepartum changes in adrenal growth and steroidogenesis are under the control of an intact hypothalamo-pituitary axis in late gestation and are dependent on an increase in circulating ACTH(1-39), rather than on ACTH precursors. We have found no evidence, however, for a direct-relationship between fetal adrenal growth or steroidogenesis and adrenal IGF-II m

  6. 3,5-Diiodo-L-Thyronine (3,5-T2) Exerts Thyromimetic Effects on Hypothalamus-Pituitary-Thyroid Axis, Body Composition, and Energy Metabolism in Male Diet-Induced Obese Mice

    PubMed Central

    Lietzow, Julika; Wohlgemuth, Franziska; Hoefig, Carolin S.; Wiedmer, Petra; Schweizer, Ulrich; Köhrle, Josef; Schürmann, Annette

    2015-01-01

    Effective and safe antiobesity drugs are still needed in face of the obesity pandemic worldwide. Recent interventions in rodents revealed 3,5-diiodo-L-thyronine (3,5-T2) as a metabolically active iodothyronine affecting energy and lipid metabolism without thyromimetic side effects typically associated with T3 administration. Accordingly, 3,5-T2 has been proposed as a potential hypolipidemic agent for treatment of obesity and hepatic steatosis. In contrast to other observations, our experiments revealed dose-dependent thyromimetic effects of 3,5-T2 akin to those of T3 in diet-induced obese male C57BL/6J mice. 3,5-T2 treatment exerted a negative feedback regulation on the hypothalamus-pituitary-thyroid axis, similar to T3. This is demonstrated by decreased expression of genes responsive to thyroid hormones (TH) in pituitary resulting in a suppressed thyroid function with lower T4 and T3 concentrations in serum and liver of 3,5-T2-treated mice. Analyses of hepatic TH target genes involved in lipid metabolism revealed T3-like changes in gene expression and increased type I-deiodinase activity after application of 3,5-T2 (2.5 μg/g body weight). Reduced hepatic triglyceride and serum cholesterol concentrations reflected enhanced lipid metabolism. Desired increased metabolic rate and reduction of different fat depots were, however, compromised by increased food intake preventing significant body weight loss. Moreover, enlarged heart weights indicate potential cardiac side effects of 3,5-T2 beyond hepatic thyromimetic actions. Altogether, the observed thyromimetic effects of 3,5-T2 in several mouse TH target tissues raise concern about indiscriminate administration of 3,5-T2 as powerful natural hormone for the treatment of hyperlipidemia and pandemic obesity. PMID:25322465

  7. Evidence suggesting that ghrelin O-acyl transferase inhibitor acts at the hypothalamus to inhibit hypothalamo-pituitary-adrenocortical axis function in the rat.

    PubMed

    Rucinski, Marcin; Ziolkowska, Agnieszka; Szyszka, Marta; Hochol, Anna; Malendowicz, Ludwik K

    2012-06-01

    Production of n-octanoyl-modified ghrelin (GHREL), an active form of the peptide requires prohormone processing protease and GHREL O-acyltransferase (GOAT), as well as n-octanoic acid. Recently a selective GOAT antagonist (GO-CoA-Tat) was invented and this tool was used to study the possible role of endogenous GHREL in regulating HPA axis function in the rat. Administration of GOAT inhibitor (GOATi) resulted in a notable decrease in plasma ACTH, aldosterone and corticosterone concentrations at min 60 of experiment. Octanoic acid (OA) administration had no effect on levels of studied hormones. Plasma levels of unacylated and acylated GHREL remained unchanged for 60min after either GOATi or OA administration. Under experimental conditions applied, no significant changes were observed in the levels of GOAT mRNA in hypothalamus, pituitary, adrenal and stomach fundus. After GOATi injection hypothalamic CRH mRNA levels were elevated at 30 min and pituitary POMC mRNA levels at 60 min. Both GOATi and OA lowered basal, but not K(+)-stimulated CRH release by hypothalamic explants and had no effect on basal or CRH-stimulated ACTH release by pituitary slices. Neither GOATi nor OA affected corticosterone secretion by freshly isolated or cultured rat adrenocortical cells. Thus, results of our study suggest that in the rat endogenous GHREL exerts tonic stimulating effect on hypothalamic CRH release. This effect could be demonstrated by administering rats with selected inhibitor of ghrelin O-acyltransferase, the enzyme responsible for GHREL acylation, a process which is absolutely required for both GHSR-1a binding and its central endocrine activities. PMID:22543218

  8. Actions of pregnant mare serum gonadotropin in the immature female rat: correlative changes in blood steroids, gonadotropins, and cytoplasmic estradiol receptors of the anterior pituitary and hypothalamus.

    PubMed

    Parker, C R; Costoff, A; Muldoon, T G; Mahesh, V B

    1976-01-01

    Several blood steroids, serum gonadotropins and cytosol estradiol receptors of the anterior pituitary and hypothalamus were quantified in immature female rats which were induced to ovulate with pregnant mare's serum gonadotropin (PMSG). Studies revealed that serum levels of progesterone, 17-hydroxyprogesterone, testosterone, androstenedione and estradiol were initially elevated at 6 PM (day 30) after administration of 8 IU of PMSG at 10 AM day 30. Serum levels of estradiol and testosterone rose progressively from day 30 through the AM of day 32. A further increase in serum concentrations of progesterone, 17-hydroxyprogesterone, androstenedione, testosterone, and dehydroepiandrosterone occurred on the PM of day 32 whereas serum estradiol levels declined. Serum levels of all steroids declined on the day of estrus (33) and only progesterone levels were further elevated on day 34 (diestrus). Dihydrotestosterone concentrations were minimally altered by PMSG treatment. Saline administration resulted in no significant alterations in levels of any steroid quantified from day 29 to 34 in control animals. A progressive decline in cytosol estradiol receptor content of the anterior pituitary and hypothalamus was documented following PMSG treatment of intact female rats; there was no depletion of receptors following PMSG administration to ovariectomized immature rats. Maximal depletion of cytosol estradiol receptors occurred on day 32 with replenishment of cytosol estradiol receptor levels on estrus (day 33). The preovulatory gonadotropin surge was found to occur on the PM of day 32 after maximal receptor depletion. The cycle of depletion and replenishment of receptors was repeated during a second spontaneous estrous cycle four days later which coincided with a rise and fall in serum estradiol levels. It is suggested that the depletion of cytosol estradiol receptors of the anterior pituitary/hypothalamic unit may be causally related to the preovulatory gonadotropin surge

  9. Genetic Regulation of Pituitary Gland Development in Human and Mouse

    PubMed Central

    Kelberman, Daniel; Rizzoti, Karine; Lovell-Badge, Robin; Robinson, Iain C. A. F.; Dattani, Mehul T.

    2009-01-01

    Normal hypothalamopituitary development is closely related to that of the forebrain and is dependent upon a complex genetic cascade of transcription factors and signaling molecules that may be either intrinsic or extrinsic to the developing Rathke’s pouch. These factors dictate organ commitment, cell differentiation, and cell proliferation within the anterior pituitary. Abnormalities in these processes are associated with congenital hypopituitarism, a spectrum of disorders that includes syndromic disorders such as septo-optic dysplasia, combined pituitary hormone deficiencies, and isolated hormone deficiencies, of which the commonest is GH deficiency. The highly variable clinical phenotypes can now in part be explained due to research performed over the last 20 yr, based mainly on naturally occurring and transgenic animal models. Mutations in genes encoding both signaling molecules and transcription factors have been implicated in the etiology of hypopituitarism, with or without other syndromic features, in mice and humans. To date, mutations in known genes account for a small proportion of cases of hypopituitarism in humans. However, these mutations have led to a greater understanding of the genetic interactions that lead to normal pituitary development. This review attempts to describe the complexity of pituitary development in the rodent, with particular emphasis on those factors that, when mutated, are associated with hypopituitarism in humans. PMID:19837867

  10. Effect of Soyabean Isoflavones Exposure on Onset of Puberty, Serum Hormone Concentration and Gene Expression in Hypothalamus, Pituitary Gland and Ovary of Female Bama Miniature Pigs

    PubMed Central

    Fan, Juexin; Zhang, Bin; Li, Lili; Xiao, Chaowu; Oladele, Oso Abimbola; Jiang, Guoli; Ding, Hao; Wang, Shengping; Xing, Yueteng; Xiao, Dingfu; Yin, Yulong

    2015-01-01

    This study was to investigate the effect of soyabean isoflavones (SIF) on onset of puberty, serum hormone concentration, and gene expression in hypothalamus, pituitary and ovary of female Bama miniature pigs. Fifty five, 35-days old pigs were randomly assigned into 5 treatment groups consisting of 11 pigs per treatment. Results showed that dietary supplementation of varying dosage (0, 250, 500, and 1,250 mg/kg) of SIF induced puberty delay of the pigs with the age of puberty of pigs fed basal diet supplemented with 1,250 mg/kg SIF was significantly higher (p<0.05) compared to control. Supplementation of SIF or estradiol valerate (EV) reduced (p<0.05) serum gonadotrophin releasing hormone and luteinizing hormone concentration, but increased follicle-stimulating hormone concentration in pigs at 4 months of age. The expression of KiSS-1 metastasis-suppressor (KISS1), steroidogenic acute regulatory protein (StAR) and 3-beta-hydroxysteroid dehydrogenase/delta-5-delta-4 isomerase (3β-HSD) was reduced (p<0.01) in SIF-supplemented groups. Expression of gonadotropin-releasing hormone receptor in the pituitary of miniature pigs was reduced (p<0.05) compared to the control when exposed to 250, 1,250 mg/kg SIF and EV. Pigs on 250 mg/kg SIF and EV also showed reduced (p<0.05) expression of cytochrome P450 19A1 compared to the control. Our results indicated that dietary supplementation of SIF induced puberty delay, which may be due to down-regulation of key genes that play vital roles in the synthesis of steroid hormones. PMID:26580281

  11. The homeostatic set point of the hypothalamus-pituitary-thyroid axis – maximum curvature theory for personalized euthyroid targets

    PubMed Central

    2014-01-01

    Background Despite rendering serum free thyroxine (FT4) and thyrotropin (TSH) within the normal population ranges broadly defined as euthyroidism, many patients being treated for hyperthyroidism and hypothyroidism persistently experience subnormal well-being discordant from their pre-disease healthy euthyroid state. This suggests that intra-individual physiological optimal ranges are narrower than laboratory-quoted normal ranges and implies the existence of a homeostatic set point encoded in the hypothalamic-pituitary-thyroid (HPT) axis that is unique to every individual. Methods We have previously shown that the dose–response characteristic of the hypothalamic-pituitary (HP) unit to circulating thyroid hormone levels follows a negative exponential curve. This led to the discovery that the normal reference intervals of TSH and FT4 fall within the ‘knee’ region of this curve where the maximum curvature of the exponential HP characteristic occurs. Based on this observation, we develop the theoretical framework localizing the position of euthyroid homeostasis over the point of maximum curvature of the HP characteristic. Results The euthyroid set points of patients with primary hypothyroidism and hyperthyroidism can be readily derived from their calculated HP curve parameters using the parsimonious mathematical model above. It can be shown that every individual has a euthyroid set point that is unique and often different from other individuals. Conclusions In this treatise, we provide evidence supporting a set point-based approach in tailoring euthyroid targets. Rendering FT4 and TSH within the laboratory normal ranges can be clinically suboptimal if these hormone levels are distant from the individualized euthyroid homeostatic set point. This mathematical technique permits the euthyroid set point to be realistically computed using an algorithm readily implementable for computer-aided calculations to facilitate precise targeted dosing of patients in this modern

  12. An acute injection of corticosterone increases thyrotrophin-releasing hormone expression in the paraventricular nucleus of the hypothalamus but interferes with the rapid hypothalamus pituitary thyroid axis response to cold in male rats.

    PubMed

    Sotelo-Rivera, I; Jaimes-Hoy, L; Cote-Vélez, A; Espinoza-Ayala, C; Charli, J-L; Joseph-Bravo, P

    2014-12-01

    The activity of the hypothalamic-pituitary-thyroid (HPT) axis is rapidly adjusted by energy balance alterations. Glucocorticoids can interfere with this activity, although the timing of this interaction is unknown. In vitro studies indicate that, albeit incubation with either glucocorticoid receptor (GR) agonists or protein kinase A (PKA) activators enhances pro-thyrotrophin-releasing hormone (pro-TRH) transcription, co-incubation with both stimuli reduces this enhancement. In the present study, we used primary cultures of hypothalamic cells to test whether the order of these stimuli alters the cross-talk. We observed that a simultaneous or 1-h prior (but not later) activation of GR is necessary to inhibit the stimulatory effect of PKA activation on pro-TRH expression. We tested these in vitro results in the context of a physiological stimulus on the HPT axis in adult male rats. Cold exposure for 1 h enhanced pro-TRH mRNA expression in neurones of the hypophysiotrophic and rostral subdivisions of the paraventricular nucleus (PVN) of the hypothalamus, thyrotrophin (TSH) serum levels and deiodinase 2 (D2) activity in brown adipose tissue (BAT). An i.p. injection of corticosterone stimulated pro-TRH expression in the PVN of rats kept at ambient temperature, more pronouncedly in hypophysiotrophic neurones that no longer responded to cold exposure. In corticosterone-pretreated rats, the cold-induced increase in pro-TRH expression was detected only in the rostral PVN. Corticosterone blunted the increase in serum TSH levels and D2 activity in BAT produced by cold in vehicle-injected animals. Thus, increased serum corticosterone levels rapidly restrain cold stress-induced activation of TRH hypophysiotrophic neurones, which may contribute to changing energy expenditure. Interestingly, TRH neurones of the rostral PVN responded to both corticosterone and cold exposure with an amplified expression of pro-TRH mRNA, suggesting that these neurones integrate stress and temperature

  13. Maternal obesity leads to increased proliferation and numbers of astrocytes in the developing fetal and neonatal mouse hypothalamus.

    PubMed

    Kim, Dong Won; Glendining, Kelly A; Grattan, David R; Jasoni, Christine L

    2016-10-01

    Maternal obesity during pregnancy is associated with chronic maternal, placental, and fetal inflammation; and it elevates the risk for offspring obesity. Changes in the development of the hypothalamus, a brain region that regulates body weight and energy balance, are emerging as important determinants of offspring risk, but such changes are only beginning to be defined. Here we focused on the hypothesis that the pathological exposure of developing hypothalamic astrocytes to cytokines would alter their development. A maternal high-fat diet (mHFD) mouse model was used to investigate changes in hypothalamic astrocytes in the fetus during late gestation and in early neonates by using immunochemistry, confocal microscopy, and qPCR. The number of astrocytes and the proportion of proliferating astrocytes was significantly higher in the arcuate nucleus (ARC) and the supraoptic nucleus (SON) of the hypothalamus at both ages compared to control offspring from normal weight pregnancies. Supplemental to this we found that cultured fetal hypothalamic astrocytes proliferated significantly in response to IL6 (10ng/ml), one of the cytokines significantly elevated in fetuses of obese dams, via the JAK/STAT3 signaling pathway. Thus, maternal obesity during pregnancy stimulated the proliferation and thereby increased numbers of astrocytes in the fetal as well as early neonatal hypothalamus, which may be driven, during fetal life, by IL6. PMID:27326907

  14. Sonic hedgehog lineage in the mouse hypothalamus: from progenitor domains to hypothalamic regions

    PubMed Central

    2012-01-01

    Background The hypothalamus is a brain region with essential functions for homeostasis and energy metabolism, and alterations of its development can contribute to pathological conditions in the adult, like hypertension, diabetes or obesity. However, due to the anatomical complexity of the hypothalamus, its development is not well understood. Sonic hedgehog (Shh) is a key developmental regulator gene expressed in a dynamic pattern in hypothalamic progenitor cells. To obtain insight into hypothalamic organization, we used genetic inducible fate mapping (GIFM) to map the lineages derived from Shh-expressing progenitor domains onto the four rostrocaudally arranged hypothalamic regions: preoptic, anterior, tuberal and mammillary. Results Shh-expressing progenitors labeled at an early stage (before embryonic day (E)9.5) contribute neurons and astrocytes to a large caudal area including the mammillary and posterior tuberal regions as well as tanycytes (specialized median eminence glia). Progenitors labeled at later stages (after E9.5) give rise to neurons and astrocytes of the entire tuberal region and in particular the ventromedial nucleus, but not to cells in the mammillary region and median eminence. At this stage, an additional Shh-expressing domain appears in the preoptic area and contributes mostly astrocytes to the hypothalamus. Shh-expressing progenitors do not contribute to the anterior region at any stage. Finally, we show a gradual shift from neurogenesis to gliogenesis, so that progenitors expressing Shh after E12.5 generate almost exclusively hypothalamic astrocytes. Conclusions We define a fate map of the hypothalamus, based on the dynamic expression of Shh in the hypothalamic progenitor zones. We provide evidence that the large neurogenic Shh-expressing progenitor domains of the ventral diencephalon are continuous with those of the midbrain. We demonstrate that the four classical transverse zones of the hypothalamus have clearly defined progenitor domains

  15. Association of pain intensity, pain-related disability, and depression with hypothalamus-pituitary-adrenal axis function in female patients with chronic temporomandibular disorders.

    PubMed

    Jo, Kyung B; Lee, Young J; Lee, Il G; Lee, Sang C; Park, Jai Y; Ahn, Ryun S

    2016-07-01

    Patients with temporomandibular disorders (TMD) commonly experience myofascial and joint pain, pain-related disability, and other pain conditions including depression. The present study was carried out to explore the function of the hypothalamus-pituitary-adrenal (HPA) axis in relation to variables of the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) Axis II and comorbid depression in female patients with TMD. Cortisol and dehydroepiandrosterone (DHEA) levels were determined in saliva samples that had been collected at various periods after waking (0, 30, and 60min) and at nighttime (2100-2200h) from 52 female patients with chronic TMD pain and age- and gender-matched controls (n=54, 20-40 years old). There were no significant differences in the levels and diurnal patterns of cortisol and DHEA secretion between groups of patients with TMD and controls. In patients, the cortisol awakening response (CAR) or diurnal cortisol rhythm were not associated with any variables of the RDC/TMD Axis II or the Beck Depression Inventory (BDI)-II total scores. However, the ratio of overall cortisol secretion within the first hour after waking (CARauc) to overall DHEA secretion during the post-waking period (Daucawk), defined as CARauc/Daucawk, was significantly associated with pain-related RDC/TMD variables (pain intensity and pain-related disability) and BDI-II total scores. Pain intensity and pain-related disability scores were also significantly associated with BDI-II total scores. These results indicated that an increase in molar cortisol/DHEA ratio due to the dissociation between cortisol and DHEA secretion was associated with pain intensity, pain-related disability, and depression in female patients with TMD. PMID:27082645

  16. Antidepressant-like effect of geniposide on chronic unpredictable mild stress-induced depressive rats by regulating the hypothalamus-pituitary-adrenal axis.

    PubMed

    Cai, Li; Li, Rong; Tang, Wen-jian; Meng, Gang; Hu, Xiang-yang; Wu, Ting-ni

    2015-08-01

    Geniposide as the major active component of Gardenia jasminoides Ellis has neuroprotective activity. This study elucidated the potential antidepressant-like effect of geniposide and its related mechanisms using a depression rat model induced by 3 consecutive weeks of chronic unpredictable mild stress (CUMS). Sucrose preference test, open field test (OFT) and forced swimming test (FST) were applied to evaluate the antidepressant effect of geniposide. Adrenocorticotropic hormone (ACTH) and corticosterone (CORT) serum levels, adrenal gland index and hypothalamic corticotrophin-releasing hormone (CRH) mRNA expression were measured to assess the activity of hypothalamus-pituitary-adrenal (HPA) axis. Hypothalamic glucocorticoid receptor α (GRα) mRNA expression and GRα protein expression in hypothalamic paraventricular nucleus (PVN) were also determined by real-time PCR and immunohistochemistry, respectively. We found that geniposide (25, 50, 100mg/kg) treatment reversed the CUMS-induced behavioral abnormalities, as suggested by increased sucrose intake, improved crossing and rearing behavior in OFT, shortened immobility and prolonged swimming time in FST. Additionally, geniposide treatment normalized the CUMS-induced hyperactivity of HPA axis, as evidenced by reduced CORT serum level, adrenal gland index and hypothalamic CRH mRNA expression, with no significant effect on ACTH serum level. Moreover, geniposide treatment upregulated the hypothalamic GRα mRNA level and GRα protein expression in PVN, suggesting geniposide could recover the impaired GRα negative feedback on CRH expression and HPA axis. These aforementioned therapeutic effects of geniposide were essentially similar to fluoxetine. Our results indicated that geniposide possessed potent antidepressant-like properties that may be mediated by its effects on the HPA axis. PMID:25914157

  17. Accumulation and biotransformation of BDE-47 by zebrafish larvae and teratogenicity and expression of genes along the hypothalamus-pituitary-thyroid axis.

    PubMed

    Zheng, Xinmei; Zhu, Yuting; Liu, Chunsheng; Liu, Hongling; Giesy, John P; Hecker, Markus; Lam, Michael H W; Yu, Hongxia

    2012-12-01

    Accumulation and effects of BDE-47 and two analogues, 6-OH-BDE-47 and 6-MeO-BDE-47, on ontogeny and profiles of transcription of genes along the hypothalamus-pituitary-thyroid (HPT) axis of zebrafish (Danio rerio) embryos exposed from 4 h post fertilization (hpf) to 120 hpf were investigated. The 96 h-LC(50) of the most toxic compound, based on teratogenicity, was 330 μg of 6-OH-BDE-47/L. 6-OH-BDE-47 significantly down-regulated expression of mRNA of thyroid stimulating hormone receptor (TSHR), thyroid hormone receptors (TRs, including TRα and TRβ), sodium/iodide symporter (NIS), and transthyretin (TTR) while up-regulating expression of thyroglobulin (TG) and thyrotropin-releasing hormone (TRH). Spontaneous movement was affected by 1 mg of 6-OH-BDE-47/L or 5 mg of 6-MeO-BDE-47/L. BDE-47 did not alter activity of larvae at any concentration tested. 6-MeO-BDE-47 significantly up-regulated expression of mRNA of TRH, TRα, TRβ and NIS. Both 6-OH-BDE-47 and 6-MeO-BDE-47 affected the thyroid hormone pathway. BDE-47 and 6-MeO-BDE-47 were accumulated more than 6-OH-BDE-47. 6-MeO-BDE-47 was transformed into 6-OH-BDE-47, but BDE-47 was not transformed into it. In summary, the synthetic brominated flame retardant, BDE-47, did not elicit the adverse effects caused by the other two analogues and appeared to have less toxicological relevance than the two natural product analogues 6-OH- and 6-MeO-BDE-47. PMID:23110413

  18. A patient-specific model of the negative-feedback control of the hypothalamus-pituitary-thyroid (HPT) axis in autoimmune (Hashimoto's) thyroiditis.

    PubMed

    Pandiyan, Balamurugan; Merrill, Stephen J; Benvenga, Salvatore

    2014-09-01

    The purpose of modelling the negative-feedback control mechanism of the hypothalamus-pituitary-thyroid (HPT) axis in autoimmune (Hashimoto's) thyroiditis is to describe the clinical course of euthyroidism, subclinical hypothyroidism and overt hypothyroidism for patients. Thyroid hormone thyroxine (T4) and triiodothyronine (T3) levels are controlled by negative-feedback control through thyroid-stimulating hormone (TSH). T4, like other hormones, can be bound or unbound; the unbound T4 (FT4) is used as a marker for hypothyroidism. Autoimmune thyroiditis is a disease in which the thyroid-infiltrating lymphocytes attack autoantigens in follicle cells, destroying them over a long time. To describe the operation of the feedback control, we developed a mathematical model involving four clinical variables: TSH, FT4, anti-thyroid peroxidase antibodies and the thyroid gland's functional size. The first three variables are regularly measured while the last variable is determined through relationships between the other three variables. The problem of two different time scales for circulating hormones and thyroid damage is addressed using singular perturbation theory. Analysis of the mathematical model establishes stability and conditions under which the diseased state can maintain the slow movement toward diseased state equilibrium. Although we have used four variables in modelling the feedback control through the HPT axis, the predicted clinical course given any set of parameters is shown to depend on the steady-state levels of TSH and FT4. This observation makes possible the development of the clinical charts based only on the levels of TSH, time and potential steady-state values. To validate the model predictions, a dataset obtained from a Sicilian adult population has been employed. PMID:23639794

  19. A brain-specific gene cluster isolated from the region of the mouse obesity locus is expressed in the adult hypothalamus and during mouse development

    SciTech Connect

    Laig-Webster, M.; Lim, M.E.; Chehab, F.F.

    1994-09-01

    The molecular defect underlying an autosomal recessive form of genetic obesity in a classical mouse model C57 BL/6J-ob/ob has not yet been elucidated. Whereas metabolic and physiological disturbances such as diabetes and hypertension are associated with obesity, the site of expression and the nature of the primary lesion responsible for this cascade of events remains elusive. Our efforts aimed at the positional cloning of the ob gene by YAC contig mapping and gene identification have resulted in the cloning of a brain-specific gene cluster from the ob critical region. The expression of this gene cluster is remarkably complex owing to the multitude of brain-specific mRNA transcripts detected on Northern blots. cDNA cloning of these transcripts suggests that they are expressed from different genes as well as by alternate splicing mechanisms. Furthermore, the genomic organization of the cluster appears to consist of at least two identical promoters displaying CpG islands characteristic of housekeeping genes, yet clearly involving tissue-specific expression. Sense and anti-sense synthetic RNA probes were derived from a common DNA sequence on 3 cDNA clones and hybridized to 8-16 days mouse embryonic stages and mouse adult brain sections. Expression in development was noticeable as of the 11th day of gestation and confined to the central nervous system mainly in the telencephalon and spinal cord. Coronal and sagittal sections of the adult mouse brain showed expression only in 3 different regions of the brain stem. In situ hybridization to mouse hypothalamus sections revealed the presence of a localized and specialized group of cells expressing high levels of mRNA, suggesting that this gene cluster may also be involved in the regulation of hypothalamic activities. The hypothalamus has long been hypothesized as a primary candidate tissue for the expression of the obesity gene mainly because of its well-established role in the regulation of energy metabolism and food intake.

  20. Vision and the hypothalamus.

    PubMed

    Trachtman, Joseph N

    2010-02-01

    For nearly 2 millennia, signs of hypothalamic-related vision disorders have been noticed as illustrated by paintings and drawings of that time of undiagnosed Horner's syndrome. It was not until the 1800s, however, that specific connections between the hypothalamus and the vision system were discovered. With a fuller elaboration of the autonomic nervous system in the early to mid 1900s, many more pathways were discovered. The more recently discovered retinohypothalamic tracts show the extent and influence of light stimulation on hypothalamic function and bodily processes. The hypothalamus maintains its myriad connections via neural pathways, such as with the pituitary and pineal glands; the chemical messengers of the peptides, cytokines, and neurotransmitters; and the nitric oxide mechanism. As a result of these connections, the hypothalamus has involvement in many degenerative diseases. A complete feedback mechanism between the eye and hypothalamus is established by the retinohypothalamic tracts and the ciliary nerves innervating the anterior pole of the eye and the retina. A discussion of hypothalamic-related vision disorders includes neurologic syndromes, the lacrimal system, the retina, and ocular inflammation. Tables and figures have been used to aid in the explanation of the many connections and chemicals controlled by the hypothalamus. The understanding of the functions of the hypothalamus will allow the clinician to gain better insight into the many pathologies associated between the vision system and the hypothalamus. In the future, it may be possible that some ocular disease treatments will be via direct action on hypothalamic function. PMID:20152784

  1. Radiation necrosis of the optic chiasm, optic tract, hypothalamus, and upper pons after radiotherapy for pituitary adenoma, detected by gadolinium-enhanced, T1-weighted magnetic resonance imaging: Case report

    SciTech Connect

    Tachibana, O.; Yamaguchi, N.; Yamashima, T.; Yamashita, J. )

    1990-10-01

    A 26-year-old woman was treated for a prolactin secreting pituitary adenoma by surgery and radiotherapy (5860 rads). Fourteen months later, she developed right hemiparesis and dysarthria. A T1-weighted magnetic resonance imaging scan using gadolinium contrast showed a small, enhanced lesion in the upper pons. Seven months later, she had a sudden onset of loss of vision, and radiation optic neuropathy was diagnosed. A T1-weighted magnetic resonance imaging scan showed widespread gadolinium-enhanced lesions in the optic chiasm, optic tract, and hypothalamus. Magnetic resonance imaging is indispensable for the early diagnosis of radiation necrosis, which is not visualized by radiography or computed tomography.

  2. Hypothalamus proteomics from mouse models with obesity and anorexia reveals therapeutic targets of appetite regulation

    PubMed Central

    Manousopoulou, A; Koutmani, Y; Karaliota, S; Woelk, C H; Manolakos, E S; Karalis, K; Garbis, S D

    2016-01-01

    Objective: This study examined the proteomic profile of the hypothalamus in mice exposed to a high-fat diet (HFD) or with the anorexia of acute illness. This comparison could provide insight on the effects of these two opposite states of energy balance on appetite regulation. Methods: Four to six-week-old male C56BL/6J mice were fed a normal (control 1 group; n=7) or a HFD (HFD group; n=10) for 8 weeks. The control 2 (n=7) and lipopolysaccharide (LPS) groups (n=10) were fed a normal diet for 8 weeks before receiving an injection of saline and LPS, respectively. Hypothalamic regions were analysed using a quantitative proteomics method based on a combination of techniques including iTRAQ stable isotope labeling, orthogonal two-dimensional liquid chromatography hyphenated with nanospray ionization and high-resolution mass spectrometry. Key proteins were validated with quantitative PCR. Results: Quantitative proteomics of the hypothalamous regions profiled a total of 9249 protein groups (q<0.05). Of these, 7718 protein groups were profiled with a minimum of two unique peptides for each. Hierachical clustering of the differentiated proteome revealed distinct proteomic signatures for the hypothalamus under the HFD and LPS nutritional conditions. Literature research with in silico bioinformatics interpretation of the differentiated proteome identified key biological relevant proteins and implicated pathways. Furthermore, the study identified potential pharmacologic targets. In the LPS groups, the anorexigen pro-opiomelanocortin was downregulated. In mice with obesity, nuclear factor-κB, glycine receptor subunit alpha-4 (GlyR) and neuropeptide Y levels were elevated, whereas serotonin receptor 1B levels decreased. Conclusions: High-precision quantitative proteomics revealed that under acute systemic inflammation in the hypothalamus as a response to LPS, homeostatic mechanisms mediating loss of appetite take effect. Conversely, under chronic inflammation in the

  3. The Comparison between Circadian Oscillators in Mouse Liver and Pituitary Gland Reveals Different Integration of Feeding and Light Schedules

    PubMed Central

    Bur, Isabelle M.; Zouaoui, Sonia; Fontanaud, Pierre; Coutry, Nathalie; Molino, François; Martin, Agnès O.; Mollard, Patrice; Bonnefont, Xavier

    2010-01-01

    The mammalian circadian system is composed of multiple peripheral clocks that are synchronized by a central pacemaker in the suprachiasmatic nuclei of the hypothalamus. This system keeps track of the external world rhythms through entrainment by various time cues, such as the light-dark cycle and the feeding schedule. Alterations of photoperiod and meal time modulate the phase coupling between central and peripheral oscillators. In this study, we used real-time quantitative PCR to assess circadian clock gene expression in the liver and pituitary gland from mice raised under various photoperiods, or under a temporal restricted feeding protocol. Our results revealed unexpected differences between both organs. Whereas the liver oscillator always tracked meal time, the pituitary circadian clockwork showed an intermediate response, in between entrainment by the light regimen and the feeding-fasting rhythm. The same composite response was also observed in the pituitary gland from adrenalectomized mice under daytime restricted feeding, suggesting that circulating glucocorticoids do not inhibit full entrainment of the pituitary clockwork by meal time. Altogether our results reveal further aspects in the complexity of phase entrainment in the circadian system, and suggest that the pituitary may host oscillators able to integrate multiple time cues. PMID:21179516

  4. Three-dimensional visualization of the distribution of melanin-concentrating hormone producing neurons in the mouse hypothalamus.

