Ontogeny of vasoactive intestinal peptide and somatostatin in different structures of the rat brain: effects of hypo- and hypercorticism.

The ontogeny of the vasoactive intestinal peptide (VIP) and somatostatin (SRIF) was studied in various structures of the rat central nervous system (CNS), using specific radioimmunoassays. The effect of adrenal corticoids on the concentration of both peptides was investigated during the development of the rat from 3 days before birth to 2 months after birth. The evolution of both peptides was different since SRIF was found before birth in each structure tested while VIP appeared only after birth in the same structures. However, after birth the ontogeny of VIP and SRIF was quite similar and the maximum concentration of both peptides occurred between day 14 and day 21. Hypercorticism (implant of corticosterone) and hypocorticism (Metyrapone injections) modified the postnatal evolution of both peptides, suggesting that corticoids play an important role in the brain developmental patterns of VIP and SRIF.

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.