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Acute Effects of SU-4885 and Its Reduced Derivative (SU-5236) on the Adrenocortical Secretion of the Rat

1971; Oxford University Press; Volume: 89; Issue: 5 Linguagem: Inglês

10.1210/endo-89-5-1236

1945-7170

Alejandro F. De Nicola, Vilma Dahl,

Hormonal and reproductive studies

One hour after iv injection of rats with SU-4885, its reduced derivative SU-5236 or saline, the secretion rates (SR) of deoxycorticosterone (DOC), corticosterone, 18-hydroxydeoxycorticosterone (18-OH-DOC) and aldosterone, were measured in adrenal venous blood. Control rats had the following SR: DOC 10.0 ± 1.4, corticosterone 40.1 ± 6.1, 18-0H-D0C 20.3 ± 1.8 and aldosterone 0.50 ± 0.05 μg/hr/100 g body weight/2 adrenals (mean ± SE). Both SU-4885 and SU-5236, in doses of 20 and 5 mg/100 g body weight, inhibited the SR of corticosterone by 72 to 84%, the SR of 18-0H-D0C by 23 to 56% and increased the SR of DOC. Aldosterone was significantly decreased at these and lower dose levels. 1.2 mg/100 g of SU-5236 and SU-4885 did not have any effect on corticosterone or 18-OHDOC but they elevated DOC SR three fold (p < 0.001). SU-5236 was also effective at 0.3 mg (p < 0.01). Therefore, in high amounts, SU-4885 and SU-5236 inhibited the 11 β and 18 hydroxylases and increased DOC. In small doses, they stimulated DOC SR without inhibiting corticosterone or 18-0H-D0C, and it is possible that they act as selective aldosterone inhibitors. In an attempt to localize the site of DOC production in the adrenal, capsules (containing zona glomerulosa) and decapsulated adrenals (zona fasciculata- reticularis) were incubated with progesterone in a time course study. In the capsules DOC seemed to be an intermediate of corticosteroidogenesis; in the decapsulated portions DOC appeared to behave more like a terminal product of metabolism. These results suggest that DOC arises predominantly from the fasciculata-reticularis cells. (Endocrinology89: 1236, 1971)