In vitro modulation of growth hormone (GH) secretion from early to midgestation human fetal pituitaries by GH-releasing factor and somatostatin: role of Gs-adenylate cyclase-Gi complex and Ca2+ channels

Abstract Background: Melatonin (MEL) plays an important role in regulating the growth and development of organism and the metabolism of cells. A study was conducted to explore the effect of MEL-mediated monochromatic light on the secretion of somatostatin (SST) in the hypothalamus and pituitary.Results: The newly hatched broilers were exposed to white (WL), red (RL), green (GL) and blue (BL) lights through the pinealectomy model. The results showed that SST immunoreactive neurons and fibers were distributed in hypothalamus. The mRNA and protein levels of SST and SST receptor 2 (SSTR2) in hypothalamus and pituitary in RL were higher than those of in GL and BL. After pinealectomy, mRNA and protein levels of SST and SSTR2 in hypothalamus and pituitary in different light groups were increased and the differences were disapeared. Meanwhile, the trend of SSTR5 mRNA in pituitary is the same as the SSTR2 mRNA in pituitary. In vitro, the exogenous SST inhibited the growth hormone (GH) secretion, and SSTR2 and SSTR5 selective antogonists promoted GH secretion. While, melatonin receptor 1b (Mel1b) and Mel1c selective antagonists increased relative concentraitons of SST in adenohypophysis cells.Conclusion: Monochromatic light affected the expression of SST in chick hypothalamus and pituitary. MEL via Mel1b and Mel1c decreased SST secretion under GL, which is related to inhibiting the combination of SST, SSTR2 and SSTR5 in adenohypophysis cells.

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Effects of hypothyroidism, tri-iodothyronine and glucocorticoids on growth hormone responses to growth hormone-releasing hormone and His-d-Trp-Ala-Trp-d-Phe-Lys-NH2

Journal of Endocrinology ◽

10.1677/joe.0.1210031 ◽

1989 ◽

Vol 121 (1) ◽

pp. 31-36 ◽

Cited By ~ 17

Author(s):

C. A. Edwards ◽

C. Dieguez ◽

M. F. Scanlon

Keyword(s):

Growth Hormone ◽

Thyroid Hormones ◽

Pituitary Cells ◽

Releasing Hormone ◽

Gh Secretion ◽

Monolayer Cultures ◽

Hormone Responses

ABSTRACT The aim of this study was to investigate the role of thyroid hormones and glucocorticoids on GH secretion. Secretion of GH in response to GH-releasing hormone (GHRH) (5 μg/kg) was markedly (P < 0·001) decreased in hypothyroid rats in vivo (peak GH responses to GHRH, 635 ± 88 μg/l in euthyroid rats vs 46 ±15 μg/l in hypothyroid rats). Following treatment with tri-iodothyronine (T3; 20 μg/day s.c. daily for 2 weeks) or cortisol (100 pg/day s.c. for 2 weeks) or T3 plus cortisol, a marked (P <0·01) increase in GH responses to GHRH was observed in hypothyroid rats (peak GH responses, 326 ±29 μg/l after T3 vs 133+19 μg/l after cortisol vs 283 ± 35 μg/l after cortisol plus T3). In contrast, none of these treatments modified GH responses to GHRH in euthyroid animals. Hypothyroidism was also associated with impaired GH responses to the GH secretagogue, Hisd-Trp-Ala-Trp-d-Phe-Lys-NH2 (GHRP-6). Secretion of GH in response to GHRP-6 in vivo was reduced (P <0·01) in hypothyroid rats (peak GH responses, 508 ± 177 μg/l in euthyroid rats vs 203 ± 15 μg/l in hypothyroid rats). In-vitro studies carried out using monolayer cultures of rat anterior pituitary cells derived from euthyroid and hypothyroid rats showed a marked impairment of somatotroph responsiveness to both GHRP-6 and somatostatin in cultures derived from hypothyroid rats. In summary, our data suggest that thyroid hormones and glucocorticoids influence GH secretion by modulating somatotroph responsiveness to different GH secretagogues. Journal of Endocrinology (1989) 121, 31–36

