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Kinetic control of steroidogenesis by steroid concentration in guinea pig adrenal microsomes

1991; Elsevier BV; Volume: 1084; Issue: 3 Linguagem: Inglês

10.1016/0005-2760(91)90064-o

1879-145X

Akihiro Higuchi, Shiro Kominami, Shigeki Takemori,

Hormonal Regulation and Hypertension

For clarification of the effects of steroid concentration on steroidogenesis of adrenal microsomes, the kinetic parameters, Km and kcat, were determined in the steady-state for progesterone and 17α-hydroxyprogesterone metabolism catalyzed by P-450C21 and P-45017α,lyase, while at a low concentration, it was progesterone, it was equally metabolized by P-450C21 and P-45017α,lyase, while at a low concentration, it was hydroxylated at 17α-position with twice higher rate than at 21-position. 17α-Hydroxyprogesterone is apparently metabolized preferentially by P-450C21 at any concentration. Although the products of deoxycortisol and androstenedione from 17α-hydroxyprogesterone were strongly inhibited by progesterone, androstenedione formation from progesterone was not inhibited by a high concentration of progesterone. The addition of liposomal P-450C21 to the reaction medium containing adrenal microsomes caused a decrease in the concentration of 17α-hydroxyprogesterone released into the medium in the steady state reaction, but this had no effect on the activity of androstenedione formation from high concentrations of progesterone. It thus follows that androstenedione is produced by successive monooxygenase reactions without the release of 17α-hydroxyprogesterone from P-45017ga,lyase at a high concentration of progesterone, which is the condition of the adrenal microsomes in vivo.