GREGORY PINCUS 



obtained evidence for its production by human ovaries perfused in vitro. 

 Estradiol is oxidized to estrone by various tissues and estrone is re- 

 duced to estradiol. Which of the two is formed first in the ovary 

 cannot therefore be determined a priori. We need to know the pre- 

 cursor of both to solve the problem. 



The isolation of estrone (but not estradiol) from adrenal tissue 

 suggests that it may be supplied by the adrenal gland to the ovary for 

 conversion to estradiol. Production of estrone by the adrenal gland 

 must be in minor amount since the excision of the ovaries in adult 

 animals effectively abolishes the estrous cycle. Furthermore, adrenal- 

 ectomy in animals does not abolish estrous cycles, though irregularities 

 do occur. Finally, Samuels and collaborators have demonstrated that 

 women with Addison's disease (in which the adrenal glands are atro- 

 phied or destroyed) excrete normal amounts of folliculoids. It is clear, 

 therefore, that the adrenal glands are not essential for the produc- 

 tion of folliculoids. It is interesting to note, however, that very early 

 ovariectomy in mice leads to the eventual establishment of estrous 

 cycles and the excretion of notable amounts of folliculoid. Also, the 

 injection of pituitary adrenocorticotropic hormone into ovariectomized 

 rats stimulates folliculoid production by the adrenals. The most 

 likely conclusion is that the capacity for ovarian hormone synthesis is 

 present in adrenal tissue, but that optimal conditions are found in 

 normal ovarian tissue. This remarkable steroidogenic capacity of 

 the adrenal cortex is also confirmed by the isolation in small amounts 

 of progesterone from adrenal extracts. 



CH3 CH3 CHg 



c=o 



HO— J 



HgC 



c=o 



COH 



H3C 



VV 

 (I) 



A'- Pregnenolone 



/X 



(II) 



Progesterone 



HO- 



(III) 



Pregnanediol 



The immediate precursor of progesterone may be A^-pregneno- 

 lone, for we have recovered pregnanediol from the urine of men re- 

 ceiving pregnenolone by mouth or by injection. The transformation 



308 



