Calcitonin inhibition of growth hormone-releasing hormone-induced GH secretion in normal men

1989 ◽  
Vol 120 (4) ◽  
pp. 416-422 ◽  
Author(s):  
Gian Paolo Ceda ◽  
Licia Denti ◽  
Graziano Ceresini ◽  
Gianni Rastelli ◽  
Claudio Dotti ◽  
...  
Keyword(s):  
Serum Insulin ◽  
Primary Cultures ◽  
Hormone Secretion ◽  
Pituitary Hormone ◽  
Pituitary Cells ◽  
Gh Secretion ◽  
Inhibition Of Growth ◽  
Normal Men ◽  
Rat Pituitary Cells

Abstract. Calcitonin has been shown to modulate pituitary hormone secretion in a variety of ways. In this study we examined the effects of a salmon calcitonin infusion on GHRH-induced GH secretion in 5 normal men. In addition, in vitro experiments were performed using primary cultures of rat anterior pituitary cells in order to examine whether there is a direct pituitary effect of CT. Infusion of CT significantly blunted the GH response to GHRH in all subjects without affecting basal GH secretion or plasma calcium levels. Infusion of CT was accompanied by significant increases in ACTH, β-endorphin, cortisol and free fatty acid levels, and by a significant decrease in serum insulin levels. The addition of CT to primary cultures of rat pituitary cells did not alter basal or stimulated secretion of GH or ACTH. These results indicate that: 1) CT blunts the GH response to GHRH; 2) CT infusion results in the stimulation of the hypothalamicpituitary-adrenal axis, and 3) this effect is probably exerted at the hypothalamic level, since no direct activity of CT was documented in vitro on either GH or ACTH secretion.

Dichotomic action of glucocorticoids on growth hormone secretion

1987 ◽  
Vol 116 (2) ◽  
pp. 165-171 ◽  
Author(s):  
Koji Nakagawa ◽  
Tatsuya Ishizuka ◽  
Takao Obara ◽  
Miyao Matsubara ◽  
Kazumasa Akikawa
Keyword(s):  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Inhibitory Effect ◽  
Female Rats ◽  
Pituitary Cells ◽  
Gh Secretion ◽  
Normal Rat ◽  
Rat Pituitary Cells

Abstract. The mechanism of apparently discrepant actions of glucocorticoids (GC) on GH secretion, in vivo suppression and in vitro potentiation, was studied in rats. Dexamethasone (Dex), at the concentration of 50 nmol/l, Potentiated basal and GHRH-stimulated GH release from monolayer culture of normal rat pituitary cells in 48 h. On the other hand, in vivo administration of Dex, 165 μg daily for 3 days, consistently suppressed serum GH levels in female rats. In these rats, the hypothalamic content of immunoreactive (IR) SRIH was significantly increased, whereas that of IR-GHRH was significantly decreased in comparison with the untreated rats. Bioassayable GH-releasing activity was also lower in Dex-treated rats. These findings indicate that the suppressing effect of GC on GH release in vivo is, at least partially, due to the increase in hypothalamic SRIH release and probably also to the decrease in GHRH release, and these effects surpass the potentiating effect of GC on GH release at the pituitary level, resulting in a net inhibitory effect in vivo.

Characterization of endothelin receptors in the anterior pituitary gland

1993 ◽  
Vol 265 (4) ◽  
pp. E601-E608 ◽  
Author(s):  
B. Kanyicska ◽  
M. E. Freeman
Keyword(s):  
Primary Cultures ◽  
Hormone Secretion ◽  
Pituitary Hormone ◽  
Receptor Subtypes ◽  
Pituitary Cells ◽  
Female Rat ◽  
Response Curves ◽  
Potency Ratio ◽  
Eta Receptor ◽  
Rat Pituitary Cells

