Rapid glucocorticoid inhibition of vasoactive intestinal peptide-induced cyclic AMP accumulation and prolactin release in rat pituitary cells in culture.
Vasoactive intestinal peptide (VIP) stimulates both adenosine 3',5'-cyclic monophosphate (cAMP) accumulation and prolactin release in normal rat pituitary cells in culture. cAMP accumulation is significant (P less than 0.01) at VIP concentrations as low as 1 nM and reaches a maximum with 0.1 microM. Addition of dexamethasone as early as 15 min before VIP inhibits VIP stimulation of both cAMP production and PRL secretion. The rapid inhibition is dose-dependent: it appears at doses as low as 0.01 pM and is complete at 1 pM dexamethasone. Increasing concentrations of dexamethasone induce a noncompetitive type of inhibition, as shown by the decrease in Vmax with no change in the apparent Km for VIP. Cycloheximide (1 mM) counteracts the inhibitory effect of dexamethasone on VIP-induced cAMP production, which suggests the involvement of a rapid protein synthesis mechanism. Ru-26988, a specific glucocorticoid devoid of any mineralocorticoid activity and which does not bind to intracellular transcortin-like component, also produces an inhibition of VIP-induced cAMP accumulation. Corticosterone also inhibits VIP-induced cAMP production but at concentrations higher than those of dexamethasone. In contrast, aldosterone, progesterone, estradiol, and testosterone have no effect. These results demonstrate that, in normal rat pituitary cells in culture, glucocorticoids at physiological concentrations rapidly inhibit the cAMP production and prolactin release induced by VIP by acting through specific glucocorticoid receptors.
D000818:Animals; D002478:Cells, Cultured; D003345:Corticosterone / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D005768:Gastrointestinal Hormones / Q000037:antagonists & inhibitors*; D007700:Kinetics; D008297:Male; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000502:physiology; D012636:Secretory Rate / Q000187:drug effects; D014660:Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors*
D005768:Gastrointestinal Hormones; D011965:Receptors, Glucocorticoid; D014660:Vasoactive Intestinal Peptide; D003907:Dexamethasone; D011388:Prolactin; D003513:Cycloheximide; D000242:Cyclic AMP; D003345:Corticosterone