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)

Bombesin (BBS) has been previously shown to stimulate the secretion of PRL and GH in steroid-primed rats. To determine whether these effects were mediated by the central nervous system or were due to direct action on the pituitary gland, we studied the interaction of BBS with GH4C1 cells, a clonal strain of rat pituitary cells which synthesizes and secretes PRL and GH. The addition of 100 nM BBS to GH4C1 cells for 60 min increased PRL release to 140 +/- 3% of the control value (mean +/- SE) and GH release to 133 +/- 5% of the control value. Stimulation of hormone secretion was observed within 15 min of treatment with 100 nM BBS and continued for at least 2 h. Half-maximal stimulation of PRL release occurred with 0.5 nM BBS, and a maximal effect was observed with 10 nM peptide. The BBS analogs ranatensin, litorin, and [Tyr4]BBS, each at a concentration of 100 nM, caused the same stimulation of PRL release as maximal concentrations of BBS itself. BBS stimulated hormone release selectively in two of five different clonal pituitary cell strains examined. Pretreatment of GH4C1 cells with 1 nM estradiol and/or 100 nM insulin resulted in more powerful stimulation of PRL release by both TRH and BBS. When epidermal growth factor and vasoactive intestinal peptide were added simultaneously with BBS, PRL release was greater than in the presence of either peptide alone. In contrast, the stimulatory effects of TRH and BBS were not additive. Somatostatin inhibited both basal and stimulated PRL release. Thus, low concentrations of BBS can directly stimulate PRL and GH release by a clonal pituitary cell strain in culture. These results suggest that BBS may stimulate PRL and GH secretion in vivo by direct action on the pituitary gland.
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PMID:Bombesin stimulates prolactin and growth hormone release by pituitary cells in culture. 679 71

A variety of neuropeptides, such as TRH, somatostatin, VIP, Substance P, neurotensin, CCK, gastrin, and opioid peptides, alter secretion of GH and PRL from the pituitary. These actions differ according to the route of administration or with experimental conditions, especially anesthesia. Among these peptides, the most consistent results have been obtained with opioid peptides, which stimulate GH and PRL release. Both beta-endorphin and enkephalins are capable of stimulating GH and PRL release in anesthetized and unanesthetized, freely moving rats. The effect is blocked by naloxone, an opiate receptor antagonist. GH secretion induced by opioid peptides seems to be mediated by an alpha-adrenergic mechanism, since treatment with DDC and fusaric acid, which are dopamine-beta-hydroxylase inhibitors, reserpine, and phenoxybenzamine which is an alpha-adrenergic blocking agent, blunted GH secretion. However, pimozide, a dopamine receptor antagonist, and propranolol, a beta-adrenergic blocking agent, were without effect. On the other hand, basal PRL secretion was augmented by pimozide, suggesting the possible involvement of dopamine. It is also possible that serotonin is involved in the GH and PRL release induced by opioid peptides. The physiological significance of opioid peptides in regulating GH and PRL secretion is still unclear. Contradictory results (12,25) have been obtained concerning the effect of naloxone on basal or stimulated GH and PRL secretion in rats, monkeys and humans when tested by the continuous blood sampling method, which rules out the erroneous evaluation of results caused by episodicity of plasma hormone levels. Further studies should clarify the physiological role of opioid peptides in regulating pituitary function.
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PMID:Effect of CNS peptides on hypothalamic regulation of pituitary secretion. 701 Sep 47

Bombesin, a peptide with widespread biological actions, has been demonstrated in human tissues by immunological methods. To investigate its effect in man, synthetic bombesin was infused at low doses in six male volunteers. Bombesin at 2.4 pmol kg-1 min-1 produced significant rises in plasma insulin, glucagon, pancreatic polypeptide, gastrin, cholecystokinin, motilin, glucose-dependent insulinotropic polypeptide, neurotensin, enteroglucagon, vasoactive intestinal polypeptide, and serum calcium. In contrast, bombesin caused a profound fall in parathyroid hormone levels and reduced plasma glucose concentrations. A late rise in plasma calcitonin was also observed. Bombesin had no significant effect on the pituitary hormones, TSH, GH, PRL, or cortisol. No hormonal changes or alterations in calcium were noted during saline infusions. Bombesin has a marked stimulatory effect on gastrointestinal hormones, which is unique and opposite to the effect of somatostatin, a potent inhibitor of gut hormone release. Bombesin also influences calcium-regulating hormones, either directly or through its action on gut hormones. The bombesin concentrations achieved with the dosages used were low enough to indicate a possible physiological role for the endogenous peptide.
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PMID:Bombesin: action on gut hormones and calcium in man. 706 3