    PubMed

    Reinitz, László Zoltán; Szőke, Balázs; Várkonyi, Emese Éva; Sótonyi, Péter; Jancsik, Veronika

    2016-01-01

    We present here a new procedure to represent the 3D distribution of neuronal cell bodies within the brain, using exclusively softwares free for research purposes. Our technique is based on digitalized photos of brain slices processed by immunohistochemical technique, and the 3D Slicer software. The technique presented enables transposition of immunohistochemical or in situ hybridization data to the stereotaxic mouse brain atlas (e.g. Paxinos, G., Franklin, K.B.J., 2001. The Mouse Brain in Stereotaxic Coordinates. second ed. Academic Press, San Diego). By exporting the finalized models into a popular 3D design software (3DS Max) arbitrary environment and motion simulation can be created to improve the visual understanding of the area studied. Application of this technique provides the possibility to store, analyze and compare data - e.g. on the hypothalamic neuropeptides - across experimental techniques and laboratories. The method is exemplified by visualizing the distribution of immunohistochemically identified melanin-concetrating hormone (MCH) containing perikarya within the mouse hypothalamus. PMID:26686291

  5. Opposite effects of a high-fat diet and calorie restriction on ciliary neurotrophic factor signaling in the mouse hypothalamus

    PubMed Central

    Severi, Ilenia; Perugini, Jessica; Mondini, Eleonora; Smorlesi, Arianna; Frontini, Andrea; Cinti, Saverio; Giordano, Antonio

    2013-01-01

    In the mouse hypothalamus, ciliary neurotrophic factor (CNTF) is mainly expressed by ependymal cells and tanycytes of the ependymal layer covering the third ventricle. Since exogenously administered CNTF causes reduced food intake and weight loss, we tested whether endogenous CNTF might be involved in energy balance regulation. We thus evaluated CNTF production and responsiveness in the hypothalamus of mice fed a high-fat diet (HFD), of ob/ob obese mice, and of mice fed a calorie restriction (CR) regimen. RT-PCR showed that CNTF mRNA increased significantly in HFD mice and decreased significantly in CR animals. Western blotting confirmed that CNTF expression was higher in HFD mice and reduced in CR mice, but high interindividual variability blunted the significance of these differences. By immunohistochemistry, hypothalamic tuberal and mammillary region tanycytes stained strongly for CNTF in HFD mice, whereas CR mice exhibited markedly reduced staining. RT-PCR and Western blotting disclosed that changes in CNTF expression were paralleled by changes in the expression of its specific receptor, CNTF receptor α (CNTFRα). Injection of recombinant CNTF and detection of phospho-signal transducer and activator of transcription 3 (P-STAT3) showed that CNTF responsiveness by the ependymal layer, mainly by tanycytes, was higher in HFD than CR mice. In addition, in HFD mice CNTF administration induced distinctive STAT3 signaling in a large neuron population located in the dorsomedial and ventromedial nuclei, perifornical area and mammillary body. The hypothalamic expression of CNTF and CNTFRα did not change in the hyperphagic, leptin-deficient ob/ob obese mice; accordingly, P-STAT3 immunoreactivity in CNTF-treated ob/ob mice was confined to ependymal layer and arcuate neurons. Collectively, these data suggest that hypothalamic CNTF is involved in controlling the energy balance and that CNTF signaling plays a role in HFD obese mice at specific sites. PMID:24409114

  6. Cholinergic neurons in the dorsomedial hypothalamus regulate mouse brown adipose tissue metabolism

    PubMed Central

    Jeong, Jae Hoon; Lee, Dong Kun; Blouet, Clemence; Ruiz, Henry H.; Buettner, Christoph; Chua, Streamson; Schwartz, Gary J.; Jo, Young-Hwan

    2015-01-01

    Objective Brown adipose tissue (BAT) thermogenesis is critical in maintaining body temperature. The dorsomedial hypothalamus (DMH) integrates cutaneous thermosensory signals and regulates adaptive thermogenesis. Here, we study the function and synaptic connectivity of input from DMH cholinergic neurons to sympathetic premotor neurons in the raphe pallidus (Rpa). Methods In order to selectively manipulate DMH cholinergic neuron activity, we generated transgenic mice expressing channelrhodopsin fused to yellow fluorescent protein (YFP) in cholinergic neurons (choline acetyltransferase (ChAT)-Cre::ChR2-YFP) with the Cre-LoxP technique. In addition, we used an adeno-associated virus carrying the Cre recombinase gene to delete the floxed Chat gene in the DMH. Physiological studies in response to optogenetic stimulation of DMH cholinergic neurons were combined with gene expression and immunocytochemical analyses. Results A subset of DMH neurons are ChAT-immunopositive neurons. The activity of these neurons is elevated by warm ambient temperature. A phenotype-specific neuronal tracing shows that DMH cholinergic neurons directly project to serotonergic neurons in the Rpa. Optical stimulation of DMH cholinergic neurons decreases BAT activity, which is associated with reduced body core temperature. Furthermore, elevated DMH cholinergic neuron activity decreases the expression of BAT uncoupling protein 1 (Ucp1) and peroxisome proliferator-activated receptor γ coactivator 1 α (Pgc1α) mRNAs, markers of BAT activity. Injection of M2-selective muscarinic receptor antagonists into the 4th ventricle abolishes the effect of optical stimulation. Single cell qRT-PCR analysis of retrogradely identified BAT-projecting neurons in the Rpa shows that all M2 receptor-expressing neurons contain tryptophan hydroxylase 2. In animals lacking the Chat gene in the DMH, exposure to warm temperature reduces neither BAT Ucp1 nor Pgc1α mRNA expression. Conclusion DMH cholinergic neurons directly

  7. A voltammetric and mathematical analysis of histaminergic modulation of serotonin in the mouse hypothalamus.

    PubMed

    Samaranayake, Srimal; Abdalla, Aya; Robke, Rhiannon; Nijhout, H Frederik; Reed, Michael C; Best, Janet; Hashemi, Parastoo

    2016-08-01

    Histamine and serotonin are neuromodulators which facilitate numerous, diverse neurological functions. Being co-localized in many brain regions, these two neurotransmitters are thought to modulate one another's chemistry and are often implicated in the etiology of disease. Thus, it is desirable to interpret the in vivo chemistry underlying neurotransmission of these two molecules to better define their roles in health and disease. In this work, we describe a voltammetric approach to monitoring serotonin and histamine simultaneously in real time. Via electrical stimulation of the axonal bundles in the medial forebrain bundle, histamine release was evoked in the mouse premammillary nucleus. We found that histamine release was accompanied by a rapid, potent inhibition of serotonin in a concentration-dependent manner. We developed mathematical models to capture the experimental time courses of histamine and serotonin, which necessitated incorporation of an inhibitory receptor on serotonin neurons. We employed pharmacological experiments to verify that this serotonin inhibition was mediated by H3 receptors. Our novel approach provides fundamental mechanistic insights that can be used to examine the full extent of interconnectivity between histamine and serotonin in the brain. Histamine and serotonin are co-implicated in many of the brain's functions. In this paper, we develop a novel voltammetric method for simultaneous real-time monitoring of histamine and serotonin in the mouse premammillary nucleus. Electrical stimulation of the medial forebrain bundle evokes histamine and inhibits serotonin release. We show voltammetrically, mathematically, and pharmacologically that this serotonin inhibition is H3 receptor mediated. PMID:27167463

  8. Endocrine Disruption throughout the Hypothalamus-Pituitary-Gonadal-Liver (HPGL) Axis in Marine Medaka (Oryzias melastigma) Chronically Exposed to the Antifouling and Chemopreventive Agent, 3,3'-Diindolylmethane (DIM).

    PubMed

    Chen, Lianguo; Ye, Rui; Zhang, Weipeng; Hu, Chenyan; Zhou, Bingsheng; Peterson, Drew R; Au, Doris W T; Lam, Paul K S; Qian, Pei-Yuan

    2016-06-20

    Despite being proposed as a promising antifouling and chemopreventive agent, the environmental risks of 3,3'-diindolylmethane (DIM) are scarcely investigated. Therefore, this study used adult marine medaka (Oryzias melastigma) as a model organism to examine the toxicological effects and underlying mechanism of DIM throughout the hypothalamus-pituitary-gonadal-liver (HPGL) axis following 28 days of exposure to low DIM concentrations (0 and 8.46 μg/L). The results showed that altered gene transcription in the hypothalamus, pituitary, and gonads contributed to the great imbalance in hormone homeostasis. The lowered estradiol (E2)/testosterone (T) and E2/11-keto-testosterone (11-KT) ratios in female plasma resulted in decreased synthesis and levels of vitellogenin (VTG) and choriogenin in the liver and plasma, and vice versa in males. Subsequently, VTG and choriogenin deficiency blocked the reproductive function of the ovary as indicated by decreased fecundity and offspring viability, whereas in male medaka, DIM mainly targeted the liver and induced severe vacuolization. Proteomic profiling of plasma revealed that the sex-specific susceptibility to DIM could be attributed to the increased detoxification and oxidative defense in males. Overall, this study identified the endocrine disruption and reproductive impairment potency of DIM and first elucidated its mechanisms of action in medaka. The differential responses to DIM (estrogenic activities in the male but antiestrogenic activities in the female) provided sensitive biomarkers characteristic of each sex. Considering the chemical stability and potent endocrine disturbance at low concentration, the application of DIM either as an antifouling or chemopreventive agent should be approached with caution in marine environments. PMID:27092574

  9. Angiogenesis in Pituitary Adenomas: Human Studies and New Mutant Mouse Models

    PubMed Central

    Cristina, Carolina; Demarchi, Gianina; Lopez Vicchi, Felicitas; Perez Millan, Maria Ines; Perrone, Sofia; Ornstein, Ana Maria; Berner, Silvia Inés; Becu-Villalobos, Damasia

    2014-01-01

    The role of angiogenesis in pituitary tumor development has been questioned, as pituitary tumors have been usually found to be less vascularized than the normal pituitary tissue. Nevertheless, a significantly higher degree of vasculature has been shown in invasive or macropituitary prolactinomas when compared to noninvasive and microprolactinomas. Many growth factors and their receptors are involved in pituitary tumor development. For example, VEGF, FGF-2, FGFR1, and PTTG, which give a particular vascular phenotype, are modified in human and experimental pituitary adenomas of different histotypes. In particular, vascular endothelial growth factor, VEGF, the central mediator of angiogenesis in endocrine glands, was encountered in experimental and human pituitary tumors at different levels of expression and, in particular, was higher in dopamine agonist resistant prolactinomas. Furthermore, several anti-VEGF techniques lowered tumor burden in human and experimental pituitary adenomas. Therefore, even though the role of angiogenesis in pituitary adenomas is contentious, VEGF, making permeable pituitary endothelia, might contribute to adequate temporal vascular supply and mechanisms other than endothelial cell proliferation. The study of angiogenic factor expression in aggressive prolactinomas with resistance to dopamine agonists will yield important data in the search of therapeutical alternatives. PMID:25505910

  10. Emotional exhaustion and overcommitment to work are differentially associated with hypothalamus-pituitary-adrenal (HPA) axis responses to a low-dose ACTH1-24 (Synacthen) and dexamethasone-CRH test in healthy school teachers.

    PubMed

    Wolfram, Maren; Bellingrath, Silja; Feuerhahn, Nicolas; Kudielka, Brigitte M

    2013-01-01

    Evidence for a detrimental impact of chronic work stress on health has accumulated in epidemiological research. Recent studies indicate altered hypothalamus-pituitary-adrenal (HPA) axis regulation as a possible biological pathway underlying the link between stress and disease. However, the direction of dysregulation remains unclear, with reported HPA hyper- or hyporeactivity. To disentangle potential effects on different functional levels in the HPA axis, we examined responses using two pharmacological stimulation tests in 53 healthy teachers (31 females, 22 males; mean age: 49.3 years; age range: 30-64 years): a low-dose adrenocorticotrophic hormone (ACTH(1-24), Synacthen) test was used to assess adrenal cortex sensitivity and the combined dexamethasone-corticotropin releasing hormone (DEX-CRH) test to examine pituitary and adrenal cortex reactivity. Blood and saliva samples were collected at - 1,+15,+30,+45,+60,+90,+120 min. Emotional exhaustion (EE), the core dimension of burnout, was measured with the Maslach Burnout Inventory. Overcommitment (OC) was assessed according to Siegrist's effort-reward-imbalance model. We found a significant association between EE and higher plasma cortisol profiles after Synacthen (p = 0.045). By contrast, OC was significantly associated with attenuated ACTH (p = 0.045), plasma cortisol (p = 0.005), and salivary cortisol (p = 0.023) concentrations following DEX-CRH. Results support the notion of altered HPA axis regulation in chronically work-stressed teachers, with differential patterns of hyper- and hyporeactivity depending on individual stress condition and the tested functional level of the HPA axis. PMID:22564145

  11. From Pituitary Expansion to Empty Sella: Disease Progression in a Mouse Model of Autoimmune Hypophysitis

    PubMed Central

    Lupi, Isabella; Zhang, Jiangyang; Gutenberg, Angelika; Landek-Salgado, Melissa; Tzou, Shey-Cherng; Mori, Susumu

    2011-01-01

    Lymphocytic hypophysitis has a variable clinical course, where a swelling of the pituitary gland at presentation is thought to be followed by pituitary atrophy and empty sella. Data in patients, however, are scanty and contradictory. To better define the course of hypophysitis, we used an experimental model based on the injection of pituitary proteins into SJL mice. A cohort of 33 mice was divided into three groups: 18 cases were immunized with pituitary proteins emulsified in complete Freund's adjuvant; six controls were injected with adjuvant only; and nine controls were left untreated. Mice were followed by cranial magnetic resonance imaging (MRI) for up to 300 d, for a total of 106 MRI scans, and killed at different time points to correlate radiological and pathological findings. Empty sella was defined as a reduction in pituitary volume greater than 2 sd below the mean volume. All immunized mice showed by MRI a significant expansion of pituitary volume during the early phases of the disease. The volume then decreased gradually in the majority of cases (14 of 18, 78%), reaching empty sella values by d 300 after immunization. In a minority of cases (four of 18, 22%), the decrease was so rapid and marked to induce a central area of necrosis accompanied by hemorrhages, mimicking the condition known in patients as pituitary apoplexy. No radiological or pathological changes were observed in controls. Overall, these findings indicate that the evolution of hypophysitis is complex but can lead, through different routes, to the development of empty sella. PMID:21862619

  12. Chronic Exposure of Marine Medaka (Oryzias melastigma) to 4,5-Dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT) Reveals Its Mechanism of Action in Endocrine Disruption via the Hypothalamus-Pituitary-Gonadal-Liver (HPGL) Axis.

    PubMed

    Chen, Lianguo; Zhang, Weipeng; Ye, Rui; Hu, Chenyan; Wang, Qiangwei; Seemann, Frauke; Au, Doris W T; Zhou, Bingsheng; Giesy, John P; Qian, Pei-Yuan

    2016-04-19

    In this study, marine medaka (Oryzias melastigma) were chronically exposed for 28 days to environmentally realistic concentrations of 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT) (0, 0.76, 2.45, and 9.86 μg/L), the active ingredient in commercial antifouling agent SeaNine 211. Alterations of the hypothalamus-pituitary-gonadal-liver (HPGL) axis were investigated across diverse levels of biological organization to reveal the underlying mechanisms of its endocrine disruptive effects. Gene transcription analysis showed that DCOIT had positive regulatory effects mainly in male HPGL axis with lesser extent in females. The stimulated steroidogenic activities resulted in increased concentrations of steroid hormones, including estradiol (E2), testosterone (T), and 11-KT-testosterone (11-KT), in the plasma of both sexes, leading to an imbalance in hormone homeostasis and increased E2/T ratio. The relatively estrogenic intracellular environment in both sexes induced the hepatic synthesis and increased the liver and plasma content of vitellogenin (VTG) or choriogenin. Furthermore, parental exposure to DCOIT transgenerationally impaired the viability of offspring, as supported by a decrease in hatching and swimming activity. Overall, the present results elucidated the estrogenic mechanisms along HPGL axis for the endocrine disruptive effects of DCOIT. The reproductive impairments of DCOIT at environmentally realistic concentrations highlights the need for more comprehensive investigations of its potential ecological risks. PMID:27035644

  13. [Dynamic behavior of the adaptive control system, hypothalamus--anterior pituitary--adrenal cortex. Animal experimental study of the adequate system dynamics of the direct and indirect parameters of the adaptive control system].

    PubMed

    Zintzsch, I; Seidel, H; Lantzsch, C; Lantzsch, M

    1979-01-01

    The dynamic response of the adaptive closed-loop control system hypothalamus-anterior pituitary-adrenal cortex after application of short-time disturb pulses were examined experimentally in the pig. Blood sampling was performed biologically non-reactive by chronically implanted vascular catheters in the upper vena cava. A circadian biphase periodical dynamics characterizes the distrubance response of the adaptive control system, respectively, its direct and indirect parameters. After distrubance variables induced initial excess the plasma corticosteriods undershoot the basic level over a long period. Conversely, the dynamics of the eosinophils is determined through an initial eosinopenic phase and a subsequent typical overshoot. Periodical dynamic is absent in the steady state. The controller of the adaptive system does not show any spontaneous activity in the steady state without stress. The absence of an endogenic periodicity of the dependent parameters likewise gives evidence of an active oscillator. On the other hand, the controlling unit of the adaptive system constitutes a control response of circadian periodicty after activation by disturbance variables in pulse shape. The high damping of the control system terminates the transient state within 24 hours, and the corticosteriods and the eosinophils reach the steady state level. This control quality of the adaptive control system gains a high importance in the origination of the spontaneous circadian periodicity by corticosteriods and eosinophils and for the biological compensation of exogenous distrubance variables. PMID:233184

  14. Effect of pituitary hollow fiber units and thyroid supplementation on growth in the little mouse (41949)

    NASA Technical Reports Server (NTRS)

    Harkness, John E.; Hymer, W. C.; Rosenberger, James L.; Grindeland, Richard E.

    1984-01-01

    It is shown that the implantation of encapsulated pituitary cells into heterozygous lit/+ mice inhibited the average percentage change in weight gain as compared to controls. However, homozygous lit/lit mice receiving cell-filled capsules consistently had higher percentage weight gains than their control counterparts. It was also found that thyroid-supplemented mutant mice with pituitary cell implants had significantly higher organ and carcass weights than other mutant groups.

  15. Expression and Activity of Acid-Sensing Ion Channels in the Mouse Anterior Pituitary

    PubMed Central

    Du, Jianyang; Reznikov, Leah R.; Welsh, Michael J.

    2014-01-01

    Acid sensing ion channels (ASICs) are proton-gated cation channels that are expressed in the nervous system and play an important role in fear learning and memory. The function of ASICs in the pituitary, an endocrine gland that contributes to emotions, is unknown. We sought to investigate which ASIC subunits were present in the pituitary and found mRNA expression for all ASIC isoforms, including ASIC1a, ASIC1b, ASIC2a, ASIC2b, ASIC3 and ASIC4. We also observed acid-evoked ASIC-like currents in isolated anterior pituitary cells that were absent in mice lacking ASIC1a. The biophysical properties and the responses to PcTx1, amiloride, Ca2+ and Zn2+ suggested that ASIC currents were mediated predominantly by heteromultimeric channels that contained ASIC1a and ASIC2a or ASIC2b. ASIC currents were also sensitive to FMRFamide (Phe-Met-Arg-Phe amide), suggesting that FMRFamide-like compounds might endogenously regulate pituitary ASICs. To determine whether ASICs might regulate pituitary cell function, we applied low pH and found that it increased the intracellular Ca2+ concentration. These data suggest that ASIC channels are present and functionally active in anterior pituitary cells and may therefore influence their function. PMID:25506946

  16. Expression and activity of acid-sensing ion channels in the mouse anterior pituitary.

    PubMed

    Du, Jianyang; Reznikov, Leah R; Welsh, Michael J

    2014-01-01

    Acid sensing ion channels (ASICs) are proton-gated cation channels that are expressed in the nervous system and play an important role in fear learning and memory. The function of ASICs in the pituitary, an endocrine gland that contributes to emotions, is unknown. We sought to investigate which ASIC subunits were present in the pituitary and found mRNA expression for all ASIC isoforms, including ASIC1a, ASIC1b, ASIC2a, ASIC2b, ASIC3 and ASIC4. We also observed acid-evoked ASIC-like currents in isolated anterior pituitary cells that were absent in mice lacking ASIC1a. The biophysical properties and the responses to PcTx1, amiloride, Ca2+ and Zn2+ suggested that ASIC currents were mediated predominantly by heteromultimeric channels that contained ASIC1a and ASIC2a or ASIC2b. ASIC currents were also sensitive to FMRFamide (Phe-Met-Arg-Phe amide), suggesting that FMRFamide-like compounds might endogenously regulate pituitary ASICs. To determine whether ASICs might regulate pituitary cell function, we applied low pH and found that it increased the intracellular Ca2+ concentration. These data suggest that ASIC channels are present and functionally active in anterior pituitary cells and may therefore influence their function. PMID:25506946

  17. Effects of perchlorate on BDE-47-induced alteration thyroid hormone and gene expression of in the hypothalamus-pituitary-thyroid axis in zebrafish larvae.

    PubMed

    Zhao, Xuesong; Wang, Shutao; Li, Dongmei; You, Hong; Ren, Xin

    2013-11-01

    To investigate the effects of perchlorate on thyroid hormone disturbances induced by 2,2',4',4-tetrabromodiphenyl ether (BDE-47) via thyroid hormone (TH)-mediated pathways, zebrafish embryos were exposed to a combination of BDE-47 and PER from the time of fertilisation to 14 d (dpf). The whole-body content of TH and the expression of genes and proteins related to the hypothalamic-pituitary-thyroid (HPT) axis were analysed. Co-exposure to BDE-47 and PER decreased the body weight and increased malformation rates relative to the effects of exposure to only BDE-47. Compared with the exposure to BDE-47 alone, the exposure to a combination of BDE-47 (10 μg/L) and PER (3.5 mg/L) significantly up-regulated the expression of genes involved in TH synthesis (NIS and Nkx2.1a) and significantly down-regulated the expression of genes related to the regulation of the HPT axis (CRH and TSHβ). The expression of TG at the gene and protein levels was significantly up-regulated, but the expression of TTR was significantly down-regulated in the co-exposures relative to BDE-47 treated alone. In addition, the larger reduction in the T4 level resulting from exposure to the mixture of BDE-47 and PER demonstrated that PER enhanced the thyroid-disruptive effects of BDE-47. These results help to elucidate the complicated chemical interactions and the molecular mechanism of action of these two TH disruptors. PMID:24177579

  18. Long-term effects of bisphenol AF (BPAF) on hormonal balance and genes of hypothalamus-pituitary-gonad axis and liver of zebrafish (Danio rerio), and the impact on offspring.

    PubMed

    Shi, Jiachen; Jiao, Zhihao; Zheng, Sai; Li, Ming; Zhang, Jing; Feng, Yixing; Yin, Jie; Shao, Bing

    2015-06-01

    Bisphenol AF (BPAF) is one of the analogues of bisphenol A (BPA) and is widely used as a raw material in the plastics industry. The potential toxicity to fish from exposure to BPAF in the aquatic environment is largely unknown. In this study, zebrafish (Danio rerio) were exposed to BPAF at 5, 25 and 125 μg L(-1), from 4 hour-post-fertilization (hpf) to 120 day-post-fertilization (dpf), representing the period from embryo to adult. The levels of plasma hormones were measured and the expression of selected representative genes along the hypothalamus-pituitary-gonad (HPG) axis and liver were examined. The concentration of 17β-estradiol (E2) was significantly increased in male and female fish and a significant decrease of testosterone (T) was observed in male fish. The mRNA expression of genes along the HPG axis and in liver tissues in F0 generation fish demonstrated that the steroid hormonal balances of zebrafish were modulated through the alteration of steroidgenesis. The significant decrease of egg fertilization among offspring indicates the possibility of sperm deterioration of parent following exposure to BPAF. The higher occurrence of malformation and lower survival rate in the offspring from the exposure group suggested a possibility of maternal transfer of BPAF, which could be responsible for the increased prevalence of adverse health signs in the offspring. The hatching delay in 5 μg L(-1) BPAF indicated that parental exposure to environmentally relevant concentration of BPAF would result in delayed hatching of the offspring. A potential consequence of adverse effects in the offspring by BPAF deserves further investigation. PMID:25723718

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

    PubMed

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

    2006-02-01

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

  20. Genetic differentiation of hypothalamus parentally biased transcripts in populations of the house mouse implicate the Prader-Willi syndrome imprinted region as a possible source of behavioral divergence.

    PubMed

    Lorenc, Anna; Linnenbrink, Miriam; Montero, Inka; Schilhabel, Markus B; Tautz, Diethard

    2014-12-01

    Parentally biased expression of transcripts (genomic imprinting) in adult tissues, including the brain, can influence and possibly drive the evolution of behavioral traits. We have previously found that paternally determined cues are involved in population-specific mate choice decisions between two populations of the Western house mouse (Mus musculus domesticus). Here, we ask whether this could be mediated by genomically imprinted transcripts that are subject to fast differentiation between these populations. We focus on three organs that are of special relevance for mate choice and behavior: The vomeronasal organ (VNO), the hypothalamus, and the liver. To first identify candidate transcripts at a genome-wide scale, we used reciprocal crosses between M. m. domesticus and M. m. musculus inbred strains and RNA sequencing of the respective tissues. Using a false discovery cutoff derived from mock reciprocal cross comparisons, we find a total of 66 imprinted transcripts, 13 of which have previously not been described as imprinted. The largest number of imprinted transcripts were found in the hypothalamus; fewer were found in the VNO, and the least were found in the liver. To assess molecular differentiation and imprinting in the wild-derived M. m. domesticus populations, we sequenced the RNA of the hypothalamus from individuals of these populations. This confirmed the presence of the above identified transcripts also in wild populations and allowed us to search for those that show a high genetic differentiation between these populations. Our results identify the Ube3a-Snrpn imprinted region on chromosome 7 as a region that encompasses the largest number of previously not described transcripts with paternal expression bias, several of which are at the same time highly differentiated. For four of these, we confirmed their imprinting status via single nucleotide polymorphism-specific pyrosequencing assays with RNA from reciprocal crosses. In addition, we find the

  1. Genetic Differentiation of Hypothalamus Parentally Biased Transcripts in Populations of the House Mouse Implicate the Prader–Willi Syndrome Imprinted Region as a Possible Source of Behavioral Divergence

    PubMed Central

    Lorenc, Anna; Linnenbrink, Miriam; Montero, Inka; Schilhabel, Markus B.; Tautz, Diethard

    2014-01-01

    Parentally biased expression of transcripts (genomic imprinting) in adult tissues, including the brain, can influence and possibly drive the evolution of behavioral traits. We have previously found that paternally determined cues are involved in population-specific mate choice decisions between two populations of the Western house mouse (Mus musculus domesticus). Here, we ask whether this could be mediated by genomically imprinted transcripts that are subject to fast differentiation between these populations. We focus on three organs that are of special relevance for mate choice and behavior: The vomeronasal organ (VNO), the hypothalamus, and the liver. To first identify candidate transcripts at a genome-wide scale, we used reciprocal crosses between M. m. domesticus and M. m. musculus inbred strains and RNA sequencing of the respective tissues. Using a false discovery cutoff derived from mock reciprocal cross comparisons, we find a total of 66 imprinted transcripts, 13 of which have previously not been described as imprinted. The largest number of imprinted transcripts were found in the hypothalamus; fewer were found in the VNO, and the least were found in the liver. To assess molecular differentiation and imprinting in the wild-derived M. m. domesticus populations, we sequenced the RNA of the hypothalamus from individuals of these populations. This confirmed the presence of the above identified transcripts also in wild populations and allowed us to search for those that show a high genetic differentiation between these populations. Our results identify the Ube3a–Snrpn imprinted region on chromosome 7 as a region that encompasses the largest number of previously not described transcripts with paternal expression bias, several of which are at the same time highly differentiated. For four of these, we confirmed their imprinting status via single nucleotide polymorphism-specific pyrosequencing assays with RNA from reciprocal crosses. In addition, we find the

  2. Anatomy, Physiology, and Laboratory Evaluation of the Pituitary Gland.

    PubMed

    Hong, Gregory K; Payne, Spencer C; Jane, John A

    2016-02-01

    The pituitary gland functions prominently in the control of most endocrine systems in the body. Diverse processes such as metabolism, growth, reproduction, and water balance are tightly regulated by the pituitary in conjunction with the hypothalamus and various downstream endocrine organs. Benign tumors of the pituitary gland are the primary cause of pituitary pathology and can result in inappropriate secretion of pituitary hormones or loss of pituitary function. First-line management of clinically significant tumors often involves surgical resection. Understanding of normal pituitary physiology and basic testing strategies to assess for pituitary dysfunction should be familiar to any skull base surgeon. PMID:26614827

  3. Cortex-, Hippocampus-, Thalamus-, Hypothalamus-, Lateral Septal Nucleus- and Striatum-specific In Utero Electroporation in the C57BL/6 Mouse.

    PubMed

    Baumgart, Jan; Baumgart, Nadine

    2016-01-01

    In utero electroporation is a widely used technique for fast and efficient spatiotemporal manipulation of various genes in the rodent central nervous system. Overexpression of desired genes is just as possible as shRNA mediated loss-of-function studies. Therefore it offers a wide range of applications. The feasibility to target particular cells in a distinct area further increases the range of potential applications of this very useful method. For efficiently targeting specific regions knowledge about the subtleties, such as the embryonic stage, the voltage to apply and most importantly the position of the electrodes, is indispensable. Here, we provide a detailed protocol that allows for specific and efficient in utero electroporation of several regions of the C57BL/6 mouse central nervous system. In particular it is shown how to transfect regions the develop into the retrosplenial cortex, the motor cortex, the somatosensory cortex, the piriform cortex, the cornu ammonis 1-3, the dentate gyrus, the striatum, the lateral septal nucleus, the thalamus and the hypothalamus. For this information about the appropriate embryonic stage, the appropriate voltage for the corresponding embryonic stage is provided. Most importantly an angle-map, which indicates the appropriate position of the positive pole, is depicted. This standardized protocol helps to facilitate efficient in utero electroporation, which might also lead to a reduced number of animals. PMID:26862715

  4. Functional characterization of neural-restrictive silencer element in mouse pituitary adenylate cyclase-activating polypeptide (PACAP) gene expression.

