Stimulation of adenosine 3',5'-monophosphate production by growth hormone-releasing factor and its inhibition by somatostatin in anterior pituitary cells in vitro.
The stimulation of GH secretion from the anterior pituitary by synthetic GRF (hpGRF) is associated with a rapid increase in cAMP production. Within 5 min of the addition of 1 nM hpGRF to cultured rat anterior pituitary cells, intracellular cAMP levels are elevated 6-fold, with a maximal response being observed at 30 min. cAMP accumulation in the extracellular medium is also enhanced by this peptide. Comparison of the two cellular responses (GH secretion and cAMP formation) at various concentrations of hpGRF indicates that 10 times more hpGRF is required to obtain half-maximal stimulation of cAMP production than for GH secretion. Somatostatin totally blocks hpGRF-stimulated GH release, but only partially attenuates cAMP production in the presence or absence of a phosphodiesterase inhibitor. Verapamil also inhibits GH release in response to hpGRF, but, unlike somatostatin, this effect is not associated with an attenuation of cAMP production. In fact, intracellular cAMP levels are slightly augmented in the presence of verapamil, indicating that Ca2+ is required for hormone release but not for the activation of adenylate cyclase. Consistent with this is the observation that the release of GH due to 8-bromo-cAMP is also blocked by verapamil. A requirement for Ca2+ is further indicated by the inhibitory effects of CoCl2 and CdCl2 on both basal and hpGRF-stimulated GH release. These results suggest that cAMP may play a role as an intracellular mediator of GRF action in somatotrophs and that Ca2+ is required for the release process. Somatostatin may exert its inhibitory effects on GH secretion either by interfering with cAMP production or by an action on the secretory process subsequent to cAMP production.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D013006:Growth Hormone / Q000378:metabolism; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D008297:Male; D010868:Pimozide / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000494:pharmacology*; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology
D010868:Pimozide; D015124:8-Bromo Cyclic Adenosine Monophosphate; D013004:Somatostatin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D014700:Verapamil; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine