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)

The hypothalamic regulatory hormones used for clinical studies are TRH, Gn-RH and somatostatin. In addition, as dopamine appears to be a physiological PIF, the dopamine agonists such as bromocriptine, could be considered as functional analogues of PIF. Gn-RH can be used to study the hypothalamic-pituitary gonadal relationship and to test the secretory reserve capacity of the gonadotrophs in disease states. Unfortunately Gn-RH testing discrimulates between pituitary and hypothalamic diseases only poorly. However gonadotrophin deficient men or women may be successfully treated with long-term Gn-RH with induction of puberty, potency, spermatogenesis and ovulation. Somatostatin has multiple actions in inhibiting endocrine and exocrine secretion but its actions are still being explored in diabetes. Bromocriptine, a long acting dopamine agonist (a functional analogue of PIF), suppresses prolactin and is highly effective in treating many hypogonadal states since hyperprolactinaemia is common. It also lowers growth hormone in acromegaly. TRH has provided a major, accurate, sensitive and safe test of thyroid function.
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PMID:Hypothalamic regulatory hormones: physiological and clinical implications. 2 68

A 35-yr-old woman is described as having atypical McCune-Albright syndrome, associated with acromegaly and hyperprolactinemia due to pituitary adenoma. The patient did not present sexual precocity, but primary amenorrhea. After transphenoidal adenomectomy, the GH plasma levels returned to normal, whereas the PRL values decreased; bromocriptine therapy normalized PRL levels and induced ovulatory menses. After 4 uneventful yr the patient developed relapse of active acromegaly that did not recover after a second neurosurgical exploration. Bromocriptine treatment maintained normal PRL levels but did not significantly reduce GH ones; the association with long-acting somatostatin analog SMS 201-995 by continuous sc pump infusion induced definitive control of GH and somatomedin-C secretion. These results suggest an additive inhibitory effect on GH secretion exerted by the two drugs.
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PMID:Atypical McCune-Albright syndrome associated with growth hormone-prolactin pituitary adenoma: natural history, long-term follow-up, and SMS 201-995--bromocriptine combined treatment results. 140 Aug 88

Practical approaches to the management of acromegaly are discussed. The roles of surgery, radiotherapy, and medical treatment with oral dopamine agonists such as bromocriptine or the long-acting somatostatin analogue octreotide given subcutaneously are reviewed. Most cases need surgery, but cure is rare in patients with macroadenomas, although common with microadenomas. Radiotherapy should be considered in surgical failures, but takes several years to be effective. Medical treatment with octreotide is effective in the majority, for whom it represents a major advance, but it needs to be administered subcutaneously and the development of gallstones and gastritis in long-term treatment are problems. Bromocriptine is usually less effective, but occasionally still plays a role in the therapeutic program. Combinations of the different modalities are usually required in the management of acromegalic patients.
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PMID:Proceedings of the workshop, "Practical approaches to the diagnosis and treatment of acromegaly". 151 40

Various drugs and hormones influence the light microscopic and especially the electron microscopic structure of the anterior pituitary and its tumors. Many structural effects are known only from animal experiments since specimens from human pituitaries are mostly not available. The structure of growth hormone (GH) cells is relatively stable. A massive GH cell hyperplasia is known only in rare cases with growth hormone releasing factor (GRF) excess from tumors. Prolactin cells can be stimulated by drugs, neurotransmitters, and hormones which decrease the dopamine inhibition. Adrenocorticotropic hormone (ACTH) cells are stimulated by stress, some hormones, loss of adrenals, and drugs which activate the alpha 1- and beta-receptors or inhibit the alpha 2-receptors. They are suppressed and changed into Crooke's cells by treatment with glucocorticoids. Thyroid-stimulating hormone (TSH) cells increase in number and size in states for overstimulation especially by thyrotropin releasing hormone (TRH). A decrease results from hyperthyroidism and possibly from somatostatin, L-dopa, and dopamine. Gonadotroph cells transform into castration cells in strongly hyperactive states (gonadectomy, antiandrogens, gonadotropin releasing hormone [Gn-RH]agonists, aminoglutethimide). Special types of pituitary adenomas can be treated with drugs which suppress hormone production and proliferation. Dopamine agonists and somatostatin reduce the tumor size of varying proportions of GH secreting adenomas in acromegaly. Ultrastructurally, a decrease of cytoplasmic and nuclear volume and an increase of lysosomes are found. Bromocriptine and other dopamine agonists are established in the treatment of prolactin secreting adenomas. They induce a shrinkage in many cases. Ultrastructurally, a reduction of cellular and nuclear size, an increase in number of secretory granules and of lysosomes, and a reduction of rough endoplasmic reticulum can be demonstrated.
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PMID:Effect of drugs on pituitary ultrastructure. 154 57

