Function-specific calcium stores selectively regulate growth hormone secretion, storage, and mRNA level

2002 ◽  
Vol 282 (4) ◽  
pp. E810-E819 ◽  
Author(s):  
James D. Johnson ◽  
Christian Klausen ◽  
Hamid R. Habibi ◽  
John P. Chang
Keyword(s):  
Growth Hormone ◽  
Secretory Pathway ◽  
Mrna Level ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Signal Amplitude ◽  
Calcium Stores ◽  
Mrna Levels ◽  
Intracellular Ca

Ca+ stores may regulate multiple components of the secretory pathway. We examined the roles of biochemically independent intracellular Ca2+stores on acute and long-term growth hormone (GH) release, storage, and mRNA levels in goldfish somatotropes. Thapsigargin-evoked intracellular Ca2+ concentration ([Ca2+]i) signal amplitude was similar to the Ca2+-mobilizing agonist gonadotropin-releasing hormone, but thapsigargin (2 μM) did not acutely increase GH release, suggesting uncoupling between [Ca2+]i and exocytosis. However, 2 μM thapsigargin affected long-term secretory function. Thapsigargin-treated cells displayed a steady secretion of GH (2, 12, and 24 h), which decreased GH content (12 and 24 h), but not GH mRNA/production (24 h). In contrast to the results with thapsigargin, activating the ryanodine (Ry) receptor (RyR) with 1 nM Ry transiently increased GH release (2 h). Prolonged activation of RyR (24 h) reduced GH release, contents and apparent production, without changing GH mRNA levels. Inhibiting RyR with 10 μM Ry increased GH mRNA levels, production, and storage (2 h). Increasing [Ca2+]i independently of Ca2+stores with the use of 30 mM KCl decreased GH mRNA. Collectively, these results suggest that parts of the secretory pathway can be controlled independently by function-specific Ca2+ stores.

Intracellular calcium stores are involved in growth hormone-releasing hormone signal transduction in rat somatotrophs

1999 ◽  
Vol 77 (7) ◽  
pp. 520-528 ◽  
Author(s):  
Audrey Petit ◽  
Catherine Bleicher ◽  
Benoît T Lussier
Keyword(s):  
Growth Hormone ◽  
Intracellular Calcium ◽  
Calcium Release ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Calcium Stores ◽  
Growth Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Intracellular Ca ◽  
Calcium Induced Calcium Release

In rat pituitary somatotrophs, the stimulation of growth hormone secretion by growth hormone-releasing hormone (GHRH) is a Ca2+-dependent event involving Ca2+ influx. The presence of calcium-induced calcium release (CICR) Ca2+ stores has been suggested in these cells. The aim of our study was to demonstrate the presence of CICR stores in rat somatotrophs and to determine their function in GHRH Ca2+ signalling. To this end we measured cytosolic free Ca2+ concentration ([Ca2+]i), using indo-1 in purified rat somatotrophs in primary culture, while altering intracellular Ca2+ stores. Ionomycin (10 µM) or 4-bromo-A23187 (10 µM), used to mobilise organelle-bound Ca2+, raised [Ca2+]i in the absence of extracellular Ca2+. Caffeine (5 to 50 mM), used to mobilise Ca2+ from CICR stores, transiently raised [Ca2+]i in 65% of cells tested. The response to 40 mM caffeine was abolished when Ca2+ stores were depleted, with 1 µM thapsigargin or with 10 µM ryanodine. All cells that responded to 40 mM caffeine responded to 10 nM GHRH. The [Ca2+]i response to 10 nM GHRH was reversible and repeatable. However, the second response was 38% smaller than the first. Ryanodine treatment abolished the reduction in the second [Ca2+]i response, while thapsigargin increased the reduction by 67%. We conclude that rat somatotrophs possess CICR Ca2+ stores and that they account for 30-35% of the GHRH-induced increase in [Ca2+]i, and that their partial depletion is involved in somatotroph desensitization.Key words: somatotrophs, growth hormone-releasing hormone, intracellular calcium, calcium stores, calcium-induced calcium release.