    PubMed

    Sugawara, Hideki; Tominaga, Aiko; Inoue, Kazuhiko; Takeda, Yasuo; Yamada, Katsushi; Miyata, Atsuro

    2014-11-01

    Pituitary adenylate cyclase-activating polypeptide (PACAP) is predominantly localized in the nervous system, but the underlying mechanism in its neuron-specific expression remains unclear. In addition to two neural-restrictive silencer-like element (NRSLE1 and 2), as reported previously, we have identified the third element in -1,601 to -1,581 bp from the translational initiation site of mouse PACAP gene and termed it as NRSLE3, of which, the sequence and location were highly conserved among mouse, rat, and human PACAP genes. In luciferase reporter assay, the deletion or site-directed mutagenesis of NRSLE3 in the reporter gene construct, driven by heterologous SV40 promoter, cancelled the repression of luciferase activity in non-neuronal Swiss-3T3 cells. Furthermore, its promoter activity was significantly repressed in Swiss-3T3 cells, but not in neuronal-differentiated PC12 cells. The electrophoretic mobility shift assay (EMSA) with nuclear extracts of Swiss-3T3 cells demonstrated a specific complex with NRSLE3 probe that exhibited the same migration with the neural-restrictive silencer element (NRSE) probe of rat type II sodium channel gene. During neuronal differentiation of PC12 cells, the increment of PACAP mRNA exhibited the correlation with that of REST4 mRNA, which is a neuron-specific variant form of neural-restrictive silencer factor (NRSF). In undifferentiated PC12 cells, trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, which indirectly inhibits NRSF-mediated gene silencing, increased PACAP mRNA level and attenuated the repression of promoter activity of 5' flanking region of mouse PACAP gene containing NRSLEs. These suggest that the NRSE-NRSF system implicates in the regulatory mechanism of neuron-specific expression of PACAP gene. PMID:24939248

  5. Changes in testosterone concentration in the fetal rabbit testis after removal of the hypothalamus (encephalectomy)

    SciTech Connect

    Proshlyakova, E.V.; Rumyantseva, O.N.; Mitskevich, M.S.

    1986-10-01

    The aim of this investigation was to obtain direct data on the role of the hypothalamus in regulation of the adrogen function of the testes in rabbit fetuses. Testosterone was determined by radioimmunoassay. Changes in testostereone concentration in rabbit fetal testis after encephalectomy and after injection of luteinizing hormone releasing hormone (LHRH) into encephalectomized fetuses is shown. Results obtained are evidence that the hypothalamus, pituitary and testes in the rabbit aged 23-25 days of prenatal development constitute a single functional system. It is concluded that in both rabbit and hog fetuses, the hypothalamus begins to regulate pituitary gonadotrophic activity after LHRH can be detected in the hypothalamus itself.

  6. Effects of long-term voluntary exercise on the mouse hypothalamic-pituitary-adrenocortical axis.

    PubMed

    Droste, Susanne K; Gesing, Angela; Ulbricht, Sabine; Müller, Marianne B; Linthorst, Astrid C E; Reul, Johannes M H M

    2003-07-01

    We studied the effects of long-term (i.e. 4 wk) voluntary exercise on the hypothalamic-pituitary-adrenocortical (HPA) axis in male mice. Voluntary exercise was provided by giving mice access to a running wheel, in which they indeed ran for about 4 km/d. Exercising mice showed similar body weights as control animals but presented less abdominal fat, lighter thymuses, and heavier adrenal glands. Exercise resulted in asymmetric structural changes in the adrenal glands. Whereas control mice had larger left than right adrenals, this condition was abolished in exercising animals, mainly because of enlargement of the right adrenal cortex. Tyrosine hydroxylase mRNA expression in the adrenal medullas of exercising mice was increased. In exercising mice, early-morning baseline plasma ACTH levels were decreased, whereas plasma corticosterone levels at the start of the dark phase were twice as high as those in control animals. To forced swimming and restraint stress, exercising mice responded with higher corticosterone levels than those of the control animals but with similar ACTH levels. However, if exposed to a novel environment, then exercising mice presented decreased ACTH responses. Interestingly, exercising mice showed a decreased corticosterone response to novelty only when the novel environment contained a functioning running wheel. Glucocorticoid receptor levels were unchanged, whereas mineralocorticoid receptor levels were decreased, in hippocampus of exercising animals. Corticotropin-releasing factor mRNA levels in the paraventricular nucleus were lower in exercising mice. Thus, voluntary exercise results in complex, adaptive changes at various levels within the HPA axis as well as in sympathoadrenomedullary and limbic/neocortical afferent control mechanisms. These changes seem to underlie the differential responsiveness of the HPA axis to physical vs. emotional challenges. PMID:12810557

  7. The pituitary hormones arginine vasopressin-neurophysin II and oxytocin-neurophysin I show close linkage with interleukin-1 on mouse chromosome 2

    SciTech Connect

    Marini, J.C.; Nelson, K.K.; Siracusa, L.D. ); Battey, J. )

    1993-01-01

    Arginine vasopressin (AVP) and oxytocin (OXT) are posterior pituitary hormones. AVP is involved in fluid homeostasis, while OXT is involved in lactation and parturition. AVP is derived from a larger precursor, prepro-arginine-vasopressin-neurophysin II (prepro-AVP-NP II; AVP), and is physically linked to prepro-oxytocin-neurophysin I (prepro-OXT-NPI1; OXT). The genes for AVP and OXT are separated by only 12 kb of DNA in humans, whereas in the mouse 3.5 kb of intergenic sequence lies between Avp and Oxt. Interspecific backcross analysis has now been used to map the Avp/Oxt complex to chromosome 2 in the mouse. This map position confirms and extends the known region of linkage conservation between mouse chromosome 2 and human chromosome 20. 16 refs., 2 figs., 1 tab.

  8. Divergent Effects of Dioxin- or Non-Dioxin-Like Polychlorinated Biphenyls on the Apoptosis of Primary Cell Culture from the Mouse Pituitary Gland

    PubMed Central

    Raggi, Francesco; Russo, Dania; Urbani, Claudio; Sardella, Chiara; Manetti, Luca; Cappellani, Daniele; Lupi, Isabella; Tomisti, Luca; Martino, Enio; Marcocci, Claudio; Bogazzi, Fausto

    2016-01-01

    Polychlorinated biphenyls (PCBs) can disrupt the endocrine function, promote neoplasms and regulate apoptosis in some tissues; however, it is unknown whether PCBs can affect the apoptosis of pituitary cells. The study evaluated the effect of PCBs on the apoptosis of normal pituitary cells and the underlying mechanisms. Primary cell cultures obtained from mouse pituitary glands were exposed to Aroclor 1254 or selected dioxin-like (PCB 77, PCB 126) or non-dioxin-like (PCB 153, PCB 180) congeners. Apoptosis was evaluated by Annexin V staining, DNA fragmentation, and TUNEL assay. Both the expression and activity of caspases were analyzed. Selective thyroid hormone receptor (TR) or aryl-hydrocarbon receptor (AhR) or CYP1A1 antagonist were used to explore the mechanisms underlying PCBs action. Our results showed that Aroclor 1254 induced the apoptosis of pituitary cells as well as the final caspase-3 level and activity through the extrinsic pathway, as shown by the increased caspase-8 level and activity. On the other hand, the intrinsic pathway evaluated by measuring caspase-9 expression was silent. The selected non-dioxin-like congeners either increased (PCB 180) or reduced (PCB 153) pituitary cell apoptosis, affecting the extrinsic pathway (PCB 180), or both the extrinsic and intrinsic pathways (PCB 153), respectively. In contrast, the dioxin-like congeners (PCB 77 and PCB 126) did not affect apoptosis. The anti-apoptotic phenotype of PCB 153 was counteracted by a TR or a CYP1A1 antagonist, whereas the pro-apoptotic effect of PCB 180 was counteracted by an AhR antagonist. The induced apoptosis of Aroclor 1254 or PCB 180 was associated with a reduction of cell proliferation, whereas the decreased apoptosis due to PCB 153 increased cell proliferation by 30%. In conclusion, our data suggest that non-dioxin-like PCBs may modulate apoptosis and the proliferation rate of pituitary cells that have either pro- or anti-apoptotic effects depending on the specific congeners

  9. Development of the Neuroendocrine Hypothalamus.

    PubMed

    Burbridge, Sarah; Stewart, Iain; Placzek, Marysia

    2016-01-01

    The neuroendocrine hypothalamus is composed of the tuberal and anterodorsal hypothalamus, together with the median eminence/neurohypophysis. It centrally governs wide-ranging physiological processes, including homeostasis of energy balance, circadian rhythms and stress responses, as well as growth and reproductive behaviours. Homeostasis is maintained by integrating sensory inputs and effecting responses via autonomic, endocrine and behavioural outputs, over diverse time-scales and throughout the lifecourse of an individual. Here, we summarize studies that begin to reveal how different territories and cell types within the neuroendocrine hypothalamus are assembled in an integrated manner to enable function, thus supporting the organism's ability to survive and thrive. We discuss how signaling pathways and transcription factors dictate the appearance and regionalization of the hypothalamic primordium, the maintenance of progenitor cells, and their specification and differentiation into neurons. We comment on recent studies that harness such programmes for the directed differentiation of human ES/iPS cells. We summarize how developmental plasticity is maintained even into adulthood and how integration between the hypothalamus and peripheral body is established in the median eminence and neurohypophysis. Analysis of model organisms, including mouse, chick and zebrafish, provides a picture of how complex, yet elegantly coordinated, developmental programmes build glial and neuronal cells around the third ventricle of the brain. Such conserved processes enable the hypothalamus to mediate its function as a central integrating and response-control mediator for the homeostatic processes that are critical to life. Early indications suggest that deregulation of these events may underlie multifaceted pathological conditions and dysfunctional physiology in humans, such as obesity. © 2016 American Physiological Society. Compr Physiol 6:623-643, 2016. PMID:27065164

  10. Pituitary abscess.

    PubMed

    Rudwan, M A

    1977-05-28

    Three cases of pituitary abscess are presented. The history of recurrent attacks of aseptic meningitis, together with radiological and clinical features suggestive of pituitary tumor, appear to form a fairly typical picture of the condition. Long follow-up was possible in two of the cases. There are no radiological features which distinguish the lesion from pituitary tumor, hence the importance of recognizing the significance of such a clinical presentation with radiological evidence of sellar enlargement. Pituitary abscesses seem to occur in preexisting pituitary tumors. The possible relationship with pituitary infarction is discussed. PMID:865667

  11. Transcription factor 7-like 1 is involved in hypothalamo–pituitary axis development in mice and humans

    PubMed Central

    Gaston-Massuet, Carles; McCabe, Mark J.; Scagliotti, Valeria; Young, Rodrigo M.; Carreno, Gabriela; Gregory, Louise C.; Jayakody, Sujatha A.; Pozzi, Sara; Gualtieri, Angelica; Basu, Basudha; Koniordou, Markela; Wu, Chun-I; Bancalari, Rodrigo E.; Rahikkala, Elisa; Veijola, Riitta; Lopponen, Tuija; Graziola, Federica; Turton, James; Signore, Massimo; Mousavy Gharavy, Seyedeh Neda; Charolidi, Nicoletta; Sokol, Sergei Y.; Merrill, Bradley J.; Dattani, Mehul T.; Martinez-Barbera, Juan Pedro

    2016-01-01

    Aberrant embryonic development of the hypothalamus and/or pituitary gland in humans results in congenital hypopituitarism (CH). Transcription factor 7-like 1 (TCF7L1), an important regulator of the WNT/β-catenin signaling pathway, is expressed in the developing forebrain and pituitary gland, but its role during hypothalamo–pituitary (HP) axis formation or involvement in human CH remains elusive. Using a conditional genetic approach in the mouse, we first demonstrate that TCF7L1 is required in the prospective hypothalamus to maintain normal expression of the hypothalamic signals involved in the induction and subsequent expansion of Rathke’s pouch progenitors. Next, we reveal that the function of TCF7L1 during HP axis development depends exclusively on the repressing activity of TCF7L1 and does not require its interaction with β-catenin. Finally, we report the identification of two independent missense variants in human TCF7L1, p.R92P and p.R400Q, in a cohort of patients with forebrain and/or pituitary defects. We demonstrate that these variants exhibit reduced repressing activity in vitro and in vivo relative to wild-type TCF7L1. Together, our data provide support for a conserved molecular function of TCF7L1 as a transcriptional repressor during HP axis development in mammals and identify variants in this transcription factor that are likely to contribute to the etiology of CH. PMID:26764381

  12. Leukemia inhibitory factor regulates glucocorticoid receptor expression in the hypothalamic-pituitary-adrenal axis.

    PubMed

    Kariagina, Anastasia; Zonis, Svetlana; Afkhami, Mahta; Romanenko, Dmitry; Chesnokova, Vera

    2005-11-01

    Leukemia inhibitory factor (LIF) is a pleiotropic cytokine belonging to the gp130 family. LIF is induced peripherally and within the brain during inflammatory or chronic autoimmune diseases and is a potent stimulator of the hypothalamic-pituitary-adrenal (HPA) axis. Here we investigated the role of LIF in mediating glucocorticoid receptor (GR) expression in the HPA axis. LIF treatment (3 microg/mouse, i.p.) markedly decreased GR mRNA levels in murine hypothalamus (5-fold, P < 0.01) and pituitary (1.7-fold, P < 0.01) and downregulated GR protein levels. LIF decreased GR expression in murine corticotroph cell line AtT20 within 2 h, and this effect was sustained for 8 h after treatment. LIF-induced GR mRNA reduction was abrogated in AtT20 cells overexpressing dominant-negative mutants of STAT3, indicating that intact JAK-STAT signaling is required to mediate LIF effects on GR expression. Conversely, mice with LIF deficiency exhibited increased GR mRNA levels in the hypothalamus and pituitary (3.5- and 3.5-fold, respectively; P < 0.01 for both) and increased GR protein expression when compared with wild-type littermates. The suppressive effects of dexamethasone on GR were more pronounced in LIF-null animals. These data suggest that LIF maintains the HPA axis activation by decreasing GR expression and raise the possibility that LIF might contribute to the development of central glucocorticoid resistance during inflammation. PMID:15985451

  13. The pituitary gland: a brief history.

    PubMed

    Kaplan, Solomon Alexander

    2007-01-01

    The functions of the pituitary gland as an important constituent of the endocrine system were not understood until the latter part of the nineteenth century and the first half of the 20th century. At one time, the pituitary was deemed to be the "leader of the endocrine orchestra," but more recent studies have shown that its secretions are influenced by external stimuli and that it is largely under the control of the hypothalamus. PMID:17690988

  14. A truncated, activin-induced Smad3 isoform acts as a transcriptional repressor of FSHβ expression in mouse pituitary.

    PubMed

    Kim, So-Youn; Zhu, Jie; Woodruff, Teresa K

    2011-08-01

    The receptor-regulated protein Smad3 is key player in the signaling cascade stimulated by the binding of activin to its cell surface receptor. Upon phosphorylation, Smad3 forms a heterocomplex with Smad2 and Smad4, translocates to the nucleus and acts as a transcriptional co-activator. We have identified a unique isoform of Smad3 that is expressed in mature pituitary gonadotropes. 5' RACE revealed that this truncated Smad3 isoform is transcribed from an ATG site within exon 4 and consists of 7 exons encoding half of the linker region and the MH2 region. In pituitary cells, the truncated Smad3 isoform was phosphorylated upon activin treatment, in a manner that was temporally distinct from the phosphorylation of full-length Smad3. Activin-induced phosphorylation of Smad3 and the truncated Smad3 isoform was blocked by both follistatin and siRNA-mediated knockdown of Smad3. The truncated Smad3 isoform antagonized Smad3-mediated, activin-responsive promoter activity. We propose that the pituitary gonadotrope contains an ultra-short, activin-responsive feedback loop utilizing two different isoforms of Smad3, one which acts as an agonist (Smad3) and another that acts as an intracrine antagonist (truncated Smad3 isoform) to regulate FSHβ production. PMID:21664424

  15. Pituitary tumor

    MedlinePlus

    ... The pituitary is a small gland at the base of the brain. It regulates the body's balance of many hormones. ... cause symptoms and are never diagnosed during the person's lifetime. ... at the base of the brain. The pituitary helps control the ...

  16. Cathepsin L Plays a Major Role in Cholecystokinin Production in Mouse Brain Cortex and in Pituitary AtT-20 Cells: Protease Gene Knockout and Inhibitor Studies

    PubMed Central

    Beinfeld, Margery C.; Funkelstein, Lydiane; Foulon, Thierry; Cadel, Sandrine; Kitagawa, Kouki; Toneff, Thomas; Reinheckel, Thomas; Peters, Christoph; Hook, Vivian

    2009-01-01

    Cholecystokinin (CCK) is a peptide neurotransmitter whose production requires proteolytic processing of the proCCK precursor to generate active CCK8 neuropeptide in brain. This study demonstrates the significant role of the cysteine protease cathepsin L for CCK8 production. In cathepsin L knockout (KO) mice, CCK8 levels were substantially reduced in brain cortex by an average of 75%. To evaluate the role of cathepsin L in producing CCK in the regulated secretory pathway of neuroendocrine cells, pituitary AtT-20 cells that stably produce CCK were treated with the specific cathepsin L inhibitor, CLIK-148. CLIK-148 inhibitor treatment resulted in decreased amounts of CCK secreted from the regulated secretory pathway of AtT-20 cells. CLIK-148 also reduced cellular levels of CCK9 (Arg-CCK8), consistent with CCK9 as an intermediate product of cathepsin L, shown by the decreased ratio of CCK9/CCK8. The decreased CCK0/CCK8 ratio also suggests a shift in the production to CCK8 over CCK9 during inhibition of cathepsin L. During reduction of the PC1/3 processing enzyme by siRNA, the ratio of CCK9/CCK8 was increased, suggesting a shift to the cathepsin L pathway for production of CCK9. The changes in ratios of CCK9 compared to CCK8 are consistent with dual roles of the cathepsin L protease pathway that includes aminopeptidase B to remove NH2-terminal Arg or Lys, and the PC1/3 protease pathway. These results suggest that cathepsin L functions as a major protease responsible for CCK8 production in mouse brain cortex, and participates with PC1/3 for CCK8 production in pituitary cells. PMID:19589362

  17. Pituitary Tumors

    MedlinePlus

    ... or milk production), sex hormones (control the menstrual cycle and other sexual functions), thyroid gland hormones (control the thyroid gland), adrenal gland hormones, and vasopressin (a hormone involved in water and electrolyte balance). Symptoms of pituitary adenoma and ...

  18. An optimized method for neurotransmitters and their metabolites analysis in mouse hypothalamus by high performance liquid chromatography-Q Exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry.

    PubMed

    Yang, Zong-Lin; Li, Hui; Wang, Bing; Liu, Shu-Ying

    2016-02-15

    Neurotransmitters (NTs) and their metabolites are known to play an essential role in maintaining various physiological functions in nervous system. However, there are many difficulties in the detection of NTs together with their metabolites in biological samples. A new method for NTs and their metabolites detection by high performance liquid chromatography coupled with Q Exactive hybrid quadruple-orbitrap high-resolution accurate mass spectrometry (HPLC-HRMS) was established in this paper. This method was a great development of the applying of Q Exactive MS in the quantitative analysis. This method enabled a rapid quantification of ten compounds within 18min. Good linearity was obtained with a correlation coefficient above 0.99. The concentration range of the limit of detection (LOD) and the limit of quantitation (LOQ) level were 0.0008-0.05nmol/mL and 0.002-25.0nmol/mL respectively. Precisions (relative standard deviation, RSD) of this method were at 0.36-12.70%. Recovery ranges were between 81.83% and 118.04%. Concentrations of these compounds in mouse hypothalamus were detected by Q Exactive LC-MS technology with this method. PMID:26812177

  19. Animal models of pituitary neoplasia

    PubMed Central

    Lines, K.E.; Stevenson, M.; Thakker, R.V.

    2016-01-01

    Pituitary neoplasias can occur as part of a complex inherited disorder, or more commonly as sporadic (non-familial) disease. Studies of the molecular and genetic mechanisms causing such pituitary tumours have identified dysregulation of >35 genes, with many revealed by studies in mice, rats and zebrafish. Strategies used to generate these animal models have included gene knockout, gene knockin and transgenic over-expression, as well as chemical mutagenesis and drug induction. These animal models provide an important resource for investigation of tissue-specific tumourigenic mechanisms, and evaluations of novel therapies, illustrated by studies into multiple endocrine neoplasia type 1 (MEN1), a hereditary syndrome in which ∼30% of patients develop pituitary adenomas. This review describes animal models of pituitary neoplasia that have been generated, together with some recent advances in gene editing technologies, and an illustration of the use of the Men1 mouse as a pre clinical model for evaluating novel therapies. PMID:26320859

  20. Making a Pituitary Gland in a Dish

    PubMed Central

    Tabar, Viviane

    2016-01-01

    The adenohypophysis secretes multiple hormones that control vital physiological functions. A recent article in Nature (Suga et al., 2011) describes a 3D protocol for the derivation of several endocrine pituitary cell types from mouse ESCs. PMID:22136918

  1. Pituitary Apoplexy.

    PubMed

    Briet, Claire; Salenave, Sylvie; Bonneville, Jean-François; Laws, Edward R; Chanson, Philippe

    2015-12-01

    Pituitary apoplexy, a rare clinical syndrome secondary to abrupt hemorrhage or infarction, complicates 2%-12% of pituitary adenomas, especially nonfunctioning tumors. Headache of sudden and severe onset is the main symptom, sometimes associated with visual disturbances or ocular palsy. Signs of meningeal irritation or altered consciousness may complicate the diagnosis. Precipitating factors (increase in intracranial pressure, arterial hypertension, major surgery, anticoagulant therapy or dynamic testing, etc) may be identified. Corticotropic deficiency with adrenal insufficiency may be life threatening if left untreated. Computed tomography or magnetic resonance imaging confirms the diagnosis by revealing a pituitary tumor with hemorrhagic and/or necrotic components. Formerly considered a neurosurgical emergency, pituitary apoplexy always used to be treated surgically. Nowadays, conservative management is increasingly used in selected patients (those without important visual acuity or field defects and with normal consciousness), because successive publications give converging evidence that a wait-and-see approach may also provide excellent outcomes in terms of oculomotor palsy, pituitary function and subsequent tumor growth. However, it must be kept in mind that studies comparing surgical approach and conservative management were retrospective and not controlled. PMID:26414232

  2. Pituitary Tumors

    MedlinePlus

    ... org Tel: 773-577-8750; 800-886-2282 Fax: 847-827-9918 National Brain Tumor Society 55Chapel ... http://www.braintumor.org Tel: 866-455-3214 Fax: 617-924-9998 Pituitary Network Association P.O. ...

  3. Muscarinic cholinergic ligand binding to intact mouse pituitary tumor cells (AtT-20/D16-16) coupling with two biochemical effectors: adenylate cyclase and phosphatidylinositol turnover.

    PubMed

    Akiyama, K; Vickroy, T W; Watson, M; Roeske, W R; Reisine, T D; Smith, T L; Yamamura, H I

    1986-03-01

    (-)-[3H]Quinuclidinyl benzilate (QNB) binding to muscarinic receptors on intact mouse pituitary tumor cells (AtT-20/D16-16) was characterized in an attempt to correlate radioligand binding properties with receptor-coupled biochemical responses. Performing rinse time studies for 2 hr produced a remarkably improved ratio of specific/total (+)-[3H]QNB binding (85%). Kinetic experiments yielded association (k+1) and dissociation (k-1) rate constants of 2.2 X 10(8) M-1 min-1 and 6.8 X 10(-3) min-1, respectively. Receptor occupancy curves demonstrated a uniform population of specific, saturable (-)-[3H]QNB binding sites with a Hill coefficient equal to 1.0 and an apparent dissociation constant (Kd) equal to 34 pM under our conditions. Stereoselectivity was observed with the enantiomers (dexetimide and levetimide) of benzetimide (a factor of 4300). Concentrations of carbachol that produced a half-maximal inhibition of cyclic AMP formation and a concentration of carbachol for producing half-maximal stimulation of phosphatidylinositol turnover in the intact cells were 0.45 and 170 microM, respectively. Schild analysis revealed that pirenzepine, a nonclassical muscarinic antagonist, had a 40-fold greater affinity for reversing carbachol-stimulated phosphatidylinositol turnover (inhibition constant or Ki = 7 nM), compared to its antagonism of the carbachol-mediated inhibition of isoproterenol-stimulated cyclic AMP formation (Ki = 280 nM). Interestingly, pirenzepine inhibited (-)-[3H]QNB binding with a Ki value of 72 nM. In contrast, atropine was nearly equipotent (Ki = 0.3-0.5 nM) in binding studies and in both effector systems. PMID:3005550

  4. Acetylcholine Acts through Nicotinic Receptors to Enhance the Firing Rate of a Subset of Hypocretin Neurons in the Mouse Hypothalamus through Distinct Presynaptic and Postsynaptic Mechanisms1,2

    PubMed Central

    Zhou, Wen-Liang; Gao, Xiao-Bing

    2015-01-01

    Abstract Hypocretin/orexin neurons regulate many behavioral functions, including addiction. Nicotine acts through nicotinic acetylcholine receptors (nAChRs) to alter firing rate of neurons throughout the brain, leading to addiction-related behaviors. While nAChRs are expressed in the hypothalamus and cholinergic fibers project to this structure, it is unclear how acetylcholine modulates the activity of hypocretin neurons. In this study, we stimulated hypocretin neurons in mouse brain slices with ACh in the presence of atropine to dissect presynaptic and postsynaptic modulation of these neurons through nAChRs. Approximately one-third of tested hypocretin neurons responded to pressure application of ACh (1 mM) with an increase in firing frequency. Stimulation of postsynaptic nAChRs with ACh or nicotine resulted in a highly variable inward current in approximately one-third of hypocretin neurons. In contrast, ACh or nicotine (1 µM) reliably decreased the frequency of miniature EPSCs (mEPSCs). Antagonism of nAChRs with mecamylamine also suppressed mEPSC frequency, suggesting that an endogenous, tonic activation of presynaptic nAChRs might be required for maintaining functional mEPSC frequency. Antagonism of heteromeric (α4β2) or homomeric (α7) nAChRs alone suppressed mEPSCs to a lesser extent. Finally, blocking internal calcium release reduced the frequency of mEPSCs, occluding the suppressive effect of presynaptic ACh. Taken together, these data provide a mechanism by which phasic ACh release enhances the firing of a subset of hypocretin neurons through postsynaptic nAChRs, but disrupts tonic, presynaptic nAChR-mediated glutamatergic inputs to the overall population of hypocretin neurons, potentially enhancing the signal-to-noise ratio during the response of the nAChR-positive subset of neurons. PMID:26322330

  5. Stages of Pituitary Tumors

    MedlinePlus

    ... tumors that may spread to bones of the skull or the sinus cavity below the pituitary gland. ... sella (the bone at the base of the skull , where the pituitary gland sits). Recurrent Pituitary Tumors ...

  6. The Structure of the Neuroendocrine Hypothalamus: The Neuroanatomical Legacy of Geoffrey Harris

    PubMed Central

    Watts, Alan G.

    2015-01-01

    In November 1955 Geoffrey Harris published a paper based on the Christian A. Herter Lecture he had given earlier that year at Johns Hopkins University in Baltimore. The paper reviewed the contemporary research that was starting to explain how the hypothalamus controlled the pituitary gland. In the process of doing this Harris introduced a set of properties that would help define the neuroendocrine hypothalamus. They included: a) three criteria that putative releasing factors for adenohypophysial hormones would have to fulfill; b) an analogy between the representation of body parts in sensory and motor cortices and the spatial localization of neuroendocrine function in the hypothalamus; and c) the idea that neuroendocrine neurons were motor neurons, with the pituitary stalk functioning as a Sherringtonian final common pathway through which the impact of sensory and emotional events on neuroendocrine neurons had to pass to control pituitary hormone release. Were these properties a sign that the major neuroscientific discoveries being made in the early 1950s were beginning to influence neuroendocrinology? The present article discusses two main points: the context and significance of Harris's Herter Lecture for how our understanding of neuroendocrine anatomy (particularly as it relates to the control of the adenohypophysis) has developed since 1955; and within this framework, how novel and powerful techniques are taking our understanding of the structure of the neuroendocrine hypothalamus to new levels. PMID:25994006

  7. Pathogenesis of pituitary tumors.

    PubMed

    Yu, Run; Melmed, Shlomo

    2010-01-01

    Pituitary tumors are common and mostly benign neoplasia which cause excess or deficiency of pituitary hormones and compressive damage to adjacent organs. Oncogene activation [e.g. PTTG (pituitary tumor-transforming gene) and HMGA2], tumor suppressor gene inactivation (e.g. MEN1 and PRKAR1A), epigenetic changes (e.g. methylation) and humoral factors (e.g. ectopic production of stimulating hormones) are all possible pituitary tumor initiators; the micro-environment of pituitary tumors including steroid milieu, angiogenesis and abnormal cell adhesion further promote tumor growth. Senescence, a cellular defence mechanism against malignant transformation, may explain the benign nature of at least some pituitary tumors. We suggest that future research on pituitary tumor pathogenesis should incorporate systems approaches, and address regulatory mechanisms for pituitary cell proliferation, development of new animal models of pituitary tumor and isolation of functional human pituitary tumor cell lines. PMID:20541667

  8. DEVELOPMENT OF A GENE-EXPRESSION ARRAY FOCUSING ON THE HYPOTHALAMUS-PITUATARY-THYROID AXIS IN XENOPUS LAEVIS

    EPA Science Inventory

    As recommended by the Endocrine Disruptor Screening and Testing Program Advisory Committee (EDSTAC), the USEPA has been developing a screening test capable of detecting effects of Endocrine Disrupting Chemicals (EDCs) on the hypothalamus-pituitary-thyroid (HPT) axis in Xenopus la...

  9. Pituitary-ovarian-splenic axis in ovulation

    PubMed Central

    Oakley, Oliver R.; Frazer, Michele L.; Ko, CheMyong

    2011-01-01

    Leukocytes are rapidly recruited to the preovulatory ovary and play a crucial role as facilitators of ovulation and luteal formation. In this article, recent findings on leukocyte trafficking to the ovary, as well as the physiological role of leukocytes in the ovary, will be summarized and discussed. We then explore the novel hypothesis that the hypothalamus-pituitary-ovarian (HPO) axis might include the spleen as a reservoir of leukocytes by summarizing recent reports on this topic, both in the fields of immunology and reproductive biology. PMID:21600783

  10. Purinergic Regulation of Hypothalamo-Pituitary Functions

    PubMed Central

    Stojilkovic, Stanko S.

