SYMPATHOADRENAL REGULATION OF ADRENAL ANDROSTENEDIONE RELEASE

The effects of epinephrine and of splanchnic nerve activation on adrenocortical androstenedione release were studied in intact isolated perfused pig adrenals with preserved nerve supply. In addition, long-term effects of epinephrine were characterized in bovine adrenocortical cells in primary culture. To investigate the contact zones of the androgen-producing cells of the zona reticularis with the catecholamine producing cells of the adrenal medulla, cortical cells were immunostained for cytochrome P450 side chain cleavage (P450scc). Perfusion of the isolated adrenals with epinephrine (10(-7) to 10(-5) M) stimulated androstenedione release in a dose-dependent manner. At a concentration of 10(-6) M, epinephrine provoked an increase to 179.11 +/- 16.14% of basal secretion (p < 0.05). Electrical stimulation of the splanchnic nerves led to an increase to 151.5 +/- 9.24% of basal values (p < 0.05). Epinephrine (10(-6) M) reached 40% and activation of the splanchnic nerves 26% of the stimulatory effect of ACTH at a physiological concentration (10(-10) M). The alpha-agonist phenylephrine had no effect on androstenedione release. In cell cultures, epinephrine stimulated the release of androstenedione in a dose-dependent manner with an ED50 of 0.75 x 10(-6) M. The maximal effect was reached at 10(-5) M with 8.92 +/- 0.66 pmol androstenedione/dish/24 h; the basal secretion was 1.44 +/- 0.54 pmol/dish/24 h. The epinephrine-stimulated androstenedione release was abolished by the beta-adrenergic antagonist propranolol while the alpha-adrenergic antagonist phentolamine had no effect. Immunohistochemical staining of paraffin sections of bovine and porcine adrenals for P450scc revealed that zona reticularis and zona medullaris are closely interwoven. Therefore, zona reticularis has a large surface exposed to secretory products of adrenomedullary cells. It is concluded that the secretion of adrenal androstenedione can be stimulated in a paracrine manner by epinephrine released from the adrenal medulla through beta-adrenergic receptors.