Progesterone metabolism

Like steroid hormones, thyroid hormones interact with receptors to alter genomic activity and affect the synthesis of specific proteins during development [25-28], As with testosterone and progesterone, metabolic transformation of thyroxine (T4) is critical to its action [25-28]. Moreover, as with steroid hormones, thyroid hormones alter brain functions in adult life in ways that both resemble and differ from their action during development [25-28]. 

Figure 23-19 Progesterone metabolism (timing of the reduction steps can vary). HSD, hydroxysteroid dehydrogenase.

G4. Greig, M., A study of progesterone metabolism in pregnancy. Ph. D. Thesis, University of St. Andrews, Scotland (1965). 

V5. ViUee, D. B., and Driscoll, S. G., Pregnenolone and progesterone metabolism in human adrenals from twin female fetuses. Endocrinology 77, 602-608 (1965). 

Fig. 7. Progesterone metabolism by oocytes of Rana pipens. Thin-layer chromatographic profiles of radioactivity in oocytes and in the medium at various times after exposure to [ H]progesterone at 1 Ag/ml for 15 minutes. The diagram below each profile shows the position of progesterone spot, origin (marked with an X), and solvent front. Mi and M are the metabolite peaks referred to in the text. See Reynhout and Smith (1973) for additional information.

The course of progesterone metabolism formulated in Fig. 17 is quite well substantiated by the observations made following administration of 21-carbon steroids. When nonisotopic progesterone was fed or given intramuscularly to man, pregnane-3o ,20a-diol (LXXXIV) was the major urinary excretion product, although only 10% to 20% of the hormone given was obtained in the form of this metabolite very small amounts of... 

The conditions for Eqs. (72) and (73) are that the disappearance rate must be equal to the appearance rate and there is insignificant binding and metabolism by the cell. These assumptions are satisfied by the steroids with the exception of testosterone and progesterone. Hence, Pe values of testosterone and progesterone based on appearance kinetics will be underestimated unless the enzyme system is saturated. 

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. 

Segal and Blair (S13) have shown that aldehydes reduce NAD to NADH2 in the presence of aldehyde dehydrogenase progesterone, menthol, and menthone inhibit this enzyme and this may account for the stimulatory action shown by these substances on galactose metabolism in vitro. 

P8. Fesch, L. A., Segal, S., and Topper, Y. J., Progesterone effects on galactose metabolism in prepubertal patients with congenital galactosemia and in rats main-tamed on high galactose diets. J. Clin. Invest. 39, 178-184 (1960). 

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). 

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