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.

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.

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.

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.

Signaling mechanisms for α2-adrenergic inhibition of PACAP-induced growth hormone secretion and gene expression grass carp pituitary cells

2007 ◽  
Vol 292 (6) ◽  
pp. E1750-E1762 ◽  
Author(s):  
Xinyan Wang ◽  
Mable M. S. Chu ◽  
Anderson O. L. Wong
Keyword(s):  
Gene Expression ◽  
Growth Hormone ◽  
Adenylate Cyclase ◽  
Grass Carp ◽  
Promoter Activity ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Pituitary Cells ◽  
Gh Secretion ◽  
Gh Gene

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a potent growth hormone (GH)-releasing factor in lower vertebrates. However, its functional interactions with other GH regulators have not been fully characterized. In fish models, norepinephrine (NE) inhibits GH release at the pituitary cell level, but its effects on GH synthesis have yet to be determined. We examined adrenergic inhibition of PACAP-induced GH secretion and GH gene expression using grass carp pituitary cells as a cell model. Through activation of pituitary α2-adrenoreceptors, NE or the α2-agonist clonidine reduced both basal and PACAP-induced GH release and GH mRNA expression. In carp pituitary cells, clonidine also suppressed cAMP production and intracellular Ca2+ levels and blocked PACAP induction of these two second messenger signals. In GH3 cells transfected with a reporter carrying the grass carp GH promoter, PACAP stimulation increased GH promoter activity, and this stimulatory effect could be abolished by NE treatment. In parallel experiments, clonidine reduced GH primary transcript and GH promoter activity without affecting GH mRNA stability, and these inhibitory actions were mimicked by inhibiting adenylate cyclase (AC), blocking protein kinase A (PKA), removing extracellular Ca2+ in the culture medium, or inactivating L-type voltage-sensitive Ca2+ channels (VSCC). Since our recent studies have shown that PACAP can induce GH secretion in carp pituitary cells through cAMP/PKA- and Ca2+/calmodulin-dependent mechanisms, these results, taken together, suggest that α2-adrenergic stimulation in the carp pituitary may inhibit PACAP-induced GH release and GH gene transcription by blocking the AC/cAMP/PKA pathway and Ca2+ entry through L-type VSCC.

Negative feedback of insulin-like growth factor-I on growth hormone secretion by porcine pituitary cells

1995 ◽  
Vol 75 (1) ◽  
pp. 57-61 ◽  
Author(s):  
C. Farmer ◽  
H. Lapierre
Keyword(s):  
Growth Hormone ◽  
Negative Feedback ◽  
Culture Media ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Late Gestation ◽  
Pituitary Cells ◽  
Gh Secretion ◽  
Age Related ◽  
Igf I

Pituitaries from female Yorkshire pig fetuses (90 d, n = 26; 110 d, n = 17) and 6-mo-old pigs (n = 5) were enzymatically dispersed, plated, and cultured for 47 h. The cells were then rinsed and incubated for 22 h with testing media containing 0, 50, 100, 200, 300 or 400 ng mL−1 of IGF-I. Half of the wells from each concentration of IGF-I were then incubated for an additional 3 h with concentrations of IGF-I similar to those in the previous incubation, while the other half also had GRF added to the testing media to reach a final concentration of 10−8 M. Culture media were then collected from all the wells, were frozen, and later assayed for GH. Irrespective of whether GRF was present, IGF-I decreased pituitary secretion of GH (P < 0.001). A significant negative response to IGF-I was already present at the dose of 50 ng mL−1 (P < 0.0001). However, the extent of the GH response to IGF-I seen in pigs of various ages differed depending on whether GRF was present. The present results therefore establish that IGF-I does exert a negative feedback on pituitary GH secretion in swine and that the age-related changes in this feedback are dependent on the presence of GRF. In swine, it appears that high circulating concentrations of GH in late-gestation fetuses are not a result of a lesser sensitivity of the somatotroph to the inhibitory actions of IGF-I. Key words: Pig, cell culture, pituitary, IGF-I, growth hormone, age

Somatostatin tonically inhibits growth hormone secretion in domestic fowl

1986 ◽  
Vol 111 (1) ◽  
pp. 91-97 ◽  
Author(s):  
S. Harvey ◽  
S.-K. Lam ◽  
T. R. Hall
Keyword(s):  
Growth Hormone ◽  
Domestic Fowl ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Passive Immunization ◽  
Inhibitory Effect ◽  
Gh Secretion ◽  
Basal Plasma ◽  
Plasma Gh

