Androgen biosynthesis

 

What happens normally?? Autocrine, paracrine and hormonal factors modulate the coordination of thecal and granulosa cell function, in terms of androgen biosynthesis.

Equal conc. of Androstenedione and Testosterone  is contributed by adrenal & ovaries. So rise of Testosterone  or androgens , as we observe in some cases of PCO may be due to abnormal functioning of either ovaries or adrenals (Z. fasciculate) or both.

 In fact both the glands secrete Androstenedione in greater amount than T. In fact 50% of circulating T is from peripheral conversion of the Androstenedione. The enzymes involved in conversion of cholesterol to A’dione are same in both the glands.

 

The rate limiting step in androgen formation is the gene expression of P450c17, which (gene expression) is dependent on tropic hormones e.g. LH in case of ovary and ACTH in case of Adrenals.

 

Control of steroidogenic response is controlled by many growth factors, particularly-insulin and insulin –like growth factors (IGF) and other array of growth factors. A’dione formed in theca cells under the influence of LH  diffuse to granulose cells converted to E2 at granulose cells. As LH stimulation increases the homologous desensitization occurs. Overstimulation with LH is 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 –lyase and 17 hydroxylase activities are decreased.

 

As a result of reduced side chain cleavage the ratio of 17-OH P to androgen increases.