    2009-01-01

    The hypothalamus controls the release of hormones by the pituitary and is involved in control of food and water intake, sexual behavior, reproduction, and daily cycles in physiological state and behavior, temperature regulation, and emotional responses. Adenosine-5′-triphosphate (ATP) and its metabolic products contribute to these functions, acting as agonists for adenosine and P2Y receptors and two-transmembrane domain P2X receptor channels. This review summarizes the recent findings on purinergic receptor expression and their roles in signaling and cellular function in secretory and supporting cells of the hypothalamo-pituitary system. ATP secretion by these tissues, the enzymes involved in ATP hydrolysis, and the relevance of this pathway for sequential activation of receptors and termination of signaling is also discussed. PMID:19800813

  11. In vivo somatostatin, vasopressin, and oxytocin synthesis in diabetic rat hypothalamus

    SciTech Connect

    Fernstrom, J.D.; Fernstrom, M.H.; Kwok, R.P. )

    1990-04-01

    The in vivo labeling of somatostatin-14, somatostatin-28, arginine vasopressin, and oxytocin was studied in rat hypothalamus after third ventricular administration of (35S)cysteine to streptozotocin-diabetic and normal rats. Immunoreactive somatostatin levels in hypothalamus were unaffected by diabetes, as was the incorporation of (35S)cysteine into hypothalamic somatostatin-14 and somatostatin-28. In contrast, immunoreactive vasopressin levels in hypothalamus and posterior pituitary (and oxytocin levels in posterior pituitary) were below normal in diabetic rats. Moreover, (35S)cysteine incorporation into hypothalamic vasopressin and oxytocin (probably mainly in the paraventricular nucleus because of its proximity to the third ventricular site of label injection) was significantly above normal. The increments in vasopressin and oxytocin labeling were reversed by insulin administration. In vivo cysteine specific activity and the labeling of acid-precipitable protein did not differ between normal and diabetic animals; effects of diabetes on vasopressin and oxytocin labeling were therefore not caused by simple differences in cysteine specific activity. These results suggest that diabetes (1) does not influence the production of somatostatin peptides in hypothalamus but (2) stimulates the synthesis of vasopressin and oxytocin. For vasopressin at least, the increase in synthesis may be a compensatory response to the known increase in its secretion that occurs in uncontrolled diabetes.

  12. Gsh-1, an orphan Hox gene, is required for normal pituitary development.

    PubMed Central

    Li, H; Zeitler, P S; Valerius, M T; Small, K; Potter, S S

    1996-01-01

    The anterior pituitary regulates the function of multiple organ systems as well as body growth, and in turn is controlled by peptides released by the hypothalamus. We find that mutation of the Gsh-1 homeobox gene results in pleiotropic effects on pituitary development and function. Homozygous mutants exhibit extreme dwarfism, sexual infantilism and significant perinatal mortality. The mutant pituitary is small in size and hypocellular, with severely reduced numbers of growth hormone- and prolactin-producing cells. Moreover, the pituitary content of a subset of pituitary hormones, including growth hormone, prolactin and luteinizing hormone, is significantly decreased. The hypothalamus, although morphologically normal, is also perturbed in mutants. The gsh-1 gene is shown to be essential for growth hormone-releasing hormone (GHRH) gene expression in the arcuate nucleus of the hypothalamus. Further, sequence and electrophoretic mobility shift data suggest the Gsh-1 and GHRH genes as potential targets regulated by the Gsh-1-encoded protein. The mutant phenotype indicates a critical role for Gsh-1 in the genetic hierarchy of the formation and function of the hypothalamic-pituitary axis. Images PMID:8631293

  13. Pulsatility of Hypothalamo-Pituitary Hormones: A Challenge in Quantification.

    PubMed

    Keenan, Daniel M; Veldhuis, Johannes D

    2016-01-01

    Neuroendocrine systems control many of the most fundamental physiological processes, e.g., reproduction, growth, adaptations to stress, and metabolism. Each such system involves the hypothalamus, the pituitary, and a specific target gland or organ. In the quantification of the interactions among these components, biostatistical modeling has played an important role. In the present article, five key challenges to an understanding of the interactions of these systems are illustrated and discussed critically. PMID:26674550

  14. Pregnancy and pituitary adenomas.

    PubMed

    Glezer, Andrea; Jallad, Raquel S; Machado, Marcio C; Fragoso, Maria C; Bronstein, Marcello D

    2016-09-01

    Infertility is frequent in patients harboring pituitary adenomas. The mechanisms involved include hypogonadism secondary to hormonal hypersecretion (prolactin, growth hormone and cortisol), stalk disconnection and pituitary damage. With the improvement of clinical and surgical treatment, pregnancy in women harboring pituitary adenomas turned into a reality. Pituitary hormonal hyper- and hyposecretion influences pregnancy outcomes, as well as pregnancy can interfere on pituitary tumors, especially in prolactinomas. We review literature about specific follow-up and management in pregnant women harboring prolactinomas, acromegaly, or Cushings disease and the impact of clinical and surgical treatment on each condition. PMID:26977888

  15. DEIODINASE TYPE I, II, AND III EXPRESSION IN AMPHIBIAN PITUITARY, THYROID, AND LIMB BUD AT KEY STAGES OF DEVELOPMENT AND AFTER EXPOSURE TO THE THYROID HORMONE SYNTHESIS MODULATORS: METHIMAZOLE, PERCHLORATE AND PROPYLTHIOURACIL

    EPA Science Inventory

    This product describes molecular aspects of a multi-endpoint screening assay being developed by EPA in response to EDSTAC recommendations to examine potential interference with the hypothalamus-pituitary-thyroid axis.

  16. Endothelin: A novel peptide in the posterior pituitary system

    SciTech Connect

    Yoshizawa, Toshihiro; Kanazawa, Ichiro; Shinmi, Osamu; Kimura, Sadao; Yanagisawa, Masashi; Masaki, Tomoh; Uchiyama, Yasuo ); Giaid, A.; Gibson, S.J.; Polak, J.M. )

    1990-01-26

    Endothelin (ET), originally characterized as a 21-residue vasoconstrictor peptide from endothelial cells, is present in the porcine spinal cord and may act as a neuropeptide. Endothelin-like immunoreactivity has now been demonstrated by immunohistochemistry in the paraventricular and supraoptic nuclear neurons and their terminals in the posterior pituitary of the pig and the rat. The presence of ET in the porcine hypothalamus was confirmed by reversed-phase high-pressure liquid chromatography and radioimmunoassay. Moreover, in situ hybridization demonstrated ET messenger RNA in porcine paraventricular nuclear neurons. Endothelin-like immunoreactive products in the posterior pituitary of the rat were depleted by water deprivation, suggesting a release of ET under physiological conditions. These findings indicate that ET is synthesized in the posterior pituitary system and may be involved in neurosecretory functions.

  17. Effects of bromocriptine on (/sup 3/H)estradiol binding in cytosol of anterior pituitary

    SciTech Connect

    De Nicola, A.F.; Weisenberg, L.S.; Arakelian, M.C.; Libertun, C.

    1981-07-01

    The hypothalamus may control hormone receptors in the anterior pituitary either by a direct trophic effect or indirectly by regulation of serum pituitary hormone levels. Rats whose medial basal hypothalamus had been destroyed in order to suppress neural control of the gland showed a reduction in (/sup 3/H)estradiol binding in the anterior pituitary and high serum PRL levels; both changes were reversed by treatment of the lesioned rats with daily injections of bromocriptine, a dopamine agonist. In nonlesioned animals, the same treatment did not modify significantly those parameters. In another hyperprolactinemic model (rats with anterior pituitaries transplanted under the kidney capsule), (/sup 3/H)estradiol binding by the in situ pituitaries of the host rats was similar to that in the nongrafted controls. These results suggest that changes due to median eminence lesion are reversible and that bromocriptine is able to act as a substitutive therapy which restores binding of estradiol in glands whose receptors have been decreased by the effect of the lesion. High PRL levels due to pituitary transplant do not account for the observed changes in the pituitary estradiol binding.

  18. Estradiol Preferentially Induces Progestin Receptor-A (PR-A) Over PR-B in Cells Expressing Nuclear Receptor Coactivators in the Female Mouse Hypothalamus1,2,3

    PubMed Central

    Acharya, Kalpana D.; Finkelstein, Sarah D.; Bless, Elizabeth P.; Nettles, Sabin A.; Mulac-Jericevic, Biserka; Conneely, Orla M.; Mani, Shaila K.

    2015-01-01

    Abstract Estrogens act in brain to profoundly influence neurogenesis, sexual differentiation, neuroprotection, cognition, energy homeostasis, and female reproductive behavior and physiology through a variety of mechanisms, including the induction of progestin receptors (PRs). PRs are expressed as two isoforms, PR-A and PR-B, that have distinct functions in physiology and behavior. Because these PR isoforms cannot be distinguished using cellular resolution techniques, the present study used isoform-specific null mutant mice that lack PR-A or PR-B for the first time to investigate whether 17β-estradiol benzoate (EB) regulates the differential expression of the PR isoforms in the ventromedial nucleus of the hypothalamus (VMN), arcuate nucleus, and medial preoptic area, brain regions that are rich in EB-induced PRs. Interestingly, EB induced more PR-A than PR-B in all three brain regions, suggesting that PR-A is the predominant isoform in these regions. Given that steroid receptor coactivator (SRC)-1 and SRC-2 are important in estrogen receptor (ER)-dependent transcription in brain, including PR induction, we tested whether the expression of these coactivators was correlated with PR isoform expression. The majority of EB-induced PR cells expressed both SRC-1 and SRC-2 in the three brain regions of all genotypes. Interestingly, the intensity of PR-A immunoreactivity correlated with SRC-2 expression in the VMN, providing a potential mechanism for selective ER-mediated transactivation of PR-A over PR-B in a brain region-specific manner. In summary, these novel findings indicate that estrogens differentially regulate PR-A and PR-B expression in the female hypothalamus, and provide a mechanism by which steroid action in brain can selectively modulate behavior and physiology. PMID:26465008

  19. Functional anterior pituitary generated in self-organizing culture of human embryonic stem cells

    PubMed Central

    Ozone, Chikafumi; Suga, Hidetaka; Eiraku, Mototsugu; Kadoshima, Taisuke; Yonemura, Shigenobu; Takata, Nozomu; Oiso, Yutaka; Tsuji, Takashi; Sasai, Yoshiki

    2016-01-01

    Anterior pituitary is critical for endocrine systems. Its hormonal responses to positive and negative regulators are indispensable for homeostasis. For this reason, generating human anterior pituitary tissue that retains regulatory hormonal control in vitro is an important step for the development of cell transplantation therapy for pituitary diseases. Here we achieve this by recapitulating mouse pituitary development using human embryonic stem cells. We find that anterior pituitary self-forms in vitro following the co-induction of hypothalamic and oral ectoderm. The juxtaposition of these tissues facilitated the formation of pituitary placode, which subsequently differentiated into pituitary hormone-producing cells. They responded normally to both releasing and feedback signals. In addition, after transplantation into hypopituitary mice, the in vitro-generated corticotrophs rescued physical activity levels and survival of the hosts. Thus, we report a useful methodology for the production of regulator-responsive human pituitary tissue that may benefit future studies in regenerative medicine. PMID:26762480

  20. Functional anterior pituitary generated in self-organizing culture of human embryonic stem cells.

    PubMed

    Ozone, Chikafumi; Suga, Hidetaka; Eiraku, Mototsugu; Kadoshima, Taisuke; Yonemura, Shigenobu; Takata, Nozomu; Oiso, Yutaka; Tsuji, Takashi; Sasai, Yoshiki

    2016-01-01

    Anterior pituitary is critical for endocrine systems. Its hormonal responses to positive and negative regulators are indispensable for homeostasis. For this reason, generating human anterior pituitary tissue that retains regulatory hormonal control in vitro is an important step for the development of cell transplantation therapy for pituitary diseases. Here we achieve this by recapitulating mouse pituitary development using human embryonic stem cells. We find that anterior pituitary self-forms in vitro following the co-induction of hypothalamic and oral ectoderm. The juxtaposition of these tissues facilitated the formation of pituitary placode, which subsequently differentiated into pituitary hormone-producing cells. They responded normally to both releasing and feedback signals. In addition, after transplantation into hypopituitary mice, the in vitro-generated corticotrophs rescued physical activity levels and survival of the hosts. Thus, we report a useful methodology for the production of regulator-responsive human pituitary tissue that may benefit future studies in regenerative medicine. PMID:26762480

  1. General Information about Pituitary Tumors

    MedlinePlus

    ... tumors that may spread to bones of the skull or the sinus cavity below the pituitary gland. ... sella (the bone at the base of the skull , where the pituitary gland sits). Recurrent Pituitary Tumors ...

  2. Treatment Option Overview (Pituitary Tumors)

    MedlinePlus

    ... tumors that may spread to bones of the skull or the sinus cavity below the pituitary gland. ... sella (the bone at the base of the skull , where the pituitary gland sits). Recurrent Pituitary Tumors ...

  3. Hypothalamus

    MedlinePlus

    ... of the brain that produces hormones that control: Body temperature Hunger Mood Release of hormones from many glands, ... Extreme thirst and frequent urination ( diabetes insipidus ) Low body temperature Slow heart rate

  4. Diethylstilbestrol increases the density of prolactin cells in male mouse pituitary by inducing proliferation of prolactin cells and transdifferentiation of gonadotropic cells.

    PubMed

    Shukuwa, Keiko; Izumi, Shin-Ichi; Hishikawa, Yoshitaka; Ejima, Kuniaki; Inoue, Satoshi; Muramatsu, Masami; Ouchi, Yasuyoshi; Kitaoka, Takashi; Koji, Takehiko

    2006-07-01

    Diethylstilbestrol (DES) has been implicated in mammalian abnormalities. We examined the effects of DES on follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL) cells in the pituitaries of male mice treated with various doses of DES for 20 days. DES reduced the density of FSH and LH cells in a dose-dependent manner, but increased that of PRL cells. When the expression of estrogen receptor (ER) alpha and beta was assessed, an induction of ERbeta by DES was found predominantly in PRL cells. However, since these effects were abolished in ERalpha knockout mice, DES appears to act primarily through ERalpha. When the expression of Ki-67 and Pit-1 in PRL cells was examined at various time-points after DES treatment, some PRL cells became Ki-67 positive at 10-15 days, and Pit-1-positive cells were increased at 5-15 days. Furthermore, some FSH and LH cells became Pit-1 positive, and co-localized with PRL at 5-10 days. Our results indicate that DES increases PRL cells by inducing proliferation of PRL cells and transdifferentiation of FSH/LH cells to PRL cells. PMID:16468032

  5. Dysregulated estrogen receptor signaling in the hypothalamic-pituitary-ovarian axis leads to ovarian epithelial tumorigenesis in mice.

    PubMed

    Laws, Mary J; Kannan, Athilakshmi; Pawar, Sandeep; Haschek, Wanda M; Bagchi, Milan K; Bagchi, Indrani C

    2014-03-01

    The etiology of ovarian epithelial cancer is poorly understood, mainly due to the lack of an appropriate experimental model for studying the onset and progression of this disease. We have created a mutant mouse model in which aberrant estrogen receptor alpha (ERα) signaling in the hypothalamic-pituitary-ovarian axis leads to ovarian epithelial tumorigenesis. In these mice, termed ERαd/d, the ERα gene was conditionally deleted in the anterior pituitary, but remained intact in the hypothalamus and the ovary. The loss of negative-feedback regulation by estrogen (E) at the level of the pituitary led to increased production of luteinizing hormone (LH) by this tissue. Hyperstimulation of the ovarian cells by LH resulted in elevated steroidogenesis, producing high circulating levels of steroid hormones, including E. The ERαd/d mice exhibited formation of palpable ovarian epithelial tumors starting at 5 months of age with 100% penetrance. By 15 months of age, 80% of ERαd/d mice die. Besides proliferating epithelial cells, these tumors also contained an expanded population of luteinized stromal cells, which acquire the ability to express P450 aromatase and synthesize E locally. In response to the elevated levels of E, the ERα signaling was accentuated in the ovarian epithelial cells of ERαd/d mice, triggering increased ERα-dependent gene expression, abnormal cell proliferation, and tumorigenesis. Consistent with these findings, treatment of ERαd/d mice with letrozole, an aromatase inhibitor, markedly reduced circulating E and ovarian tumor volume. We have, therefore, developed a unique animal model, which serves as a useful tool for exploring the involvement of E-dependent signaling pathways in ovarian epithelial tumorigenesis. PMID:24603706

  6. The retinoblastoma gene in human pituitary tumors

    SciTech Connect

    Cryns, V.L.; Arnold, A.; Alexander, J.M.; Klibanski, A. )

    1993-09-01

    Functional inactivation of the retinoblastoma (RB) tumor suppressor gene is important in the pathogenesis of many human tumors. Recently, the frequent occurrence of pituitary tumors was reported in mice genetically engineered to have one defective RB allele, a genetic background analogous to that of patients with familial retinoblastoma. The molecular pathogenesis of human pituitary tumors is largely unknown, and the potential role of RB gene inactivation in these neoplasms has not been examined. Consequently, the authors studied 20 human pituitary tumors (12 clinically nonfunctioning tumors, 4 somatotroph adenomas, 2 prolactinomas, and 2 corticotrophy adenomas) for tumor-specific allelic loss of the RB gene using a highly informative polymorphic locus within the gene. Control leukocyte DNA samples from 18 of these 20 patients were heterozygous at this locus, permitting genetic evaluation of their paired tumor specimens. In contrast to the pituitary tumors in the mouse model, none of these 18 human tumors exhibited RB allelic loss. These findings indicate that RB gene inactivation probably does not play an important role in the pathogenesis of common types of human pituitary tumors. 24 refs., 1 fig.

  7. Familial pituitary tumors.

    PubMed

    Alband, Neda; Korbonits, Márta

    2014-01-01

    Pituitary adenomas are benign intracranial neoplasms that present a major clinical concern due to hormone overproduction and/or tumor mass effects. The majority of pituitary adenomas occur sporadically; however, familial cases are increasingly being recognized, such as multiple endocrine neoplasia type 1 (MEN1), Carney complex (CNC), and familial isolated pituitary adenoma (FIPA). Familial pituitary tumors appear to differ from their sporadic counterparts both in their genetic basis and in clinical characteristics. Evidence suggests that, especially in MEN1 and FIPA, tumors are more aggressive and affect patients at a younger age, therefore justifying the importance of early diagnosis, while in Carney complex pituitary hyperplasia is common. The genetic alterations responsible for the formation of familial pituitary syndromes include the MEN1 gene, responsible for about 80% of MEN1 cases, the regulatory subunit of the protein kinase A, PRKAR1A, responsible for about 70% of Carney complex cases, and AIP, the gene coding the aryl hydrocarbon receptor interacting protein, responsible for about 20% of FIPA cases. Rarely other genes have also been found responsible for familial pituitary adenoma cases. McCune-Albright syndrome (MAS) also has a genetic origin due to mosaic mutations in the G protein-coupled α subunit coded by the GNAS1 gene. In this chapter, we summarize the genetic and clinical characteristics of these familial pituitary syndromes and MAS. PMID:25248598

  8. Double pituitary adenomas.

    PubMed

    Iacovazzo, D; Bianchi, A; Lugli, F; Milardi, D; Giampietro, A; Lucci-Cordisco, E; Doglietto, F; Lauriola, L; De Marinis, L

    2013-04-01

    Double pituitary adenomas represent up to 2.6 % of pituitary adenomas in large surgical series and up to 3.3 % of patients with Cushing's disease have been found to have double or multiple pituitary adenomas. We report the case of a 60-year-old male patient whose medical history began in 2002 with erectile dysfunction; hyperprolactinemia was found and MRI showed a 6-mm area of delayed enhancement in the lateral portion of the right pituitary lobe. Treatment with cabergoline was started with normalization of prolactin levels; the following MRI, performed in 2005 and 2008, showed shrinkage of the pituitary lesion. In 2005, the patient began to manifest weight gain, hypertension, and facial plethora, but no further evaluations were done. In January 2010, the patient came to our attention and underwent multiple tests that suggested Cushing's disease. A new MRI was negative. Bilateral inferior petrosal sinus sampling showed significant pituitary-to-peripheral ratio and, in May 2010, the patient underwent exploratory pituitary surgery with evidence of a 1-2-mm white-coloured midline area compatible with pituitary adenoma that was surgically removed. Post-operatively, the patient's clinical conditions improved with onset of secondary hypoadrenalism. The histologic examination confirmed a pituitary adenoma (immunostaining was found to be positive for ACTH and negative for prolactin). We report the case of an ACTH-producing microadenoma metachronous to a prolactin secreting microadenoma although not confirmed histologically, shrunk by medical treatment. A review of data in the literature regarding double or multiple pituitary adenomas has also been done. PMID:23325364

  9. Essential function of the transcription factor Rax in the early patterning of the mammalian hypothalamus.

    PubMed

    Orquera, Daniela P; Nasif, Sofia; Low, Malcolm J; Rubinstein, Marcelo; de Souza, Flávio S J

    2016-08-01

    The hypothalamus is a region of the anterior forebrain that controls basic aspects of vertebrate physiology, but the genes involved in its development are still poorly understood. Here, we investigate the function of the homeobox gene Rax/Rx in early hypothalamic development using a conditional targeted inactivation strategy in the mouse. We found that lack of Rax expression prior to embryonic day 8.5 (E8.5) caused a general underdevelopment of the hypothalamic neuroepithelium, while inactivation at later timepoints had little effect. The early absence of Rax impaired neurogenesis and prevented the expression of molecular markers of the dorsomedial hypothalamus, including neuropeptides Proopiomelanocortin and Somatostatin. Interestingly, the expression domains of genes expressed in the ventromedial hypothalamus and infundibulum invaded dorsal hypothalamic territory, showing that Rax is needed for the proper dorsoventral patterning of the developing medial hypothalamus. The phenotypes caused by the early loss of Rax are similar to those of eliminating the expression of the morphogen Sonic hedgehog (Shh) specifically from the hypothalamus. Consistent with this similarity in phenotypes, we observed that Shh and Rax are coexpressed in the rostral forebrain at late head fold stages and that loss of Rax caused a downregulation of Shh expression in the dorsomedial portion of the hypothalamus. PMID:27212025

  10. Expression studies of neuronatin in prenatal and postnatal rat pituitary.

    PubMed

    Kanno, Naoko; Higuchi, Masashi; Yoshida, Saishu; Yako, Hideji; Chen, Mo; Ueharu, Hiroki; Nishimura, Naoto; Kato, Takako; Kato, Yukio

    2016-05-01

    The pituitary gland, an indispensable endocrine organ that synthesizes and secretes pituitary hormones, develops with the support of many factors. Among them, neuronatin (NNAT), which was discovered in the neonatal mouse brain as a factor involved in neural development, has subsequently been revealed to be coded by an abundantly expressing gene in the pituitary gland but its role remains elusive. We analyze the expression profile of Nnat and the localization of its product during rat pituitary development. The level of Nnat expression was high during the embryonic period but remarkably decreased after birth. Immunohistochemistry demonstrated that NNAT appeared in the SOX2-positive stem/progenitor cells in the developing pituitary primordium on rat embryonic day 11.5 (E11.5) and later in the majority of SOX2/PROP1 double-positive cells on E13.5. Thereafter, during pituitary embryonic development, Nnat expression was observed in some stem/progenitor cells, proliferating cells and terminally differentiating cells. In postnatal pituitaries, NNAT-positive cells decreased in number, with most coexpressing Sox2 or Pit1, suggesting a similar role for NNAT to that during the embryonic period. NNAT was widely localized in mitochondria, peroxisomes and lysosomes, in addition to the endoplasmic reticulum but not in the Golgi. The present study thus demonstrated the variability in expression of NNAT-positive cells in rat embryonic and postnatal pituitaries and the intracellular localization of NNAT. Further investigations to obtain functional evidence for NNAT are a prerequisite. PMID:26613603

  11. A FSH-Secreting Pituitary Macroadenoma Causing A Testosterone Deficiency Syndrome.

    PubMed

    Wang, Xiong; Ge, Li; Cui, Yuanqing; Lang, Cuihong; Hao, Cuifang

    2014-04-01

    FSH-secreting pituitary adenomas can affect sexual and reproductive function. In this article, we have reported the case of a 32-year-old male with secondary infertility. The patient had sexual and reproductive disturbances. The test results of the blood samples indicated obviously decreased testosterone (T) and estradiol (E2) levels. Based on previous hormonal results, the patient received pituitary stimulation and human chorionic gonadotropin (hCG) tests. Both follicle stimulating hormone (FSH) and luteinizing hormone (LH) showed low response during the pituitary stimulation test. The results of the hCG test indicated that T/E2 could recover to a normal level. In addition, this patient was diagnosed with pituitary macroadenoma, which was supported by the pituitary MRI. The man's sexual and reproductive functions recovered following surgery. The pathological results confirmed that the tumor tissue was an FSH-secreting pituitary adenoma by immunohistochemical staining. The purpose of this report was to review the relative literature and discuss the influence of FSH-secreting pituitary adenomas on hormones through the hypothalamus-pituitary-testis axis. PMID:24696774

  12. Effect of. beta. -endorphin on catecholamine levels in rat hypothalamus and cerebral cortex

    SciTech Connect

    Slavnov, V.N.; Valueva, G.V.; Markov, V.V.; Luchitskii, E.V.

    1986-10-01

    The authors studied the effect of beta-endorphin on catecholamine concentrations in the hypothalmus and cerebral cortex in rats, as a contribution to the explanation of the mechanism of action of this peptide on certain pituitary trophic functions. Concentrations of dopamine, noradrenalin, and adrenalin were determined by a radioenzymatic method. A Mark 3 scintillation system was used for radiometric investigation of the samples. The results of these experiments indicate that beta-endorphin has a marked effect on brain catecholamine levels mainly in the hypothalamus.

  13. What Are Pituitary Tumors?

    MedlinePlus

    ... too little makes you sluggish. If a pituitary tumor makes too much TSH, it can cause hyperthyroidism (an overactive thyroid gland). Adrenocorticotropic hormone (ACTH, also known as corticotropin ) causes ...

  14. Pituitary Tumors: Condition Information

    MedlinePlus

    ... stress. Growth hormone helps control body growth and metabolism. Thyroid-stimulating hormone is involved in growth, body temperature, and heart rate. Nonfunctioning pituitary tumors (also called nonsecretory tumors) do ...

  15. Hypothalamic-pituitary-adrenal (HPA) axis function in the California mouse (Peromyscus californicus): Changes in baseline activity, reactivity, and fecal excretion of glucocorticoids across the diurnal cycle

    PubMed Central

    Harris, Breanna N.; Saltzman, Wendy; de Jong, Trynke R.; Milnes, Matthew R.

    2012-01-01

    The California mouse, Peromyscus californicus, is an increasingly popular animal model in behavioral, neural, and endocrine studies, but little is known about its baseline hypothalamicpituitary-adrenal (HPA) axis activity or HPA responses to stressors. We characterized plasma corticosterone (CORT) concentrations in P. californicus under baseline conditions across the diurnal cycle, in response to pharmacological manipulation of the HPA axis, and in response to a variety of stressors at different times of day. In addition, we explored the use of fecal samples to monitor adrenocortical activity non-invasively. California mice have very high baseline levels of circulating CORT that change markedly over 24 hours, but that do not differ between the sexes. This species may be somewhat glucocorticoid-resistant in comparison to other rodents as a relatively high dose of dexamethasone (5 mg/kg, s.c.) was required to suppress plasma CORT for 8 h post-injection. CORT responses to stressors and ACTH injection differed with time of day, as CORT concentrations were elevated more readily during the morning (inactive period) than in the evening (active period) when compared to time-matched control. Data from 3H-CORT injection studies show that the time course for excretion of fecal CORT, or glucocorticoid metabolites, differs with time of injection. Mice injected in the evening excreted the majority of fecal radioactivity 2–4 h post-injection whereas mice injected during the morning did so at 14–16 h post-injection. Unfortunately, the antibody we used does not adequately bind the most prevalent fecal glucocorticoid metabolites and therefore we could not validate its use for fecal assays. PMID:23026495

  16. Familial Isolated Pituitary Adenomas (FIPA) and the Pituitary Adenoma Predisposition due to Mutations in the Aryl Hydrocarbon Receptor Interacting Protein (AIP) Gene

    PubMed Central

    Aaltonen, Lauri A.; Daly, Adrian F.

    2013-01-01

    Pituitary adenomas are one of the most frequent intracranial tumors and occur with a prevalence of approximately 1:1000 in the developed world. Pituitary adenomas have a serious disease burden, and their management involves neurosurgery, biological therapies, and radiotherapy. Early diagnosis of pituitary tumors while they are smaller may help increase cure rates. Few genetic predictors of pituitary adenoma development exist. Recent years have seen two separate, complimentary advances in inherited pituitary tumor research. The clinical condition of familial isolated pituitary adenomas (FIPA) has been described, which encompasses the familial occurrence of isolated pituitary adenomas outside of the setting of syndromic conditions like multiple endocrine neoplasia type 1 and Carney complex. FIPA families comprise approximately 2% of pituitary adenomas and represent a clinical entity with homogeneous or heterogeneous pituitary adenoma types occurring within the same kindred. The aryl hydrocarbon receptor interacting protein (AIP) gene has been identified as causing a pituitary adenoma predisposition of variable penetrance that accounts for 20% of FIPA families. Germline AIP mutations have been shown to associate with the occurrence of large pituitary adenomas that occur at a young age, predominantly in children/adolescents and young adults. AIP mutations are usually associated with somatotropinomas, but prolactinomas, nonfunctioning pituitary adenomas, Cushing disease, and other infrequent clinical adenoma types can also occur. Gigantism is a particular feature of AIP mutations and occurs in more than one third of affected somatotropinoma patients. Study of pituitary adenoma patients with AIP mutations has demonstrated that these cases raise clinical challenges to successful treatment. Extensive research on the biology of AIP and new advances in mouse Aip knockout models demonstrate multiple pathways by which AIP may contribute to tumorigenesis. This review assesses

  17. Sex differences in the distribution of cytoplasmic oestrogen receptors in rat brain and pituitary: effects of gonadectomy and neonatal androgen treatment.

    PubMed

    Barley, J; Ginsburg, M; MacLusky, N J; Morris, I D; Thomas, P J

    1977-07-01

    High affinity binding of 17 beta-oestradiol was measured in cytosols of hypothalamus, amygdaloid region, pituitary and (in females) uterus of adult male and female rats. There were no differences between intact or gonadectomised male and female animals in any of the tissues in the equilibrium dissociation constants (Kd). The number of available binding sites (n) in brain and pituitary in intact females at metoestrus is higher than at proestrus but only in hypothalamus is n greater than in ovariectomised animals. Binding sites in male hypothalamus, amygdala and pituitary are significantly less than in metoestrous females; the sex difference is seen also in gonadectomised rats but is significant only in pituitary. In all female animals the highest concentration of binding sites in the hypothalamus is in the anterior part and the lowest in the posterior part. The distribution of binding sites and Kd values in adult females treated neonatally with testosterone propionate were not different from those of intact proestrous rats. In intact males the highest level of n was in mid-hypothalamus; after gonadectomy the pattern reverted to that in females. It is suggest that these results support the concept that testicular androgen is conversted in brain to a substance with affinity for cytosol oestrogen receptor. PMID:560238

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

    PubMed

    Handa, Robert J; Weiser, Michael J

    2014-04-01

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

  19. Mathematical model describing the thyroids-pituitary axis with distributed time delays in hormone transportation

    NASA Astrophysics Data System (ADS)

    Neamţu, Mihaela; Stoian, Dana; Navolan, Dan Bogdan

    2014-12-01

    In the present paper we provide a mathematical model that describe the hypothalamus-pituitary-thyroid axis in autoimmune (Hashimoto's) thyroiditis. Since there is a spatial separation between thyroid and pituitary gland in the body, time is needed for transportation of thyrotropin and thyroxine between the glands. Thus, the distributed time delays are considered as both weak and Dirac kernels. The delayed model is analyzed regarding the stability and bifurcation behavior. The last part contains some numerical simulations to illustrate the effectiveness of our results and conclusions.

