Metabolism of the Steroid Hormones

The biological relationship between ac-estradiol and estrone has been established by the isolation of the latter compound from the urine of normal and ovariectomized female and normal male guinea pigs (2, 3) and man (4,5) following the administration of cu-estradiol. In view of the conclusion of Pincus (6), that a-estradiol is not converted to estrone by the ovariectomized rabbit, it was considered of interest to investigate the fate of cr-estradiol in the rabbit by methods involving the isolation of crystalline urinary metabolites. The results of such an investigation are the subject of the present communication and demonstrate that, as in the guinea pig and man, cr-estradiol is converted to estrone. Furthermore, this transformation does occur in the absence of both the ovaries and uterus. We have also been able to isolate /?-estradiol from the urine of ovariectomized-hysterectomized rabbits to which a-estradiol was administered. p-Estradiol has thus far been found in nature only in the urine of pregnant mares (7-9). Whether it is synthesized de novo in the ovaries, the placenta, or the adrenal cortex of the mare or arises as a metabolite of estrone has not been established. From the urine of normal rabbits to which estrone was administered, Stroud (10) obtained an impure phenolic compound which he believed to be p-estradiol. The work reported here demonstrates that cr-estradiol is metabolized to fi-estradiol in the rabbit, estrone presumably being an intermediate. The ovaries and uterus are not essential