A Mechanism for the Intraovarian Inhibitory Action of Estrogen on Androgen Production1

Abstract

Immature female rats were sacrificed at 0, 4, 8 or 16 h following a single s.c. injection of estradiol-17β (estradiol, 1 mg). Ovaries from each animal were incubated individually: one in the presence of LH (10 µg/ml) for 4 h, the other with progesterone-4-[¹⁴C] (10^-6 M) for 2 h. For the LH incubated ovaries, in vivo treatment with estradiol had no significant effect on progesterone accumulation, whereas production of both testosterone and androstenedione was inhibited by estradiol in a manner dependent on the duration of estradiol treatment in vivo. Analysis of the conversion of radioactive progesterone to its major metabolites by the contralateral ovaries revealed a time-dependent inhibition by estradiol in the formation of androstenedione, 5α-androstanedione and androsterone, whereas the production of 5α-pregnanedione and 3α-OH-5α-pregnan-20-one was significantly stimulated, also in a time-dependent manner. In another experiment, in vivo stimulation for 1 h with LH produced alterations in the pattern of metabolites of progesterone-4-[¹⁴C] identical to those found upon treatment with estradiol; both treatments resulted in a marked stimulation of 3α-OH-5α-pregnan-20-one, accompanied by an inhibition, of similar magnitude, of production of androsterone. These results suggest that 1) estradiol may act to inhibit ovarian androgen production by impairing the C_17α-hydroxylase/C_17,20-lyase enzyme systems, thereby diverting C₂₁-substrates through alternate metabolic pathways leading to accumulation of 5α-pregnane compounds and 2) the inhibitory action of LH upon ovarian androgen production may be mediated by estrogen.