  20. Early effects of cranial irradiation on hypothalamic-pituitary function

    SciTech Connect

    Lam, K.S.; Tse, V.K.; Wang, C.; Yeung, R.T.; Ma, J.T.; Ho, J.H.

    1987-03-01

    Hypothalamic-pituitary function was studied in 31 patients before and after cranial irradiation for nasopharyngeal carcinoma. The estimated radiotherapy (RT) doses to the hypothalamus and pituitary were 3979 +/- 78 (+/- SD) and 6167 +/- 122 centiGrays, respectively. All patients had normal pituitary function before RT. One year after RT, there was a significant decrease in the integrated serum GH response to insulin-induced hypoglycemia. In the male patients, basal serum FSH significantly increased, while basal serum LH and testosterone did not change. Moreover, in response to LHRH, the integrated FSH response was increased while that of LH was decreased. Such discordant changes in FSH and LH may be explained by a defect in LHRH pulsatile release involving predominantly a decrease in pulse frequency. The peak serum TSH response to TRH became delayed in 28 patients, suggesting a defect in TRH release. Twenty-one patients were reassessed 2 yr after RT. Their mean basal serum T4 and plasma cortisol levels had significantly decreased. Hyperprolactinemia associated with oligomenorrhoea was found in 3 women. Further impairment in the secretion of GH, FSH, LH, TSH, and ACTH had occurred, and 4 patients had hypopituitarism. Thus, progressive impairment in hypothalamic-pituitary function occurs after cranial irradiation and can be demonstrated as early as 1 yr after RT.

  1. Endothelin in human brain and pituitary gland: Presence of immunoreactive endothelin, endothelin messenger ribonucleic acid, and endothelin receptors

    SciTech Connect

    Takahashi, K.; Ghatei, M.A.; Jones, P.M.; Murphy, J.K.; Lam, H.C.; O'Halloran, D.J.; Bloom, S.R. )

    1991-03-01

    The presence of immunoreactive (IR) endothelin, endothelin mRNA, and endothelin receptors in human brain and pituitary gland has been studied by RIA, Northern blot hybridization, and receptor assay. IR endothelin was detected in all five brain regions examined (cerebral cortex, cerebellum, brain stem, basal ganglia, and hypothalamus) (6-10 fmol/g wet wt) and spinal cord (22 +/- 6 fmol/g wet wt, n = 7, mean +/- SEM). Higher concentrations of IR endothelin were found in the pituitary gland (147 +/- 30 fmol/g wet wt). Fast protein liquid chromatographic analysis of the IR endothelin in pituitary gland showed a large IR peak in the position of endothelin-3 and a smaller peak in the position of endothelin-1, whereas IR endothelin in the hypothalamus and brain stem was mainly endothelin-1. Endothelin messenger RNA was detected by Northern blot hybridization in the pituitary but not in hypothalamus. The receptor assay showed that 125I-endothelin-1 binding sites were present in large numbers in all five brain regions but were much less abundant in the pituitary gland. Binding capacity and dissociation constant were 5052 +/- 740 fmol/mg protein and 0.045 +/- 0.007 nM in brain stem and 963 +/- 181 fmol/mg protein and 0.034 +/- 0.009 nM in hypothalamus. In the pituitary gland, there were two classes of binding sites for endothelin with dissociation constants of 0.059 +/- 0.002 nM (binding capacity = 418 +/- 63 fmol/mg protein) and 0.652 +/- 0.103 nM (binding capacity = 1717 +/- 200 fmol/mg protein). Endothelin-1, -2 and -3 were almost equipotent in displacing the binding (IC50 approximately 0.04 nM). These findings are in accord with the possibility that endothelin acts as a neurotransmitter, neuromodulator or neurohormone in man.

  2. Treatment Options for Pituitary Tumors

    MedlinePlus

    ... brain, including the sella (the bone at the base of the skull , where the pituitary gland sits). ... sphenoid bone (a butterfly-shaped bone at the base of the skull ) to reach the pituitary gland . ...

  3. Notch signaling and proneural genes work together to control the neural building blocks for the initial scaffold in the hypothalamus

    PubMed Central

    Ware, Michelle; Hamdi-Rozé, Houda; Dupé, Valérie

    2014-01-01

    The vertebrate embryonic prosencephalon gives rise to the hypothalamus, which plays essential roles in sensory information processing as well as control of physiological homeostasis and behavior. While patterning of the hypothalamus has received much attention, initial neurogenesis in the developing hypothalamus has mostly been neglected. The first differentiating progenitor cells of the hypothalamus will give rise to neurons that form the nucleus of the tract of the postoptic commissure (nTPOC) and the nucleus of the mammillotegmental tract (nMTT). The formation of these neuronal populations has to be highly controlled both spatially and temporally as these tracts will form part of the ventral longitudinal tract (VLT) and act as a scaffold for later, follower axons. This review will cumulate and summarize the existing data available describing initial neurogenesis in the vertebrate hypothalamus. It is well-known that the Notch signaling pathway through the inhibition of proneural genes is a key regulator of neurogenesis in the vertebrate central nervous system. It has only recently been proposed that loss of Notch signaling in the developing chick embryo causes an increase in the number of neurons in the hypothalamus, highlighting an early function of the Notch pathway during hypothalamus formation. Further analysis in the chick and mouse hypothalamus confirms the expression of Notch components and Ascl1 before the appearance of the first differentiated neurons. Many newly identified proneural target genes were also found to be expressed during neuronal differentiation in the hypothalamus. Given the critical role that hypothalamic neural circuitry plays in maintaining homeostasis, it is particularly important to establish the targets downstream of this Notch/proneural network. PMID:25520625

  4. [Treatment of pituitary adenomas].

    PubMed

    Mezosi, Emese; Nemes, Orsolya

    2009-09-27

    According to epidemiological studies, the prevalence of pituitary adenomas is 16.5% and the majority of them are "incidentalomas". The symptoms of pituitary disorders are often non-specific; disturbances of pituitary function, compression symptoms, hypophysis apoplexy or accidental findings may help the diagnosis. The hormonal evaluation of pituitary adenomas is different from the algorithm used in the disorders of peripheral endocrine organs. The first-line therapy of prolactinomas are the dopamine agonists, and the aims of the treatment are to normalize the prolactin level, restore fertility in child-bearing age, decrease tumor mass, save or improve the residual pituitary function and inhibit the relapse of the disease. The available dopamine agonists in Hungary are bromocriptine and quinagolide. In case of tumors with good therapeutic response, medical therapy can be withdrawn after 3-5 years; hyperprolactinemia will not recur in 2/3 of these patients. Neurosurgery is the primary therapy of GH-, ACTH-, TSH-producing and inactive adenomas. In the last decades, significant improvement has been reached in surgical procedures, resulting in low mortality rates. Acromegalic patients with unresectable tumors have a great benefit from somatostatin analog treatment. The growth hormone receptor antagonist pegvisomant is the newest modality for the treatment of acromegaly. The medical therapy of Cushing's disease is still based on the inhibition of steroid production. A new, promising somatostatin analog, pasireotide is evaluated in clinical trials. The rare TSH-producing tumor can respond to both dopamine agonist and somatostatin analog therapy. The application of conventional radiotherapy has decreased; radiotherapy is mainly used in the treatment of invasive, incurable or malignant tumors. Further studies are needed to elucidate the exact role of radiosurgery and fractionated stereotaxic irradiation in the treatment of pituitary tumors. PMID:19758960

  5. Pituitary abscess: an unexpected diagnosis.

    PubMed

    Shuster, Anatoly; Gunnarsson, Thorsteinn; Sommer, Doron; Miller, Elka

    2010-02-01

    The pituitary gland can demonstrate a variety of pathologies with different clinical presentations. Amongst them, pituitary abscess is a rare infectious disease for which contrast-enhanced MRI aids the diagnostic pathway. We present a 16-year-old girl with imaging and surgical findings consistent with primary pituitary abscess. PMID:19937240

  6. Oxidant/antioxidant effects of chronic exposure to predator odor in prefrontal cortex, amygdala, and hypothalamus.

    PubMed

    Mejia-Carmona, G E; Gosselink, K L; Pérez-Ishiwara, G; Martínez-Martínez, A

    2015-08-01

    The incidence of anxiety-related diseases is increasing these days, hence there is a need to understand the mechanisms that underlie its nature and consequences. It is known that limbic structures, mainly the prefrontal cortex and amygdala, are involved in the processing of anxiety, and that projections from prefrontal cortex and amygdala can induce activity of the hypothalamic-pituitary-adrenal axis with consequent cardiovascular changes, increase in oxygen consumption, and ROS production. The compensatory reaction can include increased antioxidant enzymes activities, overexpression of antioxidant enzymes, and genetic shifts that could include the activation of antioxidant genes. The main objective of this study was to evaluate the oxidant/antioxidant effect that chronic anxiogenic stress exposure can have in prefrontal cortex, amygdala, and hypothalamus by exposition to predator odor. Results showed (a) sensitization of the HPA axis response, (b) an enzymatic phase 1 and 2 antioxidant response to oxidative stress in amygdala, (c) an antioxidant stability without elevation of oxidative markers in prefrontal cortex, (d) an elevation in phase 1 antioxidant response in hypothalamus. Chronic exposure to predator odor has an impact in the metabolic REDOX state in amygdala, prefrontal cortex, and hypothalamus, with oxidative stress being prevalent in amygdala as this is the principal structure responsible for the management of anxiety. PMID:25981530

  7. Molecular Imaging of Pituitary Pathology.

    PubMed

    de Herder, Wouter W

    2016-01-01

    The presence of large numbers and/or the high affinity of dopamine D2 and/or somatostatin receptors on pituitary adenomas may enable their visualization with radionuclide-coupled receptor agonists or antagonists. However, the role of these imaging modalities in the differential diagnosis of or therapeutic purposes for pituitary lesions is very limited. Only in very specific cases might these molecular imaging techniques become helpful. These include the differential diagnosis of pituitary lesions, ectopic production of pituitary hormones, such as adrenocorticotrophic hormone, growth hormone (GH) or their releasing hormones (corticotropin-releasing hormone and GH-releasing hormone), and the localization of metastases from pituitary carcinomas. PMID:27002335

  8. Pituitary cells in space

    NASA Technical Reports Server (NTRS)

    Hymer, W. C.; Shellenberger, K.; Grindeland, R.

    1994-01-01

    Cells of the mammalian pituitary gland synthesize and secrete several protein hormones which regulate a number of organ systems throughout the body. These include the musculoskeletal, immune, vascular and endocrine systems. Since changes occur in these tissues as a result of spaceflight, and since pituitary growth hormone (GH) and prolactin (PRL) play a role in the control of these systems on earth, we have focused attention over the last 10 years on GH and PRL cell function during and after spaceflight. The cumulative results of 4 spaceflight missions and several mimicked microgravity experiments establish 1) that production and release of biologically active GH and PRL is repeatedly and significantly attenuated (usually >50%) and 2) that changes in cell morphology also occur. In this paper we describe our results within the framework of methodologies and approaches frequently used to study pituitary cell function on earth. In so doing we hope to develop future flight experiments aimed at uncovering possible microgravity 'sensing systems' within the pituitary cell.

  9. Pituitary aspergillus infection.

    PubMed

    Moore, Lauren A; Erstine, Emily M; Prayson, Richard A

    2016-07-01

    Fungal infection should be considered in the differential diagnosis of a pituitary or sellar mass, albeit fungal infections involving the pituitary gland and sella are a rare occurrence. We report a case of Aspergillus infection involving the pituitary gland and sellar region discovered in a 74-year-old man. The patient had a history of hypertension, chronic renal disease, autoimmune hemolytic anemia and presented with right eye pain, headaches and worsening hemiparesis. Imaging studies revealed a right internal carotid artery occlusion and an acute right pontine stroke along with smaller infarcts in the right middle cerebral artery distribution. Clinically, the patient was thought to have vasculitis. An infectious etiology was not identified. He developed respiratory distress and died. At autopsy, necrotizing meningitis was discovered. A predominantly chronic inflammatory cell infiltrate consisting of benign-appearing lymphocytes, plasma cells and macrophages was accompanied by acute angle branching, angioinvasive hyphae which were highlighted on Gomori methenamine silver staining and were morphologically consistent with Aspergillus species. In previously reported cases of Aspergillus infection involving the pituitary or sella, most presented with headaches or impaired vision and were not immunocompromised. A transsphenoidal surgical approach is recommended in suspected cases in order to minimize the risk of dissemination of the infection. Some patients have responded well to antifungal medications once diagnosed. PMID:26896907

  10. Pituitary cells in space

    NASA Astrophysics Data System (ADS)

    Hymer, W. C.; Shellenberger, K.; Grindeland, R.

    1994-08-01

    Cells of the mammalian pituitary gland synthesize and secrete several protein hormones which regulate a number of organ systems throughout the body. These include the musculoskeletal, immune, vascular and endocrine systems. Since changes occur in these tissues as a result of spaceflight, and since pituitary growth hormone (GH) and prolactin (PRL) play a role in the control of these systems on earth, we have focused attention over the last 10 years on GH and PRL cell function during and after spaceflight. The cumulative results of 4 spaceflight missions and several mimicked microgravity (μG) experiments establish 1) that production and release of biologically active GH and PRL is repeatedly and significantly attenuated (usually > 50%) and 2) that changes in cell morphology also occur. In this paper we describe our results within the framework of methodologies and approaches frequently used to study pituitary cell function on earth. In so doing we hope to develop future flight experiments aimed at uncovering possible μG ``sensing systems'' within the pituitary cell.

  11. Pituitary Disorders and Osteoporosis

    PubMed Central

    Jawiarczyk-Przybyłowska, Aleksandra

    2015-01-01

    Various hormonal disorders can influence bone metabolism and cause secondary osteoporosis. The consequence of this is a significant increase of fracture risk. Among pituitary disorders such effects are observed in patients with Cushing's disease, hyperprolactinemia, acromegaly, and hypopituitarism. Severe osteoporosis is the result of the coexistence of some of these disorders and hypogonadism at the same time, which is quite often. PMID:25873948

  12. Hypothalamic-Pituitary Function in Brain Death: A Review.

    PubMed

    Nair-Collins, Michael; Northrup, Jesse; Olcese, James

    2016-01-01

    The Uniform Determination of Death Act (UDDA) states that an individual is dead when "all functions of the entire brain" have ceased irreversibly. However, it has been questioned whether some functions of the hypothalamus, particularly osmoregulation, can continue after the clinical diagnosis of brain death (BD). In order to learn whether parts of the hypothalamus can continue to function after the diagnosis of BD, we performed 2 separate systematic searches of the MEDLINE database, corresponding to the functions of the posterior and anterior pituitary. No meta-analysis is possible due to nonuniformity in the clinical literature. However, some modest generalizations can reasonably be drawn from a narrative review and from anatomic considerations that explain why these findings should be expected. We found evidence suggesting the preservation of hypothalamic function, including secretion of hypophysiotropic hormones, responsiveness to anterior pituitary stimulation, and osmoregulation, in a substantial proportion of patients declared dead by neurological criteria. We discuss several possible explanations for these findings. We conclude by suggesting that additional clinical research with strict inclusion criteria is necessary and further that a more nuanced and forthright public dialogue is needed, particularly since standard diagnostic practices and the UDDA may not be entirely in accord. PMID:24692211

  13. Hypothalamic, pituitary and thyroid dysfunction after radiotherapy to the head and neck

    SciTech Connect

    Samaan, N.A.; Vieto, R.; Schultz, P.N.; Maor, M.; Meoz, R.T.; Sampiere, V.A.; Cangir, A.; Ried, H.L.; Jesse, R.H. Jr.

    1982-11-01

    One hundred-ten patients who had nasopharyngeal cancer and paranasal sinus tumors and were free of the primary disease were studied one to 26 years following radiotherapy. There were 70 males and 40 females ranging in age from 4 to 75 years, with a mean age of 36.5 years. During therapy both the hypothalamus and the anterior pituitary gland were in the field of irradiation. The radiation dose to the hypothalamus and the anterior pituitary gland was estimated to be 400 to 7500 rad with a median dose of 5618 rad to the anterior pituitary gland and a median dose of 5000 rad to the hypothalamus. We found evidence of endocrine deficiencies in 91 of the 110 patients studied. Seventy-six patients showed evidence of one or more hypothalamic lesions and 43 patients showed evidence of primary pituitary deficiency. Forty of the 66 patients who received radiotherapy to the neck for treatment or prevention of lymph node metastasis showed evidence of primary hypothyroidism. The range of the dose to the thyroid area was 3000 to 8800 rad with a median of 5000 rad. One young adult woman who developed galactorrhea and amenorrhea 2 years following radiotherapy showed a high serum prolactin level, but had normal anterior pituitary function and sella turcica. She regained her menses and had a normal pregnancy and delivery following bromocriptine therapy. These results indicate that endocrine deficiencies after radiotherapy for tumors of the head and neck are common and should be detected early and treated. Long-term follow-up of these patients is indicated since complications may appear after the completion of radiotherapy.

  14. Effects of memantine alone and with acute 'binge' cocaine on hypothalamic-pituitary-adrenal activity in the rat.

    PubMed

    Zhou, Y; Yuferov, V P; Spangler, R; Maggos, C E; Ho, A; Kreek, M J

    1998-07-01

    The effects of memantine, a non-competitive NMDA-receptor antagonist used in the management of dementia, and its coadministration with acute 'binge' pattern cocaine on hypothalamic-pituitary-adrenal axis activity were investigated in the rat. Measurements 3 h after injections showed that memantine alone at 20 mg kg(-1) (i.p.), but not 10 mg kg(-1), increased corticotropin-releasing factor (CRF) mRNA levels in the hypothalamus and both adrenocorticotropic hormone and corticosterone levels in the blood, and decreased type I CRF receptor mRNA in the anterior pituitary. Our previous studies have shown that acute 'binge' cocaine increases CRF mRNA levels in the hypothalamus. In this study, pretreatment with memantine (10 and 20 mg kg(-1), i.p.) did not alter the up-regulation of hypothalamic CRF mRNA induced by acute 'binge' cocaine (3 x 15 mg kg(-1), i.p.). Of interest, pretreatment with memantine at 10 mg kg(-1), which alone had no effect on corticosterone levels, caused a greater elevation of corticosterone levels in combination with 'binge' cocaine than acute 'binge' cocaine alone, indicating that memantine does not attenuate 'binge' cocaine-stimulated hypothalamic-pituitary-adrenal activity. These results indicate that both memantine and acute 'binge' cocaine stimulate hypothalamic-pituitary-adrenal activity by activating CRF neurons in the hypothalamus. PMID:9718269

  15. Brain-endocrine interactions: a microvascular route in the mediobasal hypothalamus.

    PubMed

    Ciofi, Philippe; Garret, Maurice; Lapirot, Olivier; Lafon, Pierrette; Loyens, Anne; Prévot, Vincent; Levine, Jon E

    2009-12-01

    Blood-borne hormones acting in the mediobasal hypothalamus, like those controlling food intake, require relatively direct access to target chemosensory neurons of the arcuate nucleus (ARC). An anatomical substrate for this is a permeable microvasculature with fenestrated endothelial cells in the ARC, a system that has awaited comprehensive documentation. Here, the immunofluorescent detection of endothelial fenestral diaphragms in the rat ARC allowed us to quantitate permeable microvessels throughout its rostrocaudal extent. We have determined that permeable microvessels are part of the subependymal plexus irrigating exclusively the ventromedial (vm) ARC from the subadjacent neuroendocrine median eminence. Unexpectedly, permeable microvessels were concentrated proximal to the pituitary stalk. This marked topography strongly supports the functional importance of retrograde blood flow from the pituitary to the vmARC, therefore making a functional relationship between peripheral long-loop, pituitary short-loop, and neuroendocrine ultra-short loop feedback, altogether converging for integration in the vmARC (formerly known as the hypophysiotrophic area), thereby so pivotal as a multicompetent brain endocrinostat. PMID:19837874

  16. Molecular Mechanisms Underlying Pituitary Pathogenesis.

    PubMed

    Sapochnik, Melanie; Nieto, Leandro Eduardo; Fuertes, Mariana; Arzt, Eduardo

    2016-04-01

    During the last years, progress has been made on the identification of mechanisms involved in anterior pituitary cell transformation and tumorigenesis. Oncogene activation, tumor suppressor gene inactivation, epigenetic changes, and microRNAs deregulation contribute to the initiation of pituitary tumors. Despite the high prevalence of pituitary adenomas, they are mostly benign, indicating that intrinsic mechanisms may regulate pituitary cell expansion. Senescence is characterized by an irreversible cell cycle arrest and represents an important protective mechanism against malignancy. Pituitary tumor transforming gene (PTTG) is an oncogene involved in early stages of pituitary tumor development, and also triggers a senescence response by activating DNA-damage signaling pathway. Cytokines, as well as many other factors, play an important role in pituitary physiology, affecting not only cell proliferation but also hormone secretion. Special interest is focused on interleukin-6 (IL-6) because its dual function of stimulating pituitary tumor cell growth but inhibiting normal pituitary cells proliferation. It has been demonstrated that IL-6 has a key role in promoting and maintenance of the senescence program in tumors. Senescence, triggered by PTTG activation and mediated by IL-6, may be a mechanism for explaining the benign nature of pituitary tumors. PMID:26718581

  17. Expression of the putative gonadotropin-inhibitory hormone receptor, NPFFR1, in the anterior pituitary gland of the gilt is affected by age and sexual maturation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gonadotropin-inhibitory hormone (GnIH) purportedly suppresses secretion of luteinizing hormone (LH) by acting through a G-protein coupled receptor (NPFFR1) in the anterior pituitary gland and hypothalamus. The objective of these studies was to determine if expression of mRNA for NPFFR1 in the reprod...

  18. Effects of acute dieldrin exposure on neurotransmitters and global gene transcription in largemouth bass (Micropterus salmoides) hypothalamus

    PubMed Central

    Martyniuk, Christopher J.; Feswick, April; Spade, Daniel J.; Kroll, Kevin J.; Barber, David S.; Denslow, Nancy D.

    2010-01-01

    Exposure to dieldrin induces neurotoxic effects in the vertebrate CNS and disrupts reproductive processes in teleost fish. Reproductive impairment observed in fish by dieldrin is likely the result of multiple effects along the hypothalamic-pituitary-gonadal axis but the molecular signaling cascades are not well characterized. To better elucidate the mode of action of dieldrin in the hypothalamus, this study measured neurotransmitter levels and examined the transcriptomic response in female largemouth bass (LMB) to an acute treatment of dieldrin. Male and female LMB were injected with either vehicle or 10 mg dieldrin/kg and sacrificed after seven days. There were no significant changes in dopamine or DOPAC concentrations in the neuroendocrine brain of males and females after treatment but GABA levels in females were moderately increased 20–30% in the hypothalamus and cerebellum. In the female hypothalamus, there were 227 transcripts (p<0.001) identified as being differentially regulated by dieldrin. Functional enrichment analysis revealed transcription, DNA repair, ubiquitin-proteasome pathway, and cell communication, as biological processes over-represented in the microarray analysis. Pathway analysis identified DNA damage, inflammation, regeneration, and Alzheimer’s disease as major cell processes and diseases affected by dieldrin. Using multiple bioinformatics approaches, this study demonstrates that the teleostean hypothalamus is a target for dieldrin-induced neurotoxicity and provides mechanistic evidence that dieldrin activates similar cell pathways and biological processes that are also associated with the etiology of human neurological disorders. PMID:20438755

  19. The novel neuropeptide phoenixin is highly co-expressed with nesfatin-1 in the rat hypothalamus, an immunohistochemical study.

    PubMed

    Pałasz, Artur; Rojczyk, Ewa; Bogus, Katarzyna; Worthington, John J; Wiaderkiewicz, Ryszard

    2015-04-10

    The hypothalamus regulates a number of autonomic functions essential for homeostasis; therefore, investigations concerning hypothalamic neuropeptides and their functions and distribution are of great importance in contemporary neuroscience. Recently, novel regulatory factors expressed in the hypothalamus have been discovered, of which nesfatin-1 and phoenixin (PNX), show intriguing similarities in their brain distributions. There are currently few studies characterizing PNX expression, so it is imperative to accurately trace its localization, with particular attention to the hypothalamic nuclei and nesfatin-1 co-expression. Using fluorescence and classical immunohistochemical stainings on adult rat brain, we visualized the potential co-expression of nesfatin-1 and PNX immunoreactive cells. We have demonstrated a distinct PNX-immunoreactivity in 21-32% of cells in the arcuate nucleus, paraventricular nucleus, ventromedial and lateral hypothalamus. Nesfatin-1 expression reached 45-68% of all neurons in the same sites, while co-expression was strikingly seen in the vast majority (70-86%) of PNX-immunoreactive neurons in the rat hypothalamic nuclei. Our results demonstrate for the first time, a wide distribution of PNX in the hypothalamus which could implicate a potential functional relationship with nesfatin-1, possibly in the regulation of the hypothalamic-pituitary-gonadal axis or other autonomic functions, which require further study. PMID:25736948

  20. Pituitary stalk tuberculoma.

    PubMed

    Stalldecker, Graciela; Diez, Sabrina; Carabelli, Alejandra; Reynoso, Roxana; Rey, Raul; Hofmann, Nestor; Beresñak, Alejandro

    2002-01-01

    Pituitary tuberculomas are exceptionally rare. Even with no evidence of systemic tuberculosis, it is important to recognize these lesions in the differential diagnosis of the intrasuprasellar tumors because they are curable. At present, in developed countries the frequency of intracranial tuberculomas of nervous system tumors is around 0.5-4%, whereas in under developed countries is 15-30%. It mainly affects children and young adults. In some cases, an accurate diagnosis may lead to an efficient medical therapy on the basis of biological, hormonal and imaging scans examinations. The case we studied shows the difficulties encountered in the diagnosis of a thickened stalk having normal pituitary image. It is to be highlighted the usage of the Polymerase Chain Reaction (PCR) technique. PMID:12812306

  1. Familial pituitary adenomas.

    PubMed

    Vandeva, S; Vasilev, V; Vroonen, L; Naves, L; Jaffrain-Rea, M-L; Daly, A F; Zacharieva, S; Beckers, A

    2010-12-01

    Pituitary adenomas are benign intracranial neoplasms that present a major clinical concern because of hormonal overproduction or compression symptoms of adjacent structures. Most arise in a sporadic setting with a small percentage developing as a part of familial syndromes such as multiple endocrine neoplasia type 1 (MEN1), Carney complex (CNC), and the recently described familial isolated pituitary adenomas (FIPA) and MEN-4. While the genetic alterations responsible for the formation of sporadic adenomas remain largely unknown, considerable advances have been made in defining culprit genes in these familial syndromes. Mutations in MEN1 and PRKAR1A genes are found in the majority of MEN1 and CNC patients, respectively. About 15% of FIPA kindreds present with mutations of the aryl hydrocarbon receptor-interacting protein (AIP) gene. Mutations in the CDKN1B gene, encoding p27(Kip)¹ were identified in MEN4 cases. Familial tumours appear to differ from their sporadic counterparts not only in genetic basis but also in clinical characteristics. Evidence suggests that, especially in MEN1 and FIPA, they are more aggressive and affect patients at younger age, therefore justifying the importance of early diagnosis. In this review, we summarize the genetic and clinical characteristics of these familial pituitary adenomas. PMID:20961530

  2. Human Pituitary Adenoma Proteomics: New Progresses and Perspectives.

    PubMed

    Zhan, Xianquan; Wang, Xiaowei; Cheng, Tingting

    2016-01-01

    Pituitary adenoma (PA) is a common intracranial neoplasm that impacts on human health through interfering hypothalamus-pituitary-target organ axis systems. The development of proteomics gives great promises in the clarification of molecular mechanisms of a PA and discovery of effective biomarkers for prediction, prevention, early-stage diagnosis, and treatment for a PA. A great progress in the field of PA proteomics has been made in the past 10 years, including (i) the use of laser-capture microdissection, (ii) proteomics analyses of functional PAs (such as prolactinoma), invasive and non-invasive non-functional pituitary adenomas (NFPAs), protein post-translational modifications such as phosphorylation and tyrosine nitration, NFPA heterogeneity, and hormone isoforms, (iii) the use of protein antibody array, (iv) serum proteomics and peptidomics, (v) the integration of proteomics and other omics data, and (vi) the proposal of multi-parameter systematic strategy for a PA. This review will summarize these progresses of proteomics in PAs, point out the existing drawbacks, propose the future research directions, and address the clinical relevance of PA proteomics data, in order to achieve our long-term goal that is use of proteomics to clarify molecular mechanisms, construct molecular networks, and discover effective biomarkers. PMID:27303365

  3. Synchronous pituitary adenoma and pituicytoma.

    PubMed

    Neidert, Marian C; Leske, Henning; Burkhardt, Jan-Karl; Kollias, Spyros S; Capper, David; Schrimpf, Daniel; Regli, Luca; Rushing, Elisabeth J

    2016-01-01

    Pituicytoma is a rare benign neoplasm arising in the sellar region, usually found in the posterior lobe and/or pituitary stalk. Here, we report the case of a 67-year-old woman who presented with bitemporal hemianopsia and visual impairment accompanied by mildly elevated prolactin. Pathologic and molecular examination of the tissue removed transsphenoidally revealed 2 distinct tumors: pituitary adenoma and pituicytoma. To the best of our knowledge, histologically proven pituicytoma and pituitary adenoma have never been reported together. PMID:26476569

  4. Identification of Human GnIH Homologs, RFRP-1 and RFRP-3, and the Cognate Receptor, GPR147 in the Human Hypothalamic Pituitary Axis

    PubMed Central

    Ubuka, Takayoshi; Morgan, Kevin; Pawson, Adam J.; Osugi, Tomohiro; Chowdhury, Vishwajit S.; Minakata, Hiroyuki; Tsutsui, Kazuyoshi; Millar, Robert P.; Bentley, George E.

    2009-01-01

    The existence of a hypothalamic gonadotropin-inhibiting system has been elusive. A neuropeptide named gonadotropin-inhibitory hormone (GnIH, SIKPSAYLPLRF-NH2) which directly inhibits gonadotropin synthesis and release from the pituitary was recently identified in quail hypothalamus. Here we identify GnIH homologs in the human hypothalamus and characterize their distribution and biological activity. GnIH homologs were isolated from the human hypothalamus by immunoaffinity purification, and then identified as MPHSFANLPLRF-NH2 (human RFRP-1) and VPNLPQRF-NH2 (human RFRP-3) by mass spectrometry. Immunocytochemistry revealed GnIH-immunoreactive neuronal cell bodies in the dorsomedial region of the hypothalamus with axonal projections to GnRH neurons in the preoptic area as well as to the median eminence. RT-PCR and subsequent DNA sequencing of the PCR products identified human GnIH receptor (GPR147) mRNA expression in the hypothalamus as well as in the pituitary. In situ hybridization further identified the expression of GPR147 mRNA in luteinizing hormone producing cells (gonadotropes). Human RFRP-3 has recently been shown to be a potent inhibitor of gonadotropin secretion in cultured sheep pituitary cells by inhibiting Ca2+ mobilization. It also directly modulates GnRH neuron firing. The identification of two forms of GnIH (RFRP-1 and RFRP-3) in the human hypothalamus which targets human GnRH neurons and gonadotropes and potently inhibit gonadotropin in sheep models provides a new paradigm for the regulation of hypothalamic-pituitary-gonadal axis in man and a novel means for manipulating reproductive functions. PMID:20027225

  5. Leptin potentiates astrogenesis in the developing hypothalamus

    PubMed Central

    Rottkamp, Daniele M.; Rudenko, Ivan A.; Maier, Matthew T.; Roshanbin, Sahar; Yulyaningsih, Ernie; Perez, Luz; Valdearcos, Martin; Chua, Streamson; Koliwad, Suneil K.; Xu, Allison W.

