268 



HYPOPHYSIS AND GONADOTROPHIC HORMONES 



estrous rat, which ovulates with such regu- 

 larity after the administration of pro- 

 gesterone (Everett, 1940; Hillarp, 1949; 

 Greer, 1953) or testosterone (INIarvin, 

 1948), does not thus respond to estrogen 

 unless pretreated for several days with pro- 

 gesterone (Everett, 1950). The latter result 

 indicates that progesterone may synergize 

 with or otherwise facilitate the LH-releasing 

 action of estrogen. Hammond, Jr. (1945), 

 on the other hand, succeeded in obtaining 

 ovulation in anestrous sheep with low, but 

 not with high, doses of estrogen. It would 

 seem that the effect of estrogen on LH re- 

 lease varies between species and within spe- 

 cies and is greatly influenced by the age of 

 the animal, dosage used, and the time in the 

 sex cycle at which treatment is instituted. 



E. DIFFERENTIAL EFFECTS OF GONADAL 



STEROIDS ON FOLLICLE-STIMULATING 



HORMONE AND LUTEINIZING 



HORMONE SECRETION 



The root of the matter in the regulation of 

 gonadal function is the interplay of FSH 

 and LH with the sex steroids. With respect 

 to estrogens, the results do not lead to a 

 clear-cut conclusion. Paesi (1952) provided 

 data on a series of immature rats treated 

 for 7 days with doses of estradiol benzoate, 

 ranging from 0.0002 to 100 /xg. daily. The 

 dose-response curve representing the effect 

 of estrogen on ovarian weight was diphasic. 

 Doses of 0.01 to 0.05 /xg. daily decreased 

 the ovarian weight, whereas greater amounts 

 up to 10 fxg. increased the ovarian weight 

 slightly; however, only with 100 /xg. did the 

 gain attain significance. The decrease in 

 ovarian weight with low doses represents, 

 he believes, an impairment of LH release, 

 inasmuch as the ovarian interstitium seemed 

 deficient. The enhanced ovarian weight 

 with excessive dosage was presumed to be 

 due either to increased FSH release or to 

 FSH enhancement by released LH, as sug- 

 gested by the stimulated interstitium. It is 

 to be noted, however, that even in hypophy- 

 sectomized immature female rats, excessive 

 doses of estrogen produced significant ovar- 

 ian enlargement and stimulate the develop- 

 ment of an unusual number of medium 

 sized "solid" follicles (Williams, 1940; Pcn- 

 charz, 1940; Gaarenstroom and de Jongh, 

 1946; Payne and Ilellbaum, 1955). 



Bradbury (1947) proposed that the effects 

 of estrogen on pituitary gonadotrophic 

 functions are made more accountable when 

 the results are considered in terms of acute 

 and chronic estrogen treatment. The latter 

 is well known to suppress gonadotrophic 

 function and to deplete the gonadotrophin 

 content. His acute experiments lasted only 

 48 to 120 hours and revealed a significant 

 increase in ovarian weight, which confirms 

 the results reported by Price and Ortiz 

 (1944) and others. Greep and Chester Jones 

 (1950b) also obtained a confirming result 

 and showed further than the reaction was 

 dependent on the presence of the pituitary. 

 In this connection it is pertinent to note that 

 Bradbury found a concurrent reduction in 

 pituitary gonadotrophic potency at 72 to 

 120 hours after the injection of estrogen and 

 concluded that the initial action of estrogen 

 is to release gonadotrophin (unspecified, but 

 the effect is mainly that of FSH) . The stim- 

 ulated ovaries showed in addition to ac- 

 celerated follicular growth a swollen inter- 

 stitium, suggesting that both FSH and LH 

 had been released. The interstitial cell 

 change was not confirmed in a later study 

 (Greep and Chester Jones, 1950b). Thus, 

 although it seems clear that under a given 

 circumstance the immediate reaction to es- 

 trogen may be a slight upsurge in either 

 FSH release or enhancement of FSH action, 

 it is unlikely that FSH production or re- 

 lease is normally dependent on estrogenic 

 action, since both its synthesis and release 

 are greatest when no estrogen is present. 



Meyer, Biddulph and Finerty (1946), 

 Gaarenstroom and de Jongh (1948), Greep 

 and Chester Jones (1950a, b), and Byrnes 

 and Meyer (1951b) attempted involved 

 analyses of the effect of gonadal steroids on 

 pituitary function in terms of the separate 

 gonadotrophins, FSH and LH. The wide di- 

 vergence in their accounts emphasizes how 

 poorly these matters are understood. 



F. EFFECTS OF ANDROGENS ON PITUITARY 

 GOXADOTROPHINS 



Considerations similar to those enumer- 

 ated in our discussion of the estrogens apply 

 to the influence of androgens on pituitary 

 gonadotrophins, yet with well defined dif- 

 ferences. The effects of androgens have been 

 studied in females quite as much as in males. 



