Progesterones, inactivation

The correct answer = C. Progesterone is synthesized by the testes in males. Progestins decrease HDL and increase LDL. When orally administered, progesterone is largely inactivated by hepatic first-pass metabolism. Weight gain is one of the side effects of progestins. 

Case A (Fig. 36). This female patient (blood type B) with cancer of the endometrium metastatic to liver and lung showed no change in alkaline phosphatase on the first 60 days of Delalutin (progesterone) therapy, and then showed a rise for the next 80 days. The elevated values over this period showed a reasonably close proportionate rise in the LPSAP and non-LPSAP. This circumstance applies also to the heat-sensitive and -insensitive fractions. The percent heat inactivation remains constant for both LPSAP and non-LPSAP moieties at 62 and 50%... 

In the absence of a ligand, PR is associated with a complex of heat shock proteins as a monomer in an inactivated state in the cytosol. When a progestin binds to the receptor, the overall conformation changes. Heat shock proteins are liberated, and the receptor dimerizes, enters into the cell nucleus and binds to selective progesterone-responsive elements (PREs) on the DNA to induce transcriptional activity. 

Halpert, J., J.-Y. Jaw, and C. Balfour (1989). Specific inactivation by 17(3-substituted steroids of rabbit and rat liver cytochromes P-450 responsible for progesterone 21-hydroxylation. Mol Pharmacol. 34, 148-156. 

E.F. Johnson (1988). Selective inactivation by 21-chlorinated steroids of rabbit liver and adrenal microsomal cytochromes P-450 involved in progesterone hydroxylation. Arch. Biochem. Biophys. 264,462 71. 

Delorme C, PiffeteauA, Sobrio F, MarquetA(1997) Mechanism-based inactivation of bovine cytochrome P450[[p by 18-unsaturated progesterone derivatives. Eur J Biochem 248 252-260... 

Additional hepatic metabolism of steroids contributes to their inactivation and also to extra-adrenal conversion to active steroids. Both CYP3 A4 and CYP2C19 are progesterone 21-hydroxylases that yield IIDOC as a minor prodnct along with other hydroxysteroids [14]. CYP3A4 catalyzes 6p-hydroxylation of progesterone, cortisol, and... 

In the isolation of steroids from natural sources one must, of course, consider their stability prior to enzyme inactivation, which usually occurs at the commencement of the isolation procedure, when the tissue is extracted with organic solvents. Kahnt and Neher (1965) could observe in bovine adrenal homogenates only trace amounts of 20a-hydroxycholesterol and (22R)-20,22-dihydroxy-cholesterol, as well as pregnenolone or progesterone (< figlgm). As stated earlier the absence of certain derivatives may be due to either their lack of formation or their rapid disappearance from the system. Until recently, primarily because of the lack of appropriate substrates of high specific activity, quantitative studies on the elucidation of the mechanism of the desmolase reaction could not be performed. The study of Ichii et al. (1967a) appears to entail the assumption of a steady state, for which no proof seems to have been provided. Also,... 

Progesterone is produced only during certain phases of menstruation and during pregnancy. Excretion products in urine are the glucuronides of pregnanediol and some stereoisomers thereof as in the case of the adrenal corticoids, inactivation is accomplished by reduction of ring A. 

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