Aldosterone Biosynthesis from 4- 14 C-Pregnenolone and 4- 14 C-Progesterone,in the Rat and Rabbit

Abstract

In vitro experiments using 4-¹⁴C-pregnenolone and 4-¹⁴C-progesterone were performed in order to study the pathways to aldosterone formation in adrenal glands from rats and rabbits. The adrenal steroids were isolated by paper chromatography and quantitated by the double isotope derivative assay method. In both the rat and the rabbit, there seemed to be no distinction between the roles of pregnenolone and progesterone as precursors of adrenal steroids. Corticosterone, 11-dehy-drocorticosterone, and 18-hydroxycorticosterone were possible precursors of aldosterone in the rabbit, whereas in the rat the precursors were corticosterone, 18-hydroxycorticosterone, and 18-hydroxy-11-deoxycorticosterone. The immediate precursor of aldosterone in both species was 18-hydroxycorticosterone.

Introduction. The biosynthetic pathway to aldosterone⁴ has aroused considerable discussion in the past ten years since it was found to be the main mineralocorticoid in several species including man. Pregnenolone, progesterone, 11-deoxycorticosterone (DOC), and corticosterone (B_K) serve as precursors for the biosynthesis of aldosterone (1-9). Of these steroids, B_K appears to be the more immediate precursor (2). The identification of 18-hydroxy-11 -deoxycorticosterone (18-OH DOC) and 18-hydroxycorticosterone (18-OH B_K) in many different species provides the basis for an alternate pathway which remains controversial (10-14). Fazekas and co-workers (15-18) reported the conversion of 11-dehydrocorticosterone (A_K) to aldosterone via 18-hydroxy-11-dehydro-corticosterone (18-OH A_K) by rabbit adrenal tissue and by homogenates of adrenal adenomas and normal adjacent cortex of patients with Conn's syndrome.

Presently, there exists much conflicting data concerning the biosynthetic pathways to aldosterone in different species. This is particularly true in rats and rabbits. For this reason, a series of in vitro experiments using 4-¹⁴C-pregnenolone and 4-¹⁴C-progester-one as precursors were performed to determine as many intermediates as possible to aldosterone. This was done in order to elucidate the pathway to aldosterone. Basically, the results indicate that the immediate precursor of aldosterone in both the rat and the rabbit appears to be 18-OH B_K.