ABSTRACT Passive immunization of immature chickens with sheep somatostatin (SRIF) antiserum promptly increased the basal plasma GH concentration and augmented TRH-induced GH secretion. Although exogenous SRIF had no inhibitory effect on the basal GH concentration in untreated birds or birds pretreated with non-immune sheep serum, it suppressed the stimulatory effect of SRIF immunoneutralization on GH secretion. These results suggest that SRIF is physiologically involved in the control of GH secretion in birds, in which it appears to inhibit GH release tonically. J. Endocr. (1986) 111, 91–97

Effect of exogenous growth hormone administration on endogenous growth hormone secretion induced by a met-enkephalin analog

1996 ◽  
Vol 134 (1) ◽  
pp. 73-76 ◽  
Author(s):  
Giuseppe Fanciulli ◽  
Osvaldo Oliva ◽  
Paolo A Tomasi ◽  
Alessandra Pala ◽  
Alba Bertoncelli ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Endogenous Growth ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Inhibitory Effect ◽  
Growth Hormone Administration ◽  
Gh Secretion ◽  
Hormone Administration ◽  
Exogenous Growth ◽  
Serum Gh

Fanciulli G, Oliva O, Tomasi PA. Pala A. Bertoncelli A, Dettori A, Delitala G. Effect of exogenous growth hormone administration on endogenous growth hormone secretion induced by a met-enkephalin analog. Eur J Endocrinol 1996:134:73–6. ISSN 0804–4643 Exogenous growth hormone (hGH) administration in humans attenuates the endogenous growth hormone (GH) response to some pharmacological stimuli: in particular, pretreatment with hGH completely blocks the serum GH response to growth hormone-releasing hormone. In order to evaluate the mechanism(s) whereby opioids induce GH secretion in man, we gave the following treatments to six healthy male volunteers: (a) IV saline: (b) a met-enkephalin analog G-DAMME 250 μg IV as a bolus at time ′: (c) hGH 2 IU as an IV bolus at time −180′; (d) G-DAMME as above, preceded by hGH as above. In our study. G-DAMME stimulated GH secretion both basally (peak 17.9 ± 6.0 ng/ml) and, to a lesser extent, after hGH pretreatment (6.0 ± 2.7 ng/ml). Since in our study G-DAMME was able to partially overcome the inhibitory effect of hGH administration, it is suggested that opioids act through an inhibition of somatostatin release and not through a GHRH-dependent pathway. However, an additional direct effect of hGH on pituitary somatotrophes cannot be excluded. Giuseppe Delitala, Chair of Endocrinology, Viale S. Pietro 12, University of Sassari, 07100 Sassari. Italy

Effects of ovine corticotrophin-releasing factor and hydrocortisone on growth hormone secretion by pituitary adenoma cells of acromegaly in culture

1984 ◽  
Vol 106 (4) ◽  
pp. 443-447 ◽  
Author(s):  
M. Ishibashi ◽  
T. Hara ◽  
Y. Tagusagawa ◽  
T. Fukushima ◽  
H. Numata ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Pituitary Adenoma ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Cellular Membrane ◽  
Inhibitory Effect ◽  
Membrane Receptors ◽  
Dose Response Relationship ◽  
Gh Secretion ◽  
Corticotrophin Releasing Factor

Abstract. In an attempt to test the hypothesis that pituitary adenomas of acromegaly may possess altered cellular membrane receptors, the response of growth hormone (GH) secretion to ovine corticotrophin-releasing factor (CRF) in cultured adenoma cells of acromegaly was studied. In three out of seven experiments using different pituitary adenoma cells in culture, nanomolar concentrations of CRF caused a significant increase in GH release. The CRF-induced GH release was reproducible and a dose-response relationship was observed between the CRF concentrations and the amounts of GH released into the incubation media. Hydrocortisone, at a concentration of 1 μm, on the other hand, resulted in a significant decrease in GH secretion in four out of five experiments. When adenoma cells were co-incubated with CRF and 1 μm hydrocortisone, CRF-induced GH release was partially overcome. In one experiment, the inhibitory effect of hydrocortisone was reversed by coincubation with CRF, although CRF alone was ineffective in the stimulation of GH. These results suggest that CRF may stimulate GH release in some, though not all, patients with acromegaly, and that glucocorticoids may block this effect of CRF acting directly on the pituitary adenoma cells of acromegaly.

