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)

Pituitary tumors from 376 patients were investigated, using immunocytochemical techniques at the light and electron microscopic level, and autoradiography combined with immunocytochemistry for localizing somatostatin (SRIH) receptors. Prolactinomas, growth hormone-secreting adenomas causing acromegaly, and hormonally inactive adenomas were most frequently observed (153, 86, and 90 tumors, respectively). Among the latter, we could distinguish "alpha-only adenomas," many of which were oncocytomas. At the light and electron microscopic levels, cells containing (and presumably producing) simultaneously both prolactin and growth hormone, and cells containing exclusively either prolactin or growth hormone, could be demonstrated. In addition, a highly variable number and distribution of SRIH receptors could be shown in tumors secreting prolactin, growth hormone, and in tumors not associated with symptoms caused by inappropriate hormone secretion. The systematic combination of clinical, radiological, and biological techniques has currently brought great progress in the behavior and therapeutic concepts of pituitary lesions, and promises new achievements in the near future.
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PMID:Immunocytochemistry of pituitary tumors. 244 Sep 42

In an attempt to delineate the mechanism(s) of PRL secretion from human lactotrophs, the effects of dopamine and somatostatin on PRL release from adenomatous and nonadenomatous human pituitary cells in culture was studied. High K+ and the divalent cation ionophore A23187 both elevated PRL secretion, which was blocked by dopamine and somatostatin. When the cells were incubated in low calcium medium, PRL secretion was significantly inhibited. The addition of dopamine or somatostatin to low calcium medium further decreased PRL release. The stimulatory action of ionophore A23187 on PRL release was found even in the absence of extracellular calcium. Theophylline and isobutylmethylxanthine, when added to the incubation medium, increased PRL secretion, and dopamine as well as somatostatin again inhibited PRL release induced by phosphodiesterase inhibitors. No qualitative difference in these PRL responses was found in adenomatous and nonadenomatous human lactotrophs. In prolactinoma cells obtained from three different patients, cAMP generation was correlated with hormone release. Exposure of the cells to dopamine or somatostatin resulted in a parallel decrease in intracellular cAMP content and PRL secretion. The inhibitory effect of dopamine on PRL secretion and cAMP accumulation was blocked by coincubation of the cells with haloperidol. These results suggest that an increase in cytosol calcium caused by either mobilization from intracellular calcium pools or influx from the extracellular compartment and intracellular cAMP accumulation may be involved in the mechanism of PRL secretion from human lactotrophs, and dopamine and somatostatin may influence these two messengers to suppress PRL secretion.
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PMID:Mechanism of the inhibitory action of dopamine and somatostatin on prolactin secretion from human lactotrophs in culture. 257 87

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

In an attempt to characterize GH and PRL secretion in acromegaly, the effects of various stimuli on GH and PRL release by cultured pituitary adenoma cells derived from acromegalic patients were studied. In addition, the PRL responses of somatotroph adenoma cells were compared to those of prolactinoma cells. GH-releasing hormone-(1-44) (GHRH) consistently stimulated GH secretion in all 14 somatotroph adenomas studied in a dose-dependent manner. The sensitivity as well as the magnitude of the GH responses to GHRH were highly variable in individual tissues. Somatotroph adenomas that did not respond to dopamine were more sensitive and had greater GH responses to GHRH. In 8 of 9 somatotroph adenomas that concomitantly secreted PRL, the addition of GHRH likewise increased PRL release. Omission of extracellular Ca2+ blocked the stimulatory effect of GHRH on GH and PRL secretion. When cells were coincubated with 0.1 nM somatostatin, GH and PRL secretion induced by 10 nM GHRH were completely blocked in most adenomas. Similarly, coincubation of dopamine resulted in inhibition of GHRH-induced hormone secretion in some adenomas. Addition of TRH to the incubation medium, on the other hand, significantly stimulated GH secretion in 8 of 14 adenomas, while TRH stimulated PRL release in all of the adenomas. Vasoactive intestinal peptide (VIP) and corticotropin-releasing hormone (CRH) produced an increase in GH and PRL secretion in other adenomas. In prolactinoma cells, somatostatin and dopamine unequivocally suppressed PRL secretion; however, other stimuli including GHRH, VIP, and CRF were ineffective. TRH induced a significant increase in PRL secretion in only one prolactinoma. These results suggest that responsiveness to GHRH and somatostatin is preserved in somatotroph adenomas; the responsiveness to GHRH is inversely correlated to that to dopamine; and PRL cells associated with somatotroph adenomas possess characteristics similar to those of GH cells. Further, the GH stimulatory actions of TRH and VIP are different.
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PMID:Effects of hypophysiotropic factors on growth hormone and prolactin secretion from somatotroph adenomas in culture. 285 94

