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Prenatal and Postnatal Ovine Adrenal Cell responses to Prostaglandin E2

P. W. Nathanielsz, MD, PhD

Laboratory for Pregnancy and Newborn Research, College of Veterinary Medicine, Department of Biomedical Sciences, Cornell University, Ithaca, New York; Departamento de Biología de la Reproducciíon, Instituto Nacional de la Nutrición Salvador Zubirán, México D.F. México

T. J. McDonald, PhD

Departamento de Biología de la Reproducciíon, Instituto Nacional de la Nutrición Salvador Zubirán, México D.F. México; Laboratory for Pregnancy and Newborn Research, College of Veterinary Medicine, Dept. Biomedical Sciences, Box 16, Cornell University, Ithaca, NY 14853-6401 tjm2{at}cornell.edu

Objective: To examine the secretory effect of prostaglandin E₂ (PGE₂) and ACTH on the adrenal glands of prenatal and postnatal sheep.

Methods: Immunocytochemistry was used to examine the adrenal cortex and medulla for 17-hydroxylase and tyrosine hydroxylase immunoreactivity. Microphysiometric technique was used to measure [H⁺] after exposure of whole dispersed prenatal and postnatal adrenal glands to PGE₂, 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 PGE₂ deceased 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 (EC₅₀) for the ACTH response was lower in fetuses than in newborn lambs (< 1 day and 3 days old), but there was no change in EC₅₀ for PGE₂ across the ages studied. Adrenal cell response to ACTH after prior ACTH and PGE₂ 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 dispresed adrenal cell physiology. Prostaglandin E₂ stimulated dispersed adrenal cells during the mid-gestation ACTH refractory period, but this effect decreased with increasing age. Prostaglandin E₂ sensitized adrenal cells to ACTH at 110 days' gestation but inhibited ACTH effects at postnatal day 3.

Key Words: Fetal sheep • pregnancy • microphysiometer • H+ production • ACTH • in vitro

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