To characterize endothelin (ET) receptors modulating pituitary hormone secretion, potencies of ET-like agonists were compared on prolactin (PRL), thyrotropin (TSH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) secretion from primary cultures of female rat pituitary cells. ET-1 was more potent than ET-3 in all cases. Sarafotoxin (SRTX) S6b an ETA agonist, was also more potent than ET-3 in all cases. SRTX-c, an ETB receptor agonist, was inactive. The ET-1-to-ET-3 potency ratio was three orders of magnitude higher on PRL or TSH secretion than on LH and FSH secretion, whereas SRTX-b-to-ET-3 potency ratios were similar on all four hormones. The ETA antagonist BQ-123 caused a parallel dextral displacement of dose-response curves of ET-1 and ET-3 on all four hormones. Schild regressions for BQ-123 on ET-1-induced PRL, TSH, LH, and FSH secretion indicated that BQ-123 has a similar affinity for the receptors mediating ET-1's effects. When BQ-123 was assessed against ET-3, Schild regressions indicated greater affinity for ET-3 on lactotrophs and thyrotrophs than gonadotrophs. Thus changes in pituitary hormone secretion are mediated by ETA-like receptors. ET receptors in lactotrophs and thyrotrophs are clearly distinguishable from gonadotrophs. We suggest the existence of distinct ETA receptor subtypes (ETA1 and ETA2) on these differing pituitary cells.

Effects of trifluoperazine on rat prolactin, growth hormone, thyroid stimulating hormone and adrenocorticotrophin secretion in vitro

1983 ◽  
Vol 103 (4) ◽  
pp. 492-496 ◽  
Author(s):  
Ruth C. Powell ◽  
Mark Daniels ◽  
Graham K. Innes ◽  
Michael J. Ashby ◽  
Keith Mashiter
Keyword(s):  
Growth Hormone ◽  
Primary Cultures ◽  
Hormone Secretion ◽  
Thyroid Stimulating Hormone ◽  
Pituitary Hormone ◽  
Gh Secretion ◽  
Tsh Secretion ◽  
Stimulation Of ◽  
Stimulating Hormone

Abstract. We have studied the effects of trifluoperazine, a proposed inhibitor of calmodulin directed cellular function, on adrenocorticotrophic hormone (ACTH), thyroid stimulating hormone (TSH), prolactin (Prl) and growth hormone (GH) secretion from primary cultures of rat adenohypophyseal cells. 5 × 10−6 m and 10−5 m trifluoperazine caused a significant (P < 0.005) reversible dose-related decrease in basal Prl secretion but was less effective on basal GH secretion, significant reversible inhibition (P< 0.005) occurring only with 10−5 m. Trifluoperazine did not consistently alter basal ACTH or TSH secretion but did inhibit 10−2 m theophylline stimulation of ACTH, Prl and GH secretion and 1.5 × 10−7 m TRH stimulation of TSH and Prl secretion. Paradoxically 10−5 m trifluoperazine enhanced theophylline stimulation of TSH secretion. Our results show trifluoperazine to have differential effects on Prl, GH, ACTH and TSH secretion, which are consistent with the known calcium dependence of pituitary hormone secretion and may suggest a role for calmodulin in this process.

Effects of recombinant human activin A on growth hormone secretion by human somatotrophinomas in vitro

1993 ◽  
Vol 137 (2) ◽  
pp. 329-334 ◽  
Author(s):  
M. Daniels ◽  
P. E. Harris ◽  
R. A. James ◽  
S. J. Turner ◽  
J. H. Dewar ◽  
...  
Keyword(s):  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Cell Types ◽  
Activin A ◽  
Pituitary Cells ◽  
In Vitro Techniques ◽  
Gh Secretion ◽  
Wide Range ◽  
Rat Pituitary Cells