To characterize the functional aspect of prolactin (Prl) cells coexisting with corticotroph adenomas, pituitary adenoma cells obtained from a patient with Cushing's disease and a patient with Nelson's syndrome, who were associated with hyperprolactinaemia, were cultured in monolayer and their Prl responses to various secretagogues were compared with those of prolactinoma cells in culture. Immunohistochemistry performed in one of these two adenomas demonstrated the presence of Prl-containing cells in addition to ACTH cells. When ACTH-Prl adenoma cells were exposed to ovine corticotrophin-releasing factor (CRF), a dose-dependent increase in both ACTH and Prl secretion was observed, which was blocked by coincubation with hydrocortisone. In contrast, no stimulatory effect of CRF on Prl release was observed in all of the experiments using prolactinoma cells. Thyrotrophin-releasing hormone, which consistently stimulated Prl secretion in ACTH-Prl adenomas, was effective in triggering Prl release in only 25% of the prolactinomas. Exposure of the cultured cells to lysine vasopressin, growth hormone-releasing factor and vasoactive intestinal peptide resulted in an increase in ACTH and Prl secretion in one ACTH-Prl adenoma, however, none of the prolactinomas responded to these stimuli to secrete Prl. Dopamine and somatostatin, on the other hand, uniformly suppressed Prl secretion from ACTH-Prl adenomas as well as from prolactinoma cells. These results suggest that the mode of Prl secretion by mixed ACTH-Prl pituitary adenomas is not identical to that by pure prolactinomas and is, at least in part, common to that of ACTh secretion.
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PMID:Prolactin secretion by mixed ACTH-prolactin pituitary adenoma cells in culture. 285 25

The somatostatin analogue SMS 201-995 has recently been shown to be effective in suppressing GH secretion in most acromegalic patients. In the present study it was investigated whether PRL release in prolactinoma and acromegalic patients might also be sensitive to SMS 201-995 and whether co-secretion of PRL in acromegaly plays a role in determining the sensitivity of GH secretion to SMS 201-995. The s.c. administration of 50 micrograms SMS 201-995 did not affect high plasma PRL levels in four microprolactinoma patients. Therapy of one of these patients for 3 d with 50 micrograms three times a day also did not affect PRL levels. The single administration of 50 micrograms SMS 201-995 in 22 acromegalic patients lowered plasma GH levels for 2-6 h to less than 5 micrograms/l in 14 patients and to less than 50% of control values in 16 patients. In 18 of these 22 patients the immunohistochemical picture of the pituitary tumour was known. Eleven patients had pure GH-containing tumours and in seven patients there were mixed GH/PRL-containing tumours. In two of these latter patients there was evidence for GH and PRL being secreted by the same tumour cells. The sensitivity of GH secretion to SMS 201-995 did not differ between the patients with pure GH or mixed GH/PRL-containing adenomas. Plasma PRL levels were not affected by SMS 201-995 in the patients with pure GH-secreting tumours, but were significantly suppressed in four of the seven patients with mixed GH/PRL containing tumours. Chronic treatment for 16 weeks of one patient with a mixed GH/PRL-containing tumour with SMS 201-995 (100 micrograms three times a day) resulted in normalization of both the increased GH and PRL levels. It is concluded that SMS 201-995 does not affect tumorous PRL secretion in patients with pure prolactinomas. In acromegalic patients with mixed GH/PRL-containing tumours PRL secretion in some patients is sensitive to SMS 201-995, making these patients good candidates for chronic treatment with the analogue. The simultaneous presence of PRL in the GH-secreting pituitary tumour or the presence of hyperprolactinaemia in acromegalics does not play a role in the sensitivity of GH secretion to the somatostatin analogue.
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PMID:The sensitivity of growth hormone and prolactin secretion to the somatostatin analogue SMS 201-995 in patients with prolactinomas and acromegaly. 287 48

The effect of somatostatin (SRIF: 10 micrograms/min during 120 min) on serum prolactin (PRL) levels was studied in eleven patients with hyperprolactinemia of varying causes: 2 patients with acromegaly; 2 with primary hypothyroidism; 4 with prolactinoma and 3 with drug (sulpiride) induced hyperprolactinemia. During SRIF infusion, no significant change in PRL levels was observed in any of the 4 groups studied except in one female patient with a prolactinoma. The biological activity of SRIF was demonstrated by the significant inhibition (P less than 0.05) of insulin levels seen in all 11 patients (52% fall in relation to basal) without simultaneous modification of glycemia. These data suggest that SRIF does not decrease PRL secretion in most patients with hyperprolactinemia.
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PMID:Absence of suppressive effect of somatostatin on prolactin levels in patients with hyperprolactinemia. 288 2