This study was conducted to examine the release of immunoreactive prolactin (IR-PRL) in vitro by 14 cases of decidual obtained from women with 6 to 13 weeks of gestation. 1) The dilution curve of IR-PRL released from the decidua was parallel to the pituitary standard PRL. 2) A highly significant rise of IR-PRL during the incubation of the decidua was found. In decidua of 11-13 weeks of gestation, the summarised IR-PRL level during 90 minutes was the highest, viz. 359.4 +/- 87.4 ng/0.1 g wet weight. 3) The villi showed scarcely any IR-PRL release, and the accumulated IR-PRL level was 2.4% of the decidual incubation value. Little IR-PRL release was found in the incubation of endometrium of luteal phase. 4) The temperature and pH of the medium influenced the IR-PRL release, but dopamine, bromocriptine and somatostatin had no effects on the PRL releasing activity of the decidua. 5) According to the gel filtration, the elution pattern of IR-PRL released from the decidua was similar to that of the amniotic fluid rather than that of the maternal plasma. From the above results, we suggested that the decidua was the original source of the PRL released in the amniotic fluid.
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PMID:[Studies on the prolactin releasing activity of Decidua in early pregnancy in vitro (author's transl)]. 722 56

The purpose of this investigation was to examine the role of somatostatin (SRIF) and electrical stimulation of the lateral hypothalamic-medial forebrain bundle (LH-MFB) on dynamics of pulsatile GH secretion in freely behaving, chronically cannulated male rats with implanted brain electrodes. The effects of administration of anti-SRIF serum (AS-SRIF) on pulsatile GH and on TSH and PRL secretion was also studied. The results are: 1) circulating AS-SRIF increases trough levels of GH in freely behaving rats but has no significant effect on the amplitude of GH secretory bursts or mean GH levels; 2) LH-MFB excitation can stimulate GH release if delivered when circulating GH levels are low; 3) LH-MFB stimulation inhibits secretion of GH if given at the time of a spontaneous GH burst; 4) stimulation-induced GH inhibition is prevented by pretreatment with AS-SRIF, suggesting that this response is mediated by endogenous SRIF; and 5) AS-SRIF increases TSH secretion but has no effect on PRL. These results provide evidence to support the hypothesis that pituitary GH secretion is regulated by a combination of excitatory and inhibitory influences, the inhibitory component of which is mediated by SRIF.
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PMID:The effects of lateral hypothalamic-medial forebrain stimulation and somatostatin antiserum on pulsatile growth hormone secretion in freely behaving rats: evidence for a dual regulatory mechanism. 725 62

We have reported previously that differentiation of PRL-secreting cells in rats is regulated by a maternal peptide transferred to the neonatal circulation after ingestion of mothers' milk. Inasmuch as milk contains numerous hormones and biologically active peptides, the present study was designed to test the capacity of various growth factors and hypothalamic peptides at inducing the differentiation of PRL cells in vitro. Anterior pituitary cells from 1-day-old rat pups were cultured in a serum-free system for 6 days with a wide concentration range of each test peptide. After this culture period, lactotrope differentiation was assessed by subjecting the anterior pituitary cells to reverse hemolytic plaque assays for PRL. Our efforts were focused on those growth factors and hypophysiotropic peptides found in milk and/or known to regulate pituitary function. Included among these were TRH, GH-releasing factor, somatostatin, vasoactive intestinal peptide, angiotensin-II, insulin-like growth factor-I and -II, LH-releasing hormone, arginine vasopressin, and acidic and basic fibroblast growth factors (aFGF and bFGF, respectively). Of these peptides, only aFGF and bFGF were capable of stimulating lactotrope differentiation. Specifically, we found that maximally effective concentrations of aFGF and bFGF increased the percentage of PRL-releasing cells by almost 8-fold, from about 0.5% to over 4% of all pituitary cells. In addition, bFGF was found to be about 10-fold more potent than aFGF at inducing the differentiation of PRL secretors, with minimum effective doses approaching 10(-11) and 10(-10) M for bFGF and aFGF, respectively. These results suggest that bFGF is a strong candidate to subserve a role in regulating the differentiation of lactotropes in vivo.
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PMID:Stimulation of lactotrope differentiation in vitro by fibroblast growth factor. 750 4

