Role of Exogenous and Endogenous Prostaglandins in Steroidogenesis by Isolated Frog Interrenal Gland: Evidence for Dissociation in Adrenocorticotropin and Angiotensin Action*

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Abstract
The role of prostaglandins (PG) in the regulation of glucocorticoid and mineralocorticoid production by the frog interrenal (adrenal) gland was studied in vitro by means of continous perifusion. No change in corticosteroid production was observed upon perifusion with PGA1 or PGA2 (up to 10-6 M). Six other primary PGs, and the prostacyclin I2 (PGI2), significantly stimulated corticosteroidogenesis: the order of potency being PGE1 > PGI2 > PGE2 > PGB2 > PGB1 > PGF2.alpha. > PGF1.alpha.. The ability of the PGs to stimulate corticosterone and aldosterone production indicated that PGs may contribute to corticosteroid biosynthesis and that endogenous PGs could act as mediators for certain corticosteroid-stimulating factors. The essential role of endogenous PGs for spontaneous corticosteroid biosynthesis was demonstrated by the marked inhibition of corticosterone and aldosterone production induced by indomethacin (IDM) and meclofenamic acid, 2 specific inhibitors of cyclooxygenase which reduced significantly PG formation in the interrenal tissue. Stimulation of steroidogenesis by ACTH or cAMP was not affected by infusion of IDM or meclofenamic acid. In addition, ACTH did not modify the production of PGs by interrenal tissue. The stimulatory effect of the angiotensin II analog [Sar1-Val5]AII, was markedly reduced in the presence of these 2 PG synthetase inhibitors and a direct stimulatory effect of the AII analog on PGE2 release was demonstrated. The effects of a supramaximal dose of [Sar1-Val5]AII could not be enhanced by PGE1 indicating that the corticosteroid response to angiotensin II is dependent upon endogenous PG synthesis, whereas the additivity of the stimulatory effects of PGE1 and a maximal dose of ACTH confirmed that PG are not involved in the mechanism of action of ACTH. Endogenous and exogenous PG are implicated in corticosteroidogenesis in the frog. Since, in fish and amphibia the adrenocortical tissue is in close contact with the kidney (a major source of PGE), a physiological relationship between the kidney and the interrenal gland in lower vertebrates is suggested. In addition, the first evidence that the action of angiotensin II on both corticosterone and aldosterone production may be mediated by PGs, whereas ACTH and cAMP stimulate corticosteroidogenesis through another mechanism. ACTH and angiotensin II apparently activate the early steps of corticosteroid biosynthesis via different pathways.