Acromegaly and hyperprolactinemia have been reported in association with the McCune-Albright syndrome, but the pathophysiology of the GH and PRL hypersecretion that occurs in patients with this disorder has not been defined. We studied GH and PRL secretory dynamics in three patients with McCune-Albright syndrome and hypersecretion of these hormones. Each patient had excessive linear growth, glucose-non-suppressible plasma GH concentration, and GH responsiveness to TRH and GHRH. In response to exogenous GHRH, plasma GH concentrations rose approximately 2-fold in all three patients. Plasma GHRH levels were 20-40 ng/L (normal, less than 30). Study of the spontaneous GH secretory pattern in two patients indicated nocturnal augmentation of GH release. Bromocriptine therapy failed to reduce plasma GH in all patients; in one patient treatment with octreotide, a long-acting somatostatin analog, partially suppressed plasma GH and insulin-like growth factor I levels. These results suggest that hypersecretion of GH in the McCune-Albright syndrome is not due to ectopic GHRH production or autonomous somatotroph function. The results are similar to those described in classic acromegaly due to GH-secreting pituitary tumors. However, the lack of radiographic pituitary enlargement, the variable pituitary pathology reported in similar patients, and frequent concordance of GH and PRL excess suggest that the pathogenesis of this disorder may differ fundamentally from other forms of acromegaly or gigantism. The pathophysiology may reflect abnormal hypothalamic regulation and/or an embryological defect in pituitary cellular differentiation and function.
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PMID:Hypersecretion of growth hormone and prolactin in McCune-Albright syndrome. 249 85

Bromocriptine therapy normalizes PRL secretion in most, but not all, patients with prolactinomas. This study was undertaken to determine the mechanism(s) responsible for bromocriptine resistance in patients with a PRL-secreting macroadenomas (n = 5) or microadenomas (n = 3). Their mean basal plasma PRL value was 807 +/- 220 (+/- SE) micrograms/L before treatment, and their nadir mean value was 354 +/- 129 micrograms/L during chronic therapy with 15-30 mg bromocriptine daily; four of the eight patients had an increase in tumor size during therapy. In cultures of prolactinoma cells from patients normally responsive to bromocriptine therapy (n = 10), considered as controls, 10(-9) mol/L bromocriptine inhibited PRL release by 71 +/- 6% (+/- SE), and the half-inhibitory dose was 7 x 10(-11) mol/L. In contrast, in cultures of prolactinoma cells from five patients resistant to bromocriptine, PRL release was inhibited by only 3-42% at 10(-9) mol/L bromocriptine. This partial inhibition was reversed by a 100-fold excess of haloperidol. In contrast, the effects of other inhibitors of PRL release (10(-8) mol/L T3 and 10(-8) mol/L somatostatin) or of a stimulator (10(-8) mol/L angiotensin-II) on cells from resistant and normally responsive patients were similar. In cell membranes from five bromocriptine-responsive adenomas the density of dopaminergic binding sites, labeled by [3H] spiroperidol was 243 +/- 65 (+/- SE) fmol/mg protein. In adenomas from the eight patients resistant to bromocriptine therapy the density of [3H]spiroperidol-binding sites lower (145 +/- 31 fmol/mg protein). In adenomas from five resistant patients whose tumor had grown during therapy the density of binding sites was 25 +/- 3 fmol/mg protein, 10% of that in normally responsive patients. The effects of dopamine on adenylate cyclase activity also were different in the three groups of adenomas. Dopamine inhibited adenylate cyclase activity by 28.8 +/- 5.6% in five bromocriptine-responsive tumors and by 16.5 +/- 4.3% in adenomas from eight resistant patients. In contrast, in the five patients whose tumors grew during therapy dopamine paradoxically stimulated adenylate cyclase activity (+26.4 +/- 9.8%). There was a very good correlation between the density of dopaminergic binding sites and maximal inhibition of adenylate cyclase activity in bromocriptine-responsive prolactinoma patients (r = 0.90) and resistant patients who had no tumor growth during therapy (r = 0.94).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Resistance to bromocriptine in prolactinomas. 276 Jan 67