    2015-01-01

    Background The proper establishment of hypothalamic feeding circuits during early development has a profound influence on energy homeostasis, and perturbing this process could predispose individuals to obesity and its associated consequences later in life. The maturation of hypothalamic neuronal circuitry in rodents takes place during the initial postnatal weeks, and this coincides with a dramatic surge in the circulating level of leptin, which is known to regulate the outgrowth of key neuronal projections in the maturing hypothalamus. Coincidently, this early postnatal period also marks the rapid proliferation and expansion of astrocytes in the brain. Methods Here we examined the effects of leptin on the proliferative capacity of astrocytes in the developing hypothalamus by treating postnatal mice with leptin. Mutant mice were also generated to conditionally remove leptin receptors from glial fibrillary acidic protein (GFAP)-expressing cells in the postnatal period. Results and conclusions We show that GFAP-expressing cells in the periventricular zone of the 3rd ventricle were responsive to leptin during the initial postnatal week. Leptin enhanced the proliferation of astrocytes in the postnatal hypothalamus and conditional removal of leptin receptors from GFAP-expressing cells during early postnatal period limited astrocyte proliferation. While increasing evidence demonstrates a direct role of leptin in regulating astrocytes in the adult brain, and given the essential function of astrocytes in modulating neuronal function and connectivity, our study indicates that leptin may exert its metabolic effects, in part, by promoting hypothalamic astrogenesis during early postnatal development. PMID:26629411

  6. In vivo and in vitro effects of chromium VI on anterior pituitary hormone release and cell viability

    SciTech Connect

    Quinteros, Fernanda A.; Poliandri, Ariel H.B.; Machiavelli, Leticia I.; Cabilla, Jimena P.; Duvilanski, Beatriz H. . E-mail: neuroend@ffyb.uba.ar

    2007-01-01

    Hexavalent chromium (Cr VI) is a highly toxic metal and an environmental pollutant. Different studies indicate that Cr VI exposure adversely affects reproductive functions. This metal has been shown to affect several tissues and organs but Cr VI effects on pituitary gland have not been reported. Anterior pituitary hormones are central for the body homeostasis and have a fundamental role in reproductive physiology. The aim of this study was to evaluate the effect of Cr VI at the pituitary level both in vivo and in vitro. We showed that Cr VI accumulates in the pituitary and hypothalamus, and decreases serum prolactin levels in vivo but observed no effects on LH levels. In anterior pituitary cells in culture, the effect of Cr VI on hormone secretion followed the same differential pattern. Besides, lactotrophs were more sensitive to the toxicity of the metal. As a result of oxidative stress generation, Cr VI induced apoptosis evidenced by nuclear fragmentation and caspase 3 activation. Our results indicate that the anterior pituitary gland can be a target of Cr VI toxicity in vivo and in vitro, thus producing a negative impact on the hypothalamic-pituitary-gonadal axis and affecting the normal endocrine function.

  7. Resting state functional MRI connectivity predicts hypothalamus-pituitary-axis status in healthy males.

    PubMed

    Kiem, Sara A; Andrade, Kátia C; Spoormaker, Victor I; Holsboer, Florian; Czisch, Michael; Sämann, Philipp G

    2013-08-01

    Homeostasis of the human stress response system is critically maintained by a hierarchical system of neural and endocrine elements for which intact negative feedback is important to prevent maladaptation towards stress. Such feedback is efficiently probed by the established combined dexamethasone-suppression/corticotropin-releasing hormone stimulation (dex/CRH) test. Here we investigate which suprahypothalamic networks might modulate the response assessed by this neuroendocrine test. Combined resting state fMRI (rs-fMRI)/EEG was acquired in 20 healthy male volunteers along with dex/CRH profiles obtained on a different day outside the scanner. Seed-based network analysis and inter-seed cross correlation analysis for selected atlas-based limbic, paralimbic and medial prefrontal cortex seeds were correlated with stimulated cortisol and adrenocorticotropin hormone (ACTH) concentrations. Lower connectivity between a left hippocampus-based network and the right hippocampus significantly predicted stimulated cortisol concentration (R(2)=0.70, corrected pcluster=0.001). Six further significantly negative correlations were detected mainly in the left anterior cingulate cortex (ACC) and the medial prefrontal cortex (mPFC). The strongest positive correlation with stimulated hormone concentration was detected for the left subcallosal ACC (ACTH, R(2)=0.57, corrected pcluster=0.009). Inter-seed connectivity mainly pointed to hippocampal/amygdala interactions as correlates of the dex/CRH response. In conclusion, resting state functional connectivity patterns of limbic, particularly hippocampal, as well as cingulate and medial prefrontal areas can explain some of the variance of the dex/CRH test in healthy subjects. Functional connectivity analysis can be considered useful to study supra-hypothalamic control systems of the HPA axis. PMID:23279846

  8. Hypothalamus-Pituitary-Adrenal Axis, Hair Cortisol and the Metabolic Syndrome.

    PubMed

    Gaete, Helen Patricia

    2015-09-01

    In this paper we discuss the possibility of using Hair Cortisol in Clinical Practice to monitor HPA status in patents at risk of developing the Metabolic Syndrome, and also its possible use to assess effectiveness of the effectiveness of treatment in patients with the Metabolic Syndrome. PMID:26417828

  9. Anxiety, coping skills and hypothalamus-pituitary-adrenal (HPA) axis in patients with endometriosis

    PubMed Central

    Quiñones, Maria; Urrutia, Rebecca; Torres-Reverón, Annelyn; Vincent, Katy; Flores, Idhaliz

    2015-01-01

    Background Endometriosis is an inflammatory disease that is defined by growth of endometrial tissue outside the uterus, resulting in pain, infertility, and emotional distress. Previous studies have shown that the HPA axis is compromised in patients with chronic, painful diseases, including endometriosis. However, the underlying mechanisms and the physiological and emotional consequences of dysfunctions in the HPA axis in these patients are largely unknown. We aimed to understand whether diurnal circulating cortisol levels in women with endometriosis are affected and how this impacts their emotional and behavioral responses. Methods Thirty-two patients with endometriosis and 36 healthy control women provided saliva samples and completed a series of psychological questionnaires. Salivary cortisol levels were measured in duplicate using a colorimetric immunoassay. Results There were significant differences in average cortisol levels between endometriosis patients and controls. A negative correlation was found between cortisol levels and infertility and dyspareunia. Furthermore, incapacitating pain was found to be a strong predictor of hypocortisolism. Women with endometriosis reported higher levels of trait anxiety, but showed no differences in perceived stress or in coping styles compared to the control group. Conclusions This study supports previous reports of hypocortisolism as a biomarker of aberrant HPA responses in women with endometriosis. Moreover, it provides further insight into the link between HPA axis dysregulation, emotional responses, and the high comorbidity between endometriosis and other inflammatory conditions. PMID:26900480

  10. Imaging of pediatric pituitary endocrinopathies

    PubMed Central

    Chaudhary, Vikas; Bano, Shahina

    2012-01-01

    Accurate investigation of the hypothalamic-pituitary area is required in pediatric patients for diagnosis of endocrine-related disorders. These disorders include hypopituitarism, growth failure, diencephalic syndrome, delayed puberty, precocious puberty, diabetes insipidus, syndrome of inappropriate antidiuretic hormone (SIADH) secretion, and hyperpituitarism. Magnetic resonance imaging (MRI) is the modality of choice to visualize hypothalamic-pituitary axis and associated endocrinopathies. Neuroimaging can be normal or disclose abnormalities related to pituitary-hypothalamic axis like (i) congenital and developmental malformations; (ii) tumors; (iii) cystic lesions; and (iv) infectious and inflammatory conditions. Classical midline anomalies like septo-optic dysplasias or corpus callosum agenesis are commonly associated with pituitary endocrinopathies and also need careful evaluation. In this radiological review, we will discuss neuroendocrine disorders related to hypothalamic pituitary-axis. PMID:23087850

  11. Establishment and culture optimization of a new type of pituitary immortalized cell line

    SciTech Connect

    Kokubu, Yuko; Asashima, Makoto; Kurisaki, Akira

    2015-08-07

    The pituitary gland is a center of the endocrine system that controls homeostasis in an organism by secreting various hormones. The glandular anterior pituitary consists of five different cell types, each expressing specific hormones. However, their regulation and the appropriate conditions for their in vitro culture are not well defined. Here, we report the immortalization of mouse pituitary cells by introducing TERT, E6, and E7 transgenes. The immortalized cell lines mainly expressed a thyrotroph-specific thyroid stimulating hormone beta (Tshb). After optimization of the culture conditions, these immortalized cells proliferated and maintained morphological characteristics similar to those of primary pituitary cells under sphere culture conditions in DMEM/F12 medium supplemented with N2, B27, basic FGF, and EGF. These cell lines responded to PKA or PKC pathway activators and induced the expression of Tshb mRNA. Moreover, transplantation of the immortalized cell line into subcutaneous regions and kidney capsules of mice further increased Tshb expression. These results suggest that immortalization of pituitary cells with TERT, E6, and E7 transgenes is a useful method for generating proliferating cells for the in vitro analysis of pituitary regulatory mechanisms. - Highlights: • Mouse pituitary cell lines were immortalized by introducing TERT, E6, and E7. • The immortalized cell lines mainly expressed thyroid stimulating hormone beta. • The cell lines responded to PKA or PKC pathway activators, and induced Tshb.

  12. Leptin modulates the expression of its receptors in the hypothalamic-pituitary-ovarian axis in a differential way.

    PubMed

    Di Yorio, M P; Bilbao, M G; Pustovrh, M C; Prestifilippo, J P; Faletti, A G

    2008-08-01

    To investigate the expression of leptin receptors (Ob-R) in the rat hypothalamus-pituitary-ovarian axis, immature rats were treated with eCG/hCG and Ob-R expression was evaluated by western blot analysis. The Ob-R expression increased 24 h after eCG administration in all the tissues assayed. In the hypothalamus, these levels immediately decreased to those obtained without treatment. In the pituitary, the Ob-R expression continued to be elevated 48 h after eCG administration, whereas the hCG injection did not modify these levels. Similar results were obtained with the ovarian long isoform. To assess the effect of leptin on its receptors, Ob-R was assessed in hypothalamus, pituitary and ovarian explants cultured in the presence or absence of leptin (0.3-500 ng/ml). In the hypothalamus, we found a biphasic effect: the Ob-R expression was either reduced or increased at low or high concentrations of leptin respectively. LH-releasing hormone secretion increased at 1 ng/ml. In the pituitary, Ob-R increased at 10 or 30 ng/ml of leptin for the long and short isoforms respectively. Leptin also induced an increase in LH release at 30 ng/ml. In the ovarian culture, the presence of leptin produced an increase in Ob-R expression at different ranges of concentrations and a dose-dependent biphasic effect on the progesterone production. In conclusion, all these results clearly suggest that leptin is able to modulate the expression of its own receptors in the reproductive axis in a differential way. Moreover, the positive or negative effect that leptin exerts on the ovulatory process may be dependent on this regulation. PMID:18515494

  13. MicroRNAs Regulate Pituitary Development, and MicroRNA 26b Specifically Targets Lymphoid Enhancer Factor 1 (Lef-1), Which Modulates Pituitary Transcription Factor 1 (Pit-1) Expression*

    PubMed Central

    Zhang, Zichao; Florez, Sergio; Gutierrez-Hartmann, Arthur; Martin, James F.; Amendt, Brad A.

    2010-01-01

    To understand the role of microRNAs (miRNAs) in pituitary development, a group of pituitary-specific miRNAs were identified, and Dicer1 was then conditionally knocked out using the Pitx2-Cre mouse, resulting in the loss of mature miRNAs in the anterior pituitary. The Pitx2-Cre/Dicer1 mutant mice demonstrate growth retardation, and the pituitaries are hypoplastic with an abnormal branching of the anterior lobe, revealing a role for microRNAs in pituitary development. Growth hormone, prolactin, and thyroid-stimulating hormone β-subunit expression were decreased in the Dicer1 mutant mouse, whereas proopiomelanocortin and luteinizing hormone β-subunit expression were normal in the mutant pituitary. Further analyses revealed decreased Pit-1 and increased Lef-1 expression in the mutant mouse pituitary, consistent with the repression of the Pit-1 promoter by Lef-1. Lef-1 directly targets and represses the Pit-1 promoter. miRNA-26b (miR-26b) was identified as targeting Lef-1 expression, and miR-26b represses Lef-1 in pituitary and non-pituitary cell lines. Furthermore, miR-26b up-regulates Pit-1 and growth hormone expression by attenuating Lef-1 expression in GH3 cells. This study demonstrates that microRNAs are critical for anterior pituitary development and that miR-26b regulates Pit-1 expression by inhibiting Lef-1 expression and may promote Pit-1 lineage differentiation during pituitary development. PMID:20807761

  14. Sensitization of the Hypothalamic-Pituitary-Adrenal Axis in a Male Rat Chronic Stress Model.

    PubMed

    Franco, Alier J; Chen, Chun; Scullen, Tyler; Zsombok, Andrea; Salahudeen, Ahmed A; Di, Shi; Herman, James P; Tasker, Jeffrey G

    2016-06-01

    Stress activation of the hypothalamic-pituitary-adrenal (HPA) axis is regulated by rapid glucocorticoid negative feedback. Chronic unpredictable stress animal models recapitulate certain aspects of major depression in humans, which have been attributed to impaired glucocorticoid negative feedback. We tested for an attenuated HPA sensitivity to fast glucocorticoid feedback inhibition in male rats exposed to a chronic variable stress (CVS) paradigm. In vitro, parvocellular neuroendocrine cells of the hypothalamic paraventricular nucleus recorded in slices from CVS rats showed an increase in basal excitatory synaptic inputs and a decrease in basal inhibitory synaptic inputs compared with neurons from control rats. There was no difference between control and CVS-treated rats in the rapid glucocorticoid suppression of excitatory synaptic inputs, a fast feedback mechanism. In vivo, CVS-treated rats showed an increase in ACTH secretion at baseline and after both iv CRH and acute stress and no impairment of the corticosterone suppression of the ACTH response, compared with controls. In an in vitro pituitary preparation, an increase in basal ACTH release, a small increase in CRH-induced ACTH release, and no decrement in the glucocorticoid suppression of ACTH release were seen in pituitaries from CVS rats. Thus, CVS does not suppress rapid glucocorticoid negative feedback at the hypothalamus or pituitary, but increases the synaptic excitability of paraventricular nucleus CRH neurons and the CRH sensitivity of the pituitary. Therefore, increased HPA activity in chronically stressed male rats is due to sensitization of the HPA axis, rather than to desensitization to rapid glucocorticoid feedback. PMID:27054552

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

    PubMed

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

    2016-08-01

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

  16. Novel FGF8 Mutations Associated with Recessive Holoprosencephaly, Craniofacial Defects, and Hypothalamo-Pituitary Dysfunction

    PubMed Central

    McCabe, Mark J.; Gaston-Massuet, Carles; Tziaferi, Vaitsa; Gregory, Louise C.; Alatzoglou, Kyriaki S.; Signore, Massimo; Puelles, Eduardo; Gerrelli, Dianne; Farooqi, I. Sadaf; Raza, Jamal; Walker, Joanna; Kavanaugh, Scott I.; Tsai, Pei-San; Pitteloud, Nelly; Martinez-Barbera, Juan-Pedro

    2011-01-01

    Context: Fibroblast growth factor (FGF) 8 is important for GnRH neuronal development with human mutations resulting in Kallmann syndrome. Murine data suggest a role for Fgf8 in hypothalamo-pituitary development; however, its role in the etiology of wider hypothalamo-pituitary dysfunction in humans is unknown. Objective: The objective of this study was to screen for FGF8 mutations in patients with septo-optic dysplasia (n = 374) or holoprosencephaly (HPE)/midline clefts (n = 47). Methods: FGF8 was analyzed by PCR and direct sequencing. Ethnically matched controls were then screened for mutated alleles (n = 480–686). Localization of Fgf8/FGF8 expression was analyzed by in situ hybridization in developing murine and human embryos. Finally, Fgf8 hypomorphic mice (Fgf8loxPNeo/−) were analyzed for the presence of forebrain and hypothalamo-pituitary defects. Results: A homozygous p.R189H mutation was identified in a female patient of consanguineous parentage with semilobar HPE, diabetes insipidus, and TSH and ACTH insufficiency. Second, a heterozygous p.Q216E mutation was identified in a female patient with an absent corpus callosum, hypoplastic optic nerves, and Moebius syndrome. FGF8 was expressed in the ventral diencephalon and anterior commissural plate but not in Rathke's pouch, strongly suggesting early onset hypothalamic and corpus callosal defects in these patients. This was consolidated by significantly reduced vasopressin and oxytocin staining neurons in the hypothalamus of Fgf8 hypomorphic mice compared with controls along with variable hypothalamo-pituitary defects and HPE. Conclusion: We implicate FGF8 in the etiology of recessive HPE and potentially septo-optic dysplasia/Moebius syndrome for the first time to our knowledge. Furthermore, FGF8 is important for the development of the ventral diencephalon, hypothalamus, and pituitary. PMID:21832120

  17. Sim2 contributes to neuroendocrine hormone gene expression in the anterior hypothalamus.

    PubMed

    Goshu, Eleni; Jin, Hui; Lovejoy, John; Marion, Jean-François; Michaud, Jacques L; Fan, Chen-Ming

    2004-05-01

    Paraventricular (PVN) and supraoptic nuclei of the hypothalamus maintain homeostasis by modulating pituitary hormonal output. PVN and supraoptic nuclei contain five major cell types: oxytocin-, vasopressin-, CRH-, somatostatin-, and TRH-secreting neurons. Sim1, Arnt2, and Otp genes are essential for terminal differentiation of these neurons. One of their common downstream genes, Brn2, is necessary for oxytocin, vasopressin, and CRH cell differentiation. Here we show that Sim2, a paralog of Sim1, contributes to the expression of Trh and Ss genes in the dorsal preoptic area, anterior-periventricular nucleus, and PVN. Sim2 expression overlaps with Trh- and Ss-expressing cells, and Sim2 mutants contain reduced numbers of Trh and Ss cells. Genetically, Sim1 acts upstream of Sim2 and partially compensates for the loss of Sim2. Comparative expression studies at the anterior hypothalamus at early stages reveal that there are separate pools of Trh cells with distinctive molecular codes defined by Sim1 and Sim2 expression. Together with previous reports, our results demonstrate that Sim1 and Otp utilize two common downstream genes, Brn2 and Sim2, to mediate distinctive sets of neuroendocrine hormone gene expression. PMID:14988428

  18. [Leptin and hypothalamus-hypophysis-thyroid axis].

    PubMed

    Riccioni, G; Menna, V; Lambo, M S; Della Vecchia, R; Di Ilio, C; De Lorenzo, A; D'Orazio, N

    2004-01-01

    The leptin system is a major regulator of food intake and metabolic rate. The leptin, an adipose tissue hormone whose plasma levels reflect energy stores, plays an important rule in the pathogenesis of such eating disorders like bulimia and anorexia. Thyroid hormones are major regulators of energy homeostasis. It is possible that leptin and thyroid hormone exert their actions on thermogenesis and energy metabolism via the same common effector patways. Leptin influences feedback regulation of the hypotalamic TRH-secreting neurons by thyroid hormone. Low serum levels of thyroid hormones reflect a dysfunction of the hypotalamic-pituitary-thyroid (HPT) and hypotalamic-pituitary-adrenal (HPA) axis in patients with nervosa anorexia. Neuroendocrine effects of leptin include effects on the HPT and HPA axis. The aim of this work is to evaluated the interactions between leptina and HPT axis on the basis of recent published works and reviews in literature. PMID:15147079

  19. Hypothalamic, pituitary and thyroid dysfunction after radiotherapy to the head and neck

    SciTech Connect

    Samaan, N.A.; Vieto, R.; Schultz, P.N.; Maor, M.; Meoz, R.T.; Sampiere, V.A.; Cangir, A.; Ried, H.L.; Jesse, R.H. Jr.

    1982-11-01

    One hundred-ten patients who had nasopharyngeal cancer and paranasal sinus tumors and were free of the primary disease were studied one to 26 years following radiotherapy. There were 70 males and 40 females ranging in age from 4 to 75 years, with a mean age of 36.5 years. During therapy both the hypothalamus and the anterior pituitary gland was estimated to be 400 to 7500 rad with a median dose of 5618 rad to the anterior pituitary gland and a median dose of 5000 rad to the hypothalamus. Seventy-six patients showed evidence of one or more hypothalamic lesions and 43 patients showed evidence of primary pituitary deficiency. Forty of the 66 patients who received radiotherapy to the neck for treatment or prevention of lymph node metastasis showed evidence of primary hypothyroidism. The range of the dose to the thyroid area was 3000 to 8800 rad with a median of 5000 rad. These results indicate that endocrine deficiencies after radiotherapy for tumors of the head and neck are common and should be detected early and treated. Long-term follow-up of these patients is indicated since complications may appear after the completion of radiotherapy.

  20. Increase of kisspeptin-positive cells in the hypothalamus of a rat model of polycystic ovary syndrome.

    PubMed

    Kondo, Mika; Osuka, Satoko; Iwase, Akira; Nakahara, Tatsuo; Saito, Ai; Bayasula; Nakamura, Tomoko; Goto, Maki; Kotani, Tomomi; Kikkawa, Fumitaka

    2016-06-01

    Kisspeptin, a hypothalamic neuropeptide, is expressed in the arcuate nucleus (ARC) that is considered as the center of the gonadotropin-releasing hormone (GnRH)-pulse generator. We hypothesized that kisspeptin expressed in the ARC is implicated in the disturbance of the hypothalamus-pituitary-ovary axis observed in polycystic ovary syndrome (PCOS). To test this hypothesis, we evaluated the hormonal profiles, luteinizing hormone (LH) pulse, and ARC kisspeptin immunoreactivity in a PCOS rat model using the anti-progestin RU486. We found an alteration of the LH pulse, including a trend towards an increased mean LH concentration and area under the curve, and a significant upregulation of the mean LH pulse amplitude. Additionally, a higher number of kisspeptin-positive cells was observed in the ARC of RU486-treated rats than in the ARC of intact rats. These results suggest the possible involvement of hypothalamic kisspeptin in the hypothalamus-pituitary-ovary axis and therefore, in PCOS pathophysiology. PMID:26864582

  1. Range of control of cardiovascular variables by the hypothalamus

    NASA Technical Reports Server (NTRS)

    Smith, O. A.; Stephenson, R. B.; Randall, D. C.

    1974-01-01

    New methodologies were utilized to study the influence of the hypothalamus on the cardiovascular system. The regulation of myocardial activity was investigated in monkeys with hypothalamic lesions that eliminate cardiovascular responses. Observations showed that a specific part of the hypothalamus regulates changes in myocardial contractility that accompanies emotion. Studies of the hypothalamus control of renal blood flow showed the powerful potential control of this organ over renal circulation.

  2. Endoscopic pituitary surgery.

    PubMed

    Cappabianca, Paolo; Cavallo, Luigi Maria; de Divitiis, Oreste; Solari, Domenico; Esposito, Felice; Colao, Annamaria

    2008-01-01

    Pituitary surgery is a continuous evolving speciality of the neurosurgeons' armamentarium, which requires precise anatomical knowledge, technical skills and integrated appreciation of the pituitary pathophysiology. What we consider "pure" endoscopic transsphenoidal surgery is a procedure performed through the nose and the sphenoid bone, with the endoscope alone throughout the whole approach to visualize the surgical target area and without the use of any transsphenoidal retractor. It offers some advantages due to the endoscope itself: a superior close-up view of the relevant anatomy and an enlarged working angle are provided with an increased panoramic vision inside the surgical area. Concerning results in terms of mass removal, relief of clinical symptoms, cure of the underlying disease and complication rate, they are, at least, similar to those reported in the major microsurgical series, but patient compliance is by far better. Furthermore transsphenoidal endoscopy brings advantages to the patient (less nasal traumatism, no nasal packing, less post-op pain and usually quick recovery), to the surgeon (wider and closer view of the surgical target area, increase of the scientific activity as from the peer-reviewed literature on the topic in the last 10 years, smoothing of interdisciplinary cooperation), to the institution (shorter post-op hospital stay, increase of the case load). Besides, further progress and technological advance are expected from the close cooperation between different technologies and industries. Continuing works in such field of "minimalism" will offer further possibilities to provide the surgeon with even more effectiveness and safety, and, on the other hand, the patient with improvement of results. PMID:18286374

  3. Leptin-dependent neuronal NO signaling in the preoptic hypothalamus facilitates reproduction.

    PubMed

    Bellefontaine, Nicole; Chachlaki, Konstantina; Parkash, Jyoti; Vanacker, Charlotte; Colledge, William; d'Anglemont de Tassigny, Xavier; Garthwaite, John; Bouret, Sebastien G; Prevot, Vincent

    2014-06-01

    The transition to puberty and adult fertility both require a minimum level of energy availability. The adipocyte-derived hormone leptin signals the long-term status of peripheral energy stores and serves as a key metabolic messenger to the neuroendocrine reproductive axis. Humans and mice lacking leptin or its receptor fail to complete puberty and are infertile. Restoration of leptin levels in these individuals promotes sexual maturation, which requires the pulsatile, coordinated delivery of gonadotropin-releasing hormone to the pituitary and the resulting surge of luteinizing hormone (LH); however, the neural circuits that control the leptin-mediated induction of the reproductive axis are not fully understood. Here, we found that leptin coordinated fertility by acting on neurons in the preoptic region of the hypothalamus and inducing the synthesis of the freely diffusible volume-based transmitter NO, through the activation of neuronal NO synthase (nNOS) in these neurons. The deletion of the gene encoding nNOS or its pharmacological inhibition in the preoptic region blunted the stimulatory action of exogenous leptin on LH secretion and prevented the restoration of fertility in leptin-deficient female mice by leptin treatment. Together, these data indicate that leptin plays a central role in regulating the hypothalamo-pituitary-gonadal axis in vivo through the activation of nNOS in neurons of the preoptic region. PMID:24812663

  4. GABA Regulates Corticotropin Releasing Hormone Levels in the Paraventricular Nucleus of the Hypothalamus in Newborn Mice

    PubMed Central

    Stratton, Matthew S.; Searcy, Brian T.; Tobet, Stuart A.

    2011-01-01

    The paraventricular nucleus of the hypothalamus (PVN) is a major regulator of stress responses via release of Corticotropin Releasing Hormone (CRH) to the pituitary gland. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is characteristic of individuals with Major Depressive Disorder (MDD). Postmortem data from individuals diagnosed with MDD show increased levels of CRH mRNA and CRH immunoreactive neurons in the PVN. In the current study, an immunohistochemical (IHC) analysis revealed increased levels of CRH in the PVN of newborn mice lacking functional GABAB receptors. There was no difference in the total number of CRH immunoreactive cells. By contrast, there was a significant increase in the amount of CRH immunoreactivity per cell. Interestingly, this increase in CRH levels in the GABAB receptor R1 subunit knockout was limited to the rostral PVN. While GABAergic regulation of the HPA axis has been previously reported in adult animals, this study provides evidence of region-specific GABA modulation of immunoreactive CRH in newborns. PMID:21236282

  5. Pituitary: Non-Secretory Tumors

    MedlinePlus

    ... categories—tumor mass effects and hyposecretion effects. Tumor mass effects Visual field disturbances, most commonly loss of ... surgery. The goal is to completely remove the mass or cyst and preserve normal pituitary, brain, and ...

  6. Tanycytes: a gateway to the metabolic hypothalamus.

    PubMed

    Langlet, F

    2014-11-01

    The central regulation of energy balance relies on the ability of the brain to promptly and efficiently sense variations of metabolic state. To achieve this, circulating hormonal and metabolic signals have to cross the blood-brain interface, where unusual glial cells named tanycytes have been described to play a key role in this process. Tanycytes are specialised polarised ependymoglial cells that line the floor of the third ventricle and send a single process to contact hypothalamic neurones and blood vessels. Although their role in the regulation of energy balance via the modulation of neuronal activity or their chemosensitivity has been already described, recent studies ascribe a new function to tanycytes in the regulation of energy homeostasis as a result of their capacity to regulate the access of metabolic signals to the hypothalamus. This review discusses the peculiar place of tanycytes within the blood-hypothalamus interface, as well as a striking capacity to remodel their own interface to ensure an adaptive metabolic response to energy imbalances. PMID:25131689

  7. Prosomeric organization of the hypothalamus in an elasmobranch, the catshark Scyliorhinus canicula

    PubMed Central

    Santos-Durán, Gabriel N.; Menuet, Arnaud; Lagadec, Ronan; Mayeur, Hélène; Ferreiro-Galve, Susana; Mazan, Sylvie; Rodríguez-Moldes, Isabel; Candal, Eva

    2015-01-01

    The hypothalamus has been a central topic in neuroanatomy because of its important physiological functions, but its mature organization remains elusive. Deciphering its embryonic and adult organization is crucial in an evolutionary approach of the organization of the vertebrate forebrain. Here we studied the molecular organization of the hypothalamus and neighboring telencephalic domains in a cartilaginous fish, the catshark, Scyliorhinus canicula, focusing on ScFoxg1a, ScShh, ScNkx2.1, ScDlx2/5, ScOtp, and ScTbr1 expression profiles and on the identification α-acetylated-tubulin-immunoreactive (ir), TH-ir, 5-HT-ir, and GFAP-ir structures by means of immunohistochemistry. Analysis of the results within the updated prosomeric model framework support the existence of alar and basal histogenetic compartments in the hypothalamus similar to those described in the mouse, suggesting the ancestrality of these subdivisions in jawed vertebrates. These data provide new insights into hypothalamic organization in cartilaginous fishes and highlight the generality of key features of the prosomeric model in jawed vertebrates. PMID:25904850

  8. Substance P-like peptides and vasopressin release from posterior pituitary lobe incubated in situ after intracarotid injections of hypertonic solution in rats.

