Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anterior pituitary hormones are known to exert dynamic negative feedback effects on their respective regulatory ("hypophysiotropic") neurons in the hypothalamus. The purpose of this review is to present the evidence for a theory that the effect of pituitary hormones on these hypophysiotropic neurons is neurotrophic, extending beyond dynamic feedback to influence upon cell survival, phenotypic differentiation, and axonal connectivity. To that end, the adult condition and the development of hypophysiotropic neurons in mutant mice which lack pituitary growth hormone (GH) and prolactin (PRL) are presented as models of the effect of absent specific neurotrophic signals. The expression of the neurohormones which inhibit PRL and GH secretion, dopamine (DA) and somatostatin, respectively, is markedly reduced in the hypothalamus of the hypopituitary dwarf mouse, and this adult condition is the result of postnatal failure to develop or actual regression, which may include neuronal cell death. The deficit in DA may be reversed by PRL replacement, but only if initiated at an identified critical postnatal period. Conversely, expression of the stimulatory GH-releasing hormone (GHRH) is markedly increased in the dwarf mouse hypothalamus. The loss of DA and the increase in GHRH occur in the same hypothalamic area, suggesting neuronal phenotypic plasticity in response to absence of pituitary feedback signals. The axonal terminations of extant GH- and PRL-regulating neurons in external median eminence appear to be reduced, suggesting that pituitary signals are required for appropriate axonal guidance during development, even though an endocrine vascular route intervenes between these regulatory neurons and their target secretory cells. The collective observations indicate that GH and PRL may be regarded as neurotrophic factors for their respective regulatory neurons in the hypothalamus.
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PMID:Pituitary hormones as neurotrophic signals: anomalous hypophysiotrophic neuron differentiation in hypopituitary dwarf mice. 791 Apr 9

Interleukin-1 (IL-1) has been suggested to directly affect pituitary growth hormone (GH) release, although other investigators have failed to observe this effect. We examined the effects of IL-1 beta on GH secretion from single somatotrophs by means of reverse hemolytic plaque assay (RHPA). Anterior pituitary cells of adult male rats were enzymatically dispersed and subjected to RHPA. IL-1 beta at 100 pM and 1 nM, increased both the mean plaque area and the fraction of somatotrophs forming large plaques. IL-1 beta did not increase the mean plaque area in the presence of the IL-1 receptor antagonist (IL-1ra). IL-1 beta (1 nM) added together with GH-releasing hormone (GHRH; 10 nM), showed no additive effect on GHRH-induced GH release. The stimulatory action of IL-1 beta on the release of GH was suppressed by somatostatin. In conclusion, our data show that IL-1 beta stimulates GH-secretion through direct action on the pituitary.
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PMID:Analysis of growth hormone release from rat anterior pituitary cells by reverse hemolytic plaque assay: influence of interleukin-1. 796 61

Recent findings indicate that excitatory amino acids (EAAs) can modulate growth hormone (GH) secretion in several mammalian species in vivo and in vitro. In this study, we examined the effects of EAA receptor antagonists [N-methyl-D,L-aspartate (NMDA), kainic acid, L-glutamate] on GH secretion by the reverse hemolytic plaque assay (RHPA). Anterior pituitary cells of adult male Sprague-Dawley rats were enzymatically dispersed and subjected to RHPA. EAA receptor agonists increased the mean plaque area in a dose-dependent manner: the maximal increase was observed at 10 microM and increased the fraction of somatotrophs forming large plaques. NMDA (10 microM) did not increase the mean plaque area in the presence of the NMDA receptor antagonists 10 microM AP-7 and 10 microM MK-801. Coincubation of kainic acid with the non-NMDA receptor antagonist CNQX blocked the kainic-acid-stimulated increase in GH secretion. The addition of MK-801, AP-7 or CNQX to glutamate caused a partial reduction of the mean plaque area. Ten micromoles per liter glutamate with 10 nM GH-releasing hormone (GHRH) produced an additive effect on GHRH-induced GH release. Somatostatin suppressed the stimulatory action of glutamate. We speculate that glutamate plays a role in the regulation of GH secretion.
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PMID:Effect of excitatory amino acid receptor agonists on secretion of growth hormone as assessed by the reverse hemolytic plaque assay. 796 75

