MAMMALIAN OVARY 



475 



circulating in the fluids of the body may be 

 less important than the minimal amount. 

 The ewes secreting less than the minimum 

 may be unable to maintain pregnancy, 

 whereas those secreting more may simply 

 have surpluses which are of little signifi- 

 cance. The same principle may be extended 

 to the human female (Davis, Plotz, Lupu 

 and Ejarque, 1960 ». 



An observation new to the reviewer could 

 l)e important. When two corpora lutea were 

 present in one ovary the concentration of 

 I)rogesterone was in the same range as that 

 for the ewes with one corpus luteum (Edgar 

 and Ronaldson, 1958). In another ewe there 

 were 2 corpora lutea in one ovary and 1 in 

 the other, but the concentrations in the 

 blood from the 2 ovarian veins were almost 

 the same. 



A facet of the problem of the rate of pro- 

 duction of ovarian estrogen and proges- 

 terone which has become apparent is that 

 endogenously and exogenously administered 

 estrogen (Rakoff, Cantarow, Paschkis, Han- 

 sen and Walkling, 1944; Pearlman, 1957) 

 and progesterone (Haskins, 1950; Zander, 

 1954; Rappaport, Goldstein and Haskins, 

 1957; Davis and Plotz, 1957; Plotz and 

 Davis, 1957; Pearlman, 1957; Cohen, 1959) 

 disai)i:)ear from the blood very cjuickly, in 

 the human female and in such laboratory 

 mammals as the dog, rabbit, and mouse. 

 Zander, for example, injected 200 mg. of 

 progesterone intravenously into menopausal 

 and ovariectomized women. The concentra- 

 tion of this hormone in the blood was 1.44 

 /xg. per ml. after 3.5 minutes and 0.116 yu,g. 

 per ml. after 2 hours; 24 hours after the 

 injection progesterone could not be found by 

 the method he employed. The data obtained 

 by the other investigators were similar.^ 

 Using some of these data obtained from re- 

 ports in the literature and from his own 

 studies, Pearlman (1957) divided the total 

 amount of circulating hormone (M) by the 



■'To a cpitain extent, and possibly to a consider- 

 able extent, the rapid disappearance of progester- 

 one from the blood is explained by its storage in 

 the fat tissue of the body (Davis and Plotz, 1957; 

 Davis, Plotz, Lupu and Ejarque, 1960). Following 

 intramuscular injection of C"-4-progesterone, and 

 assuming an even distribution of radioactivity in 

 the fat of the body, about 17.7 per cent, 33.7 per 

 cent, and 19.6 per cent of the administered dose 

 was present 12, 24, and 48 hours, respectively, after 

 the administration of the labeled hormone. 



endogenous production rate (r) as a means 

 of obtaining the turnover time iT), i.e., the 

 time refjuired for a complete replacement 

 of the circulating hormone by a fresh supply 

 from the endocrine gland. His method was 

 not free from criticism by discussants; 

 nevertheless, informative estimates were 

 made. The turnover time of the various 

 estrogens was calculated to be about 6 min- 

 utes or less, that of progesterone, about 3.3 

 minutes. 



Not unrelated to the i)roblem of the 

 amounts of hormone produced is the sul)ject 

 of plasma (and erythrocyte) binding of the 

 ovarian hormones. Especial attention was 

 given the subject by Rakoff, Paschkis and 

 Cantarow ( 1943 ) who reported that as much 

 as 50 per cent of the total estrogen content 

 of the serum of women is present in a com- 

 bined or conjugated (bound) form, and 

 that almost all of the estrogens of preg- 

 nancy are bound to the protein fractions of 

 the serum. Shortly thereafter, Szego and 

 Roberts (1946) reported that two-thirds of 

 the total estrogen in the blood in human 

 l)lasma is normally associated with jn-otein 

 constituents, and in a subsequent series 

 of publications (Roberts and Szego, 1946, 

 1947; Szego, 1953, 1957; and others) that 

 the liver is the site of the formation of the 

 protein-estrogen complex or estroprotein. 

 The nature of the complex soon become con- 

 troversial and has not yet been resolved 

 (Eik-Nes, Schellman, Lumry and Samuels, 

 1954; Antoniades, McArthur, Pennell, In- 

 gersoll, Ulfelder and Oncley, 1957; Sand- 

 berg, Slaunwhit(> and Antoniades, 1957; 

 Daughaday, 1959). In the jiresent context, 

 however, othei- considei'ations are more im- 

 portant. 



Protein-liinding is not confined to the es- 

 trogens and their metabolites, but other 

 steroidal hormones, progesterone, testoster- 

 one, and corticosteroids, are also present 

 in the blood in a bound-state. In studies of 

 the binding relationships of serum albumin, 

 the link to the esti'ogens was found to be 

 strongest, that to the corticosteroids rela- 

 tively weak, and that to ])rogesterone and 

 testosterone intermediate (Sandberg, Slaun- 

 white and Antoniades, 1957; Slaunwhite and 

 Sandberg, 1958; Daughaday, 1959). The i;- 

 lationships in the case of other components 

 of i^rotein mixtures have been sliown to be 



