Effects of two novel dopaminergic drugs, CV 205-502 and CQP 201-403, on prolactin and growth hormone secretion by human pituitary tumours in vitro

1987 ◽  
Vol 116 (2) ◽  
pp. 287-292 ◽  
Author(s):  
Maria S. Venetikou ◽  
Jacky M. Burrin ◽  
Christine A. Woods ◽  
Tom H. Yeo ◽  
Judith Brownell ◽  
...  
Keyword(s):  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Pituitary Cells ◽  
Pituitary Tumours ◽  
Human Pituitary ◽  
Dopaminergic Drugs ◽  
Gh Secretion ◽  
Normal Rat ◽  
In Vitro Effects

Abstract. Two novel dopaminergic drugs, designated CV 205-502 and CQP 201-403 have recently been developed by Sandoz Pharmaceuticals Ltd (Basle, Switzerland). The effects of these drugs on PRL and GH secretion by normal rat and tumorous human pituitary cells in vitro have been investigated. Low doses of both CV 205-502 and CQP 201-403 immediately and profoundly suppressed PRL secretion, which failed to recover up to 7 h after removal of the drugs. Similarly, CQP 201-403 significantly suppressed basal GH secretion by human pituitary somatotropic tumours in culture, and both drugs significantly reduced the stimulatory effect of GHRH. These effects are more potent and longer acting than the previously described in vitro effects of bromocriptine. It is concluded that CV 205502 and CQP 201-403 hold potential for the treatment of patients with hyperprolactinaemia and, possibly, also in patients with acromegaly.

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.

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.

Neuropeptide Y directly inhibits growth hormone secretion by human pituitary somatotropic tumours

1987 ◽  
Vol 115 (1) ◽  
pp. 149-154 ◽  
Author(s):  
Eric F. Adams ◽  
Maria S. Venetikou ◽  
Christine A. Woods ◽  
S. Lacoumenta ◽  
J. M. Burrin
Keyword(s):  
Growth Hormone ◽  
Neuropeptide Y ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Inhibitory Effect ◽  
Pituitary Cells ◽  
Maximal Effect ◽  
Human Pituitary ◽  
Amino Acid Peptide ◽  
Gh Secretion

Abstract. Neuropeptide Y (NPY) is a 36 amino acid peptide, widely distributed throughout the brain and is found in hypothalamic neurones. This latter finding suggests that NPY may possess a hypophysiotropic function. A number of studies have demonstrated effects of NPY on LH and GH secretion by rat pituitary cells. We report here the results of experiments investigating the effects of NPY on GH secretion by tumorous human somatotropic pituitary cells in culture. NPY (0.25–25 nmol/l) inhibited GH secretion by 20–53%, the maximal effect depending upon the tumour studied. The potency of NPY was less than that of somatostatin (SRIH). The stimulatory effects of growth hormone releasing factor (GHRH) and theophylline were reduced by NPY, but NPY did not modify the inhibitory effect of SRIH on GH secretion. It is concluded that NPY may be involved in the control of GH secretion, at least by tumorous human pituitary somatotropes.

Melanin-concentrating hormone stimulates human growth hormone secretion: a novel effect of MCH on the hypothalamic-pituitary axis

2006 ◽  
Vol 290 (5) ◽  
pp. E982-E988 ◽  
Author(s):  
Gabriella Segal-Lieberman ◽  
Hadara Rubinfeld ◽  
Moran Glick ◽  
Noga Kronfeld-Schor ◽  
Ilan Shimon
Keyword(s):  
Growth Hormone ◽  
Energy Homeostasis ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Pituitary Hormones ◽  
Thyroid Stimulating Hormone ◽  
Pituitary Cells ◽  
Human Pituitary ◽  
Gh Secretion ◽  
Melanin Concentrating Hormone

Melanin-concentrating hormone (MCH), a 19-amino acid orexigenic (appetite-stimulating) hypothalamic peptide, is an important regulator of energy homeostasis. It is cleaved from its precursor prepro-MCH (ppMCH) along with several other neuropeptides whose roles are not fully defined. Because pituitary hormones such as growth hormone (GH), ACTH, and thyroid-stimulating hormone affect body weight and composition, appetite, insulin sensitivity, and lipoprotein metabolism, we investigated whether MCH exerts direct effects on the human pituitary to regulate energy balance using dispersed human fetal pituitaries (21–22 wk gestation) and cultured GH-secreting adenomas. We found that MCH receptor-1 (MCH-R1), but not MCH receptor-2, is expressed in both normal (fetal and adult) human pituitary tissues and in GH cell adenomas. MCH (10 nM) stimulated GH release from human fetal pituitary cultures by up to 62% during a 4-h incubation ( P < 0.05). Interestingly, neuropeptide EI (10 nM), which is also cleaved from ppMCH, increased human GH secretion by up to 124% in fetal pituitaries. A milder, albeit significant, induction of GH secretion by MCH (20%) was seen in cultured GH-secreting pituitary adenomas. A comparable stimulation of GH secretion was seen when cultured mouse pituitary cells were treated with MCH. Treatment of cultured GH adenoma cells with MCH (100 nM) induced extracellular signal-regulated kinases 1 and 2 phosphorylation, suggesting activation of MCH-R1. In aggregate, these data suggest that MCH may regulate pituitary GH secretion and imply a potential cross-talk mechanism between appetite-regulating neuropeptides and pituitary hormones.

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.

EFFECT OF CHICKEN HYPOTHALAMUS ON PROLACTIN AND GROWTH HORMONE SECRETION IN MALE CHICKENS

1979 ◽  
Vol 82 (2) ◽  
pp. 193-197 ◽  
Author(s):  
S. HARVEY ◽  
C. G. SCANES ◽  
A. CHADWICK ◽  
G. BORDER ◽  
N. J. BOLTON
Keyword(s):  
Growth Hormone ◽  
Medulla Oblongata ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Pituitary Cells ◽  
Plasma Prolactin ◽  
Gh Secretion ◽  
Brain Tissues

SUMMARY The effects of a chicken hypothalamic extract (HE) on the secretion of prolactin and growth hormone (GH) in vivo have been investigated by radioimmunoassay in the domestic fowl. Different i.v. doses of HE (0·25–25 HE equivalents/kg body weight) had no effect on GH secretion in conscious or anaesthetized cockerels. In both groups of birds the concentration of plasma prolactin was significantly increased within 10 min of administration of the extract. Extracts of other brain tissues (cerebral cortex, cerebellum and medulla oblongata) had no stimulatory effect on prolactin or GH secretion. Release of both prolactin and GH by dispersed pituitary cells and by hemipituitary glands in vitro was enhanced following incubation with HE (5 hypothalami equivalents/ml) or with single whole hypothalami respectively. Other brain tissues (cerebellum, optic lobes and medulla oblongata) had no effect on the concentration of prolactin or GH released by incubated hemipituitary glands.

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.

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