In-Vitro Regulation of Human Pituitary Hormone Secretion by Gut-Brain Peptides

1982 ◽  
Vol 62 (2) ◽  
pp. 34P-34P
Author(s):  
M.C. White ◽  
E.F. Adams ◽  
M. Loizou ◽  
K. Mashiter
Keyword(s):  
Hormone Secretion ◽  
Pituitary Hormone ◽  
Human Pituitary ◽  
Brain Peptides

scholarly journals Novel ghrelin analogs with improved affinity for the GH secretagogue receptor stimulate GH and prolactin release from human pituitary cells

2004 ◽  
pp. 787-795 ◽  
Author(s):  
H Rubinfeld ◽  
M Hadani ◽  
JE Taylor ◽  
JZ Dong ◽  
J Comstock ◽  
...  
Keyword(s):  
Hormone Secretion ◽  
Pituitary Hormone ◽  
Pituitary Cells ◽  
Human Pituitary ◽  
Amino Acid Peptide ◽  
Gh Secretion ◽  
Therapeutic Benefits ◽  
Releasing Effect ◽  
Ghs Receptor

OBJECTIVE: Ghrelin, a recently identified 28-amino acid peptide is a potent GH secretagogue (GHS) produced predominantly by the stomach. Ghrelin stimulates GH secretion through binding to the GHS receptor in the hypothalamus and pituitary. In addition to the GH-releasing action, ghrelin has been found to be a powerful orexigenic factor. To assess the direct in vitro effects of ghrelin on human pituitary hormone secretion we have produced a panel of novel ghrelin analogs (molecular weight, 3323-3384; human native ghrelin, 3371) with enhanced affinity for the human GHS receptor (IC(50) 0.38-1.09 nM; human ghrelin, 1.2-2.2 nM). METHODS: The peptidic analogs were tested for their effect on GH secretion using dispersed human fetal pituitaries (21 to 23 weeks of gestation) and cultured GH- and prolactin (PRL)-secreting adenomas. The expression of the GHS receptor in normal (fetal and adult) human pituitary tissues, GH- and PRL-cell adenomas was established using RT-PCR. RESULTS: The effects of ghrelin, its analogs and GH-releasing hormone (GHRH) alone or in combination on GH and PRL secretion were compared at various concentrations. The ghrelin analogs stimulated GH release by 35-60% from human fetal pituitary cells (1-10 nM; P<0.05) and by 50-75% from cultured pituitary adenomas (10 nM; P<0.05). This releasing effect was dose-dependent, achieving maximal stimulation with analog concentrations at 100 nM. Human ghrelin was less potent as compared with its analogs in stimulating human GH, in keeping with the improved binding affinity of the analogs for the GHS-1a receptor. The ghrelin analogs and GHRH had comparable effects on GH secretion from both normal and adenomatous cells, and in combination produced an additive stimulatory effect on GH (150%; P<0.0001). In contrast, ghrelin and its analogs induced a comparable increase in PRL release ranging between 25 and 40% (P<0.05) from fetal cells and 30 and 70% (P<0.001) from cultured PRL-cell and mixed GH-PRL adenomas. CONCLUSIONS: Our results have demonstrated for the first time that ghrelin analogs with enhanced affinity for the GHS receptor are potent stimulators of GH secretion from human pituitary cells, and thus may possess potential clinical therapeutic benefits.

Vasopressin as a neuroendocrine regulator of anterior pituitary hormone secretion

1993 ◽  
Vol 129 (6) ◽  
pp. 489-496 ◽  
Author(s):  
Andreas Kjær
Keyword(s):  
Arginine Vasopressin ◽  
Mode Of Action ◽  
Anterior Pituitary ◽  
Hormone Secretion ◽  
Pituitary Hormones ◽  
Pituitary Hormone ◽  
Anterior Pituitary Hormones ◽  
Anterior Pituitary Hormone

Secretion of the anterior pituitary hormones adrenocorticotropin (ACTH), β-endorphin and prolactin (PRL) is complex and involves a variety of factors. This review focuses on the involvement of arginine-vasopressin (AVP) in neuroendocrine regulation of these anterior pituitary hormones with special reference to receptor involvement, mode of action and origin of AVP. Arginine-vasopressin may act via at least two types of receptors: V1− and V2−receptors, where the pituitary V1−receptor is designated V1b. The mode of action of AVP may be mediating, i.e. anterior pituitary hormone secretion is transmitted via release of AVP, or the mode of action may be permissive, i.e. the presence of AVP at a low and constant level is required for anterior pituitary hormones to be stimulated. Under in vivo conditions, the AVP-induced release of ACTH and β-endorphin is mainly mediated via activation of hypothalamic V1− receptors, which subsequently leads to the release of corticotropin-releasing hormone. Under in vitro conditions, the AVP-stimulated release of ACTH and β-endorphin is mediated via pituitary V1b− receptors. The mode of action of AVP in the ACTH and β-endorphin response to stress and to histamine, which is involved in stress-induced secretion of anterior pituitary hormones, is mediating (utilizing V1− receptors) as well as permissive (utilizing mainly V1− but also V2−receptors). The AVP-induced release of PRL under in vivo conditions is conveyed mainly via activation of V1−receptors but V2−receptors and probably additional receptor(s) may also play a role. In stress- and histamine induced PRL secretion the role of AVP is both mediating (utilizing V1 −receptors) and permissive (utilizing both V1− and V2− receptors). Arginine-vasopressin may be a candidate for the PRL-releasing factor recently identified in the posterior pituitary gland. Arginine-vasopressin of both magno- and parvocellular origin may be involved in the regulation of anterior pituitary hormone secretion and may reach the corticotrophs and the lactotrophs via three main routes: the peripheral circulation, the long pituitary portal vessels or the short pituitary portal vessels.