    PubMed

    Traczyk, W Z; Strumillo-Dyba, E

    1977-01-01

    The experiments were performed on male rats, drinking 2% NaCl solution ad libitum for 12 days instead of tap water. The pituitary gland was exposed by the transpharyngeal approach under urethane-chloralose anaesthesia. The posterior lobe remained in neural and partial vascular connection with the hypothalamus, whereas the anterior lobe was entirely removed. Samples of the outflow medium from the incubated in situ rat posterior pituitary lobe were collected during 30 min intervals. Substance P-like peptides and vasopressin activities were assayed by the biological tests. Injections of hypertonic solution into the internal carotid artery did not change vasopressin release, but induced an increase in Substance P release from the posterior pituitary lobe into the incubation medium. Under conditions of unexcitability of the osmosensitive cells, triggering vasopressin release, the injection of hypertonic solution into the internal carotid artery stimulated the Substance P-like peptides release from the posterior pituitary lobe. PMID:22985

  9. Modeling the brain-pituitary-gonad axis in salmon

    SciTech Connect

    Kim, Jonghan; Hayton, William L.; Schultz, Irv R.

    2006-08-24

    To better understand the complexity of the brain-pituitary-gonad axis (BPG) in fish, we developed a biologically based pharmacodynamic model capable of accurately predicting the normal functioning of the BPG axis in salmon. This first-generation model consisted of a set of 13 equations whose formulation was guided by published values for plasma concentrations of pituitary- (FSH, LH) and ovary- (estradiol, 17a,20b-dihydroxy-4-pregnene-3-one) derived hormones measured in Coho salmon over an annual spawning period. In addition, the model incorporated pertinent features of previously published mammalian models and indirect response pharmacodynamic models. Model-based equations include a description of gonadotropin releasing hormone (GnRH) synthesis and release from the hypothalamus, which is controlled by environmental variables such as photoperiod and water temperature. GnRH stimulated the biosynthesis of mRNA for FSH and LH, which were also influenced by estradiol concentration in plasma. The level of estradiol in the plasma was regulated by the oocytes, which moved along a maturation progression. Estradiol was synthesized at a basal rate and as oocytes matured, stimulation of its biosynthesis occurred. The BPG model can be integrated with toxico-genomic, -proteomic data, allowing linkage between molecular based biomarkers and reproduction in fish.

  10. Evaluation of the Hypothalamic-Pituitary-Adrenal Axis Function in Childhood and Adolescence

    PubMed Central

    Chrousos, George P.; Kino, Tomoshige; Charmandari, Evangelia

    2009-01-01

    The hypothalamic-pituitary-adrenal (HPA) axis plays an important role in the maintenance of basal and stress-related homeostasis. The hypothalamus controls the secretion of adrenocorticotropic hormone (ACTH) from the anterior pituitary, which in turn stimulates the secretion of glucocorticoids from the adrenal cortex. Glucocorticoids, the final effectors of the HPA axis, regulate a broad spectrum of physiologic functions essential for life and exert their effects through their ubiquitously distributed intracellular receptors. Alterations in the activity of the HPA axis may present with symptoms and signs of glucocorticoid deficiency or excess. Detailed endocrinologic evaluation is of primary importance in determining the diagnosis and/or etiology of the underlying condition. We review the most common endocrinologic investigations used in the evaluation of the HPA axis integrity and function. PMID:19571588

  11. Pituitary function following treatment with reproductive toxins

    SciTech Connect

    Cooper, R.L.; Goldman, J.M.; Rehnberg, G.L.

    1986-12-01

    Appropriate regulation of reproductive processes are dependent upon the integrity of pituitary function. In this selected review, the authors evaluate the evidence that certain environmental compounds exert their effect on reproductive function via a direct action on the pituitary gland. They also discuss examples of changes in pituitary hormone secretion that occur in response to changes in neuronal or gonadal control of the pituitary. A limited number of studies suggest that measures of pituitary hormone secretion provide an early and sensitive measure of a compound's potential effects on the reproductive system. However, the most striking aspect of this area is the sparse and inconsistent information describing pituitary function following exposure to environmental pollutants.

  12. Interleukin-2 and interleukin-2 receptor expression in human corticotrophic adenoma and murine pituitary cell cultures.

    PubMed Central

    Arzt, E; Stelzer, G; Renner, U; Lange, M; Müller, O A; Stalla, G K

    1992-01-01

    The production of IL-1 and IL-6 by pituitary cells has recently been demonstrated. In this study we investigated the expression of IL-2 and its receptor (IL-2R) by pituitary cells of different species. In Northern blots, a single hybridizing band of 1 kb, identical to that in normal stimulated lymphocytes, was obtained with specific IL-2 probes. In the mouse AT-20 pituitary tumor cell line, IL-2 mRNA expression was detected after stimulation with corticotropin-releasing hormone or phorbol myristate acetate. In human corticotrophic adenoma cells, basal IL-2 mRNA expression as well as IL-2 secretion were further stimulated by phorbol myristate acetate. Both adenoma and AtT-20 cells showed detectable amounts of IL-2R mRNA and by immunofluorescence, IL-2R membrane expression. In addition, dual immunofluorescence studies in rat anterior pituitary cells demonstrated colocalization of IL-2R with ACTH-positive cells and other cell types expressing the receptor. In addition to the action of lymphocyte-produced IL-2, this cytokine may have a paracrine or autocrine regulatory role within the pituitary. It remains to be established whether IL-2 production occurs in the normal pituitary or is intrinsic to the process of tumor development of these cells. IL-2 may be involved in the growth control of pituitary cells. Images PMID:1331177

  13. Molecular mechanisms of pituitary organogenesis: in search of novel regulatory genes

    PubMed Central

    Davis, SW; Castinetti, F; Carvalho, LR; Ellsworth, BS; Potok, MA; Lyons, RH; Brinkmeier, ML; Raetzman, LT; Carninci, P; Mortensen, AH; Hayashizaki, Y; Arnhold, IJP; Mendonca, BB; Brue, T; Camper, SA

    2010-01-01

    Defects in pituitary gland organogenesis are sometimes associated with congenital anomalies that affect head development. Lesions in transcription factors and signaling pathways explain some of these developmental syndromes. Basic research studies, including the characterization of genetically engineered mice, provide a mechanistic framework for understanding how mutations create the clinical characteristics observed in patients. Defects in BMP, WNT, Notch, and FGF signaling pathways affect induction and growth of the pituitary primordium and other organ systems partly by altering the balance between signaling pathways. The PITX and LHX transcription factor families influence pituitary and head development and are clinically relevant. A few later-acting transcription factors have pituitary-specific effects, including PROP1, POU1F1 (PIT1), and TPIT (TBX19), while others, such as NeuroD1 and NR5A1 (SF1), are syndromic, influencing development of other endocrine organs. We conducted a survey of genes transcribed in developing mouse pituitary to find candidates for cases of pituitary hormone deficiency of unknown etiology. We identified numerous transcription factors that are members of gene families with roles in syndromic or nonsyndromic pituitary hormone deficiency. This collection is a rich source for future basic and clinical studies. PMID:20025935

  14. The Kampo Medicine Yokukansan Decreases MicroRNA-18 Expression and Recovers Glucocorticoid Receptors Protein Expression in the Hypothalamus of Stressed Mice

    PubMed Central

    Tanaka, Takashi; Tohyama, Masaya

    2015-01-01

    It is well known that glucocorticoid receptor (GR) signaling regulates the hypothalamic-pituitary-adrenal (HPA) axis, and GR expression level is associated with HPA axis activity. Recent studies revealed that microRNA- (miR-) 18 and/or 124a are candidate negative regulators of GR in the brain. The Kampo medicine Yokukansan (YKS) can affect psychological symptoms such as depression and anxiety that are associated with stress responses. In this study, we evaluated the effect of YKS on miR-18 and 124a and GR levels in mice exposed to stress. We found that YKS pretreatment normalized elevated plasma corticosterone levels in stress-exposed mice. In addition, GR mRNA levels were downregulated in the brain following stress exposure. While miR-124a expression levels were not altered in the hypothalamus of stress-exposed mice, miR-18 levels decreased in the hypothalamus of YKS-pretreated mice after stress exposure. Finally, GR protein levels in the paraventricular nucleus (PVN) of the hypothalamus after stress exposure recovered in YKS-pretreated mice. Collectively, these data suggest that YKS normalizes GR protein levels by regulating miR-18 expression in the hypothalamus, thus normalizing HPA axis activity following stress exposure. PMID:26106615

  15. Nesfatin-1 regulates the hypothalamo-pituitary-ovarian axis of fish.

    PubMed

    Gonzalez, Ronald; Shepperd, Erin; Thiruppugazh, Vetri; Lohan, Sneha; Grey, Caleb L; Chang, John P; Unniappan, Suraj

    2012-10-01

    Nesfatin-1 is an anorexigen in goldfish. In the present study, we provide novel data indicating the presence and regulatory effects of nesfatin-1 on the hypothalamo-pituitary-ovarian (HPO) axis of goldfish. Nucleobindin-2 (NUCB2)/nesfatin-1-like immunoreactive (ir) cells are present in the hypothalamus and in the pituitary, suggesting a hypophysiotropic role for nesfatin-1. NUCB2/nesfatin-1-like ir cells colocalize gonadotropin-releasing hormone (GnRH) in the nucleus lateralis tuberis posterioris and the nucleus anterior tuberis of the goldfish hypothalamus. The presence of nesfatin-1 with GnRH in these two nuclei implicated in pituitary hormone release suggests a role for nesfatin-1 on gonadotropin secretion. A single i.p. injection of synthetic goldfish nesfatin-1 (50 ng/g body wt) resulted in an acute decrease (∼75%) in the expression of hypothalamic chicken GnRH-II and salmon GnRH mRNAs at 15 min postinjection in goldfish. Meanwhile, pituitary luteinizing hormone (LH) beta and follicle-stimulating hormone beta mRNAs were also inhibited (∼80%), but only at 60 min postinjection. Nesfatin-1 administration also resulted in a significant reduction (∼60%) in serum LH levels at 60 min postadministration. Nesfatin-1-like immunoreactivity was also found in the follicle cells, but not the oocytes, in zebrafish and goldfish ovaries. Incubation of zebrafish follicles with nesfatin-1 resulted in a significant reduction in basal germinal vesicle breakdown (∼50%) during the oocyte maturation. In addition, nesfatin-1 also attenuated the stimulatory effects of maturation-inducing hormone on germinal vesicle breakdown. Together, the current results indicate that nesfatin-1 is a metabolic hormone with an inhibitory tone on fish reproduction. Nesfatin-1 appears to elicit this suppressive effect through actions on all three tissues in the fish HPO axis. PMID:22895855

  16. Central diabetes insipidus in an HHV6 encephalitis patient with a posterior pituitary lesion that developed after tandem cord blood transplantation.

    PubMed

    Kawamoto, Shinichiro; Hatanaka, Kazuo; Imakita, Masami; Tamaki, Toshiharu

    2013-01-01

    A 60-year-old myelodysplastic syndrome patient underwent tandem cord blood transplantation. The primary cord blood graft was rejected, and human herpesvirus 6 (HHV6) encephalitis developed after engraftment of secondary cord blood. Polyuria and adipsic hypernatremia were observed during treatment of the encephalitis. The patient died of bacteremia caused by methicillin-resistant Streptococcus epidermis. HHV6 infection in the posterior pituitary was confirmed on autopsy, as was infection of the hippocampus, but not of the hypothalamus. This is the first case report of central diabetes insipidus caused by an HHV6 posterior pituitary infection demonstrated on a pathological examination. PMID:23676599

  17. Delayed sequelae of pituitary irradiation

    SciTech Connect

    Woodruff, K.H.; Lyman, J.T.; Lawrence, J.H.; Tobias, C.A.; Born, J.L.; Fabrikant, J.I.

    1984-01-01

    Since 1958, 781 patients at Lawrence Berkeley Laboratory have received helium-particle stereotactic radiosurgery to the adenohypophysis. Autopsy findings in 15 of these patients are reported. Ten patients received pituitary radiation (average dose, 116 Gy in six fractions) for progressive neovascularization retinopathy due to diabetes mellitus. Evidence of a time-dependent course of progressive fibrosis in their pituitary glands was found. Five patients were treated for eosinophilic adenomas. Although they had lower average doses of radiation (56 Gy in six fractions), their pituitary glands showed cystic cavitation of the adenomas. The adenomas thus appeared more radiosensitive than the normal pars anterior, which, in turn, was more radiosensitive than the adjacent neurohypophysis. No significant radiation changes were found in the surrounding brain or cranial nerves. The endocrine organs under pituitary control showed varying degrees of atrophy, and clinical tests revealed progressive hypofunction. It was concluded that charged-particle therapy produced a sharply delineated focal ral tests revealed progressive hypofunction. It was concluded that charged-particle therapy produced a sharply delineated focal radiation lesion confined to the pituitary gland but did not cause injury to the critical structures of the surrounding central nervous system.

  18. GnRH decreases adiponectin expression in pituitary gonadotropes via the calcium and PKA pathways.

    PubMed

    Kim, Jonathan; Zheng, Weiming; Grafer, Constance; Mann, Merry Lynn; Halvorson, Lisa M

    2013-08-01

    As endocrinologically active cells, adipocytes are capable of secreting various adipocytokines such as leptin, resistin, and adiponectin to impact metabolic function. Although adipocytes remain to be the primary site of synthesis and secretion, there is now growing evidence that supports the presence of adiponectin and its receptors within the hypothalamic-pituitary-gonadal axis, providing a possible link between obesity and abnormal reproductive physiology. It has been demonstrated that adiponectin may reduce gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus as well as modulate gonadal steroid hormone production. Furthermore, prior data indicate that adiponectin may play a role in decreasing luteinizing hormone secretion from pituitary gonadotropes. We aimed to identify the hormonal regulators of adiponectin and its receptors, AdipoR1 and AdipoR2, in pituitary gonadotropes using immortalized gonadotropic LβT2 cells and primary rat pituitary cells. Our study shows significant alterations in adiponectin expression across the estrous cycle. In addition, we present a novel finding that GnRH suppresses pituitary adiponectin expression via the calcium and protein kinase A intracellular pathways in both cultured rat primary pituitary cells and the LβT2 gonadotrope cell line. The GnRH did not alter expression of the adiponectin receptors, AdipoR1 and AdipoR2, in cultured gonadotropes. Expression of the adiponectin receptors, AdipoR1 and AdipoR2, was not altered by GnRH in cell culture but in vivo or in vitro. Our data suggest that gonadotrope function may be modulated by GnRH-mediated changes in adiponectin expression. PMID:23239819

  19. Pituitary and testis responsiveness of young male sheep exposed to testosterone excess during fetal development.

    PubMed

    Recabarren, Mónica P; Rojas-Garcia, Pedro P; Einspanier, Ralf; Padmanabhan, Vasantha; Sir-Petermann, Teresa; Recabarren, Sergio E

    2013-06-01

    Prenatal exposure to excess testosterone induces reproductive disturbances in both female and male sheep. In females, it alters the hypothalamus-pituitary-ovarian axis. In males, prenatal testosterone excess reduces sperm count and motility. Focusing on males, this study tested whether pituitary LH responsiveness to GNRH is increased in prenatal testosterone-exposed males and whether testicular function is compromised in the testosterone-exposed males. Control males (n=6) and males born to ewes exposed to twice weekly injections of 30  mg testosterone propionate from days 30 to 90 and of 40  mg testosterone propionate from days 90 to 120 of gestation (n=6) were studied at 20 and 30 weeks of age. Pituitary and testicular responsiveness was tested by administering a GNRH analog (leuprolide acetate). To complement the analyses, the mRNA expression of LH receptor (LHR) and that of steroidogenic enzymes were determined in testicular tissue. Basal LH and testosterone concentrations were higher in the testosterone-exposed-males. While LH response to the GNRH analog was higher in the testosterone-exposed males than in the control males, testosterone responses did not differ between the treatment groups. The testosterone:LH ratio was higher in the control males than in the testosterone-exposed males of 30 weeks of age, suggestive of reduced Leydig cell sensitivity to LH in the testosterone-exposed males. The expression of LHR mRNA was lower in the testosterone-exposed males, but the mRNA expression of steroidogenic enzymes did not differ between the groups. These findings indicate that prenatal testosterone excess has opposing effects at the pituitary and testicular levels, namely increased pituitary sensitivity to GNRH at the level of pituitary and decreased sensitivity of the testes to LH. PMID:23579187

  20. The genetics of pituitary adenomas.

    PubMed

    Vandeva, Silvia; Jaffrain-Rea, Marie-Lise; Daly, Adrian F; Tichomirowa, Maria; Zacharieva, Sabina; Beckers, Albert

    2010-06-01

    Pituitary adenomas are one of the most frequent intracranial tumors with a prevalence of clinically-apparent tumors close to 1:1000 of the general population. They are clinically significant because of hormone overproduction and/or tumor mass effects in addition to the need for neurosurgery, medical therapies and radiotherapy. The majority of pituitary adenomas have a sporadic origin with recognized genetic mutations seldom being found; somatotropinomas are an exception, presenting frequent somatic GNAS mutations. In this and other phenotypes, tumorigenesis could possibly be explained by altered function of genes implicated in cell cycle regulation, growth factors or their receptors, cell-signaling pathways, specific hormonal factors or other molecules with still unclear mechanisms of action. Genetic changes, such as allelic loss or gene amplification, and epigenetic changes, usually by promoter methylation, have been implicated in abnormal gene expression, but alternative mechanisms may be present. Familial cases of pituitary adenomas represent 5% of all pituitary tumors. MEN1 mutations cause multiple endocrine neoplasia type 1 (MEN1), while the Carney complex (CNC) is characterized by mutations in the protein kinase A regulatory subunit-1alpha (PRKAR1A) gene or changes in a locus at 2p16. Recently, a MEN1-like condition, MEN4, was found to be related to mutations in the CDKN1B gene. The clinical entity of familial isolated pituitary adenomas (FIPA) is characterized by genetic defects in the aryl hydrocarbon receptor interacting protein (AIP) gene in about 15% of all kindreds and 50% of homogenous somatotropinoma families. Identification of familial cases of pituitary adenomas is important as these tumors may be more aggressive than their sporadic counterparts. PMID:20833337

  1. Mild pituitary phenotype in 3- and 12-month-old Aip-deficient male mice.

    PubMed

    Lecoq, Anne-Lise; Zizzari, Philippe; Hage, Mirella; Decourtye, Lyvianne; Adam, Clovis; Viengchareun, Say; Veldhuis, Johannes D; Geoffroy, Valérie; Lombès, Marc; Tolle, Virginie; Guillou, Anne; Karhu, Auli; Kappeler, Laurent; Chanson, Philippe; Kamenický, Peter

    2016-10-01

    Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene predispose humans to pituitary adenomas, particularly of the somatotroph lineage. Mice with global heterozygous inactivation of Aip (Aip(+/-)) also develop pituitary adenomas but differ from AIP-mutated patients by the high penetrance of pituitary disease. The endocrine phenotype of these mice is unknown. The aim of this study was to determine the endocrine phenotype of Aip(+/-) mice by assessing the somatic growth, ultradian pattern of GH secretion and IGF1 concentrations of longitudinally followed male mice at 3 and 12 months of age. As the early stages of pituitary tumorigenesis are controversial, we also studied the pituitary histology and somatotroph cell proliferation in these mice. Aip(+/-) mice did not develop gigantism but exhibited a leaner phenotype than wild-type mice. Analysis of GH pulsatility by deconvolution in 12-month-old Aip(+/-) mice showed a mild increase in total GH secretion, a conserved GH pulsatility pattern, but a normal IGF1 concentration. No pituitary adenomas were detected up to 12 months of age. An increased ex vivo response to GHRH of pituitary explants from 3-month-old Aip(+/-) mice, together with areas of enlarged acini identified on reticulin staining in the pituitary of some Aip(+/-) mice, was suggestive of somatotroph hyperplasia. Global heterozygous Aip deficiency in mice is accompanied by subtle increase in GH secretion, which does not result in gigantism. The absence of pituitary adenomas in 12-month-old Aip(+/-) mice in our experimental conditions demonstrates the important phenotypic variability of this congenic mouse model. PMID:27621108

  2. Genetic disruption of dopamine production results in pituitary adenomas and severe prolactinemia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dopamine release from tuberoinfundibular dopamine neurons into the median eminence activates dopamine-D2 receptors in the pituitary gland where it inhibits lactotroph function. We have previously described genetic dopamine-deficient mouse models which lack the ability to synthesize dopamine. Because...

  3. Role of posterior hypothalamus in hypobaric hypoxia induced pulmonary edema.

    PubMed

    Sharma, R K; Choudhary, R C; Reddy, M K; Ray, A; Ravi, K

    2015-01-01

    To investigate the role of posterior hypothalamus and central neurotransmitters in the pulmonary edema due to hypobaric hypoxia, rats were placed in a high altitude simulation chamber (barometric pressure-294.4 mmHg) for 24 h. Exposure to hypobaric hypoxia resulted in increases in mean arterial blood pressure, renal sympathetic nerve activity, right ventricular systolic pressure, lung wet to dry weight ratio and Evans blue dye leakage. There was a significant attenuation in these responses to hypobaric hypoxia (a) after lesioning posterior hypothalamus and (b) after chronic infusion of GABAA receptor agonist muscimol into posterior hypothalamus. No such attenuation was evident with the chronic infusion of the nitric oxide donor SNAP into the posterior hypothalamus. It is concluded that in hypobaric hypoxia, there is over-activity of posterior hypothalamic neurons probably due to a local decrease in GABA-ergic inhibition which increases the sympathetic drive causing pulmonary hypertension and edema. PMID:25448396

  4. [Pituitary apoplexy in a young woman.

    PubMed

    Lewis, Anna; Jarløv, Anne Elisabeth; Holm, Kirsten; Cleemann, Line

    2014-04-22

    Pituitary apoplexy occurs when a preexisting pituitary adenoma undergoes acute haemorrhage, infarct or both. The patho-genesis is not fully understood but macroadenomas and prolactinomas have been reported as being predisposed to apoplexy. Only a few cases are described in the paediatric population. We present a 17-year-old woman with secondary amenorrhoea, headache and blurred vision. An MRI showed a pituitary apoplexy in a preexisting macroadenoma. The majority of milder cases resolve spontaneously. Close monitoring of the pituitary function is important to detect pituitary insufficiency witch may need long-term hormone replacement therapy. PMID:25351468

  5. Synthetic gene network restoring endogenous pituitary-thyroid feedback control in experimental Graves' disease.

    PubMed

    Saxena, Pratik; Charpin-El Hamri, Ghislaine; Folcher, Marc; Zulewski, Henryk; Fussenegger, Martin

    2016-02-01

    Graves' disease is an autoimmune disorder that causes hyperthyroidism because of autoantibodies that bind to the thyroid-stimulating hormone receptor (TSHR) on the thyroid gland, triggering thyroid hormone release. The physiological control of thyroid hormone homeostasis by the feedback loops involving the hypothalamus-pituitary-thyroid axis is disrupted by these stimulating autoantibodies. To reset the endogenous thyrotrophic feedback control, we designed a synthetic mammalian gene circuit that maintains thyroid hormone homeostasis by monitoring thyroid hormone levels and coordinating the expression of a thyroid-stimulating hormone receptor antagonist (TSHAntag), which competitively inhibits the binding of thyroid-stimulating hormone or the human autoantibody to TSHR. This synthetic control device consists of a synthetic thyroid-sensing receptor (TSR), a yeast Gal4 protein/human thyroid receptor-α fusion, which reversibly triggers expression of the TSHAntag gene from TSR-dependent promoters. In hyperthyroid mice, this synthetic circuit sensed pathological thyroid hormone levels and restored the thyrotrophic feedback control of the hypothalamus-pituitary-thyroid axis to euthyroid hormone levels. Therapeutic plug and play gene circuits that restore physiological feedback control in metabolic disorders foster advanced gene- and cell-based therapies. PMID:26787873

  6. Differential developmental strategies by Sonic hedgehog in thalamus and hypothalamus.

    PubMed

    Zhang, Yuanfeng; Alvarez-Bolado, Gonzalo

    2016-09-01

    The traditional concept of diencephalon (thalamus plus hypothalamus) and with it the entire traditional subdivision of the developing neural tube are being challenged by novel insights obtained by mapping the expression of key developmental genes. A model in which the hypothalamus is placed in the most rostral portion of the neural tube, followed caudally by a diencephalon formed by prethalamus, thalamus and pretectum has been proposed. The adult thalamus and hypothalamus are quite unlike each other in connectivity and functions. Here we review work on the role of the secreted morphogen protein Sonic hedgehog (Shh) in the developing diencephalon and hypothalamic region to show how different these two regions are also from this point of view. Shh from the prechordal plate (PCP) induces and patterns the hypothalamus but there is no evidence that this role is fulfilled by a morphogen gradient. Later, the hypothalamic primordium itself expresses Shh and a large part of the hypothalamus belongs to the Shh lineage, including the ventral domains. Neural Shh is necessary to complete the specification (lateral hypothalamus), differentiation and growth of the hypothalamus. Although Gli2A is the major effector of Shh in this region, hypothalamic specification also depends on the suppression of Gli3R by Shh secreted by the PCP as well as the neuroepithelium. The thalamus is patterned by an Shh morphogen gradient originated in the ZLI following similar mechanisms to those in the spinal cord. The thalamus itself does not belong to the Shh lineage. Gli2A is necessary for appropriate growth and specification of the thalamic nuclei, to the exception of the medial and intralaminar groups (limbic-related), whose development depends on Gli3R. Beyond specification and patterning, the scarce data available about cell sorting and aggregation in these two regions shows key differences between them as well. In summary, not only expression patterns but also developmental mechanisms support

  7. Pituitary and hypothalamic insulin-like growth factor-I (IGF-I) and IGF-I receptor expression in food-deprived rats.

    PubMed

    Olchovsky, D; Song, J; Gelato, M C; Sherwood, J; Spatola, E; Bruno, J F; Berelowitz, M

    1993-06-01

    The present study was designed to evaluate a possible role for the insulin-like growth factor-I (IGF-I) system in mediating the suppression of growth hormone (GH) secretion observed in food-deprived rats by measuring IGF-I mRNA, receptor concentration and receptor mRNA in neuroendocrine tissues (hypothalamus and pituitary). Rats were deprived of food (food-deprived) for 72 h or had free access to food (fed). Tissues were processed for measurement of steady-state levels of: (a) IGF-I and IGF-I receptor mRNA (by solution hybridization/RNase protection assay); (b) IGF-I in serum and tissue extracts (by RIA) and (c) IGF-I displaceable [125I]IGF-I binding to plasma membrane preparations. Food deprivation resulted in decreased serum and liver levels of IGF-I. Kidney IGF-I mRNA levels were reduced 80% in food-deprived rats with a concomitant increase in IGF-I receptor concentration and mRNA levels. Refeeding of food-deprived rats fully normalized these perturbations. Pituitary IGF-I content was reduced 50% in food-deprived rats while IGF-I mRNA levels were unaffected. A modest increase was seen in pituitary IGF-I receptor concentration; however, IGF-I receptor mRNA levels were not changed. Hypothalamic IGF-I mRNA content was reduced in 72 h food-deprived rats while IGF-I receptor binding capacity and mRNA were unaffected. In conclusion, IGF-I mRNA levels are decreased in liver, kidney and hypothalamus together with a reduction in plasma IGF-I in food-deprived rats but is unaffected in anterior pituitary. IGF-I receptor gene expression and binding capacity are coordinately regulated in kidney and hypothalamus, but not in the pituitary.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8349028

  8. Comparison of the effects of spaceflight and hindlimb-suspension on rat pituitary vasopressin and brainstem norepinephrine content

    NASA Astrophysics Data System (ADS)

    Fareh, J.; Fagette, S.; Cottet-Emard, J. M.; Allevard, A. M.; Viso, M.; Gauquelin, G.; Gharib, C.

    1994-08-01

    To compare actual spaceflight to ground-based simulation (hindlimb-suspension), we measured the norepinephrine (NE) content in A1, A2, A5 and A6 (locus coeruleus) and the vasopressin content in the neurohypophysial system. The experimental period was of 9 days' duration. The NE content in the locus coeruleus decreased significantly in rats flown for 9 days (67 %,p<0.001), but showed no significant changes after hindlimb-suspension. These results demonstrated that suspended rats adapted better to weightlessness-simulation than flown rats to actual microgravity. In rats flown aboard SLS-1, the vasopressin content was significantly increased in the posterior pituitary (71 %,p<0.01), and was decreased in the hypothalamus (49 %, p<0.05). In 9-day suspended rats pituitary vasopressin levels were unchanged, while in the hypothalamus a significant decrease was noted (21 %, p<0.05). It was concluded that spaceflight changes in pituitary vasopressin levels and in the locus coeruleus NE content were consistent with a stress reaction, occurring during and/or after landing. These results confirmed that hindlimb-suspension model constitutes a valid and lesstressful ground-based simulation of microgravity in rats.