The effects of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF alpha) on basal and TRH-induced TSH release, and the effects of IL-1 beta on the uptake of [125I]T3 and [125I]T4 and on nuclear binding of [125I]T3 were examined. Furthermore, the release of other anterior pituitary hormones in the presence of IL-1 beta was measured. Anterior pituitary cells from male Wistar rats were cultured for 3 days in medium containing 10% FCS. Incubation were performed at 37 C in medium with 0.5% BSA for measurement of [125I]T3 uptake and with 0.1% BSA for measurement of [125I]T4 uptake. Exposure to IL-1 beta (1 pM-1 nM) or TNF alpha (100 pM) for 2-4 h resulted in a significant decline in TSH release, which was almost 50% (P < 0.05) for 1 nM IL-1 beta and 24% (P < 0.05) for 100 pM TNF alpha. Measurement of other anterior pituitary hormones (FSH, LH, PRL, and ACTH) in the same incubation medium showed that IL-1 beta did not alter their release. When the effects of IL-1 beta (1 pM-1 nM) and TNF alpha (100 pM) on TRH-induced TSH release were measured in short term experiments, the inhibitory effects had disappeared. The addition of 1-100 nM octreotide, a somatostatin analog, resulted in a decrease in TRH-induced TSH release up to 33% of the control value (P < 0.05). Exposure to dexamethasone (1 nM to 1 microM) affected basal and TRH-induced TSH release similar to the effect of IL-1 beta. The 15-min uptake of [125I]T3 and [125I]T4, expressed as femtomoles per pM free hormone, was not affected by the presence of IL-1 beta (1-100 pM). When IL-1 beta (100 pM) was present during 3 days of culture, TSH release was reduced to 88 +/- 2% of the control value (P < 0.05). This effect was not associated with an altered [125I]T3 uptake (15 min to 4 h) or with any change in nuclear T3 binding. We conclude that 1) IL-1 beta decreases TSH release by a direct action on the pituitary; 2) this effect is not due to elevated thyroid hormone uptake or increase T3 nuclear occupancy; 3) IL-1 beta does not affect TRH-induced TSH release or the release of other anterior pituitary hormones; and 4) TNF alpha affects basal and TRH-induced TSH release in the same way as IL-1 beta.
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PMID:Effects of interleukin-1 beta on thyrotropin secretion and thyroid hormone uptake in cultured rat anterior pituitary cells. 861 90

Anterior pituitary hormone secretion is sexually dimorphic due partially to gender differences in the postpubertal hormone environment; however, differences in the pituitary's responsiveness to these signals may also play a role. We have used simple and double in situ hybridization to determine whether lactotrophs and somatotrophs from male and female rats respond differently in vitro to growth hormone-releasing hormone (GHRH), somatostatin (SS) or insulin-like growth factor (IGF)-I and whether sex steroids modulate these responses. Cultures were treated with either 17 beta-estradiol (E; 10(-9)M), testosterone (T; 10(-7)M), dihydrotestosterone (DHT; 10(-7) M) or vehicle in combination with either GHRH (10(-7)M), SS (10(-7)M), IGF-I (10(-7)M) or vehicle. Basal mRNA levels of GH, prolactin (PRL) and pituitary transcription factor-1 (Pit-1) did not differ between the sexes. The responses to peptide hormones alone were similar between the sexes, but not in the presence of gonadal steroids. In females, DHT reduced and E increased the stimulatory effect of GHRH and inhibitory effect of SS on GH mRNA levels (two-way ANOVA: P < 0.05), while having no effect in males. An additive effect of E and GHRH on PRL mRNA levels was seen only in males. The E induced rise in PRL mRNA levels was completely inhibited by SS in females, but only partially so in males (two-way ANOVA: P < 0.001). IGF-I inhibited the E induced rise in PRL and lactotroph Pit-1 mRNA levels only in females. These results suggest that sex steroids modulate the pituitary's response to hypothalamic and circulating factors differently in males and females and that this may play a role in generating the sexually dimorphic patterns of pituitary hormone secretion.
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PMID:Sexually dimorphic interaction of insulin-like growth factor (IGF)-I and sex steroids in lactotrophs. 970 Jun 76

