474 



PHYSIOLOGY OF GONADS 



one content of unruptured follicles in the 

 ovaries of cows and sows, and in determina- 

 tions of the cjuantities of progesterone se- 

 creted by 1 or 2 corpora lutea in sheep ( Ed- 

 gar, 1953a, b; Edgar and Ronaldson, 19581. 



After allowance was made for these con- 

 siderations tentative estimates were given: 

 rhesus monkey, 200 I.U. or 20 y estrone 

 daily; human' female, 3000 I.U. or 300 y 

 estrone daily (Corner, 1940); baboon 

 {Papio porcarius) , somewhat more than 0.04 

 mg. estradiol benzoate daily (Gillman, 

 1942) ; guinea pig, less than the equivalent 

 of 1.8 fjig. estradiol daily (Barahona, Bruz- 

 zone and Lipschutz, 1950). The variation in 

 the responsiveness of individual animals 

 was recognized by all the investigators. Two 

 important variables were not considered, 

 the cyclic growth of follicles, and the num- 

 ber of developing follicles. Presumptive evi- 

 dence that the amount of secreted estrogen 

 increases as the follicle enlarges was pro- 

 vided by the demonstration that more and 

 more estrogen is required to maintain peri- 

 neal turgescence (Gillman and Gilbert, 

 1946). The number of developing follicles 

 may vary greatly within a species, in the 

 guinea pig, for example, from 1 to at least 6. 

 The fact that two corpora lutea in the ewe 

 do not produce more progesterone than one 

 (Edgar and Ronaldson, 1958) could prepare 

 us for a corresponding finding with respect 

 to estrogen. 



The problem of estimating the rate of 

 progesterone secretion is l)eset by many 

 of the difficulties that confront an investi- 

 gator attempting to estimate the rate of 

 estrogen production, but one circumstance 

 especially has facilitated progress by those 

 especially interested in progesterone. It is 

 that the amount of excreted free prcgnane- 

 diol or excreted sodium pregnanediol glu- 

 curonidate is about 1/7 the amount of in- 

 jected progesterone (Trolle, 1955a, b) ; from 

 determinations of cither of tlic former, 

 therefore, tlie amount of the latter can be 

 estimated with what is believed to be a 

 reasonable degree of accuracy. The pioneer 

 attempt of Corner (1937) to calculate the 

 amount of progesterone secreted by the rab- 

 bit, sow, and human female resulted in 

 estimates (60 mg. during the luteal phase of 

 the cycle in the latter) wliicli are much 

 lower than those made more recentlv lObei- 



and Weber, 1951, 200 mg.; Kaufmann, 1952, 

 200 mg.; Trolle, 1955a, b, 260 to 440 mg.). 

 It now seems that the lower estimate made 

 by Corner can be attributed to the uncon- 

 trolled loss of sodium pregnanediol glu- 

 curonidate during storage, owing to bac- 

 terial hydrolysis (Trolle, 1955a). The rise 

 in the 24-hour values after ovulation, the at- 

 tainment of a peak the 7th and 8th days, 

 and the decline between then and men- 

 struation, are shown nicely in Trolle's 

 (1955a) study. His data provide an excel- 

 lent confirmation of the estimates based on 

 structural changes within the cell (Brewer, 

 1942; Corner, .Jr., 1956). The amount of 

 free pregnanediol excreted during the cycle 

 and therefore the amount of secreted pro- 

 gesterone varied from woman to woman, 

 and in the same woman there was variation 

 from one cycle to another. 



Data obtained by Duncan, Bowerman, 

 Hearn and Alelampy (1960) from their 

 chromatographic study have provided the 

 basis of an estimate that the following aver- 

 age amounts of jn-ogesterone are present in 

 the luteal tissue from swine: 23 /Ag. on day 

 4 of the cycle; 213 /^g. on day 8; 335 yug. on 

 day 12; 311 [xg. on day 16; /xg. on day 18. 

 From day 16 to day 102 of pregnancy, the 

 amount rose from 477 [xg. on day 16 to 578 

 fxg. on day 48 and then decreased to a low 

 of 120 ixg. on day 102. 



Edgar and Ronaldson (1958) made direct 

 measurements of the progesterone in lilood 

 collected from the ovarian vein in ewes. The 

 assay method consisted of extraction of 20 

 ml. of blood by, and partition between, or- 

 ganic solvents, final separation by chro- 

 motographic i)artition on filter paper, and 

 subsequent estimation of the hormone by 

 ultraviolet absorjjtion spectroscopy. They 

 reported that there is great variability from 

 animal to animal. The concentration in 

 yearling sheep was not lower than that in 

 older animals. Because of the liypothesis 

 advanced by Young and Yerkes ( 1943) that 

 the amount of secreted progesterone is low 

 in adolescent chimpanzees, an extension of 

 the Edgar and Ronaldson jirocedures to 

 |)iimates would be of interest. In this con- 

 nection, Edgar and Ronaldson postulated 

 what has been brought out as a generaliza- 

 tion in so many studies of the steroid hor- 

 mones. The absolute amount of progesterone 



