Objective: To examine the secretory effect of prostaglandin E(2) (PGE(2)) and ACTH on the adrenal glands of prenatal and postnatal sheep.
Methods: Immunocytochemistry was used to examine the adrenal cortex and medulla for 17alpha-hydroxylase and tyrosine hydroxylase immunoreactivity. Microphysiometric technique was used to measure [H(+)] after exposure of whole dispersed prenatal and postnatal adrenal glands to PGE(2), ACTH, or both.
Results: Immunocytochemistry showed many cortical-type cells in all adrenal medullae and many medullary-type cells in fetal adrenal cortices. Maximum H(+) responsiveness to PGE(2) decreased with increasing age. The developmental age-related pattern of maximum percentage change in [H(+)] during ACTH exposure was similar to previous findings with cortisol production as the endpoint. ACTH stimulated H(+) production at 80 days' gestation and at all ages greater than 125 days' gestation (P <.05). The molar concentration of ligand required to elicit a response that was 50% of maximum response (EC(50)) for the ACTH response was lower in fetuses than in newborn lambs (<1 day and 3 days old), but there was no change in EC(50) for PGE(2) across the ages studied. Adrenal cell response to ACTH after prior ACTH and PGE(2) exposure was higher (P <.05) compared with ACTH after ACTH or ACTH alone at 110 days' gestation only and was lower in 3-day-old lambs.
Conclusions: Based on the ACTH results, microphysiometry was a valid method for investigating dispersed adrenal cell physiology. Prostaglandin E(2) stimulated dispersed adrenal cells during the mid-gestation ACTH refractory period, but this effect decreased with increasing age. Prostaglandin E(2) sensitized adrenal cells to ACTH at 110 days' gestation but inhibited ACTH effects at postnatal day 3.