Metabolism of progesterone

C9. Cooke, B. A., and Taylor, W., The metabolism of progesterone by animal tissues in vitro. 4. Conjugate formation during the metabolism of (4- C) progesterone by female-rat liver homogenate. Biochem. J. 86, 365-371 (1963). 

Americ SP, McCormack KM, Braselton WE, et al. 1980. Altered metabolism of progesterone by hepatic microsomes from rats following dietary exposure to polybrominated biphenyls. Toxicol Appl Pharmacol 54 187-196. 

Reviews on the biosynthesis and metabolism of progesterone and the vitamins pi7o,i7i appeared. 

The important metabolic events leading to mactivation of progesterone are reduction and conjugation. The main metabohc pathway for the metabolism of progesterone is shown in Figure 53-13. 

Figure 53-13 Metabolism of progesterone.The circled area represents the site of chemical change.

In Table 2 the major metabolites of the steroid sex hormones and some important related steroids are listed. Their relationships to their precursors are in some cases controversial at present and will be discussed in the next section of this article. Suffice it to say at the moment that simple relationships between the excretion rates of some of these metabolites and the secretion rates of their precursors are not easy to establish. On the other hand, it is fair to add that some of the complexities implied by recent work on the metabolism of testosterone and andros-tenedione, and on the metabolic activity of the placenta and fetus in pregnancy should not be allowed to obscure the relative simplicity of many aspects of the metabolism of progesterone and of estrogens. 

The endocrinological system of steroid hormones in molluscs has been established, and many reports on the biosynthesis and metabolism of progesterone, estrogens and androgens have been published [10]. 

Wang, H., K.L. Napoli, and H.W. Strobel (2000). Cytochrome P450 3A9 catalyzes the metabolism of progesterone and other steroid hormones. Mol Cell. Biochem. 213, 127-135. 

Some of the most powerful inducers of these drug-destroying enzymes are found among the chlorinated insecticides. A small dose of DDT or benzene hexachloride can make laboratory animals highly resistant to the effects of other agents. Hence such insecticides must not be used on animals when drug tests are to be carried out on them. Moreover chlorinated insecticides increase the metabolism of progesterone, estradiol, and testosterone. 

Sweat, M. L., D. L. Bebliner, M. J. Bryson, C. Nabors jr., J. Haskell, and E. G. Holm-STROM The synthesis and metabolism of progesterone in the human and bovine ovary. Biochim. biophys. Acta (Amst.) 40, 289 (1960). 

Recently, Voogt et al. [91] have reported on the d5-pathway in steroid metabolism of Asterias rubens. These workers established the existence of the d5-pathway (Scheme 20), analogous to the pathway found in mammals this conclusion was based on the observation that radiolabeled cholesterol (1) was converted to pregnenolone (112), 17a-hydroxypregnenolone (141), and androstenediol (142). Labeled pregnenolone was converted additionally to progesterone (129). Androstenediol (142) was the main metabolite of de-hydroepiandrosterone (143), a reaction catalyzed by 17/i-hydroxysteroid dehydrogenase (17/1-HSD). The metabolic conversion of androstenedione (131) to testosterone (132) is also mediated by 17/J-HSD and is related to... 

Besides catalyzing styrene and benzaldehyde, CYP enzymes play an important role in the metabolism of endogenous compounds as well as in pharmacokinetics and toxicokinetics. Joseph [228] developed a biosensor with human CYP3A4 as a novel drugscreening tool. It was constructed by assembling enzyme films on Au electrodes by alternate adsorption of a layer of CYP3A4 on top of a layer of PDDA. The biosensor was applied to detect verapamil, midazolam, quinidine, and progesterone. 

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. 

MacDonald PC, Dombroski RA, Casey ML Recurrent secretion of progesterone in large amounts an endocrine/metabolic disorder unique to young women Endocr Rev 12[4) 372-401, 1991... 

Mircioiu, C., et al. 1998. Pharmacokinetics of progesterone in postmenopausal women 1. Pharmacokinetics following intravaginal administration. Eur J Drug Metabol Pharmacokin 23 391. 

Powdered Dioscorea (wild yam) root or extract is also marketed to treat the symptoms of menopause as an alternative to hormone replacement therapy (see page 279). Although there is a belief that this increases levels of progesterone, which is then used as a biosynthetic precursor of other hormones, there is no evidence that diosgenin is metabolized in the human body to progesterone, and any beneficial effects may arise from diosgenin itself. 

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