ABSTRACT Activin A is a homodimer of inhibin βA subunits, and was first isolated from gonadal fluids on the basis of its ability to stimulate FSH secretion by rat pituitary cells in vitro. The βA subunits of activin and their mRNAs have been found in many cell types, in several species and at different stages of development, suggesting that activin A has a wide range of diverse biological roles. Apart from the modulation of gonadotroph function, in-vitro studies have demonstrated inhibitory effects of activin A on GH synthesis, GH secretion and possibly somatotroph proliferation. We have therefore investigated the potential role of activin A in the pathophysiological regulation of GH secretion by human somatotrophinoma cells using in-vitro techniques. Cell cultures were established by enzyme dispersion of adenoma tissue obtained from six patients with acromegaly, and treated for 72 h with 0·01–10 nmol recombinant human activin A/1 followed by a 2-h stimulation test with 10 nmol GH-releasing factor (GRF)/l. Medium was collected at 24, 48 and 72 h, as well as after GRF treatment, and GH concentrations were measured by immunoradiometric assay. Basal GH secretion from the cells of two tumours was significantly stimulated 12–63% above control values during treatment with 0·01–10 nmol activin A/1, whereas the peptide had no effect on GH release from cells of the remainder of the tumours. GRF significantly stimulated GH release from the cells of two different adenomas, and pretreatment with 0·01–1 nmol activin A/1 partially but significantly blocked GRF-stimulated GH release from the cells of one of these. These data demonstrate that activin A stimulates basal GH secretion from the cells of some, but not all, human somatotrophinomas in vitro. Pretreatment with the peptide may also partially block GRF-stimulated GH release from GRF-responsive somatotrophinoma cells. The importance of these actions in the pathophysiological regulation of human somatotrophinomas remains to be determined. Journal of Endocrinology (1993) 137, 329–334

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.

scholarly journals Obestatin Partially Affects Ghrelin Stimulation of Food Intake and Growth Hormone Secretion in Rodents

Endocrinology ◽  
2007 ◽  
Vol 148 (4) ◽  
pp. 1648-1653 ◽  
Author(s):  
Philippe Zizzari ◽  
Romaine Longchamps ◽  
Jacques Epelbaum ◽  
Marie Thérèse Bluet-Pajot
Keyword(s):  
Food Intake ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Male Rats ◽  
Pituitary Cells ◽  
Gh Secretion ◽  
Freely Moving ◽  
Stimulation Of

Administration of ghrelin, an endogenous ligand for the GH secretagogue receptor 1a (GHSR 1a), induces potent stimulating effects on GH secretion and food intake. However, more than 7 yr after its discovery, the role of endogenous ghrelin remains elusive. Recently, a second peptide, obestatin, also generated from proteolytic cleavage of preproghrelin has been identified. This peptide inhibits food intake and gastrointestinal motility but does not modify in vitro GH release from pituitary cells. In this study, we have reinvestigated obestatin functions by measuring plasma ghrelin and obestatin levels in a period of spontaneous feeding in ad libitum-fed and 24-h fasted mice. Whereas fasting resulted in elevated ghrelin levels, obestatin levels were significantly reduced. Exogenous obestatin per se did not modify food intake in fasted and fed mice. However, it inhibited ghrelin orexigenic effect that were evident in fed mice only. The effects of obestatin on GH secretion were monitored in superfused pituitary explants and in freely moving rats. Obestatin was only effective in vivo to inhibit ghrelin stimulation of GH levels. Finally, the relationship between octanoylated ghrelin, obestatin, and GH secretions was evaluated by iterative blood sampling every 20 min during 6 h in freely moving adult male rats. The half-life of exogenous obestatin (10 μg iv) in plasma was about 22 min. Plasma obestatin levels exhibited an ultradian pulsatility with a frequency slightly lower than octanoylated ghrelin and GH. Ghrelin and obestatin levels were not strictly correlated. In conclusion, these results show that obestatin, like ghrelin, is secreted in a pulsatile manner and that in some conditions; obestatin can modulate exogenous ghrelin action. It remains to be determined whether obestatin modulates endogenous ghrelin actions.

