508 



PHYSIOLOGY OF GONADS 



I.U. '00 



I.U. 



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Androgens 

 Curve of genital swelling 



25 27 29 



Day of cycle 



Fig. 8.6. E.strogen and androgen excretion by a female chimpanzee, Mamo. , total 



estrogens; , estradiol; -•-•, estrone; , estriol. Menstruation indicated by solid 



areas on base line. (From W. R. Fish, W. C. Young and R. I. Dorfman, Endocrinology, 28, 

 588,1941.) 



studying one woman for 2 years, found 

 single peaks at midinterval in 8 cycles and 

 double peaks in 12 cycles. On the average 

 the first peak was reached on day 12 and the 

 second on day 21. Similar double peaks were 

 noted in blood estrogen assays in a large 

 group of normal young women (Markee 

 and Berg, 1944). An additional lesser rise 

 was observed during menstruation. 



None of the available assays of urinary or 

 blood estrogen can be accepted as an abso- 

 lute measure of the rate of hormone produc- 

 tion. Urinary assays have certain advan- 

 tages, in spite of the fact that probably only 

 a variable fraction of the ovarian product 

 is measured. Intrinsically they are measures 

 of rate, whereas assays of blood estrogen 

 measure concentration alone at the moment 

 of bleeding. Attempts have been made to 

 measure estrogens in ovarian venous blood, 

 but with little success because of the ex- 

 treme dilution (Rakoff and Cantarow, 

 1950). We may hope that development of 

 sufficiently sensitive methods of detection 

 will soon allow systematic evaluation of 

 ovarian output by such direct means. Tracer 

 techniciucs have shown (Werthessen, 

 Schwenk and Baker, 1953) in perfused ova- 

 ries of the sow that C^^-acetate enters into 

 the synthesis of estrone and /^-estradiol. 



Several years ago Corner (1940) esti- 



mated, from the known amounts of injected 

 estrone required to maintain the normal 

 status of sex skin and endometrium in cas- 

 trates that the ovaries of an adult rhesus 

 monkey secrete the equivalent of about 20 

 fig. estrone daily. On a weight basis the es- 

 trone equivalent secreted by the ovaries of 

 a woman would then be on the order of 300 

 /Ag. per day. Actual substitution data from 

 castrated women gave an estimate of the 

 same order of magnitude (420 ;u,g. per day). 

 Whatever the rate of secretion may be at 

 different times, it would seem a 'priori that 

 effects on extra-ovarian tissues should be 

 more directly related to amount of estrogen 

 in circulation. The assays of human blood- 

 estrogen in normal women by Markee and 

 Berg (1944) and in gynecologic patients by 

 Fluhmann (1934), although differing in ab- 

 solute values, agree in indicating that the 

 variation of blood estrogen concentration 

 from one stage of the cycle to another may 

 be relatively small. If this is true, then it 

 nuist be supposed that cyclic changes in the 

 accessory organs are brought about by rela- 

 tively moderate changes in circulating estro- 

 gen. In support of this view Markee (1948) 

 demonstrated in the macaque that a mere 50 

 per cent reduction in the daily dose of es- 

 trogen can invoke menstruation if the 

 change is abrupt. 



