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

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.

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 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.

Inhibition of growth hormone secretion by activin A in human growth hormone-secreting tumour cells

1991 ◽  
Vol 124 (6) ◽  
pp. 666-671 ◽  
Author(s):  
Masafumi Kitaoka ◽  
Kohji Takano ◽  
Yuji Tanaka ◽  
Itaru Kojima ◽  
Akira Teramoto ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Human Growth ◽  
Activin A ◽  
Tumour Cells ◽  
Free Calcium ◽  
Gh Secretion

Abstract. Effect of activin A on growth hormone secretion was studied in primary culture of 8 human GH-secreting adenomas, which were responsive to TRH in vivo. When studied in vitro, basal GH secretion was reduced in all cases when cells were pre-incubated for 48 h with activin A at a concentration of 5×10−9 mol/l or greater. Pretreatment of GH-secreting cells with 1× 10−9 mol/l activin A did not affect either basal secretion or cellular content of GH. These tumour cells also responded to TRH in vitro and the GH response to TRH was completely blocked in cells pretreated with activin A. Activin A slightly reduced the increase in cytoplasmic free calcium concentration induced by TRH. Furthermore, pretreatment of the cells with activin A attenuated GH secretion induced by A23187 or 12-O-tetradecanoyl phorbol-4-acetate, agents which bypass receptor-mediated generation of second messengers. These results indicate that activin A inhibits GH secretion by directly acting on human GH-secreting cells and that activin A inhibits the action of TRH by acting on multiple steps in the messenger system.

Involvement of thioredoxin in the regulation of growth hormone secretion in rat pituitary cell cultures

2001 ◽  
Vol 281 (2) ◽  
pp. E269-E274 ◽  
Author(s):  
Ikue Hata ◽  
Yosuke Shigematsu ◽  
Yusei Ohshima ◽  
Hirokazu Tsukahara ◽  
Kazuo Fujisawa ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Anterior Pituitary ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Pituitary Cells ◽  
Dependent Manner ◽  
Gh Secretion ◽  
Anterior Pituitary Cells ◽  
Rat Pituitary ◽  
Rat Pituitary Cells

We report here an examination of the effect of thioredoxin (TRX) on the secretion of growth hormone (GH) from rat anterior pituitary cells in vitro. Treatment of rat pituitary cells with growth hormone-releasing factor (GRF), but not GH, led to a significant increase in intracellular TRX protein levels. GRF, recombinant human TRX (rhTRX), and a combination thereof were all shown to induce immediate GH secretion from pituitary cells, as evidenced by perifusion experiments. RhTRX, but not other reducing agents such as β-mercaptoethanol and N-acetyl-l-cysteine, augmented GRF-stimulated and -unstimulated GH secretion from rat pituitary cells in a dose-dependent manner. RhTRX did not significantly affect the GH mRNA expression of pituitary cells stimulated in the presence or absence of GRF. In addition, rhTRX-augmented GH secretion was not significantly affected by the presence of cycloheximide. Collectively, these findings suggest that TRX is induced by stimulation with GRF and plays a regulatory role in GH secretion from rat anterior pituitary cells by enhancing the secretion of stored GH, rather than by the synthesis of GH.

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.

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