Glucocorticoid modulation of growth hormone secretion in vitro. Evidence for a biphasic effect on GH-releasing hormone mediated release

1987 ◽  
Vol 114 (4) ◽  
pp. 465-469 ◽  
Author(s):  
Gian Paolo Ceda ◽  
Robert G. Davis ◽  
Andrew R. Hoffman
Keyword(s):  
Growth Hormone ◽  
Prolonged Exposure ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Inhibitory Effect ◽  
Pituitary Cells ◽  
Gh Secretion ◽  
Glucocorticoid Action

Abstract. Glucocorticoids have been shown to have both stimulatory and suppressive effects on GH secretion in vitro and in vivo. In order to study the kinetics of glucocorticoid action on the somatotrope, cultured rat pituitary cells were exposed to dexamethasone for varying periods of time. During short-term incubations (≤ 4 h), dexamethasone inhibited GHRH and forskolin-elicited GH secretion, but during longer incubation periods, the glucocorticoid enhanced both basal and GHRH-stimulated GH release. The inhibitory effect of brief dexamethasone exposure was also seen in cells which previously had been exposed to dexamethasone. In addition, growth hormone secretion from cultured rat and human somatotropinoma cells was inhibited by a brief exposure to dexamethasone. Thus, the nature of glucocorticoid action on the isolated cultured somatotrope is biphasic, with brief exposure inhibiting, and more prolonged exposure stimulating GH secretion.

scholarly journals Signal Transduction Mechanisms for Glucagon-Induced Somatolactin Secretion and Gene Expression in Nile Tilapia (Oreochromis niloticus) Pituitary Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Chaoyi Zhang ◽  
Anji Lian ◽  
Yue Xu ◽  
Quan Jiang
Keyword(s):  
Gene Expression ◽  
Oreochromis Niloticus ◽  
Nile Tilapia ◽  
Primary Cultures ◽  
Hormone Secretion ◽  
Hek293 Cells ◽  
Luciferase Reporter ◽  
Pituitary Hormone ◽  
Pituitary Cells ◽  
Mrna Levels

Glucagon (GCG) plays a stimulatory role in pituitary hormone regulation, although previous studies have not defined the molecular mechanism whereby GCG affects pituitary hormone secretion. To this end, we identified two distinct proglucagons, Gcga and Gcgb, as well as GCG receptors, Gcgra and Gcgrb, in Nile tilapia (Oreochromis niloticus). Using the cAMP response element (CRE)-luciferase reporter system, tilapia GCGa and GCGb could reciprocally activate the two GCG receptors expressed in human embryonic kidney 293 (HEK293) cells. Quantitative real-time PCR analysis revealed that differential expression of the Gcga and Gcgb and their cognate receptors Gcgra and Gcgrb was found in the various tissues of tilapia. In particular, the Gcgrb is abundantly expressed in the neurointermediate lobe (NIL) of the pituitary gland. In primary cultures of tilapia NIL cells, GCGb effectively stimulated SL release, with parallel rises in the mRNA levels, and co-incubation with the GCG antagonist prevented GCGb-stimulated SL release. In parallel experiments, GCGb treatment dose-dependently enhanced intracellular cyclic adenosine monophosphate (cAMP) accumulation with increasing inositol 1,4,5-trisphosphate (IP3) concentration and the resulting in transient increases of Ca2+ signals in the primary NIL cell culture. Using selective pharmacological approaches, the adenylyl cyclase (AC)/cAMP/protein kinase A (PKA) and phospholipase C (PLC)/IP3/Ca2+/calmodulin (CaM)/CaMK-II pathways were shown to be involved in GCGb-induced SL release and mRNA expression. Together, these results provide evidence for the first time that GCGb can act at the pituitary level to stimulate SL release and gene expression via GCGRb through the activation of the AC/cAMP/PKA and PLC/IP3/Ca2+/CaM/CaMK-II cascades.

scholarly journals Endogenous Hypothalamic Somatostatins Differentially Regulate Growth Hormone Secretion from Goldfish Pituitary Somatotropes in Vitro

Endocrinology ◽  
2003 ◽  
Vol 144 (9) ◽  
pp. 4031-4041 ◽  
Author(s):  
Warren K. Yunker ◽  
Sean Smith ◽  
Chad Graves ◽  
Philip J. Davis ◽  
Surajlal Unniappan ◽  
...  
Keyword(s):  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Signaling Cascades ◽  
Pituitary Cells ◽  
Gh Secretion ◽  
Pituitary Adenylate Cyclase ◽  
Pcr Products ◽  
Intracellular Cascades ◽  
Ss Precursors

