AJP - Regulatory, Integrative and Comparative Physiology, Vol 273, Issue 3 1163-R1172, Copyright © 1997 by American Physiological Society
Adrenal vasoactive intestinal peptide participates in neonatal corticosteroid production in the rat
M. Bodnar, A. Sarrieau, C. F. Deschepper and C. D. Walker
Department of Psychiatry, McGill University, Douglas Hospital Research Center, Montreal, Quebec, Canada.
Neonatal rats (3-14 days old) exhibit a period of adrenal
hyporesponsiveness characterized by blunted corticosterone (B) responses to
stress and reduced adrenal sensitivity to adrenocorticotropic hormone
(ACTH). Several adrenomedullary peptidergic systems like vasoactive
intestinal peptide (VIP) are postulated to influence cortical function. VIP
is known to stimulate corticosterone secretion in vitro and to be released
from the adrenal medulla following splanchnic nerve stimulation. Here, we
tested whether 1) accelerated sympathetic innervation of the adrenal gland
by daily L-thyroxine (T4) treatment modified the ontogeny of adrenal VIP
and 2) an increase in VIP synthesis could prematurely increase adrenal
sensitivity and corticosteroid output during neonatal life.
Immunohistochemical VIP staining revealed a different ontogenetic pattern
between adrenal regions from days 2-18 and different sensitivities to T4
treatment. Capsular staining was most abundant at all ages and increased
with T4 treatment, whereas medullary staining was seen by day 18 and was
not affected by T4. Throughout development, VIP receptors were detected
mostly in the capsular region, but not in the adrenal cortex. Although
receptor levels were not modified by T4 injections, T4 significantly
enhanced VIP mRNA levels in the whole adrenal at all ages. In vivo
administration of VIP (0.1-2.0 mg/kg body wt ip) to 9- to 12-day-old
neonates increased pituitary ACTH, adrenal B, and aldosterone secretion
significantly. Corticotropin-releasing factor immunoneutralization before
VIP injection diminished VIP-induced ACTH release but still produced small
but significant B and aldosterone secretion. Our results show that 1) VIP
innervation of the adrenal capsule is present soon after birth and is
increased by sympathetic activity whereas VIP appears only much later in
the medulla and does not coincide with the onset of splanchnic innervation
and 2) exogenous VIP stimulates ACTH, B, and aldosterone release during
development and the effect of VIP on steroidogenic secretion is occurring
through ACTH secretion, but also, at least in part, directly at the level
of the adrenal gland.