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Amphetamine-Decreased Progesterone and Estradiol Release in Rat Granulosa Cells: The Regulatory Role of cAMP- and Ca2+-Mediated Signaling Pathways

Biomedicines ◽

10.3390/biomedicines9050493 ◽

2021 ◽

Vol 9 (5) ◽

pp. 493

Author(s):

Chung-Yu Chen ◽

Chien-Rung Chen ◽

Chiao-Nan Chen ◽

Paulus S. Wang ◽

Toby Mündel ◽

...

Keyword(s):

Granulosa Cells ◽

Prostaglandin F2α ◽

Inhibitory Effect ◽

Inhibitory Effects ◽

Steroidogenic Enzyme ◽

Estradiol Secretion ◽

Basal Release ◽

Ca2 Channels

The purpose of this study is to evaluate the amphetamine effects on progesterone and estradiol production in rat granulosa cells and the underlying cellular regulatory mechanisms. Freshly dispersed rat granulosa cells were cultured with various test drugs in the presence of amphetamine, and the estradiol/progesterone production and the cytosolic cAMP level were measured. Additionally, the cytosolic-free Ca2+ concentrations ([Ca2+]i) were measured to examine the role of Ca2+ influx in the presence of amphetamine. Amphetamine in vitro inhibited both basal and porcine follicle-stimulating hormone-stimulated estradiol/progesterone release, and amphetamine significantly decreased steroidogenic enzyme activities. Adding 8-Bromo-cAMP did not recover the inhibitory effects of amphetamine on progesterone and estradiol release. H89 significantly decreased progesterone and estradiol basal release but failed to enhance a further amphetamine inhibitory effect. Amphetamine was capable of further suppressing the release of estradiol release under the presence of nifedipine. Pretreatment with the amphetamine for 2 h decreased the basal [Ca2+]i and prostaglandin F2α-stimulated increase of [Ca2+]i. Amphetamine inhibits progesterone and estradiol secretion in rat granulosa cells through a mechanism involving decreased PKA-downstream steroidogenic enzyme activity and L-type Ca2+ channels. Our current findings show that it is necessary to study the possibility of amphetamine perturbing reproduction in females.

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Differential Diagnosis of the Short IGF-I-Deficient Child with Apparently Normal Growth Hormone Secretion

Hormone Research in Paediatrics ◽

10.1159/000516407 ◽

2021 ◽

pp. 1-24

Author(s):

Jan M. Wit ◽

Sjoerd D. Joustra ◽

Monique Losekoot ◽

Hermine A. van Duyvenvoorde ◽

Christiaan de Bruin

Keyword(s):

Growth Hormone ◽

Differential Diagnosis ◽

Growth Hormone Secretion ◽

Normal Growth ◽

Stimulation Test ◽

Healthy Children ◽

Genetic Causes ◽

Gh Secretion ◽

Igf I

The current differential diagnosis for a short child with low insulin-like growth factor I (IGF-I) and a normal growth hormone (GH) peak in a GH stimulation test (GHST), after exclusion of acquired causes, includes the following disorders: (1) a decreased spontaneous GH secretion in contrast to a normal stimulated GH peak (“GH neurosecretory dysfunction,” GHND) and (2) genetic conditions with a normal GH sensitivity (e.g., pathogenic variants of GH1 or GHSR) and (3) GH insensitivity (GHI). We present a critical appraisal of the concept of GHND and the role of 12- or 24-h GH profiles in the selection of children for GH treatment. The mean 24-h GH concentration in healthy children overlaps with that in those with GH deficiency, indicating that the previously proposed cutoff limit (3.0–3.2 μg/L) is too high. The main advantage of performing a GH profile is that it prevents about 20% of false-positive test results of the GHST, while it also detects a low spontaneous GH secretion in children who would be considered GH sufficient based on a stimulation test. However, due to a considerable burden for patients and the health budget, GH profiles are only used in few centres. Regarding genetic causes, there is good evidence of the existence of Kowarski syndrome (due to GH1 variants) but less on the role of GHSR variants. Several genetic causes of (partial) GHI are known (GHR, STAT5B, STAT3, IGF1, IGFALS defects, and Noonan and 3M syndromes), some responding positively to GH therapy. In the final section, we speculate on hypothetical causes.