Activation of cholinergic tone by pyridostigmine reverses the inhibitory effect of corticotropin-releasing hormone on the growth hormone-releasing hormone-induced growth hormone secretion

1992 ◽  
Vol 126 (2) ◽  
pp. 113-116 ◽  
Author(s):  
SM Corsello ◽  
A Tofani ◽  
S Della Casa ◽  
R Sciuto ◽  
CA Rota ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Inhibitory Effect ◽  
Normal Male ◽  
Corticotropin Releasing Hormone ◽  
Releasing Hormone ◽  
Gh Secretion ◽  
Cholinergic Tone ◽  
Ghrh Test

Previous studies have shown that corticotropin-releasing hormone (CRH) is capable of inhibiting growth hormone (GH) secretion in response to GH-releasing hormone (GHRH). In an attempt to clarify the mechanism of the CRH action, we have studied the effect of enhanced cholinergic tone induced by pyridostigmine on the CRH inhibition of the GH response to GHRH in a group of six normal men and six normal women. All subjects presented a normal GH response to 50 μg iv GHRH administration (mean peak±sem plasma GH levels 20±2.9 μg/l in men and 28.9±2.9 μg/l in women) with a further significant increase after pyridostigmine pretreatment (60mg orally given 60 min before GHRH) in men (GH peaks 43.1±6.9 μg/l, p<0.005) but not in women (GH peaks 39.2±3.0 μg/l). In the same subjects, peripherally injected CRH (100 μg) significantly inhibited the GH response to GHRH (GH peaks 8.1±0.6 μg/l in men, p<0.005 and 9.9±0.7 μg/l in women, p<0.005). Pyridostigmine (60 mg) given orally at the same time of CRH administration (60 min before GHRH) reversed the CRH inhibition of GHRH-induced GH secretion (GH peaks 35.3±8.2 μg/l in men and 35±3.3 μg/l in women) with a response not significantly different to that seen in the pyridostigmine plus GHRH test. Our data confirm that pyridostigmine is capable of potentiating the GHRH-induced GH release in normal male but not female subjects. In addition, our studies show that the potentiating action of pyridostigmine on the GHRH-induced GH secretion prevails on the inhibiting effect of CRH when the two drugs are given together 1 h before GHRH injection. Both CRH and pyridostigmine could exert their action by modifying, in opposite ways, somatostatin release from the hypothalamus.

Growth hormone-releasing factor does not stimulate phosphoinositides breakdown in primary cultures of rat and human pituitary cells

1986 ◽  
Vol 112 (3) ◽  
pp. 345-350 ◽  
Author(s):  
Dolores Collado Escobar ◽  
Lucia M. Vicentini ◽  
Ezio Ghigo ◽  
Enrica Ciccarelli ◽  
Luciana Usellini ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Inositol Phosphates ◽  
Primary Cultures ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Cell System ◽  
Pituitary Cells ◽  
Human Pituitary ◽  
Growth Hormone Releasing Factor

Abstract. It has been reported that rat growth hormone releasing factor (rat GRF-43), similarly to the two human GRFs (GRF-40 and 44) stimulates adenylate cyclase activity in pituitary cells. Controversial findings have been presented by two different groups on the action of GRF on phosphoinositides (PI) metabolism, a phenomenon linked to Ca++ – mediated intracellular mechanisms. In the work to be reported, we evaluated the accumulation of inositol phosphates induced by GRF exposure in primary cultures of rat and human pituitary cells. Addition of rat GRF-43 to rat pituitary cells at doses up to 1 μm had no effect on inositol phosphates accumulation, while already at a dose as low as 0.05 nm it increased growth hormone secretion in the incubation medium significantly. In the same cell system, TRH, a known activator of PI breakdown, significantly increased [3H]inositol phosphates. In primary cultures of human somatotrophs from acromegalic subjects as in rats, addition of hpGRF-40 and also of TRH did not elicit any modification in the accumulation of [3H]inositol phosphates. Consistent with in vivo findings, both peptides induced a significant release of GH in the medium. Our results show that the GH releasing effect of GRF does not involve the hydrolysis of phosphatidylinositol in normal rat as well as in tumoral human somatotrophs. In addition it appears that the anomalous response of TRH on adenomatous cells from acromegalic patients is differently mediated in respect to the action of the tripeptide on normal lactotrophs and thyrotrophs.

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