5-α androstane diol stimulates the pituitary growth hormone responsiveness to growth hormone releasing hormone more effectively than testosterone or dihydrotestosterone in rats

1992 ◽  
Vol 126 (2) ◽  
pp. 162-166 ◽  
Author(s):  
E Aguilar ◽  
M Tena-Sempere ◽  
L Pinilla

The effect of different androgens and estradiol on pituitary responsiveness to growth hormone releasing hormone was studied in intact and orchidectomized adult male Wistar rats, by injecting subcutaneously immediately after orchidectomy for two weeks with testosterone, dihydrotestosterone, 5-α androstane, 3-α, 17 β-diol or estradiol dissolved in olive oil (in doses of 0.2 or 2.0 mg·kg−1·day−1) or vehicle. Pituitary responsiveness was tested in pentobarbital anaesthetized rats by measuring growth hormone plasma levels at different times after administration of growth hormone releasing hormone (1-29) NH2. We found that: (a) High doses of testosterone, dihydrotestosterone and 5-α androstane, 3α, 1 7 β-diol restored gonadotropin plasma concentrations and organ weights altered by orchidectomy; (b) both pituitary growth hormone content and concentration remained unaffected after orchidectomy or androgen replacement and decreased significantly after estradiol injection; (c) orchidectomy significantly reduced growth hormone-stimulated growth hormone releasing hormone secretion; (d) treatment with 5-α androstane, 3-α, 1 7 β-diol increased more than testosterone or dihydrotestosterone both the peak concentration and the mean growth hormone secretion after growth hormone releasing hormone stimulation: (e) no differences were observed in the treatment with testosterone or dihydrotestosterone; (f) estradiol given at a dose of 0.2 mg·kg−1·day−1 increased pituitary responsiveness to growth hormone releasing hormone. These results demonstrated that testosterone and 5-α androstane, 3-α, 17 β-diol, which do not differ in their action on pituitary growth hormone content, increased the pituitary responsiveness to growth hormone releasing hormone differently and that the low pituitary responsiveness to growth hormone releasing hormone previously described in prepubertal animals was not due mainly to the secretion of 5-α androstane, 3-α, 1 7 β-diol.

1989 ◽  
Vol 256 (2) ◽  
pp. E221-E226 ◽  
Author(s):  
G. D. Snyder ◽  
P. Yadagiri ◽  
J. R. Falck

Growth hormone secretion was stimulated in vitro by products of arachidonic acid epoxygenase, the epoxyeicosatrienoic acids. 5,6-Epoxyeicosatrienoic and 14,15-epoxyeicosatrienoic acid stimulated growth hormone release from an enriched population of somatotrophs (approximately 85%) by twofold. Inhibition of arachidonic acid metabolism by indomethacin did not affect growth hormone-releasing hormone stimulation of growth hormone release. In contrast, pretreatment of somatotrophs with an 11,12-isonitrile analogue of arachidonic acid that inhibits arachidonic acid epoxygenase, resulted in a 20-25% inhibition of growth hormone-releasing hormone-stimulated growth hormone release. 14,15-Epoxyeicosatrienoic acid stimulated a concentration-dependent increase (twofold) in the cytoplasmic concentration of adenosine 3',5'-cyclic monophosphate (cAMP) in the somatotrophs. 14,15-Epoxyeicosatrienoic acid also rapidly increased the intracellular free calcium concentration in somatotrophs from resting levels (approximately 80 nM) to greater than 250 nM. Growth hormone-releasing hormone increased the free intracellular calcium to 160-180 nM. Preincubation of somatotrophs with somatostatin inhibited growth hormone-releasing hormone-stimulated growth hormone secretion, cAMP accumulation, and 14,15-epoxyeicosatrienoic acid stimulated cAMP accumulation. These data are suggestive that the epoxyeicosatrienoic acids may have a role in the secretion of growth hormone.


1990 ◽  
Vol 24 (3) ◽  
pp. 129-134 ◽  
Author(s):  
Giovanni Murialdo ◽  
Francesco Zerbi ◽  
Ugo Filippi ◽  
Pietro Tosca ◽  
Stefano Fonzi ◽  
...  

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