GALANIN ABOLISHES THE INHIBITORY EFFECT OF CHOLINERGIC BLOCKADE ON GROWTH HORMONE-RELEASING HORMONE-INDUCED SECRETION OF GROWTH HORMONE IN MAN

1988 ◽  
Vol 116 (3) ◽  
pp. R1-R2 ◽  
Author(s):  
V.K.K. Chatterjee ◽  
J.A. Ball ◽  
C. Proby ◽  
J.M. Burrin ◽  
S.R. Bloom
Keyword(s):  
Growth Hormone ◽  
Inhibitory Effect ◽  
Normal Male ◽  
Growth Hormone Releasing Hormone ◽  
Maximal Dose ◽  
Muscarinic Antagonist ◽  
Releasing Hormone ◽  
Cholinergic Pathways ◽  
Cholinergic Blockade ◽  
Male Volunteers

ABSTRACT In five healthy normal male volunteers, pretreatment with the cholinergic muscarinic antagonist pirenzepine (30 mg i.v.) almost abolished the growth hormone (GH) response to a maximal dose (120 μg i.v.) of growth hormone-releasing hormone (GHRH) (GH response at 40 min 5.6 ± 1.3 mU/l with GHRH and pirenzepine vs 40.8 ± 5.3 mU/l with GHRH alone, P <0.02). Concomitant i.v. infusion of galanin (40 pmol/kg/min) with pirenzepine not only restored but significantly potentiated the GH response to GHRH (GH at 40 min 72.2 ± 10.5 mU/l, P <0.001 vs GHRH and pirenzepine, P <0.02 vs GHRH alone). Previous studies have proposed that cholinergic pathways control GH release via samatostatin and this study suggests that galanin may act by modulating hypothalamic somatostatinergic tone either directly or, possibly, by facilitating cholinergic neurotransmission.

Inhibitory Effect of Amylin on Growth Hormone Responsiveness to Growth-Hormone-Releasing Hormone in the Rat

1995 ◽  
Vol 62 (3) ◽  
pp. 313-318 ◽  
Author(s):  
Carmela Netti ◽  
Valeria Sibilia ◽  
Francesca Pagani ◽  
Norma Lattuada ◽  
Mariella Coluzzi ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Inhibitory Effect ◽  
Growth Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Hormone Responsiveness

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.

Low-dose growth hormone-releasing hormone tests: a dose–response study

1994 ◽  
Vol 131 (3) ◽  
pp. 238-245 ◽  
Author(s):  
Helen A Spoudeas ◽  
Andy P Winrow ◽  
Peter C Hindmarsh ◽  
Charles GD Brook
Keyword(s):  
Growth Hormone ◽  
Adult Male ◽  
Dose Response ◽  
Low Dose ◽  
Average Rate ◽  
Growth Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Male Volunteers ◽  
Dose Response Study ◽  
Serum Gh

Spoudeas HA, Winrow AP, Hindmarsh PC, Brook CGD. Low-dose growth hormone-releasing hormone tests: a dose-response study. Eur J Endocrinol 1994;131:238–45. ISSN 0804–4643 We have evaluated parameters of the serum growth hormone (GH) concentration response to saline and 1-, 10- and 100-μg intravenous bolus doses of amide analogue of GH-releasing hormone (GHRH (1–29)NH2) given in random order to 10 adult male volunteers of median body weight 68 (60–90)kg. Compared with saline, both 10- and 100-μg GHRH(1–29)NH2 doses (but not 1 μg) resulted in significant peak GH responses (means and 95% confidence intervals: 24.03 (11.22–51.29) vs 26.09 (16.40–41.50) mU/l, respectively). Although the average rate of serum GH rise was similar after both 10 μg (2.05 (1.13–2.97) mU · l−1 · min−1) and 100 μg of GHRH(1–29)NH2 (1.52 (0.69–2.35) mU·1−1 · min−1; ANOVA F = 0.93, p = 0.35), the average rate of serum GH decline after peak GH was slower after the higher dose (10 μg vs 100 μg: 0.65 (0.40–0.90) vs 0.37 (0.23–0.50) mU·1−1·min−1; ANOVA F = 5.14, p = 0.04), suggesting continued GH secretion. Increasing GHRH(1–29)NH2 doses delayed the time to peak GH (1 μg: 7.00 (3.50–10.52) min; 10 μg: 15.80 (13.62–17.98) min; 100 μg: 24.80 (18.40–31.12) min) and serum GH levels were still elevated significantly 2 h after injection of 100 μg GHRH(1–29)NH2 compared with other doses (saline: 0.98 (0.48–2.04) mU/1; 1 μg: 0.68 (0.48–0.93) mU/1; 10 μg: 1.07 (0.56–2.04) mU/1; 100 μg: 5.01 (2.34–10.86) mU/l; ANOVA F = 11.10, p < 0.001). In a second study we tested five adult male volunteers with lower doses (0.5–10 μg) of GHRH(1–29)NH2. Consistent responses were observed only at doses equal to or greater than 2.5 μg and all occurred between 10 and 25 min. The estimated ed50 for GHRH(1–29)NH2 from the combined study data was 7.5 μg (0.08 μg/kg; range 0.06–0.12 μg/kg). The 10-μg dose of GHRH(1–29)NH2 was a maximal stimulus in all release parameters examined and GH peaks of < 15 mU/l (10th centile) should be considered potentially abnormal. Lower doses of GHRH(1–29)NH2 released GH quicker than higher doses, which simply prolonged the response, possibly by causing release from different pools. Our results suggest that sampling at 0, 10, 15, 20 and 25 min after a 10-μg dose of GHRH(1–29)NH2 will identify all GH peaks. CGD Brook, The Endocrine Unit, Middlesex Hospital, Mortimer Street, London WIN 8AA, UK