Magnetic resonance imaging (MRI) has been used for the determination in vivo of rat pituitary size. In midsagittal T2-weighted sections the pituitary, having a lower T2 value than the surrounding tissue, was visible with pronounced contrast. The size has been estimated by pixel counting. A close correlation (r = 0.96) with the pituitary weights determined postmortem has been obtained, demonstrating the reliability of the in vivo method. Using MRI the effects of Sandostatin, a somatostatin analog, on the pituitary size have been monitored in a rat model of prolactinoma (estradiol-induced hyperplasia of the pituitary). Treatment with Sandostatin over 4 weeks resulted in a 40% reduction of the hyperplastic pituitaries. These results have been confirmed by determination of pituitary weights postmortem. However, due to a large interindividual variation in size of hyperplastic pituitaries, more animals are required to reach statistical significance when only endpoints of treatment can be measured. In contrast, MRI allows one to monitor individually the drug effects over a long period of time, eliminating interindividual variations.
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PMID:Quantitative magnetic resonance imaging of estradiol-induced pituitary hyperplasia in rats. 320 45

The expression of three somatostatin receptor subtypes, SSTR3, SSTR4, and SSTR5, was evaluated in 33 pituitary tumor specimens. SSTR3 expression was studied by reverse transcription coupled to polymerase chain reaction, whereas SSTR4 and SSTR5 expression was determined by ribonuclease protection assay. SSTR3 was expressed in 6 of 7 GH-secreting tumors, all 8 clinically nonfunctioning tumors, all 3 prolactinomas, and 1 of 2 ACTH-secreting tumors tested. Eight nonfunctioning adenomas had undetectable messenger ribonucleic acid levels of SSTR4, and only 1 of them expressed SSTR5. SSTR4 expression was also undetectable in 11 GH-secreting tumors, 3 prolactinomas, and 1 ACTH-secreting tumor tested. In contrast, SSTR5 was highly expressed in 10 of 11 GH-secreting adenomas and 1 prolactinoma. Two prolactinomas and 1 ACTH-secreting tumor had low levels of expression of SSTR5. The widespread pituitary adenoma expression of SSTR3, regardless of hormonal secretory type, suggests that SSTR3 might be involved in a somatostatin action(s) other than GH or TSH regulation. SSTR5 is expressed predominantly in mammosomatotroph-derived tumors, suggesting that this receptor subtype may be an important determinant of GH secretion in acromegaly.
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PMID:Expression of three somatostatin receptor subtypes in pituitary adenomas: evidence for preferential SSTR5 expression in the mammosomatotroph lineage. 752 50

Using a combination of polymerase chain reaction and genomic library screening we have cloned a human gene for a subtype of the somatostatin (SST) receptor (SSTR) termed human SSTR5 (hSSTR5), which is located on chromosome 16. The predicted amino acid sequence of hSSTR5 displays 75% sequence identity with a recently identified rat SSTR [Mol. Pharmacol. 42:939-946 (1992)], suggesting that it is the human homologue of this receptor. hSSTR5 consists of a 363-residue polypeptide exhibiting a putative seven-transmembrane domain topology typical of G protein-coupled receptors. The receptor displays considerable sequence identity to hSSTR1 (42%), hSSTR2 (48%), hSSTR3 (47%), and hSSTR4 (46%). Membranes prepared from COS-7 cells transiently expressing the hSSTR5 gene bound 125I-Leu8,D-Trp22,Tyr25-SST-28 (125I-LTT-SST-28) with high affinity and in a saturable manner. SST-14, SST-28, and various synthetic SST peptide agonists produced dose-dependent inhibition of radioligand binding with the following rank order of potency: LTT-SST-28 > SST-28 > D-Trp8-SST-14 > SST-14 approximately RC-160 approximately BIM 23014 > MK-678 > SMS 201-995. hSSTR5 bound SST-28 with a 12.6-fold greater affinity (Ki = 0.19 nM), compared with SST-14 (Ki = 2.24 nM), indicating that the receptor is SST-28 selective. Addition of GTP, guanosine-5'-O-(3-thio)triphosphate, Na+ ions, or pertusis toxin greatly reduced 125I-LTT-SST-28 binding, thereby indicating that hSSTR5 is coupled to pertussis toxin-sensitive G proteins. Both SST-14 and SST-28 displayed dose-dependent inhibition of forskolin-stimulated cAMP accumulation, consistent with functional coupling of the receptor to adenylyl cyclase inhibition. Northern blot analysis of SSTR5 mRNA revealed a 2.4-kilobase transcript in normal rat pituitary and GH3 rat pituitary tumor cells and a 4.0-kilobase transcript in normal human pituitary. Reverse transcriptase polymerase chain reaction revealed expression of the hSSTR gene in fetal human pituitary and hypothalamus but not in human cerebral cortex. In situ hybridization of the rat pituitary showed that SSTR5 mRNA is selectively localized in the anterior lobe. SSTR5 mRNA was not expressed in four human pituitary tumors (somatotroph adenoma, prolactinoma, and chromophobe adenomas) or in a human insulinoma. Although hSSTR5 displays approximately 75% sequence identity with rat SSTR5, the two receptors display significantly different pharmacological profiles, especially with respect to their binding affinities for the SST analogue SMS 201-995.
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PMID:Molecular cloning, functional characterization, and chromosomal localization of a human somatostatin receptor (somatostatin receptor type 5) with preferential affinity for somatostatin-28. 790 5


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