Increased hypothalamic somatostatin mRNA following dexamethasone administration in rats

1992 ◽  
Vol 127 (5) ◽  
pp. 416-419 ◽  
Author(s):  
Koji Nakagawa ◽  
Tatsuya Ishizuka ◽  
Chikara Shimizu ◽  
Yoshito Ito ◽  
Ichiji Wakabayashi
Keyword(s):  
Growth Hormone ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Female Rats ◽  
Mrna Levels ◽  
Plasma Growth Hormone ◽  
Hormone Production ◽  
Blot Technique ◽  
Series Of Experiments

There is increasing evidence to suggest that supraphysiological doses of glucocorticoids suppress growth hormone secretion in vivo by augmenting somatostatin release from the hypothalamus; previously, we reported an increase in hypothalamic somatostatin content in dexamethasone-treated rats. To further examine whether the production of somatostatin really is augmented, hypothalamic somatostatin mRNA levels were determined by the Northern blot technique in female rats receiving 330 μg of dexamethasone daily for three days. In two series of experiments, hypothalamic somatostatin mRNA levels in dexamethasone-treated rats were significantly (p<0.05) increased to 133±19 (mean±sd)% and 153±38% of the controls. In the dexamethasone-treated rats, plasma growth hormone levels were markedly suppressed compared with those of the controls. These results further support the hypothesis that pharmacological doses of glucocorticoids increase the production and release of somatostatin from the hypothalamus and thus inhibit growth hormone secretion, overriding the direct stimulatory effect of glucocorticoids on growth hormone production at the pituitary level.

Desensitization from long-term intranasal treatment with hexarelin does not interfere with the biological effects of this growth hormone-releasing peptide in short children

1996 ◽  
Vol 134 (6) ◽  
pp. 716-719 ◽  
Author(s):  
Beatrice Klinger ◽  
Aviva Silbergeld ◽  
Romano Deghenghi ◽  
Jenny Frenkel ◽  
Zvi Laron
Keyword(s):  
Growth Hormone ◽  
Growth Velocity ◽  
Biological Effects ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Human Growth ◽  
Pediatric Endocrinology ◽  
Short Children ◽  
The Mean

Klinger B, Silbergeld A, Deghenghi R, Frenkel J, Laron Z. Desensitization from long-term intranasal treatment with hexarelin does not interfere with the biological effects of this growth hormonereleasing peptide in short children. Eur J Endocrinol 1996;134:716–9. ISSN 0804–4643 A clinical, prospective experiment was carried out to determine whether long-term intranasal administration of the growth hormone-releasing peptide hexarelin (His-d-2-methyl-Trp-Ala-Trp-d-Phe-Lys-NH2) affects pituitary growth hormone secretion. Hexarelin (60 μg/kg t.i.d.) was administered to seven prepubertal constitutionally short children (mean age ±sd = 7.6 ± 2.4 years). Serum human growth hormone (hGH) response to an intranasal (20 μg/kg) and intravenous (1 μg/kg) bolus of hexarelin before, during and after 6–10 months of treatment was measured. The mean (±sd) peak rise of hGH to the intranasal bolus before treatment was 70.6 ± mU/I. After 7 days of hexarelin treatment, mean peak values dropped to 34.1 ±15.7 mU/l (p < 0.002) and thereafter remained constant for 6 months of treatment at 37.5 10.3 ±mU/l (p < 0.03). The pretreatment peak to the iv hexarelin bolus was 84.8 52.5 ±mU/l, and at the end of the treatment period it was 19.8 10.9 ±mU/l (p < 0.05). Three months after stopping treatment the mean (±sd) hGH response rose to 42.1 ±4.7 mU/l (p < 0.005). Growth velocity increased from 5.3±0.9 cm/year (before treatment) to 7.4 1.6 cm/year at ±6–10 months of treatment (p < 0.005). In conclusion, the partial suppression of pituitary hGH responsiveness to long-term intranasal hexarelin treatment, probably due to desensitization, does not affect the observed increase in growth velocity. Z Laron, Pediatric Endocrinology, 11 El Al Street, Ramat Efal, 52960, Israel

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