GH secretion and mRNA levels were measured in cultured cells obtained from six human pituitary somatotroph tumors to investigate their hormonal and intracellular regulation. The responses were variable between tumors, but, in general, mRNA levels were less responsive than GH release to in vitro manipulation. GH-releasing factor [GRF-(1-29) amide; 10 nM] increased GH release and mRNA levels in three of four tumors tested to 30-97% above control values, but the fourth tumor was unresponsive. Somatostatin (1 microM) inhibited GH release significantly in four of the six cases, to 35-79% of control levels, but had no inhibitory effect on GH mRNA accumulation, in contrast to earlier studies on rat pituitary tissue. Bromocriptine (100 nM) likewise inhibited GH release (50-75% of control), but not GH mRNA levels, in the four tumors tested. Forskolin (10 microM; used to activate adenylate cyclase) stimulated GH release and mRNA levels in the two cases that responded most clearly to GRF, but had no significant effect in the other tumors; however, the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (100 nM) had no consistent effect on mRNA levels despite stimulating secretion in four of six cases. Thus, there was considerable variation in responses among the tumors tested; however, the responsiveness to GRF was approximately paralleled by that to forskolin, consistent with the suggestion that adenylate cyclase activity and responsiveness are variable among these tumors. Furthermore, the divergent effects of somatostatin on GH release and mRNA suggest uncoupling between its receptor and transcriptional regulatory mechanisms.
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PMID:Regulation of growth hormone secretion and messenger ribonucleic acid accumulation in human somatotropinoma cells in vitro. 277 32

The relationship between basal and stimulated plasma GH and somatomedin-C (SmC) levels in acromegalic patients was evaluated. The basal plasma SmC levels of 66 patients were significantly correlated (P less than 0.01) with mean daily plasma GH levels, but not with the percent GH increase after GH-releasing hormone or TRH or the GH decrease after acute bromocriptine administration. Bromocriptine (7.5-15 mg/day) administration for 9.2 +/- 0.9 (+/- SD) months in 20 patients significantly (P less than 0.05) decreased GH levels. SmC decreased significantly [from 9.8 +/- 1.9 to 5.1 +/- 0.7 U/ml (mean +/- SE)] only in the 10 patients who had the more marked GH inhibition. The administration of a somatostatin analog, SMS 201-995 (100 micrograms twice daily), to 12 patients for 16 weeks significantly decreased plasma GH and SmC levels beginning on the second day of therapy; normal SmC levels were achieved in 5 of 12 patients. Pituitary adenomectomy resulted in normal GH and SmC levels in 10 of 12 and 8 of 12 patients, respectively. Our data indicate an overall dependency of plasma SmC levels on plasma GH levels in acromegaly, although similar GH levels may have differing somatomedin-stimulating activities. A derangement in the feedback mechanisms controlling GH secretion is indicated by the failure of elevated SmC levels to influence the GH responsiveness to releasing hormones. In evaluating pharmacological or surgical treatments of acromegaly, a single plasma SmC value can reliably replace several plasma GH determinations.
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PMID:Relationship between somatomedin-C and growth hormone levels in acromegaly: basal and dynamic evaluation. 287 7

