Ectopic growth hormone-releasing factor and dibutyryl cyclic adenosine monophosphate-stimulated growth hormone release in vitro: effects of corticosterone and estradiol.
Glucocorticoids and estrogens each affect GH secretion in vivo. The effects of corticosterone and estradiol (E2) were studied singly and in combination on GH secretion and cell content of primary cultures of rat adenohypophyseal cells grown in media containing intact or hormone-deficient serum. Secretion was measured under basal conditions and in response to maximally stimulatory doses of ectopic GH-releasing factor (E-GHRF) derived from a carcinoid tumor and dibutyryl cAMP [(DBcAMP) 10(-3) M]. Basal GH release measured over a 4-h period was suppressed by 40% (P less than 0.001) when hormone-deficient serum was substituted for normal serum in the growth media, and the stimulatory responses to DBcAMP and E-GHRF were markedly attenuated (P less than 0.001). The GH content of unstimulated cells was also decreased [29 +/- (SE) 7%, P less than 0.001]. The addition of corticosterone, 3 X 10(-8) M to 3 X 10(-6) M, to the 4-day growth media resulted in dose-related increases in basal and DBcAMP-stimulated GH release during the 4-h test period which was proportional to the increases in total cellular GH content. In contrast, corticosterone exposure caused a dose-related enhancement of E-GHRF-stimulated release above that accounted for by the increase in total GH content alone. Concomitant exposure to the releasing stimuli and corticosterone during a 4-h incubation, however, reduced the effects of the releasing stimuli. The addition of E2, 10(-10) M to 10(-8) M, during the 4-day growth period and/or the 4-h stimulation period did not affect the secretion of GH either basally or in response to the stimuli. E2 did increase the cell content of GH, but the effects were not additive to those of corticosterone. These studies indicate that long term (4-day) exposure to corticosterone increases net GH synthesis and E-GHRF-stimulated release, but that acute (4 h) exposure inhibits stimulated release. Although E2 also increases cellular content of GH, it exhibits no demonstrable direct effects on GH secretion or content in the presence of corticosterone.
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D003345:Corticosterone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004958:Estradiol / Q000494:pharmacology*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D008297:Male; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D004958:Estradiol; D003994:Bucladesine; D013007:Growth Hormone-Releasing Hormone; D003345:Corticosterone