scholarly journals The role of pit-1 in the regulation of the rat growth hormone-releasing hormone receptor gene transcription by glucocorticoids

2005 ◽  
Vol 35 (3) ◽  
pp. 477-488 ◽  
Author(s):  
Haruo Nogami ◽  
Yoshiki Hiraoka ◽  
Kiyomoto Ogasawara ◽  
Sadakazu Aiso ◽  
Setsuji Hisano
Keyword(s):  
Growth Hormone ◽  
Gene Transcription ◽  
Receptor Gene ◽  
Inhibitory Effect ◽  
Growth Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Proper Distance ◽  
Ghrh Receptor ◽  
Rat Growth

Glucocorticoids are involved in the regulation of the rat growth hormone-releasing hormone (GHRH) receptor gene expression, but they act only in the presence of the pituitary specific transcription factor, pit-1. In this study, the role of pit-1 in the glucocorticoid stimulation of the GHRH-receptor gene transcription was examined. The results suggest the presence of a silencer element in the promoter and it is postulated that pit-1 permits glucocorticoid action through suppressing the inhibitory effect of an as yet unknown factor that binds to this element. The present results also suggest that the synergistic activation of the rat GHRH-receptor gene transcription depends on the proper distance between the proximal glucocorticoid response element and the pit-1 binding site.

scholarly journals Growth hormone-releasing hormone receptor antagonists inhibit human gastric cancer through downregulation of PAK1–STAT3/NF-κB signaling

2016 ◽  
Vol 113 (51) ◽  
pp. 14745-14750 ◽  
Author(s):  
Jinfeng Gan ◽  
Xiurong Ke ◽  
Jiali Jiang ◽  
Hongmei Dong ◽  
Zhimeng Yao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Growth Hormone ◽  
Cell Lines ◽  
Cultured Cells ◽  
Nuclear Factor Κb ◽  
Inhibitory Effect ◽  
Human Gastric Cancer ◽  
Growth Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
P21 Activated Kinase

Gastric cancer (GC) ranks as the fourth most frequent in incidence and second in mortality among all cancers worldwide. The development of effective treatment approaches is an urgent requirement. Growth hormone-releasing hormone (GHRH) and GHRH receptor (GHRH-R) have been found to be present in a variety of tumoral tissues and cell lines. Therefore the inhibition of GHRH-R was proposed as a promising approach for the treatment of these cancers. However, little is known about GHRH-R and the relevant therapy in human GC. By survival analyses of multiple cohorts of GC patients, we identified that increased GHRH-R in tumor specimens correlates with poor survival and is an independent predictor of patient prognosis. We next showed that MIA-602, a highly potent GHRH-R antagonist, effectively inhibited GC growth in cultured cells. Further, this inhibitory effect was verified in multiple models of human GC cell lines xenografted into nude mice. Mechanistically, GHRH-R antagonists target GHRH-R and down-regulate the p21-activated kinase 1 (PAK1)-mediated signal transducer and activator of transcription 3 (STAT3)/nuclear factor-κB (NF-κB) inflammatory pathway. Overall, our studies establish GHRH-R as a potential molecular target in human GC and suggest treatment with GHRH-R antagonist as a promising therapeutic intervention for this cancer.

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