MAMMALIAN REPRODUCTIVE CYCLE 



519 



investigated the synergism in rabl^ts. Em- 

 ploying estrogen-primed animals, he found 

 that ovulation was facilitated when pro- 

 gesterone was injected less than 4 hours 

 before either mating, mechanical stimula- 

 tion of the vagina, or intravenous injec- 

 tion of copper acetate. Inhibition was ob- 

 tained when progesterone was injected 24 

 hours before such stimulation, thus confirm- 

 ing the often-cited observations of ]Make- 

 peace, Weinstein and Friedman (1937 » and 

 Friedman (1941) that progesterone inhiijits 

 ovulation in rabbits. 



Preovulatory secretion of gestagens now 

 seems likely. Morphologic luteal changes in 

 preovulatory follicles are considered in the 

 chapter on the ovary. A variety of evidence 

 in primates indicates that progestational 

 clianges in the endometrium begin before 

 ovulation (Bartelmez, Corner and Hart- 

 man, 1951). Several workers have reported 

 tiie excretion of small amounts of preg- 

 nanediol during the follicular phase of the 

 human cycle (Wilson, Randall and Oster- 

 berg, 1939; Smith, Smith and Schiller, 1943; 

 Davis and Fugo, 1948). Determination of 

 plasma progesterone in women by the 

 Hooker-Forbes test indicates the presence 

 of significant amounts a day or two before 

 a major rise in basal body temperature 

 (Forbes, 1950). In monkeys a small quan- 

 tity (ca. 0.5 to 1.0 ixg. per ml.) was detected 

 l)etween the 4th and 9th days, rising in the 

 10- to 15-day period to concentrations of 2 

 to 6 jxg. per ml. (Forbes, Hooker and Pfeif- 

 fer, 1950; Bryans, 1951). In both species a 

 transient decline seems to intervene before 

 the marked rise to still higher concentra- 

 tions during the luteal phase. In the rat, 

 Constantinides (1947) studied the stromal 

 nuclei of the endometrium at different 

 stages of the cycle and found that by the 

 Hooker-Forbes criteria there is evidence of 

 progesterone secretion during proestrum. 

 Astwood (1939) on the basis of water con- 

 tent of rat uteri concluded that progesterone 

 secretion begins with proestrum. In the rab- 

 l)it, Forbes (1953) assayed peripheral blood 

 at various intervals after mating or gonado- 

 trophin injection. Although no progesterone 

 was detectable in controls, significant 

 amounts appeared an average of 97 minutes 

 after mating and 66 minutes after gonado- 



trophin injection. As much as 2.5 /xg. ])er ml. 

 was found during the first 8 to 10 hours, 

 although marked fluctuations were noted 

 from time to time in the blood of individual 

 animals. Verly (1951) reported that soon 

 after mating the urine of rabbits contains 

 significant amounts of pregnanediol. 



It has become customary to state that 

 the gestagen that appears during the follicu- 

 lar phase of the cycle is probably formed by 

 the maturing follicle itself. Indeed, assays 

 of fluid from Graafian follicles and cysts 

 have indicated the presence of the hormone 

 (Duyvene de Wit, 1942; Hooker and 

 Forbes, 1947; Edgar, 1952, 1953). However, 

 if it is to take part in the release of ovulat- 

 ing hormone gestagen must be secreted ear- 

 lier than preovulatory maturation. For this 

 also there is some evidence. Two reports 

 cited above indicate that in monkeys, at 

 least, there is a detectable amount present 

 in the blood during the early follicular 

 phase. The known fact that a waning cor- 

 pus luteum favors the experimental induc- 

 tion of estrus and/or ovulation in sheep and 

 cattle (Hammond, Jr., 1945; Robinson, 

 1951 ; Alarden, 1952) is suggestive. Although 

 Hammond, Jr., Hammond and Parkes 

 (1942) tested this possibility by progester- 

 one sul)stitution with negative results, the 

 amount given may have been too small, as 

 Robinson suggested. A waning corpus lut- 

 eum in the rat favors ovulation, as dis- 

 closed in persistent-estrous animals in which 

 pseudopregnancy had been induced (Eve- 

 rett, 1939). Each of three pseudopregnancies 

 was followed b}' a short cycle before the 

 animals returned to persistent estrus. 



In the course of studies growing out of 

 this observation evidence was advanced 

 (Everett, 1945) which indicated that cor- 

 pora lutea of the normal rat are not wholly 

 inactive during the short cycle. Transient 

 depletion of cholesterol was observed in 

 such corpora lutea during the proestrum 

 that followed their formation. This implies 

 a transient increase of luteotrophin secre- 

 tion. Significantly this occurs before the re- 

 lease of LH. It is this writer's opinion that 

 gestagen from such sources is not essential 

 for the induction of ovulation but that it 

 does facilitate the action of estrogen. 