Reexamination of the hexapeptide GH-releasing peptide (GHRP-6) structure/function has lead to the development of four novel classes of compound that stimulate GH release. Each class is represented as follows: a pentapeptide, G-7039; a tetrapeptide, G-7134; a pseudotripeptide, G-7502; and a rigid cyclic heptapeptide, G-7203. The EC50 values for these compounds, determined by GH dose-response curves using primary cultures of rat pituitary cells, were 0.18, 0.34, 10.6, and 0.43 nM, respectively. To demonstrate that these compounds were acting at the putative GHRP receptor, challenges were made using combinations that included GHRP-6 and GH-releasing hormone (GHRH). All four new classes further increased GH release in combination with GHRH, but not with GHRP-6. Homologous desensitization occurred after 45 min of exposure to the new compounds while the cells remained sensitive to GHRH. Somatostatin inhibited all of these compounds. Additionally, G-7039 elevated free calcium, as occurs with GHRP-6. All four classes elicited a robust GH release, a small increase in PRL, and no change in LH, FSH, ACTH, or TSH. We conclude that these novel compounds are potent and direct stimulators of pituitary GH release, with in vitro attributes that suggest mediation via a specific GHRP-like mechanism.
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PMID:In vitro characterization of four novel classes of growth hormone-releasing peptide. 758 25

The pathophysiology of mammosomatotroph adenomas remains unclear. We studied a mammosomatotroph adenoma removed from an 8-year old boy with a 5-year history of growth acceleration and acromegalic gigantism at presentation. Elevated basal GH (mean 28 micrograms/l) and PRL (mean 120 micrograms/l) plasma levels were observed, as well as paradoxical responses of GH to L-dopa, TRH and oral glucose administration; PRL was reduced by L-dopa and slightly increased by TRH; GHRH stimulated release of both GH and PRL. Two operations were required to remove the very large tumour and the patient was treated with bromocriptine before the second. Hormonal secretion by tumour explants in culture was evaluated under basal conditions and after stimulation or inhibition. High levels of GH and PRL were secreted for up to 24 days. Furthermore, GHRH and TRH caused a dose-related stimulation of both hormones, while somatostatin and dopamine were effective in suppressing either basal or stimulated hormone release only at very high (microM) concentrations. Intracellular events were studied by determination of the guanosine triphosphate binding (G) protein levels and adenylate cyclase (AC) activity in the tumour tissue. Before bromocriptine treatment, AC activity was very high in the tumour and could be further stimulated by various agents; very high levels of the AC-stimulatory G protein alpha subunit Gs alpha and very low amounts of the AC-inhibiting G protein alpha subunit Gi3 alpha and of the phospholipase C-stimulating G protein alpha subunit Gq alpha were found in the tumour. After bromocriptine, baseline AC activity was normalized and could no longer be stimulated; Gs alpha and Gi3 alpha levels were unchanged while those of Gq alpha were normalized. Screening of tumour DNA after amplification by polymerase chain reaction followed by single-strand conformational polymorphism analysis did not reveal any mutations in the hot spots of G protein alpha subunits (alpha s, alpha i2, alpha o2 and alpha 11) genes or in the H-ras and p53 genes. Gs alpha and GH transcription factor-1 (pit-1) expression were evaluated by amplification of cDNA. While the mRNA expression of pit-1 decreased after bromocriptine treatment, that of Gs alpha increased. These data suggest the possibility of an oncogenic process involving overexpression of Gs alpha, resulting in chronic activation of adenylate cyclase. Furthermore, our results suggest that the anti-secretory and anti-proliferative effects of bromocriptine may be mediated through a decrease in Pit-1 secondary to the inhibition of adenylate cyclase activity.
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PMID:Mammosomatotroph adenoma causing gigantism in an 8-year old boy: a possible pathogenetic mechanism. 762 75