To clarify the role of the breakdown of phosphatidylinositol 4,5-bisphosphate (PIP2) in GH secretion in human somatotrophs and the effects of inhibitors of GH secretion on this mechanism, we studied the effects of 12-tetradecanoylphorbol-13-acetate (TPA) and phospholipase C (Plase C) on GH secretion and the interactions of somatostatin (SRIH), bromocriptine, and pertussis toxin (IAP) with TPA or Plase C, using human GH-secreting pituitary adenoma cells in culture. SRIH (10(-9)-10(-7) M) inhibited and TPA (10(-10)-10(-8) M) and Plase C (0.125-1.0 U/mL) stimulated GH secretion. SRIH (10(-9)-10(-7) M) inhibited GH release induced by TPA (10(-8) M) or Plase C (1.0 U/mL). Bromocriptine (10(-8) M) also inhibited 10(-8) M TPA-induced GH secretion. When adenoma cells were treated with 100 ng/mL IAP for 24 h, basal and TPA-induced GH secretion rates did not change. However, the inhibitory effects of SRIH (10(-8) M) or bromocriptine (10(-8) M) on basal and 10(-8) M TPA-stimulated GH secretion were attenuated. In addition, IAP reduced GH secretion induced by 0.5 U/mL Plase C, while SRIH inhibition of Plase C-evoked GH release was diminished by IAP. We conclude that the hydrolysis of PIP2 by Plase C, which causes activation of protein kinase C by 1,2-diacylglycerol and Ca2+ mobilization by inositol 1,4,5-triphosphate, is a physiological intracellular mechanism leading to GH secretion in human somatotrophs; SRIH inhibits GH secretion mediated by this mechanism, and bromocriptine blocks at least protein kinase C-mediated GH release; the inhibitory guanine nucleotide-binding protein (Ni) is involved in these inhibitory effects of SRIH and bromocriptine; and Ni modulates the breakdown of PIP2 by Plase C.
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PMID:Phorbol ester and phospholipase C-induced growth hormone secretion from pituitary somatotroph adenoma cells in culture: effects of somatostatin, bromocriptine, and pertussis toxin. 288 Aug 63

Dynamic studies of GH and GH-releasing hormone (GHRH) secretion were performed in a man with a GHRH-producing carcinoid tumor and acromegaly. Insulin hypoglycemia stimulated and metoclopramide inhibited both GH and GHRH acutely. Bromocriptine suppressed GH both acutely and chronically without altering circulating GHRH levels and also blunted the GH response to exogenous GHRH. TRH acutely stimulated GH, but not GHRH, secretion, and iv bolus doses of synthetic GHRH-(1-40) stimulated GH release acutely. Somatostatin infusion decreased both GH and GHRH concentrations and blunted the GH responses to TRH and GHRH-(1-40). We conclude that prolonged exposure of the pituitary gland to high concentrations of GHRH is associated with chronic GH hypersecretion and may be accompanied by a preserved acute GH response to exogenous GHRH; a paradoxical response of GH to TRH may be mediated at the pituitary level, consequent to prolonged pituitary exposure to GHRH; bromocriptine suppression of GH in acromegaly is due to a direct pituitary effect of the drug; and somatostatin inhibits both ectopic GHRH secretion as well as GH responsiveness to GHRH in vivo. Since GH secretory responses in patients with somatotroph adenomas are similar to those in this patient, augmented GHRH secretion may play a role in development of the "classic" form of acromegaly.
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PMID:Acromegaly due to ectopic growth hormone (GH)-releasing hormone (GHRH) production: dynamic studies of GH and ectopic GHRH secretion. 309 17


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