  9. Management of nonfunctioning pituitary incidentaloma.

    PubMed

    Galland, Françoise; Vantyghem, Marie-Christine; Cazabat, Laure; Boulin, Anne; Cotton, François; Bonneville, Jean-François; Jouanneau, Emmanuel; Vidal-Trécan, Gwénaelle; Chanson, Philippe

    2015-07-01

    Prevalence of pituitary incidentaloma is variable: between 1.4% and 27% at autopsy, and between 3.7% and 37% on imaging. Pituitary microincidentalomas (serendipitously discovered adenoma <1cm in diameter) may increase in size, but only 5% exceed 10mm. Pituitary macroincidentalomas (serendipitously discovered adenoma>1cm in diameter) show increased size in 20-24% and 34-40% of cases at respectively 4 and 8years' follow-up. Radiologic differential diagnosis requires MRI centered on the pituitary gland. Initial assessment of nonfunctioning (NF) microincidentaloma is firstly clinical, the endocrinologist looking for signs of hypersecretion (signs of hyperprolactinemia, acromegaly or Cushing's syndrome), followed up by systematic prolactin and IGF-1 assay. Initial assessment of NF macroincidentaloma is clinical, the endocrinologist looking for signs of hormonal hypersecretion or hypopituitarism, followed up by hormonal assay to screen for hypersecretion or hormonal deficiency and by ophthalmologic assessment (visual acuity and visual field) if and only if the lesion is near the optic chiasm (OC). NF microincidentaloma of less than 5mm requires no surveillance; those of≥5mm are not operated on but rather monitored on MRI at 6months and then 2years. Macroincidentaloma remote from the OC is monitored on MRI at 1year, with hormonal exploration (for anterior pituitary deficiency), then every 2years. When macroincidentaloma located near the OC is managed by surveillance rather than surgery, MRI is recommended at 6months, with hormonal and visual exploration, then annual MRI and hormonal and visual assessment every 6months. Surgery is indicated in the following cases: evolutive NF microincidentaloma, NF macroincidentaloma associated with hypopituitarism or showing progression, incidentaloma compressing the OC, possible malignancy, non-compliant patient, pregnancy desired in the short-term, or context at risk of apoplexy. PMID:26054868

  10. Concise Review: Paracrine Role of Stem Cells in Pituitary Tumors: A Focus on Adamantinomatous Craniopharyngioma

    PubMed Central

    2016-01-01

    Abstract The existence of tissue‐specific progenitor/stem cells in the adult pituitary gland of the mouse has been demonstrated recently using genetic tracing experiments. These cells have the capacity to differentiate into all of the different cell lineages of the anterior pituitary and self‐propagate in vitro and can therefore contribute to normal homeostasis of the gland. In addition, they play a critical role in tumor formation, specifically in the etiology of human adamantinomatous craniopharyngioma, a clinically relevant tumor that is associated with mutations in CTNNB1 (gene encoding β‐catenin). Mouse studies have shown that only pituitary embryonic precursors or adult stem cells are able to generate tumors when targeted with oncogenic β‐catenin, suggesting that the cell context is critical for mutant β‐catenin to exert its oncogenic effect. Surprisingly, the bulk of the tumor cells are not derived from the mutant progenitor/stem cells, suggesting that tumors are induced in a paracrine manner. Therefore, the cell sustaining the mutation in β‐catenin and the cell‐of‐origin of the tumors are different. In this review, we will discuss the in vitro and in vivo evidence demonstrating the presence of stem cells in the adult pituitary and analyze the evidence showing a potential role of these stem cells in pituitary tumors. Stem Cells 2016;34:268–276 PMID:26763580

  11. Hypothalamic-pituitary thyroid axis alterations in female mice with deletion of the neuromedin B receptor gene.

    PubMed

    Oliveira, Karen J; Paula, Gabriela S M; Império, Guinever E; Bressane, Nina O; Magalhães, Carolina M A; Miranda-Alves, Leandro; Ortiga-Carvalho, Tania M; Pazos-Moura, Carmen C

    2014-11-01

    Neuromedin B, a peptide highly expressed at the pituitary, has been shown to act as autocrine/paracrine inhibitor of thyrotropin (TSH) release. Here we studied the thyroid axis of adult female mice lacking neuromedin B receptor (NBR-KO), compared to wild type (WT) littermates. They exhibited slight increase in serum TSH (18%), with normal pituitary expression of mRNA coding for α-glycoprotein subunit (Cga), but reduced TSH β-subunit mRNA (Tshb, 41%), lower intra-pituitary TSH content (24%) and increased thyroid hormone transporter MCT-8 (Slc16a2, 44%) and thyroid hormone receptor β mRNA expression (Thrb, 39%). NBR-KO mice exhibited normal thyroxine (T4) and reduced triiodothyronine (T3) (30%), with no alterations in the intra-thyroidal content of T4 and T3 or thyroid morphological changes. Hypothalamic thyrotropin-releasing hormone (TRH) mRNA (Trh) was increased (68%), concomitant with a reduction in type 2 deiodinase mRNA (Dio2, 30%) and no changes in MCT-8 and thyroid hormone receptor mRNA expression. NBR-KO mice exhibited a 56% higher increase in serum TSH in response to an acute single intraperitoneal injection of TRH concomitant with a non-significant increase in pituitary TRH receptor (Trhr) mRNA at basal state. The phenotype of female NBR-KO mice at the hypothalamus-pituitary axis revealed alterations in pituitary and hypothalamic gene expression, associated with reduced serum T3, and higher TSH response to TRH, with apparently normal thyroid morphology and hormonal production. Thus, results confirm that neuromedin B pathways are importantly involved in secretory pathways of TSH and revealed its participation in the in vivo regulation of gene expression of TSH β-subunit and pituitary MCT8 and Thrb and hypothalamic TRH and type 2 deiodinase. PMID:25454367

  12. Pituitary hyperplasia: case series and literature review of an under-recognised and heterogeneous condition

    PubMed Central

    Earls, Peter; McCormack, Ann I

    2015-01-01

    Summary Pituitary hyperplasia (PH) occurs in heterogeneous settings and remains under-recognised. Increased awareness of this condition and its natural history should circumvent unnecessary trans-sphenoidal surgery. We performed an observational case series of patients referred to a single endocrinologist over a 3-year period. Four young women were identified with PH manifesting as diffuse, symmetrical pituitary enlargement near or touching the optic apparatus on MRI. The first woman presented with primary hypothyroidism and likely had thyrotroph hyperplasia given prompt resolution with thyroxine. The second and third women were diagnosed with pathological gonadotroph hyperplasia due to primary gonadal insufficiency, with histopathological confirmation including gonadal-deficiency cells in the third case where surgery could have been avoided. The fourth woman likely had idiopathic PH, though she had concomitant polycystic ovary syndrome which is a debated cause of PH. Patients suspected of PH should undergo comprehensive hormonal, radiological and sometimes ophthalmological evaluation. This is best conducted by a specialised multidisciplinary team with preference for treatment of underlying conditions and close monitoring over surgical intervention. Learning points Normal pituitary dimensions are influenced by age and gender with the greatest pituitary heights seen in young adults and perimenopausal women.Pituitary enlargement may be seen in the settings of pregnancy, end-organ insufficiency with loss of negative feedback, and excess trophic hormone from the hypothalamus or neuroendocrine tumours.PH may be caused or exacerbated by medications including oestrogen, GNRH analogues and antipsychotics.Management involves identification of cases of idiopathic PH suitable for simple surveillance and reversal of pathological or iatrogenic causes where they exist.Surgery should be avoided in PH as it rarely progresses. PMID:26124954

  13. NG2 targets tumorigenic Rb inactivation in Pit1-lineage pituitary cells.

    PubMed

    Tateno, Toru; Nakano-Tateno, Tae; Ezzat, Shereen; Asa, Sylvia L

    2016-05-01

    The proteoglycan neuron-glial antigen 2 (NG2) is expressed by oligodendrocyte progenitors, pericytes, and some cancerous cells where it is implicated in tumor development. We examined mice with NG2-driven pRb inactivation. Unexpectedly, NG2-Cre:pRb(flox/flox) mice developed pituitary tumors with high penetrance. Adenohypophysial neoplasms developed initially as multifocal lesions; by 1 year, large tumors showed brain invasion. Immunohistochemistry identified these as Pit1-lineage neoplasms, with variable immunoreactivity for growth hormone, prolactin, thyrotropin, and α-subunit of glycoprotein hormones. Other than modest hyperprolactinemia, circulating hormone levels were not elevated. To determine the role of NG2 in the pituitary, we investigated NG2 expression. Immunoreactivity was identified in anterior and posterior lobes but not in the intermediate lobe of the mouse pituitary; in the adenohypophysis, folliculostellate cells had the strongest NG2 immunoreactivity but showed no proliferation in response to Rb inactivation. Pit1-positive adenohypophysial cells were positive for NG2, but corticotroph and gonadotroph cells were negative. RT-PCR revealed NG2 expression in normal human pituitary and human pituitary tumors; immunohistochemistry localized NG2 in nontumorous human adenohypophysis with strongest positivity in folliculostellate cells, and in tumors of all types except corticotrophs. Functional studies in GH4 mammosomatotrophs showed that NG2 increases prolactin (PRL), reduces growth hormone (GH) expression, and enhances cell adhesion without influencing proliferation. In conclusion, NG2-driven pRb inactivation results in pituitary tumors that mimic endocrinologically inactive Pit1-lineage human pituitary tumors. This model identifies a role for NG2 in pituitary cell-type-specific functions and unmasks a protective role from Rb inactivation in folliculostellate cells; it can be used for further research, including preclinical testing of novel therapies

  14. Uptake of (/sup 3/H)testosterone and its metabolites by the brain and pituitary gland of the fetal macaque

    SciTech Connect

    Michael, R.P.; Bonsall, R.W.; Rees, H.D.

    1989-03-01

    Testosterone is secreted by the fetal testis during gestation, and this is thought to influence certain aspects of the brain's subsequent development. To study this action at the neuronal level, nine macaque fetuses were injected with 250 microCi (3H)testosterone via the umbilical vein at about 120 days gestation. After 60 min, samples of brain and peripheral tissue were studied by autoradiography or HPLC. Purified nuclear pellets were prepared, and radioactivity in ether extracts was fractionated by HPLC and identified by coelution with internal standard steroids. Concentrations of radioactivity were significantly higher (P less than 0.05) in the hypothalamus-preoptic area than in amygdala, hippocampus, midbrain, and cerebral and cerebellar cortexes, and most of the radioactivity (75%) in the hypothalamus-preoptic area coeluted with 17 beta-estradiol. Radioactivity coeluting with 17 beta-estradiol was also detected in nuclear fractions from amygdala (44%). In contrast, 80% of the radioactivity extracted from pituitary gland nuclei coeluted with testosterone. Most of the neurons labeled in autoradiograms were located in the hypothalamus and preoptic area, fewer were found in the amygdala, and labeling in the frontal or motor cortex did not exceed chance levels. Results suggested that aromatization and, consequently, estrogen receptors play a role in the effects of testosterone on the hypothalamus and amygdala of the primate fetus at this stage of development.

  15. Er-Xian Decoction, a traditional Chinese herbal formula, intervening early in hypothalamic-pituitary axis of male rats with delayed puberty

    PubMed Central

    Zhu, Zheng; Li, LiHong; Jin, Xin; Fang, JianWei; Zhang, DongFang

    2014-01-01

    Background: Er-Xian Decoction (EXD) is one of the traditional Chinese medicine (TCM) with unique effect on osteoporosis, menopausal syndrome and delayed puberty in China for many years. Objective: We aim to evaluate the potential activity of starting hypothalamic–pituitary–testicular (HPT) axis of male rats with delayed puberty. Materials and Methods: Delayed puberty model of male Sprague–Dawley (SD) rats were established with soy isoflavones (90 mg·kg-1) and were treated by EXD extract at doses of 5, 10 g·kg-1 or Testosterone undecanoate (TU) for 8 weeks. Body weight, body length, testis weight, T, E2 and luteinizing hormone (LH) in serum, gonadotropin releasing hormone (GnRH) in hypothalamus, follicle stimulating hormone (FSH) and LH in pituitary gland were determined by ELISA. Immunohistochemistry was used to detect LH in pituitary gland. Results: Soy isoflavones could significantly decrease body weight, body length, testicular organ coefficient T in serum, GnRH in hypothalamus, FSH and LH in pituitary gland. Both of EXD and TU could improve the condition. E2 and LH in serum of all groups were non-significance of difference (P > 0.05). The immunohistochemical results were well consistent with LH in pituitary gland. Conclusion: The results of the present research indicate that EXD extract is effective to start the HPT axis in puberty and can significantly improve sexual developmental inhibition caused by soy isoflavones. PMID:25422555

  16. Serotonin and acetylcholine affect the release of prolactin and growth hormone from pituitary glands of domestic fowl in vitro in the presence of hypothalamic tissue.

    PubMed

    Hall, T R; Harvey, S; Chadwick, A

    1984-04-01

    Anterior pituitary glands from broiler fowl were incubated alone or with hypothalamic tissue in medium containing either serotonin or serotoninergic drugs, acetylcholine or cholinergic drugs, and the release of prolactin (Prl) and growth hormone (GH) measured by homologous radioimmunoassays. The neurotransmitters and drugs affected the release of hormones from the pituitary gland only when hypothalamic tissue was also present. Serotonin and its agonist quipazine stimulated the release of Prl and inhibited release of GH in a concentration-related manner. The antagonist methysergide blocked the effects of serotonin and quipazine on Prl. Acetylcholine and its agonist pilocarpine also stimulated release of Prl and inhibited release of GH in a concentration-related manner. Atropine blocked these responses. The results show that serotonin and acetylcholine affect pituitary hormone secretion by acting on the hypothalamus. They may stimulate the secretion of a Prl releasing hormone and somatostatin. PMID:6144226

  17. Advanced virtual endoscopic pituitary surgery.

    PubMed

    Neubauer, André; Wolfsberger, Stefan; Forster, Marie-Thérèse; Mroz, Lukas; Wegenkittl, Rainer; Bühler, Katja

    2005-01-01

    Endoscopy has recently been introduced to endonasal transsphenoidal pituitary surgery as a minimally invasive procedure for the removal of various kinds of pituitary tumors. To reduce morbidity and mortality with this new technique, the surgeon must be well-trained and well-prepared. Virtual endoscopy can be beneficial as a tool for training, preoperative planning, and intraoperative support. This paper introduces STEPS, a virtual endoscopy system designed to aid surgeons in getting acquainted with the endoscopic view of the anatomy, the handling of instruments, the transsphenoidal approach, and challenges associated with the procedure. STEPS also assists experienced surgeons in planning a real endoscopic intervention by getting familiar with the individual patient anatomy, identifying landmarks, planning the approach, and deciding upon the ideal target position of the actual surgical activity. The application provides interactive visualization, navigation, and perception aids and the possibility of simulating the procedure, including haptic feedback and simulation of surgical instruments. PMID:16144247

  18. Induction of Autophagy in the Striatum and Hypothalamus of Mice after 835 MHz Radiofrequency Exposure.

    PubMed

    Kim, Ju Hwan; Huh, Yang Hoon; Kim, Hak Rim

    2016-01-01

    The extensive use of wireless mobile phones and associated communication devices has led to increasing public concern about potential biological health-related effects of the exposure to electromagnetic fields (EMFs). EMFs emitted by a mobile phone have been suggested to influence neuronal functions in the brain and affect behavior. However, the affects and phenotype of EMFs exposure are unclear. We applied radiofrequency (RF) of 835 MHz at a specific absorption rate (SAR) of 4.0 W/kg for 5 hours/day for 4 and 12 weeks to clarify the biological effects on mouse brain. Interestingly, microarray data indicated that a variety of autophagic related genes showed fold-change within small range after 835 MHz RF exposure. qRT-PCR revealed significant up-regulation of the autophagic genes Atg5, LC3A and LC3B in the striatum and hypothalamus after a 12-week RF. In parallel, protein expression of LC3B-II was also increased in both brain regions. Autophagosomes were observed in the striatum and hypothalamus of RF-exposed mice, based on neuronal transmission electron microscopy. Taken together, the results indicate that RF exposure of the brain can induce autophagy in neuronal tissues, providing insight into the protective mechanism or adaptation to RF stress. PMID:27073885

  19. Induction of Autophagy in the Striatum and Hypothalamus of Mice after 835 MHz Radiofrequency Exposure

    PubMed Central

    Kim, Hak Rim

    2016-01-01

    The extensive use of wireless mobile phones and associated communication devices has led to increasing public concern about potential biological health-related effects of the exposure to electromagnetic fields (EMFs). EMFs emitted by a mobile phone have been suggested to influence neuronal functions in the brain and affect behavior. However, the affects and phenotype of EMFs exposure are unclear. We applied radiofrequency (RF) of 835 MHz at a specific absorption rate (SAR) of 4.0 W/kg for 5 hours/day for 4 and 12 weeks to clarify the biological effects on mouse brain. Interestingly, microarray data indicated that a variety of autophagic related genes showed fold-change within small range after 835 MHz RF exposure. qRT-PCR revealed significant up-regulation of the autophagic genes Atg5, LC3A and LC3B in the striatum and hypothalamus after a 12-week RF. In parallel, protein expression of LC3B-II was also increased in both brain regions. Autophagosomes were observed in the striatum and hypothalamus of RF-exposed mice, based on neuronal transmission electron microscopy. Taken together, the results indicate that RF exposure of the brain can induce autophagy in neuronal tissues, providing insight into the protective mechanism or adaptation to RF stress. PMID:27073885

  20. Molecular analysis of rat pituitary and hypothalamic growth hormone secretagogue receptors.

    PubMed

    McKee, K K; Palyha, O C; Feighner, S D; Hreniuk, D L; Tan, C P; Phillips, M S; Smith, R G; Van der Ploeg, L H; Howard, A D

    1997-04-01

    GH release is thought to occur under the reciprocal regulation of two hypothalamic peptides, GH releasing hormone (GHRH) and somatostatin, via their engagement with specific cell surface receptors on the anterior pituitary somatotroph. In addition, GH-releasing peptides, such as GHRP-6 and the nonpeptide mimetics, L-692,429 and MK-0677, stimulate GH release through their activation of a distinct receptor, the GH secretagogue receptor (GHS-R). The recent cloning of the GHS-R from human and swine pituitary gland identifies yet a third G protein-coupled receptor (GPC-R) involved in the control of GH release and further supports the existence of an undiscovered hormone that may activate this receptor. Using the human GHS-R as a probe, we report the isolation of a rat pituitary GHS-R cDNA derived from an unspliced, precursor mRNA. The rat cDNA encodes a protein of 364 amino acids containing seven transmembrane domains (7-TM) with >90% sequence identity to both the human and swine GHS-Rs. A single intron of approximately 2 kb divides the open reading frame into two exons encoding TM 1-5 and TM 6-7, thus placing the GHS-R into the intron-containing class of GPC-Rs. The intron maps to the site of sequence divergence between the human and swine type 1a and 1b GHS-R mRNAs. In addition, determination of the nucleotide sequence for the human GHS-R gene confirmed the position of an intron in the human GHS-R gene at this position. A full-length contiguous cDNA from rat hypothalamus was isolated and shown to be identical in its nucleotide and deduced amino acid sequence to the rat pituitary GHS-R. The cloned rat GHS-R binds [35S]MK-0677 with high affinity [dissociation constant (K(D)) = 0.7 nM] and is functionally active when expressed in HEK-293 cells. Expression of the rat GHS-R was observed specifically in the pituitary and hypothalamus when compared with control tissues. PMID:9092793

  1. Estrogen alters proenkephalin RNAs in the paraventricular nucleus of the hypothalamus following stress.

    PubMed

    Yukhananov, R Y; Handa, R J

    1997-08-01

    Gonadal steroids modulate activity of the hypothalamo-pituitary-adrenal axis (HPA) following stress, but the regulatory pathways of this modulation are unknown. A possible site of action is the synthesis of CRH and/or enkephalin in cells of the paraventricular nucleus of the hypothalamus (PVN). To investigate this possibility, we utilized two stressors, i.p. hypertonic saline injection (HSI) or exposure to novel environment, and examined the response of CRH or c-fos mRNAs and proenkephalin (PPE) mRNA and heteronuclear RNA (hnRNA, primary transcript). Male rats were gonadectomized and treated with estrogen or dihydrotestosterone propionate (DHTP) for 2 weeks. In situ hybridization revealed that novelty or HSI elevated levels of PPE hnRNA and c-fos mRNA in the PVN. Estrogen attenuated the elevation of PPE hnRNA in the PVN following HSI, and enhanced the c-fos mRNA response to novelty. In contrast, DHTP did not affect PPE hnRNA, but inhibited the c-fos mRNA response to novelty. These data indicate that in male rats estrogen receptor but not androgen receptor may modulate the endocrine stress response by altering PPE transcription in the PVN and that this effect depends on the type of stressor. PMID:9295199

  2. Pituitary function following treatment with reproductive toxins.

    PubMed Central

    Cooper, R L; Goldman, J M; Rehnberg, G L

    1986-01-01

    Appropriate regulation of reproductive processes are dependent upon the integrity of pituitary function. In this selected review, we evaluate the evidence that certain environmental compounds exert their effect on reproductive function via a direct action on the pituitary gland. We also discuss examples of changes in pituitary hormone secretion that occur in response to changes in neuronal or gonadal control of the pituitary. A limited number of studies suggest that measures of pituitary hormone secretion provide an early and sensitive measure of a compound's potential effects on the reproductive system. However, the most striking aspect of this area is the sparse and inconsistent information describing pituitary function following exposure to environmental pollutants. PMID:3830104

  3. Gamma knife radiosurgery for pituitary adenomas.

    PubMed

    Ježková, Jana; Marek, Josef

    2016-09-01

    Pituitary adenomas are frequently occurring intracranial neoplasms. The aim of the treatment of pituitary adenomas is to normalize hormonal hypersecretion, to preserve the normal pituitary function, to reserve or treat impaired pituitary function and to control tumor growth and its mechanical effects on the surrounding structures. Treatment modalities include surgical, medical and radiation therapy. Radiosurgery is mainly used as a secondary line treatment after surgery for residual or recurrent tumors. The antiproliferative effect is achieved by LKG irradiation in more than 90% of patients. Regarding the functioning pituitary adenomas, the manifestation of the treatment effect is slow and depends mainly on the type of adenoma. Gamma knife irradiation is safe when the maximal doses to pituitary and infundibulum are respected. PMID:26899535

  4. Lateral-Medial Dissociation in Orbitofrontal Cortex-Hypothalamus Connectivity.

    PubMed

    Hirose, Satoshi; Osada, Takahiro; Ogawa, Akitoshi; Tanaka, Masaki; Wada, Hiroyuki; Yoshizawa, Yasunori; Imai, Yoshio; Machida, Toru; Akahane, Masaaki; Shirouzu, Ichiro; Konishi, Seiki

    2016-01-01

    The orbitofrontal cortex (OFC) is involved in cognitive functions, and is also closely related to autonomic functions. The OFC is densely connected with the hypothalamus, a heterogeneous structure controlling autonomic functions that can be divided into two major parts: the lateral and the medial. Resting-state functional connectivity has allowed us to parcellate the cerebral cortex into putative functional areas based on the changes in the spatial pattern of connectivity in the cerebral cortex when a seed point is moved from one voxel to another. In the present high spatial-resolution fMRI study, we investigate the connectivity-based organization of the OFC with reference to the hypothalamus. The OFC was parcellated using resting-state functional connectivity in an individual subject approach, and then the functional connectivity was examined between the parcellated areas in the OFC and the lateral/medial hypothalamus. We found a functional double dissociation in the OFC: the lateral OFC (the lateral orbital gyrus) was more likely connected with the lateral hypothalamus, whereas the medial OFC (the medial orbital and rectal gyri) was more likely connected with the medial hypothalamus. These results demonstrate the fundamental heterogeneity of the OFC, and suggest a potential neural basis of the OFC-hypothalamic functional interaction. PMID:27303281

  5. Lateral–Medial Dissociation in Orbitofrontal Cortex–Hypothalamus Connectivity

    PubMed Central

    Hirose, Satoshi; Osada, Takahiro; Ogawa, Akitoshi; Tanaka, Masaki; Wada, Hiroyuki; Yoshizawa, Yasunori; Imai, Yoshio; Machida, Toru; Akahane, Masaaki; Shirouzu, Ichiro; Konishi, Seiki

    2016-01-01

    The orbitofrontal cortex (OFC) is involved in cognitive functions, and is also closely related to autonomic functions. The OFC is densely connected with the hypothalamus, a heterogeneous structure controlling autonomic functions that can be divided into two major parts: the lateral and the medial. Resting-state functional connectivity has allowed us to parcellate the cerebral cortex into putative functional areas based on the changes in the spatial pattern of connectivity in the cerebral cortex when a seed point is moved from one voxel to another. In the present high spatial-resolution fMRI study, we investigate the connectivity-based organization of the OFC with reference to the hypothalamus. The OFC was parcellated using resting-state functional connectivity in an individual subject approach, and then the functional connectivity was examined between the parcellated areas in the OFC and the lateral/medial hypothalamus. We found a functional double dissociation in the OFC: the lateral OFC (the lateral orbital gyrus) was more likely connected with the lateral hypothalamus, whereas the medial OFC (the medial orbital and rectal gyri) was more likely connected with the medial hypothalamus. These results demonstrate the fundamental heterogeneity of the OFC, and suggest a potential neural basis of the OFC–hypothalamic functional interaction. PMID:27303281

  6. The Recreational Drug Ecstasy Disrupts the Hypothalamic-Pituitary-Gonadal Reproductive Axis in Adult Male Rats

    PubMed Central

    Dickerson, Sarah M.; Walker, Deena M.; Reveron, Maria E.; Duvauchelle, Christine L.; Gore, Andrea C.

    2009-01-01

    Reproductive function involves an interaction of three regulatory levels: hypothalamus, pituitary, and gonad. The primary drive upon this system comes from hypothalamic gonadotropin-releasing hormone (GnRH) neurosecretory cells, which receive afferent inputs from other neurotransmitter systems in the central nervous system to result in the proper coordination of reproduction and the environment. Here, we hypothesized that the recreational drug ±-3,4-Methylenedioxymethamphetamine (MDMA; “ecstasy”), which acts through several of the neurotransmitter systems that affect GnRH neurons, suppresses the hypothalamic-pituitary-gonadal (HPG) reproductive axis of male rats. Adult male Sprague-Dawley rats self-administered saline or MDMA or saline either once (acute) or for 20 days (chronic), and were euthanized 7 days following last administration. We quantified hypothalamic GnRH mRNA, serum luteinizing hormone (LH) concentrations, and serum testosterone levels, as indices of hypothalamic, pituitary, and gonadal functions, respectively. The results indicate that the hypothalamic and gonadal levels of the HPG axis are significantly altered by MDMA, with GnRH mRNA and serum testosterone levels suppressed in rats administered MDMA compared to saline. Furthermore, our finding that hypothalamic GnRH mRNA levels are suppressed in the context of low testosterone concentrations suggests that the central GnRH neurosecretory system may be a primary target of inhibitory regulation by MDMA usage. PMID:18309234

  7. The effect of glucocorticoids on mouse oocyte in vitro maturation and subsequent fertilization and embryo development.

    PubMed

    González, Raquel; Ruiz-León, Yolanda; Gomendio, Montserrat; Roldan, Eduardo R S

    2010-02-01

    Increased glucocorticoid levels, due to medical therapy or stress-related, may affect reproduction via the hypothalamus-pituitary-axis or directly at the oocyte level. We examined the effects of natural (corticosterone) or synthetic (dexamethasone) glucocorticoids on mouse oocyte maturation and underlying changes in extracellular signal-regulated kinase (ERK) phosphorylation patterns. Fertilization and progression up to the blastocyst stage were also evaluated. Oocytes were exposed to corticosterone or dexamethasone (0, 0.25, 2.5, 25 or 250microM) for 17h during in vitro maturation. After maturation, ERK-1/2 activation in oocytes was assessed by SDS-PAGE and immunoblotting, and fertilization and developmental capacity were examined in vitro. Corticosterone exposure during oocyte maturation significantly decreased progression to metaphase II, fertilization and embryo development at the highest concentration. Corticosterone caused a concentration-dependent inhibition of ERK-1/2 activation, with the highest concentration resulting in considerable inhibition of oocyte ERK-1/2 phosphorylation and no blastocyst development. In contrast, dexamethasone had no effect on maturation, fertilization and cleavage, and no effect was seen on ERK-1/2 phosphorylation. Based on these in vitro findings, high glucocorticoid levels may have consequences for subsequent development, although a short exposure to physiologic or stress-related glucocorticoid levels may not represent a hazard to meiosis progression of the oocyte. PMID:19733225

  8. Orexin and neuropeptide Y: tissue specific expression and immunoreactivity in the hypothalamus and preoptic area of the cichlid fish Cichlasoma dimerus.

    PubMed

    Pérez Sirkin, D I; Suzuki, H; Cánepa, M M; Vissio, P G

    2013-12-01

    Neuropeptide Y (NPY) and orexin are neuropeptides involved in the regulation of feeding in vertebrates. In this study we determined the NPY and orexin mRNA tissue expression and their immunoreactivity distribution in both preoptic area and hypothalamus, regions involved in the regulation of feeding behavior. Both peptides presented a wide expression in all tissues examined. The NPY-immunoreactive (ir) cells were localized in the ventral nucleus posterioris periventricularis (NPPv) and numerous ir-NPY fibers were found in the nucleus lateralis tuberis (NLT), the nucleus recess lateralis (NRL) and the neurohypophysis. Ir-orexin cells were observed in the NPPv, dorsal NLT, ventral NLT, lateral NLT (NLTl) and the lateral NRL. Ir-orexin fibers were widespread distributed along all the hypothalamus, especially in the NLTl. Additionally, we observed the presence of ir-orexin immunostaining in adenohypophyseal cells, especially in somatotroph cells and the presence of a few ir-orexin-A fibers in the neurohypophysis. In conclusion, both peptides have an ubiquitous mRNA tissue expression and are similarly distributed in the hypothalamus and preoptic area of Cichlasoma dimerus. The presence of ir-orexin in adenohypohyseal cells and the presence of ir-orexin and NPY fibers in the neurohypophysis suggest that both peptides may play an important neuroendocrine role in anterior pituitary. PMID:24138942

  9. Central stress-integrative circuits: Forebrain glutamatergic and GABAergic projections to the dorsomedial hypothalamus, medial preoptic area, and bed nucleus of the stria terminalis

    PubMed Central

    Myers, Brent; Dolgas, C. Mark; Kasckow, John; Cullinan, William E.; Herman, James P.

    2013-01-01

    Central regulation of hypothalamo-pituitary-adrenocortical (HPA) axis stress responses is mediated by a relatively circumscribed group of projections to the paraventricular hypothalamus (PVN). The dorsomedial hypothalamus (DMH), medial preoptic area (mPOA), and bed nucleus of the stria terminalis (BST) provide direct, predominantly inhibitory, innervation of the PVN. These PVN-projecting neurons are controlled by descending information from limbic forebrain structures, including the prefrontal cortex, amygdala, hippocampus, and septum. The neurochemical phenotype of limbic circuits targeting PVN relays has not been systematically analyzed. The current study combined retrograde tracing and immunohistochemistry/in situ hybridization to identify the specific sites of glutamatergic and GABAergic inputs to the DMH, mPOA, and BST. Following Flouro-Gold (FG) injections in the DMH, retrogradely-labeled cells co-localized with vesicular glutamate transporter mRNA in the prefrontal cortex, ventral hippocampus, and paraventricular thalamus. Co-localization of FG and glutamic acid decarboxylase mRNA was present throughout the central and medial amygdaloid nuclei and septal area. Additionally, the mPOA received predominantly GABAergic input from the septum, amygdala, and BST. The BST received glutamatergic projections from the hippocampus and basomedial amygdala, whereas GABAergic inputs arose from central and medial amygdaloid nuclei. Thus, discrete sets of neurons in the hypothalamus and BST are positioned to summate limbic inputs into PVN regulation and may play a role in HPA dysfunction and stress-related illness. PMID:23661182

  10. Seasonal changes in RFamide-related peptide-3 neurons in the hypothalamus of a seasonally breeding marsupial species, the brushtail possum (Trichosurus vulpecula).

    PubMed

    Harbid, Anan A; McLeod, Bernie J; Caraty, Alain; Anderson, Greg M

    2013-09-01

    RFamide-related peptide-3 (RFRP-3) neurons have been shown to inhibit gonadotropin-releasing hormone (GnRH) neuronal activity and hence reproduction in birds and eutherian mammals. They have also been proposed to have a direct hypophysiotropic effect on pituitary gonadotropin release. We used a new RFRP-3 antibody to characterize the cell body distribution and fiber projections of RFRP-3 neurons in the adult female brushtail possum brain. RFRP-3-immunoreactive cell bodies were found scattered within the dorsomedial hypothalamus and the dorsomedial half of the ventromedial hypothalamus, while GnRH neurons were observed scattered rostrocaudally along the lateral septum, rostral to the medial septum. There was a significant 2-fold increase in the RFRP-3 cell body number during the nonbreeding season (summer) compared to the breeding season (winter). Immunoreactive RFRP-3 fibers were distributed throughout the thalamus, preoptic area, and hypothalamus. Very few fibers were observed in the median eminence, especially in the external zone. Intraperitoneal injection of the retrograde tracer Fluoro-Gold resulted in the labeling of 40% of hypophysiotropic tuberoinfundibular dopaminergic (tyrosine hydroxylase-positive) neurons; however, <10% of zona incerta dopaminergic neurons (which are not hypophysiotropic) or RFRP-3 neurons were labeled with this tracer. These observations suggest that RFRP-3 exhibits a seasonal fluctuation in cell numbers, as seen in sheep and birds, which is consistent with an increased inhibitory tone during the nonbreeding season. The lack of RFRP-3 fibers in the median eminence and of Fluoro-Gold uptake from the periphery imply that the actions of this peptide occur primarily centrally rather than at the anterior pituitary gland. PMID:23504980