The peptide galanin is synthesized within and secreted from specific cell types of the rat anterior pituitary gland. The small size of the rat anterior pituitary gland is somewhat limiting for studying the regulation of galanin gene expression and peptide synthesis/secretion. We examined the mammotropic rat pituitary tumor MtTW-10 as a possible model system to study galanin. The objectives of this study were to 1) determine if galanin is secreted from MtTW-10 cells in vitro in a regulated manner, 2) characterize the molecular forms of immunoreactive galanin secreted by MtTW-10 cells, and 3) assess whether galanin gene expression in MtTW-10 tumors is regulated by estradiol. MtTW-10 pituitary tumors were transplanted to female Wistar-Furth rats that were implanted with estradiol-filled capsules. Cells were harvested from the MtTW-10 tumors and cultured for 4 days. When examined by electron microscopy, the MtTW-10 cells maintained in culture were irregular in shape with microvilli on their surface and contained numerous large secretory granules. Immunoreactive galanin, PRL, and GH were secreted from the cells in a time-dependent fashion during static incubations. LH, ACTH, and TSH were undetectable in the culture medium. Somatostatin (10 and 100 nM) inhibited galanin, PRL, and GH release in a dose-dependent manner. In contrast, dopamine, TRH, LH-releasing hormone, CRH, and GH-releasing hormone at concentrations of 10-100 nM failed to alter hormone secretion. Only high concentrations of dopamine (1 microM) inhibited the secretion of galanin, PRL, and GH. HPLC fractionation of peptides secreted by MtTW-10 cells cultures showed that approximately 84% of the galanin immunoreactivity coeluted with synthetic rat galanin. In tumor-bearing rats, plasma levels of immunoreactive galanin were 10-fold higher after estradiol treatment than levels in ovariectomized controls. Galanin mRNA levels were increased 20-fold by estradiol in MtTW-10 tumors, as determined by solution hybridization, and peptide levels were elevated nearly 100-fold. We conclude that 1) galanin is secreted from MtTW-10 cells in vitro, and its secretion is inhibited by somatostatin; and 2) estradiol increases galanin gene expression and peptide secretion in MtTW-10 tumors in vivo. These data show that MtTW-10 tumors may be useful to study the regulation of pituitary galanin gene expression, peptide synthesis, and secretion.
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PMID:MtTW-10 pituitary tumor cells: galanin gene expression and peptide secretion. 769 42

At present, four main types of serotonin (5-HT) receptors have been identified in the brain (5-HT1, 5-HT2, 5-HT3, and 5-HT4). In addition, the 5-HT1 have been further subclassified. We have taken advantage of a new selective 5-HT1D receptor agonist 3-[2-(dimethylamino)ethyl]-N-methyl-1H-indole-5-methanesulfonamide succinate, Sumatriptan, to evaluate the role of 5-HT1D receptors on GH secretion. To this end, several tests with or without sumatriptan were undertaken in normal prepubertal children. Furthermore, we assessed the effect of Sumatriptan on basal GH secretion and the GH response to GHRH in obese children. In normal children, Sumatriptan administration (3 mg, sc) resulted in an increase in basal GH levels at 30 min (7.7 +/- 1.5 micrograms/L; P < 0.05) and increased GH responses to GHRH (47.3 +/- 6.4 vs. 29.6 +/- 9.7 micrograms/L; P < 0.05). The Sumatriptan-induced increase in GH responses to GHRH was dependent on the stimulus tested. Pretreatment with Sumatriptan did not modify the GH response to clonidine or pyridostigmine, as assessed by the peak GH response and the area under the curve. In contrast, it increased the GH response to arginine. In the obese subjects, the GH response to GHRH was reduced (7.3 +/- 1.0 vs. 29.6 +/- 9.7 micrograms/L at 30 min) compared to that in control children (P < 0.05). Sumatriptan administration did not alter the basal GH value (peak GH, 1.7 +/- 0.3 micrograms/L at 30 min). However, Sumatriptan administration clearly increased the effect of GHRH, resulting in a GH peak of 14.6 +/- 3.1 micrograms/L at 30 min (P < 0.01). To assess the specificity of Sumatriptan on anterior pituitary hormone secretion, we studied its effect on TSH and PRL responses to TRH as well as LH-releasing hormone-induced LH and FSH secretion. Administration of Sumatriptan did not alter the response of any of these hormones. Our results indicate that 5-HT1D receptors have a stimulatory effect on GH secretion, possibly by inhibiting hypothalamic somatostatin release.
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PMID:Role of the serotonin receptor subtype 5-HT1D on basal and stimulated growth hormone secretion. 777 48


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