The Effects of Vasoactive Intestinal Peptide on Adrenal Steroid Hormone Secretion

Abstract

Vasoactive intestinal peptide (VIP)-immunoreactive nerve fibers have been demonstrated in the rat adrenal cortex in close association with zona glomerulosa cells (Holzwarth, 1984). We have studied the effects of VIP on steroid hormone secretion from the outer zones of the normal rat adrenal cortex. Intact capsule-glomerulosa preparations, consisting of the capsule, zona glomerulosa, and a small portion of the zona fasciculata were perifused in vitro. The secretory responsiveness was assessed by measuring aldosterone and corticosterone release following stimulation with the physiological secretagogues ACTH and angiotensin II. ACTH (10$\sp{-12}$ to 10$\sp{-8}$ M) stimulated dose-dependent increases in aldosterone secretion (1.9 to 36.9 fold over basal secretion) and corticosterone secretion (1.4 to 14.0 fold over basal secretion). VIP (10$\sp{-6}$ to 10$\sp{-4}$ M) stimulated dose-dependent increases of both aldosterone (1.7 to 41.0 fold) and corticosterone secretion (1.8 to 5.3 fold). However, glucagon and (N-Ac-Tyr$\sp1$-D-Phe$\sp2$)-GRF(1-29)-NH$\sb2$, peptides structurally related to VIP, stimulated neither aldosterone nor corticosterone secretion indicating that VIP effects were specific for this peptide. In addition, VIP (10$\sp{-5}$ M) potentiated the aldosterone but not the corticosterone secretory response to subthreshold concentrations of ACTH (10$\sp{-13}$ and 10$\sp{-12}$ M) by approximately 65-70% whereas it had no effect on the secretory response to angiotensin II. The distribution of adrenal VIP receptors was assessed by in vitro autoradiography of $\sp{125}$I-VIP binding. $\sp{125}$I-VIP (0.75 and 2.0 nM) binding was concentrated in the capsule and zona glomerulosa, coincident with the distribution of VIP nerve fibers which aborize extensively in this region. The specificity of this binding was demonstrated using unlabelled VIP, ACTH and angiotensin II.

These studies demonstrate the effects of VIP on zona glomerulosa cell steroid hormone secretion indicating that the VIP innervation of the adrenal cortex provides an important regulation of adrenal steroidogenesis. The potentiated aldosterone secretory response observed with concurrent VIP and ACTH stimulation suggests that this innervation may regulate zona glomerulosa cell responsiveness to hormonal secretagogues. Further evidence for a functional interaction between the VIP innervation and zona glomerulosa cell secretion is the anatomical correlation between VIP-containing nerve fibers and specific $\sp{125}$I-VIP binding to adrenocortical cells in the capsule-zona glomerulosa.