Central opioid receptors mediate glucoprivic inhibition of pituitary LH secretion

1997 ◽  
Vol 272 (4) ◽  
pp. E517-E522 ◽  
Author(s):  
K. P. Briski
Keyword(s):  
Receptor Antagonist ◽  
Opioid Receptor ◽  
Hormone Secretion ◽  
Male Rats ◽  
Pituitary Hormone ◽  
Intracerebroventricular Administration ◽  
Receptor Antagonists ◽  
Opioid Receptor Antagonist ◽  
Opioid Receptor Antagonists

The present studies investigated the significance of glucoprivic metabolic signals, particularly those of central origin, to the regulation of pituitary luteinizing hormone (LH). Groups of gonadectomized (GDX) adult male rats were treated with 2-deoxy-D-glucose (2-DG), an inhibitor of glycolysis, by either intravenous (50, 100, or 200 mg/kg) or intracerebroventricular (5, 20, or 100 microg/rat) administration. Systemic drug treatment caused a significant decrease in mean plasma LH levels compared with saline-treated controls. Intracerebroventricular administration of 2-DG was also efficacious in suppressing circulating LH; animals treated with either of the two highest doses of the drug exhibited a significant reduction in plasma LH. In vitro studies examined direct effects of 2-DG on pituitary gonadotrope secretory activity. Exposure of anterior pituitary tissue to 2-DG during short-term perfusion had no significant impact upon either basal or gonadotropin-releasing hormone-stimulated LH release. Finally, groups of GDX rats were pretreated by intracerebroventricular administration of either the nonselective opioid receptor antagonist, naltrexone, or the selective mu-opioid receptor antagonist, beta-funaltrexamine (beta-FNA), before intravenous injection of 2-DG. Both receptor antagonists were observed to attenuate the suppressive effects of 2-DG on circulating LH in these animals. In summary, treatment of GDX rats with the glucose antimetabolite, 2-DG, decreased plasma LH, suggesting that metabolic signaling of cellular glucose oxidation is of physiological importance to the regulation of pituitary hormone secretion. Findings that plasma LH was diminished in animals treated intracerebroventricularly with 2-DG implicate central glucoprivic receptors in neuroendocrine mechanisms governing the reproductive endocrine axis. Attenuation of 2-DG-induced decreases in circulating LH by opioid receptor antagonists suggests that these receptors, particularly the mu-subtype, mediate central effects of glucoprivation on circulating LH.

The Role of Brain Peptides in the Control of Anterior Pituitary Hormone Secretion

1986 ◽  
pp. 89-99
Author(s):  
S. M. McCann ◽  
W. K. Samson ◽  
M. C. Aquila ◽  
J. Bedran De Castro ◽  
N. Ono ◽  
...  
Keyword(s):  
Anterior Pituitary ◽  
Hormone Secretion ◽  
Pituitary Hormone ◽  
Anterior Pituitary Hormone ◽  
Brain Peptides

The Role of Brain Peptides in the Control of Anterior Pituitary Hormone Secretion

1986 ◽  
pp. 101-111 ◽  
Author(s):  
S. M. McCann ◽  
W. K. Samson ◽  
M. C. Aguila ◽  
J. Bedran de Castro ◽  
N. Ono ◽  
...  
Keyword(s):  
Anterior Pituitary ◽  
Hormone Secretion ◽  
Pituitary Hormone ◽  
Anterior Pituitary Hormone ◽  
Brain Peptides

scholarly journals Screening for GPR101 defects in pediatric pituitary corticotropinomas

2016 ◽  
Vol 23 (5) ◽  
pp. 357-365 ◽  
Author(s):  
Giampaolo Trivellin ◽  
Ricardo R Correa ◽  
Maria Batsis ◽  
Fabio R Faucz ◽  
Prashant Chittiboina ◽  
...  
Keyword(s):  
Adrenocorticotropic Hormone ◽  
Somatic Mutations ◽  
Hormone Secretion ◽  
Camp Signaling ◽  
Pituitary Hormone ◽  
Significant Percentage ◽  
Functional Studies ◽  
Acth Secreting ◽  
G Protein Coupled

Cushing’s disease (CD) in children is caused by adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas. Germline or somatic mutations in genes such as MEN1, CDKIs, AIP, and USP8 have been identified in pediatric CD, but the genetic defects in a significant percentage of cases are still unknown. In this study, we investigated the orphan G-protein-coupled receptor GPR101, a gene known to be involved in somatotropinomas, for its possible involvement in corticotropinomas. We performed GPR101 sequencing, expression analyses by RT-qPCR and immunostaining, and functional studies (cell proliferation, pituitary hormone secretion, and cAMP measurement) in a series of patients with sporadic CD secondary to ACTH-secreting adenomas in whom we extracted DNA from peripheral blood and pituitary tumor samples (n=36). No increased GPR101 expression was observed in tumors compared with normal pituitary (NP) tissues, nor did we find a correlation between GPR101 and ACTH expression levels. Sequence analysis revealed a very rare germline heterozygous GPR101 variant (p.G31S) in one patient with CD. Overexpression of the p.G31S variant did not lead to increased growth and proliferation, although modest effects on cAMP signaling were observed. GPR101 is not overexpressed in ACTH-secreting tumors compared with NPs. In conclusion, rare germline GPR101 variant was found in one patient with CD, but in vitro studies did not support a consistent pathogenic effect. GPR101 is unlikely to be involved in the pathogenesis of CD.

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