PHYSIOLOGY OF ANTERIOR HYPOPHYSIS 



!71 



prising and one can only conjecture that the 

 release of FSH was not being interfered 

 with. The higher doses were obviously 

 adequate for direct tubular maintenance ir- 

 respective of ICSH or FSH inhibition. 



G. OTHER STEROIDS AND 

 OXIDATION PRODUCTS 



Several synthetic steroids related to the 

 sex hormones but which exhibit no estro- 

 genic activity have proved to be without ef- 

 fect on pituitary gonadotrophin content 

 (]\Iortimore, Paulsen and Heller, 1951). 

 Lipoadrenal extract and desoxycorticoster- 

 one acetate produced some uterine develop- 

 ment and some inhibition of hypophyseal 

 secretion of gonadotrophins, whereas corti- 

 sone was neither estrogenic nor inhibitory of 

 gonadotrophin secretion (Byrnes and Ship- 

 ley, 1950). Although exogenous estrogens 

 and androgens inhibited the development of 

 intrasplenic ovarian grafts in guinea pigs 

 (Lipschiitz, Iglesias, Bruzzone, Humerez 

 and Penaranda, 1948), and rats (Takewaki 

 and Maekawa, 1952), progesterone and 

 desoxycorticosterone failed to do so. 



O. W. Smith (1944, 1945) maintained on 

 the basis of her investigations that it is not 

 the circulating gonadal hormones per se 

 which influence pituitary function and po- 

 tency but the oxidation products of these 

 hormones. She used mainly the lactone of 

 estrone prepared by W. W. Westerfeld and 

 by Alan Mather. In her hands the lactone 

 both increased the size of the pituitary and 

 decreased its^gonadotrophic potency. The 

 studies of Bradbury (1947) and of Morti- 

 more, Paulsen and Heller (1951) suggested 

 that any pituitary responses induced by es- 

 trololactone may be attributable to its es- 

 trogenicity, which is approximately 1/100 

 that of estrone in regard to both estrogenic 

 activity and pituitary gonadotroiihic in- 

 hii)ition. 



H. EFFECT OF PROGESTERONE ON PITUITARY 

 GONADOTROPHIC FUNCTIONS 



Species vary in the extent to which the 

 secretion of gonadotrophins is influenced by 

 progesterone. In the guinea pig which has a 

 16- to 17-day cycle, progesterone inhibits 

 the preovulatory swelling (generally at- 

 tributed to LH) , but growth up to this point 

 is unaffected (Dempsey, 1937). In rodents 



with short estrous cycles the influence of 

 progesterone on the secretion of gonado- 

 trophins appears to be minor, in that mod- 

 erate doses do not alter ovarian maturation 

 or cyclic functions (Greep and Chester 

 Jones, 1950b). Although some inhibition of 

 gonadal functions can be demonstrated after 

 massive doses of progesterone, interpreta- 

 tion is always complicated by the weak es- 

 trogenicity and androgenicity of the com- 

 l)ound. Similarly, total gonadotrophin 

 content of the pituitary is little altered by 

 progesterone. 



Although progesterone is primarily a 

 product of the corpus luteum and exerts a 

 major function during the luteal (and 

 gravid ) phase of the cycle, there are strong 

 indications that in some species the secre- 

 tion of progesterone is initiated in follicles 

 before ovulation (guinea pig, Dempsey, 

 Hertz, and Young, 1936; rat, Astwood, 

 1939; Boling and Blandau, 1939; mouse, 

 Ring, 1944). Consistent with this conclu- 

 sion is the finding that the peak level of 

 progesterone in the blood of cyclic rats 

 coincides with the proestrum as determined 

 by the Hooker-Forbes assay (Constan- 

 tinides, 1947). By the same means proges- 

 terone activity has been found in the blood 

 of laying hens but not in nonlaying hens or 

 roosters (Fraps, Hooker and Forbes, 1948. 

 1949). The preovulatory appearance of pro- 

 gesterone is believed to be important in the 

 elicitation of behavioral estrus (see chapter 

 by Young ) and as a component of the hypo- 

 thalamo-pituitary triggering mechanism for 

 ovulation (see chapter by Everett). 



Current interest in the progesterone regu- 

 lation of gonadotrophic functions has been 

 focused on the latter mechanism. Proges- 

 terone induces or at least hastens ovulation 

 in cyclic-estrous rats (Everett and Sawyer, 

 1949a), persistent-estrous rats (Everett, 

 1940), rabbits (Sawyer, Everett and Mar- 

 kee, 1950), hens (Fraps and Dury, 1943; 

 Rothchild and Fraps, 1949), cattle (Hansel 

 and Trimberger, 1952), anestrous ewes (T. 

 J. Robinson, 1954), anovulatory monkeys 

 (Pfeiffer, 1950) , and women (Rothchild and 

 Koh, 1951 ) . Notably too, both ovulation and 

 luteinization have been observed in ovar- 

 ian grafts in castrated male rats following 

 administration of progesterone (Kempf, 

 1949, 1950) . Such grafts normally show only 