Growth hormone (GH) secretion is altered in poorly controlled diabetic animals. However, modifications in the hypothalamic neuropeptides that control GH secretion, somatostatin and GH-releasing hormone (GHRH), as well as changes in the sensitivity of the hypothalamus and pituitary to the feedback effects of GH, are less clear. We have used RNase protection assays and in-situ hybridization to address whether the mRNA expression of GH, somatostatin and GHRH, as well as of the GH receptor (GHR) in the hypothalamus and anterior pituitary, are altered in streptozotocin-induced diabetic rats. After induction of diabetes, rats were treated with insulin twice daily for 3 weeks to obtain either poorly controlled (mean plasma glucose >300 mg/dl) or well-controlled diabetic rats. Although no significant change in pituitary GH mRNA expression was found, the hypothalamic expression of GHRH and somatostatin mRNA was reduced in poorly-controlled diabetic rats and returned to control values with normalisation of plasma glucose concentrations (P<0.0001 and P<0.002, respectively). Somatostatin mRNA expression was reduced only in the central portion of the periventricular nucleus, with no change being seen in the other areas of the periventricular nucleus or in the arcuate, suprachiasmatic or paraventricular nuclei. A significant decline in GHRH mRNA expression was observed in both the arcuate nucleus and ventromedial hypothalamus. Anterior pituitary GHR mRNA expression was significantly reduced in both well and poorly-controlled diabetic rats, while there was no change in the hypothalamus. To examine whether the evolution time of the diabetes influences these parameters, in a subsequent experiment, diabetic rats received no insulin for 2 months. A significant decline in GHRH and somatostatin mRNA expression was also observed in these rats. In addition, pituitary GH mRNA expression declined significantly in long-term diabetic rats. These results demonstrate that: (1) the expression of both GHRH and somatostatin declines specifically in anatomical areas involved in anterior pituitary hormone control; (2) GHR mRNA expression is decreased in the pituitary of diabetic rats, but not in the hypothalamus, and does not return to control values with normalisation of mean blood glucose concentrations; and (3) the evolution time of the diabetes is important for detecting some changes, including the decrease in pituitary GH mRNA expression.
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PMID:Anatomically specific changes in the expression of somatostatin, growth hormone-releasing hormone and growth hormone receptor mRNA in diabetic rats. 1069 41

Initially, the distinction between "functional" and "non-functional" adenomas was a purely clinical notion. A "non-secreting" adenoma was not considered to cause acromegaly nor Cushing's syndrome nor amenorrhea-galactorrhea syndrome. The term "chromophobe adenoma" has been used since the advent Herlant tetrachrome. More recently immunocytochemistry methods have demonstrated that most of the "clinically non functional" adenomas (chromophobe with classical histology) are actually gonadotrophin secreting adenomas or gonadotroph adenomas. Due to progress in immunocytochemistry applied to operated adenomas, it is now known that gonadotroph tumors account for 15 to 20% of all pituitary adenomas. Gonadotroph adenomas are monoclonal but their pathogenesis, unlike somatotroph adenomas causing acromegaly and despite numerous molecular studies, remains unknown. Gonadotroph adenomas are most always discovered in patients presenting a pituitary syndrome (half to three-quarters consult for a visual field disorder). Pituitary imaging almost always demonstrates a macroadenoma: two-thirds of the macroadenomas are enclosed. Anterior pituitary insufficiency is much more frequent than gonad hyperstimulation whether testicular (macro-orchidia) or ovarian (ovarian hyperstimulation similar to that observed in ovulation induction). A careful analysis of hormone assay results shows that baseline concentrations of gonadotrophin or their free sub-units is elevated in 30 to 50% of cases (especially FSH in men, and the free a sub-unit in premenopausal women). Dynamic tests contribute little to diagnosis: the GnRH test is positive in 75 to 100% of cases, the TRH test in 60 to 70% for FSH (or alpha) and when there is already a baseline hypersecretion of FSH (or a) in 20 to 30% of the cases for the LH when the baseline LH concentration is high. The immunocytochemistry of gonadotroph adenomas is slightly different from that of other adenomas: generally, only 5 to 10% of the cells, grouped in islets of variable size, dispersed in the tumoral parenchyma, bind anti-FH, anti-LH and/or anti-sub-unit a antisera. Surgery is the primary treatment for gonadotroph adenomas. Complementary radiotherapy may be discussed in case of a postoperative remnant. It is probably effective against recurrence. Medical treatment (dopaminergic agonists, somatostatin analogs, GnRH agonists and antagonists) have given disappointing results.
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PMID:[Gonadotroph pituitary adenomas]. 1097 Sep 52

