Endocrinology, Vol 115, 2464-2472, Copyright © 1984 by Endocrine Society

ARTICLES

Self-suppression of corticosteroidogenesis: evidence for a role of adrenal 5 alpha-reductase

RV Carsia, CG Scanes and S Malamed

Exogenous corticosterone (B), the natural glucocorticoid product of rats, suppressed endogenous B production of isolated rat adrenocortical cells induced by alpha ACTH-(1-24), [9-tryptophan (O- nitrophenylsulfenyl)]ACTH-(1-24) [( Trp (Nps)9]ACTH-(1-24], and cAMP as well as pregnenolone supported-steroidogenesis. This self-suppression occurred within 2 h. It was dependent on the concentration of exogenous B. However, self-suppression did not alter the half-maximal steroidogenic concentration (ED50) of each steroidogenic agent. In addition, exogenous B did not suppress ACTH-induced cAMP production or gross protein synthesis, as measured by leucine incorporation into bulk cellular proteins. These results with isolated cells suggested at least two mechanisms for self-suppression: 1) exogenous B inhibited steroidogenic steps in a noncompetitive manner, and/or 2) exogenous B induced B degradation. In this study we examined the effect of exogenous B on the degradation of B. Accordingly, we measured the adrenal 5 alpha-reductase activity (5 alpha RA) of cell homogenates prepared from treated cells. Isolated adrenocortical cells were incubated for 2 h with alpha ACTH-(1-24), ovine PRL (oPRL), and B. They were then homogenized and assayed for 5 alpha RA, as indicated by the disappearance of exogenous B, as shown by RIA. In addition, the percentage of exogenous tritium-labeled B [( 3H]B) converted to 5 alpha- dihydrocorticosterone (DHB), the principal reduced metabolite of B, was determined by TLC. Isolated adrenocortical cells from intact rats showed insignificant 5 alpha RA and DHB formation when incubated with or without alpha ACTH-(1-24) and with or without oPRL. However, with exogenous B, there was significant 5 alpha RA and DHB formation. oPRL plus B decreased DHB formation. The effects of B and oPRL were more demonstrable with cells from hypophysectomized rats. These cells exhibited high 5 alpha RA and DHB formation; exogenous B increased these values, whereas oPRL acutely reversed the effects of hypophysectomy and exogenous B. In other work avoiding cell homogenization, exogenous B suppressed ACTH-induced B accumulation and increased DHB formation in intact cell suspensions from intact rats and intact male domestic fowl. Furthermore, exogenous B increased the conversion of [3H] pregnenolone to DHB in intact cell suspensions from intact rats, showing that B synthesized de novo as well as exogenous B can be degraded during self-suppression. These data indicate that acute self-suppression of corticosteroidogenesis is at least partly mediated by an increase in 5 alpha RA.

This article has been cited by other articles:

				J. Castillo, B. Castellana, L. Acerete, J. V Planas, F. W Goetz, S. Mackenzie, and L. Tort Stress-induced regulation of steroidogenic acute regulatory protein expression in head kidney of Gilthead seabream (Sparus aurata) J. Endocrinol., February 1, 2008; 196(2): 313 - 322. [Abstract] [Full Text] [PDF]

				R.-S. Ge, D. O. Hardy, J. F. Catterall, and M. P. Hardy Developmental Changes in Glucocorticoid Receptor and 11{beta}-Hydroxysteroid Dehydrogenase Oxidative and Reductive Activities in Rat Leydig Cells Endocrinology, December 1, 1997; 138(12): 5089 - 5095. [Abstract] [Full Text] [PDF]

				A. Yamada, M. Yamada, Y. Fujita, T. Nishigami, K. Nakasho, and K. Uematsu Self-augmentation Effect of Male-specific Products on Sexually Differentiated Progesterone Metabolism in Adult Male Rat Liver Microsomes J. Biol. Chem., February 9, 2001; 276(7): 4604 - 4610. [Abstract] [Full Text] [PDF]