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Analysis of the effect of pituitary adenylate cyclase-activating polypeptide (PACAP) on growth hormone (GH) secretion in GH3 cells

The Peptidergic Neuron ◽

10.1007/978-3-0348-9010-6_26 ◽

1996 ◽

pp. 245-249

Author(s):

K. Koshimura ◽

T. Miyake ◽

Y. Murakami ◽

Y. Kato

Keyword(s):

Growth Hormone ◽

Adenylate Cyclase ◽

Gh3 Cells ◽

Gh Secretion ◽

Pituitary Adenylate Cyclase

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Mechanism of action of Hexarelin. I. Growth hormone-releasing activity in the rat

Acta Endocrinologica ◽

10.1530/eje.0.1350481 ◽

1996 ◽

Vol 135 (4) ◽

pp. 481-488 ◽

Cited By ~ 9

Author(s):

Antonio Torsello ◽

Roberta Grilli ◽

Marina Luoni ◽

Margherita Guidi ◽

Maria Cristina Ghigo ◽

...

Keyword(s):

Growth Hormone ◽

Mechanism Of Action ◽

Direct Action ◽

Male Rats ◽

Surgical Ablation ◽

Adult Rats ◽

Gh Secretion ◽

Plasma Gh

Torsello A, Grilli R, Luoni M, Guidi M, Ghigo MC, Wehrenberg WB, Deghenghi R, Müller EE, Locatelli V. Mechanism of action of Hexarelin. I. Growth hormone-releasing activity in the rat. Eur J Endocrinol 1996;135:481–8. ISSN 0804–4643 We have reported Hexarelin (HEXA), an analog of growth hormone-releasing peptide 6 (GHRP-6), potently stimulates growth hormone (GH) secretion in infant and adult rats. This study was undertaken to further investigate Hexarelin's mechanisms of action. In 10-day-old pups, treatments with HEXA (80 μg/kg, b.i.d.) for 3–10 days significantly enhanced, in a time-related fashion, the GH response to an acute HEXA challenge. Qualitatively similar effects were elicited in pups passively immunized against growth hormone-releasing hormone (GHRH) from birth. In adult male rats, a 5-day pretreatment with HEXA (150 μg/kg, b.i.d.) did not enhance the effect of the acute challenge, and the same pattern was present after a 5-day pretreatment in male rats with surgical ablation of the mediobasal hypothalamus (MBH-ablated rats). In addition, in adult sham-operated rats, Hexarelin (300 μg/kg, iv) induced a GH response greater (p < 0.05) than that induced by GHRH (2 μg/kg, iv). However, in MBH-ablated rats 7 days after surgery, GHRH was significantly (p < 0.05) more effective than HEXA, and 30 days after surgery HEXA and GHRH evoked similar rises of plasma GH. Finally, the in vitro Hexarelin (10−6 mol/l) effect was transient while GHRH (10−8 mol/l) induced a longer lasting and greater GH release. Three different mechanisms, not mutually exclusive, are postulated for Hexarelin stimulation of GH secretion in vivo: a direct action on the pituitary, though of minor relevance; an indirect action that involves release of GHRH, of relevance only in adult rats; and an action through the release of a still unknown hypothalamic "factor", which in infant and adult rats elicits GH release acting sinergistically with GHRH. Antonio Torsello, Department of Pharmacology, via Vanvitelli 32, 20129 Milano, Italy

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