The aim of this study was to examine the effect of recombinant human leptin on growth hormone (GH) secretion in perifused anterior pituitary slices from adult pigs. Anterior pituitary slices from sows were perifused and treated with recombinant human leptin (10 nM) and GH-releasing hormone (GHRH; 1 nM). In some experiments, pituitary slices were coincubated with stalk median eminence (SME). In a subset of the coincubation experiments, immunoneutralization of endogenous GHRH and somatostatin (SRIH) release was performed with antisera to GHRH and SRIH. Leptin increased GH secretion in pituitary slices alone (up to 100% vs. control at 40 min) as well as in pituitary slices coincubated with SME (up to 122% vs. control at 40 min). A significant difference was observed in GH secretion from pituitary slices when the tissue was coincubated with leptin and GHRH at a low concentration (0.1 nM), but not when GHRH was used at 1 and 10 nM. Furthermore, anti-SRIH antiserum increased GH release from pituitary slices in coincubation experiments with SME. Finally, SRIH secretion was significantly reduced by leptin (down by 35% vs. control from 0 to 30 min of treatment) in cultured SME. These data show that leptin is effective in stimulating GH secretion by acting at two different levels: (1) it stimulates GH secretion directly from pituitary slices, and (2) it reduces SRIH tone from the median eminence and, indirectly, increases GH secretion from the pituitary. These results support the hypothesis that leptin may be an interesting hormonal mediator of growth and related metabolic effects by acting directly on the hypothalamic-pituitary axis.
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PMID:Leptin stimulates growth hormone secretion via a direct pituitary effect combined with a decreased somatostatin tone in a median eminence-pituitary perifusion study. 1515 55

Anterior pituitary hormone secretion is under tonic suppression by hypothalamic somatostatin signaling through somatostatin receptor subtypes (SSTs). Because some hormonal axes are known to be abnormally regulated by ligand-independent constitutively active G protein-coupled receptors, we tested pituitary SSTs for selective constitutive signaling. We therefore differentially silenced endogenous SST2, SST3, and SST5 in somatostatin-sensitive ACTH-secreting mouse AtT-20 pituitary corticotroph cells using small inhibitory RNA (siRNA) and analyzed downstream SSTs-regulated pathways. Transfection with siRNA reduced specific receptor subtype mRNA expression up to 82%. Specificity of receptor silencing was validated against negative controls with different gene-selective siRNAs, concordance of mRNA and cAMP changes, reduced potency of receptor-selective agonists, and phenotype rescue by overexpression of the silenced receptor. Mouse SST3 > SST5 > SST2 knockdown increased basal cAMP accumulation (up to 200%) and ACTH secretion (up to 60%). SST2- and SST5-selective agonist potencies were reduced by SST3- and SST5-silencing, respectively. SST5 > SST2 = SST3 silencing also increased basal levels of ERK1/2 phosphorylation. SST3- and SST5-knockdown increased cAMP was only partially blocked by pertussis toxin. The results show that SST2, SST3, and SST5 exhibit constitutive activity in mouse pituitary corticotroph cells, restraining adenylate cyclase and MAPK activation and ACTH secretion. SST3 mainly inhibits cAMP accumulation and ACTH secretion, whereas SST5 predominantly suppresses MAPK pathway activation. Therefore, SST receptor subtypes control pituitary cell function not only through somatostatin binding to variably expressed cell membrane receptor subtypes, but also by differential ligand-independent receptor-selective constitutive action.
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PMID:Selective regulation of somatostatin receptor subtype signaling: evidence for constitutive receptor activation. 1760 35

5 Human somatostatin receptor subtypes (sst1-5) mediate the antisecretory and antiproliferative effects of somatostatin. We examined somatostatin receptor protein expression in 28 human normal tissues. Immunostaining was performed with specific polyclonal antibodies for sst1-5. Staining pattern and distribution of ssts were evaluated. Anterior pituitary was positively stained for all 5 ssts. Pancreatic islets exhibited a positive staining for sst1-3 and sst5. Adrenal cortex expressed all 5 receptor subtypes, while the medulla was positive for sst3 and sst5 only. The thyroid expressed sst5 only, limited to single interfollicular cells. All 5 ssts were detected in the ovary, limited to luteinized granulosa cells of the corpus luteum. In the testis, sst2A was detected in the basal parts of the tubules, while sst5 was positively stained in the luminal parts. Sst1 was found in Leydig cells only. Stomach was positively stained for all 5 ssts. Investigation of the kidney revealed differential expression, with sst2A being found in the glomerules. The tubules expressed all 5 ssts. In the bone marrow cells of the granulocytopoiesis expressed sst2A only. The cerebellum expressed sst5 in a certain cell type, representing presumably Purkinje cells, while sst2A was stained in intercellular fibers. The expression of somatostatin receptor subtypes in a variety of human normal tissues may indicate a physiological role in these organs. Somatostatin analogues may offer new diagnostic and therapeutic implications for tumours related to these tissues. However, treatment of defined tumours with somatostatin analogues may also alter other normal tissues.
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PMID:Differential expression of somatostatin receptor subtype 1-5 proteins in numerous human normal tissues. 2297 14


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