Localization, Characterization, and Second Messenger Coupling of Pituitary Adenylate Cyclase-Activating Polypeptide Receptors in the Fetal Human Adrenal Gland during the Second Trimester of Gestation*

International audienceThe distribution and pharmacological properties of pituitary ad-enylate cyclase-activating polypeptide (PACAP) receptors were studied in the fetal human adrenal gland during the second trimester of gestation. Autoradiographic studies, using [ 125 I]PACAP27 as a ra-dioligand, revealed that PACAP-binding sites are exclusively located on chromaffin cells of adrenals from fetuses 14 –20 weeks old. Biochemical characterization of binding revealed the occurrence of a single class of PACAP-binding sites with a dissociation constant value of 0.32– 0.74 nmol/L and a binding capacity of 0.30 – 0.81 pmol/mg wet tissue. PACAP27 and PACAP38 were equipotent in competing for [ 125 I]PACAP27 binding (IC 50 0.28 – 0.64 nmol/L and 0.15– 0.81 nmol/L, respectively), and the Hill coefficients were close to 1. In contrast, vasoactive intestinal polypeptide was much less efficient in displacing the tracer (IC 50 4 –362 nmol/L), and the Hill coefficients were less than 0.6. PACAP38 induced a dose-dependent increase in cAMP production in fetal human adrenal cell suspension (ED 50 0.07 0.02 nmol/L), as well as in cells maintained in culture for 5 days (5.4 1.8 nmol/L). In constrast, PACAP38 induced a modest increase in inositol phosphate formation. These data indicate that type I PACAP receptors are present in the early stages of the human me-dulla organization during the process of migration of chromaffin cells from the periphery to the central part of the gland. The present results suggest that PACAP could be involved in the regulation of the human adrenochromaffin cells during ontogenesis. (J Clin Endocrinol Metab 83: 1299 –1305, 1998

Occurrence and Effect of PACAP in the Human Fetal Adrenal Gland

International audienceIn the study reported in this paper, we characterized PACAP in the human fetal adrenal gland and we investigated the effect of PACAP on ste-roid secretion from cultured fetal adrenal cells. The adrenal gland from 20-week-old fetuses contained substantial concentrations of PACAP-immunore-active material (88.6 ng/g wet tissue). HPLC analysis of adrenal extracts revealed the presence of both PACAP27 and PACAP38, the latter being the predominant form. Incubation of cultured fetal adrenal cells with PACAP38 (10-7 M) significantly increased cortisol and DHEAS secretion. Administration of the ␤-adrenoreceptor agonist isoproterenol mimicked the stimulatory effect of PACAP on both steroid secretion whereas preincubation of fetal cells with the ␤-adrenoreceptor antagonist propranolol suppressed the steroidogenic effect of PACAP. These data, together with the observation that PACAP receptors are exclusively located on chromaffin cells, suggest that, in the fetal human adrenal gland, the effect of PACAP on steroid secretion is mediated via the local release of catecholamines