Progesterone biosynthesis

Progesterone biosynthesis is initiated when LFI, secreted from the anterior pituitary, binds to the target cell surface LFI receptor. 

Downregulation of progesterone biosynthesis was observed in rat granulosa cells treated with an extract of the bran of Job s tears (Hsia et al. 2006). 

Hsia, S.M., W. Chiang, Y.H. Kuo, and PS. Wang. 2006. Downregulation of progesterone biosynthesis in rat granulosa cells by adlay Coix lachryma-jobi L. var. ma-yuen Stapf.) bran extracts. Int. J. Impotence Res. 18(3) 264-274. 

Figure 42-5. Pathways of testosterone biosynthesis. The pathway on the left side of the figure is called the or dehydroepiandrosterone pathway the pathway on the right side is called the A" or progesterone pathway. The asterisk indicates that the 17a-hydroxy-lase and 17,20-lyase activities reside in a single protein, P450cl7.

Congenital defects in the biosynthesis of steroid hormones can lead to severe developmental disturbances, in the adrenogenital syndrome (AGS), which is relatively common, there is usually a defect in 21-hydroxylase, which is needed for synthesis of cortisol and aldosterone from progesterone. Reduced synthesis of this hormone leads to increased formation of testosterone, resulting in masculin-ization of female fetuses. With early diagnosis, this condition can be avoided by providing the mother with hormone treatment before birth. 

The steroid Ci7(20)lyase is an enzyme that is involved in the biosynthesis of andro-stenedione and of dehydroepiandrosterone from progesterone and pregnenolone, respectively. As androgen and estrogen hormones are necessary for the growth of tumors, this enzyme is a potential therapeutic target for the treatment of prostate cancer and in hormone-dependent breast cancers. 

FI6URE28 1. Biosynthesis and metabolism of neurosteroids. Solid arrows refer to enzyme activities demonstrated in the central nervous system (CNS) dashed arrows refer to enzyme activities not demonstrated in the CNS. allo-THDOC = allotetrahydro-deoxycorticosterone 5a-DHDOC = 5a-dihydro-deoxycorticosterone 5a-DHP = 5a-dihydro-progesterone. 

Eur J Neuropsychopharmacol 6 (suppl 3) 207, 1996 Julius D, McDermott AB, Axel R, et al Molecular characterization of a functional cDNA encoding the serotonin 1C receptor. Science 241 558-564, 1988 Jung-Testas 1, Hu ZY, Beaulieu EE, et al Neurosteroids biosynthesis of pregnenolone and progesterone in primary cultures of rat glial cells. Endocrinology 125 2083-2091, 1989... 

Fig. 2. Biosynthesis of testosterone (a) Pregnenolone (b) 17-hydroxy pregneno-line (c) dehydrois-oandrosterone (d) progesterone (e) 17-hydroxypro ges terone If androstenedione (g) testosterone...

Biosynthesis of progesterone. Desmolase is found in the mitochondria of steroid-producing tissues. Cholesterol is converted to pregnenolone in the mitochondria and then transferred to the endoplasmic reticulum, where it is converted to progesterone. Progesterone is a hormone as well as the precursor of several other hormones. 

The step-by-step synthesis of the steroid hormones pregnenolone and progesterone from cholesterol (C27) was presented in chapter 20 (see fig 20.22). Note that pregneno-lone (C2i) and progesterone (table 20.4) (C2 ) are intermediates in the biosynthesis of all of the major adrenal steroids, including cortisol (C2i), corticosterone (C21), and aldosterone (C21). The same two compounds are intermediates in the synthesis of the gonadal steroid hormones, testosterone (C,9) and 17/3-estradiol (CI8). Because the synthesis of all these hormones follows a common pathway, a defect in the activity or amount of an enzyme along that pathway can lead to both a deficiency in the hormones beyond the affected step and an excess of the hormones, or metabolites, prior to that step. 

---