Androgen Production in ovary's mechanisms

What are the changes induced at ovarian level by Aromatase enzymes.  Such enzyme inhibitors cause many changes in the autocrine, paracrine and hormonal factors that modulate the coordination of thecal and granulose cell function, in terms of androgen biosynthesis. We know that equal conc. of Androstenedione and T is contributed by adrenal & ovaries. So rise of T4 or androgens in any woman may be due to abnormal functioning of either ovaries or adrenals (Z. fasciculate) or both. We are also aware that both the glands secrete Androstenedione in greater amount than T4.  In fact 50% of circulating T is from peripheral conversion of the Androstenedione. The enzymes involved in conversion of cholesterol to DHA & Androstenedione ARE the SAME IN BOTH THE GLANDS. The rate limiting step in androgen formation is the gene expression of P450_c17, which (gene expression) is dependent on tropic hormones e.g. LH in case of ovary and ACTH in case of Adrenals. Aromatase enzymes modify conversion of Androgens to Oestrogel thereby decreasing serum E2à as result Hypothalamus gets stimulated to release GNRH pulse. But there is definite accumulation of ovarian androgens inside the ovaries if one consumes AI (Aromatase Inhibitors).

Control of steroidogenic response is controlled by many growth factors, particularly-insulin and insulin –like growth factors (IGF) and other array of growth factors.

In theca cells under the influence of LH à diffuse to granulose cellsà converted to E2 at granulose cells. As LH stimulation increases the homologous desensitization occurs. Overstimulation with LH in a time & dose dependent manner, cause DOWN REGULATION OF LH RECEPTORS à resulting in reduced rate of cholesterol side chain cleavage activity-> Both 17-20 –lease and 17 hydroxylase activity are decreased . As a result of reduced side chain cleavage the ratio of 17-OH P to androgen increases. Androgens and oestrogens are negative are negative modulators of LH effects. But IGF play a positive modulator role on the effects in production of androgen biosynthesis in the gonads.ABC of Female Subfertility.