Glucocorticoid Inhibition of Immunoreactive β-Endorphin Release from the Anterior Lobe of the Rat Pituitary: In Vitro and in Vivo Studies

Abstract

Glucocorticoid control of pituitary β-endorphin (β-END) release was investigated in vitro and in vivo. Cultured cells of both rat anterior (AL) and neurointermediate (NIL) lobe released β-END-like immunoreactivity (β-END-LI) in response to epinephrine (10^-7 M); however, only the response of AL cells was prevented by corticosterone (10^-8-10^-6 M) or dexamethasone (10^-9-10^-7 M). Gel chromatographic analysis (Sephadex G-50) revealed that the major forms of β-END-LI released by AL cells corresponded to β-END and β-lipotropin (β-LPH) in molecular size, whereas virtually all of the immunoreactivity released by NIL cells resembled β-END. In vivo administration of dexamethasone attenuated the stress-induced release of β-END-LI in a dose- and time-related fashion, having a more pronounced effect on plasma levels of β-END-LI corresponding to β-LPH in molecular size. Metyrapone (100 mg/ kg), an inhibitor of glucocorticoid synthesis, evoked a rapid (20-40 min) four- to sixfold increase in total plasma β-END-LI and 75% of this rise was due to immunoreactivity resembling β-LPH in size. This response was diminished by coadministration of either dexamethasone (0.05-1.25 mg/kg) or corticosterone (0.05-1.25 mg/kg) and completely prevented by 4-hr pretreatment with dexamethasone (50 μg/kg). The briskness of the plasma β-END-LI response to acute changes in glucocorticoid status suggests that a “rapid” feedback mechanism operates in the physiologic control of pituitary β-END-LI secretion. Moreover, the ability of glucocorticoids to selectively inhibit AL release of β-END-LI in vitro and their pronounced effect on plasma levels of β-END-LI resembling β-LPH, a marker of AL secretion, together indicate that glucocorticoids exert a selective influence over the secretion of AL corticotrophs in vivo. This demonstration of differential regulation of the AL versus IL secretion of β-END-LI in vivo most likely reflects a phenomena having biologic importance related to the different physiologic actions of the several molecular forms of β-END-LI secreted by the two tissues.