How is biosynthesis of testosterone compartmentalized and regulated within the cell?

 

Testosterone can be synthesised via multiple pathways in the adrenal cortex that is in the zona fasciculata and zona reticularis, in the ovaries and in the testes. As for the synthesis of cortisol ACTH increases expression of StAR and P450scc in the zona fasciculata and zona reticularis of the adrenal cortex.

In the theca, interstitial and luteal cells of the ovary, LH increases expression of both StAR and P450scc. In the leydig cells of the testis, LH only increases StAR. In the adrenal cortex, pregnenolone is converted via the Delta 5 pathway to 17-hydroxypregnenolone and then to DHEA by P450c17 in the SER.

DHEA is the principal androgen produced by the adrenals and is rapidly sulfated to DHEAS, which is inactive. Some DHEA is converted by 3 beta HSD in the SER to androstenedione, which is then converted to testosterone by 17 beta HSD in the SER. Alternatively, some DHEA is converted by 17beta HSD to androstenediol, which is then converted to testosterone by 3 beta HSD.

In leydig cells pregnenolone is converted preferentially via the Delta 4 pathway to progesterone by 3 beta HSD which is in the SER and then to 17-hydroxyprogesterone and androstendione by the SER enzyme P450c17. Androstenedione is converted rapidly to testosterone by 17 beta HSD in Leydig cells. In ovarian theca, interstitial and luteal cells, production of androgens proceeds similarly to leydig cells except that LH increases expression of 3 beta HSD and P450c17 in the ovary and androstendione is the principal androgen synthesised.

In adult males, almost all testosterone originates from the testes. In premenopausal females, the adrenals and the ovaries each contribute approximately half of plasma testosterone. However ovarian androstenedione production is about 10 times higher than testosterone production in premenopausal women.