Biogenesis of Estrogens

It has recently been clearly demonstrated that estrogens can arise (1) from acetate, (2) by conversion of cholesterol and of progesterone, and (3) by aromatization of neutral Cig- and Cjs-steroids. Evidence has been pre- 

Using cell-free homogenates of testis from man, dog, and cat, Rabinowitz (1956) observed the formation of radioactive estradiol-17/8 from radioactive 

the conversion of acetate to estrogens has been demonstrated in vivo and in vitro in several species, and it seems justifiable to conclude that acetate is a precursor not only of cholesterol and the neutral steroids, but of the estrogens as well. 

It is now certain that cholesterol is the precursor of neutral adrenal and testicular steroids. As will be shown in Section II, C, several neutral steroids can be converted to estrogens it seems, therefore, that cholesterol may act as an intermediate in the biogenesis of estrogens. 

Heard and his colleagues (19.54) studied this question and came to the conclusion that cholesterol cannot act as a precursor of the estrogens. After the injection of cholesterol-. -C into the pregnant mare, the authors were unable to find any radioactivity associated with the estrogen fraction in the urine. In a re-examination of the.se data, Engel (1957) drew attention to the fact that the amount of radioactive cholesterol administered (409 mg) was relatively small compared with the large size of a pregnant mare (750 

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Biosynthesis of j5-hydroxy-/5-methyl-glutaric acid (HMG). Fed. Proc. 15, 342 (1956). Ryan, K. J., and 0. W. Smith Biogenesis of estrogens by the human ovary. IV. Formation... 

The biogenesis of estrogens has been discussed in Chapt. XlV-fi. The precursor is testosterone, which is hydroxylated at C-19 this angular group is then lost in the course of aromatization of ring A. 

D4. Diczfalusy, E., In vivo biogenesis and metabolism of estrogens in the foeto-placental unit. Proc. 2nd Intern. Congr. Endocrinol. London, 1964 Vol. 2, p. 732. Exoerpta Med. Found., Amsterdam, 1965. 

The experiments on biogenesis carried out by Ryan and Dorfman and their co-workers leave no room for doubt that the greatest part, if not all, of the estrogens arise by aromatization of neutral steroids. It can be taken as proved that, from a quantitative point of view, this reaction plays a decisive role. The important question which now has to be asked is what factors control the process of aromatization of neutral steroids, and thus of... 

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