Abstract Using Southern blot analysis of RT-PCR products, mRNA for three different somatostatin (SS) precursors (PSS-I, -II, and -III), which encode for SS14, goldfish brain (gb)SS28, and [Pro2]SS14, respectively, were detected in goldfish hypothalamus. PSS-I and -II mRNA, but not PSS-III mRNA, were also detected in cultured pituitary cells. We subsequently examined the effects of the mature peptides, SS14, gbSS28, and [Pro2]SS14, on somatotrope signaling and GH secretion. The gbSS28 was more potent than either SS14 or [Pro2]SS14 in reducing basal GH release but was the least effective in reducing basal cellular cAMP. The ability of SS14, [Pro2]SS14, and gbSS28 to attenuate GH responses to GnRH were comparable. However, gbSS28 was less effective than SS14 and [Pro2]SS14 in diminishing dopamine- and pituitary adenylate cyclase-activating polypeptide-stimulated GH release, as well as GH release resulting from the activation of their underlying signaling cascades. In contrast, the actions of a different 28-amino-acid SS, mammalian SS28, were more similar to those of SS14 and [Pro2]SS14. We conclude that, in goldfish, SSs differentially couple to the intracellular cascades regulating GH secretion from pituitary somatotropes. This raises the possibility that such differences may allow for the selective regulation of various aspects of somatotrope function by different SS peptides.

Effects of tri-iodothyronine, cortisol and transcriptional inhibitors on vitamin D3-enhanced thyrotrophin secretion by rat pituitary cells in vitro

1989 ◽  
Vol 121 (3) ◽  
pp. 451-458 ◽  
Author(s):  
M. C. d'Emden ◽  
J. D. Wark
Keyword(s):  
Primary Cultures ◽  
Relative Increase ◽  
Pituitary Cells ◽  
Dihydroxyvitamin D ◽  
Rat Pituitary ◽  
Tsh Secretion ◽  
Dependent Inhibition ◽  
Rat Pituitary Cells

ABSTRACT The hormone 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) has been shown to selectively enhance agonist-induced TSH release in the rat thyrotroph in vitro. The interaction of 1,25-(OH)2D3 with tri-iodothyronine (T3) and cortisol was studied in primary cultures of dispersed anterior pituitary cells. TRH (1 nmol/l)-induced TSH release over 1 h was enhanced by 70% (P<0·01) following exposure to 10 nmol 1,25-(OH)2D3/l for 24 h. Pretreatment with T3 (1 pmol/l–1 μmol/l) for 24 h caused a dose-dependent inhibition of TRH-induced TSH release. Net TRH-induced TSH release was inhibited by 85% at T3 concentrations of 3 nmol/l or greater. Co-incubation with 1,25-(OH)2D3 resulted in enhanced TRH-induced TSH release at all T3 concentrations tested (P<0·001). The increment of TRH-induced TSH release resulting from 1,25-(OH)2D3 pretreatment was equivalent in the presence or absence of maximal inhibitory T3 concentrations. At 1 nmol T3/1, there was a two- to threefold relative increase in 1,25-(OH)2D3-enhanced TRH-induced TSH release. Incubation with cortisol (100 pmol/l–100 nmol/l) had no effect on basal or TRH-induced TSH release, nor did it alter 1,25-(OH)2D3-enhanced TRH-induced TSH release when added 24 h before, or at the time of addition of 1,25-(OH)2D3. Actinomycin D and α-amanitin abolished 1,25-(OH)2D3-enhanced TSH secretion. These data demonstrate that the action of 1,25-(OH)2D3 in the thyrotroph required new RNA transcription, and was not affected by cortisol. In the presence of T3, the response of the thyrotroph to TRH induced by 1,25-(OH)2D3 was increased. We have shown that 1,25-(OH)2D3 has significant effects on the action of TRH and T3 in vitro. These findings support the proposal that 1,25-(OH)2D3 may modulate TSH secretion in vivo. Journal of Endocrinology (1989) 121, 451–458

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