530 



physioloc;y of gonads 



chorionic gonadotroi)hin (Selye, 1940; 

 Bradbury, 1940, 1941), estrogen, progester- 

 one, or desoxycorticosterone (Hale, 1944; 

 Takasugi, 1954). The adult ovaries develop 

 ])rominent follicles which never luteinize. 

 Pfeiffer reported that his constant-estrous 

 animals would not copulate. The conclusion 

 was reached that the hypophyses of these 

 rats had been masculinized by the early ac- 

 tion of androgen. Subsequently (1941), he 

 attempted unsuccessfully to invoke ovula- 

 tion in similar animals by daily injection of 

 small amounts of progesterone. Kempf 

 (1950) later accomplished this with 2 in- 

 jections, more widely spaced (interval, 1 

 week ) . Takasugi was unable to produce 

 corpora lutea in postnatally estrogenized 

 rats by chronic progesterone treatment after 

 puberty, although vaginal cycles were ob- 

 served. The further addition of androgen, 

 interestingly enough, brought about luteini- 

 zation. It would seem that a prime effect of 

 the hormones during infancy is to produce 

 a permanently high threshold in the hypo- 

 thalamic ovulating mechanism without de- 

 stroying it. 



VII. The Luteal Phase 



The luteal phase presents more enigmas 

 than the phases that precede it. What initi- 

 ates it? What keeps it going? What brings it 

 to an end? How is its duration determined? 



Its beginning may arbitrarily be defined 

 as the moment of ovulation, yet gestagen se- 

 cretion may start during the follicular 

 phase, and structural changes in the follicle 

 wall during pre-ovulatory maturation may 

 be considered as first steps in luteinization. 

 Fi'om the time of follicle rupture onward the 

 ac(iuisition of full secretory activity by the 

 cori)ora lutea roughly parallels their mor- 

 phologic differentiation. It is even then a 

 gi'adual process. 



Luteinization as a structural change does 

 not insure the attainment of secretory ac- 

 tivity. The former is the ultimate effect of 

 the preovulatory discharge of hypojihyseal 

 luteinizing hormone; some other (lutcotro- 

 l)hic) factor must come into play to bring 

 about and maintain gestagen secretion. We 

 must, then, hv concerned with the special 

 character of luteotrophins, with nieclia- 

 nisnis tliat favor their secretion by the hy- 

 po])hysis, with mechanisms that shortcMi or 



lengtlien the Hfc of the corpus luteum and, 

 therefore, witli the mechanisms that nor- 

 mally bring the corpus luteum phase to an 

 end. In the final analysis this last has an 

 im])oi-tance equal to the ovulation mecha- 

 nism in the timing of recurrent cycles. 



1. Lutcotrophic Snbst(niccs 



The term luteotropliin was proposed by 

 Astwood ( 1941 j to I'efer to a substance that 

 maintains function of corpora lutea, in dis- 

 tinction to substances that cause them to 

 form. It is now conceded that the substance 

 desci'ibed in that paper was probably the 

 lactogenic hormone. Evans, Simpson, Lyons 

 and Turpeincn (1941) demonstrated that 

 purified lactogen is luteotrophic in hypophy- 

 sectomized rats. This has been confirmed by 

 several later investigations (Tobin, 1942; 

 Nelson and Pichette, 1943; Everett, 1944b; 

 Desclin, 1948; Gaarenstroom and de Jongh, 

 1946 ) . Although lactogen seems to be the 

 hypophyseal luteotrophin in rats, such is not 

 necessarily true for all species (Bradbury, 

 Brown and Gray, 1950). Nevertheless, the 

 expression luteotrophin in the generic sense 

 continues to be desirable. 



In the rabbit, lactogen is said to have lit- 

 tle, if any, luteotrophic effect (Klein and 

 Mayer, 1943; Mayer, 1951). Yet rabbits 

 have never been tested with rabbit lactogen. 

 Several workers have failed to demonstrate 

 a luteotrophic function of lactogen prepara- 

 tions in monkeys (Hisaw, 1944; Bryans, 

 1951) and women (Holmstrom and Jones, 

 1949; Bradbury, Brown and Gray, 1950). 

 Positi^•e evidence of such activity in pri- 

 mates furnished by Fried and Rakoff ( 1952) 

 and more recently by Lyon (1956) lias not 

 gained wide acceptance. The former authors 

 re])orted that amounts of chorionic gonado- 

 ti'ophin which were tluMUseh-es inadequate, 

 wlicii siipplciiicnrcd by lacrogcii ( Luteo- 

 ti-()pliiii, S(|uil)l>l prolonged the functional 

 life of the coi'pus luteuni in nonpregnant 

 women. Lyon rejjorted such prolongation 

 using lactogen alone. The Squibl) lactogen 

 was also used by Moore and Nalbandov 

 (1955) in prolonging the luteal phase of the 

 cycle in the ewe. As in the human experi- 

 ments, howe\-er. one would like to know 

 whether lactogen is capable of initial stimu- 

 l.'iiioii of secretory activity of corpora lutea 

 and of maintaining their function in the ab- 



