MAMMALIAN REPRODUCTIVE CYCLE 



507 



been touched. Pointing up our ignorance, 

 Sturgis (1949) in a careful study of atresia 

 of large follicles in the monkey ovary, spec- 

 ulated that their hypertrophied thecal tissue 

 may serve the useful purpose of estrogen 

 secretion during the interim between follicle 

 rupture and organization of the corpus 

 luteum. 



We are in need of ciuantitative appraisals 

 not only of the total numbers of healthy and 

 atretic follicles of all categories present in 

 representative species at progressive stages 

 of the cycle, as in the work on the rat by 

 Mandl and Zuckerman (1952), but also of 

 the respective volumes of theca, granulosa, 

 interstitial tissue, and corpora lutea. Lane 

 and Davis (1939) determined in rat ovaries 

 at four stages of the cycle the respective 

 total volumes of theca, granulosa, and antra 

 in all healthy follicles, as well as the sepa- 

 rate mitotic indices of theca and granulosa. 

 Such differential information on multiplica- 

 tion of cells and increase of antral volume 

 is important. Although the latter accounts 

 for a major part of the increase in volume 

 of the larger follicles, it represents a func- 

 tion quite apart from protoplasmic growth 

 per se. 



There is now considerable evidence that 

 estrogen itself exerts a growth -promoting 

 influence on the follicle and, furthermore, 

 sensitizes it to gonadotrophic stimulation. 

 Details may be found in papers by Pencharz 

 (1940), Williams (1940, 1944, 1945a, b), 

 Simpson, Evans, Fraenkel-Conrat and Li 

 (1941) , Gaarenstroom and de Jongh (1946) , 

 and Desclin (1949a,) . Although it seems that 

 these effects have not been elicited by phys- 

 iologic doses, the possibility remains that 

 estrogen operates within the confines of the 

 ovary as a mediator of some of the effects 

 of the gonadotrophins. In the neighborhood 

 of cells that produce it the estrogen concen- 

 tration is probably far above that which 

 would be considered physiologic for the re- 

 mainder of the body. 



A. CORRELATION OF OVARIAN SECRETION 

 W^ITH THE FOLLICULAR CYCLE 



Knowledge of the secretory output of 

 the ovary during the cycle is almost entirely 

 indirect and derives chiefly from (1) sub- 

 stitution experiments carried out in a vari- 



ety of si)ecies, and (2) assays of urine, 

 mainly human but occasionally from other 

 forms. Satisfactory assays of blood estrogen 

 have been very limited and chemical analy- 

 sis of the steroid content of ovarian venous 

 blood is in only its preliminary stages. 



The early substitution experiments are 

 chiefly of historic interest (Allen, Danforth 

 and Doisy, 1939). In great measure these 

 investigations constitute crucial steps in 

 proof that the ovary secretes steroid hor- 

 mones which are fundamentally responsible 

 for the manifestations of estrus. Con- 

 versely, then, these manifestations might be 

 considered to reflect an increase of estrogen 

 secretion and their absence a relative de- 

 crease. It has been learned, however, that 

 the action of estrogen in certain instances 

 may be greatly modified by progesterone, 

 androgens, and certain adrenocortical ster- 

 oids (notably desoxycorticosterone). Andro- 

 gens are known to be secreted in the female 

 by the adrenal cortex (Dorfman and van 

 Wagenen, 1941 ; Gassner, 1952) and by the 

 ovaries (Hill, 1937a, b; Parkes, 1950; 

 Deanesly, 1938; Burrill and Greene, 1941; 

 Pfeiffer and Hooker, 1942; Alloiteau, 1952). 

 Progesterone secretion is probably not con- 

 fined to the luteal phase of the cycle (see p. 

 519j. Evidence for its secretion during fol- 

 licle maturation is considerable and its pos- 

 sible production even earlier cannot be 

 excluded. These considerations make it un- 

 wise, therefore, to regard phenomena such 

 as vaginal cornification, turgescence of 

 vulva and sex skin, uterine growth, as direct 

 ciuantitative measures of estrogen output. 

 This point may be illustrated by certain ob- 

 servations made in chim])anzees by Fish, 

 Young and Dorfman (1941) and illustrated 

 in Figure 8.6. Assays of urinary estrogens 

 during the cycle exhibited two peaks, only 

 the first of which coincided with the swelling 

 of sex skin. The second peak of estrogen ex- 

 cretion was unaccompanied by swelling, pre- 

 sumably because of the coordinate increase 

 of progesterone secretion. Had swelling been 

 the only guide only the first peak would 

 have been apparent. 



Assays of urinary estrogen in primates 

 have often shown double peaks such as il- 

 lustrated for the chimpanzee. Pedersen- 

 Bjergaard and Pederson-Bjergaard (1948i. 



