PHYSIOLOGY OF ANTERIOR HYPOPHYSIS 



265 



will be increased, decreased, or left unaf- 

 fected. For practical reasons alone it has 

 been disappointing that the results achieved 

 have been predominantly those of inhibi- 

 tion. Consequently the physician is today 

 fairly well armed with ways of slowing, but 

 not of arousing, pituitary gonadotrophic ac- 

 tivities. 



C. EFFECTS OF ESTROGENS ON FOLLICLE- 

 STIMULATING HORMONE SECRETION 



The result of the administration of ster- 

 oids to animals depends on not only the 

 state of the animal, but also the dose of the 

 hormone and duration of the treatment. 

 Among the ^nown inhibitors of pituitary 

 gonadotrophin secretion, the estrogens are 

 the most effective. There is complete agree- 

 ment that estrogen in moderate to high 

 dosage inhibits FSH synthesis and libera- 

 tion. No clear qualitative differences have 

 been encountered in the effect of a variety 

 of natural and synthetic estrogenic steroids 

 in this regard. Quantitative differences in 

 the capacity of the many available estro- 

 gens to suppress FSH secretion, however, 

 are readily demonstrable and are directh" 

 referable to the estrogenicity of the steroid. 

 Present evidence suggests that, although 

 l)hysiologically equivalent dosages of a num- 

 ber of estrogenic substances do not produce 

 precisely comparable effects on the pitui- 

 tary, a close correspondence exists between 

 the ability of an estrogen to induce vaginal 

 estrus and its inhibitory action on the pi- 

 tuitary. "^^^-- 



The influence of relatively large amounts 

 of estrogens on the secretion of gonadotro- 

 ])hins is of interest, but particularly helpful 

 in resolving the problems of normal physiol- 

 ogy are those experiments in w^iich low 

 dosages of estrogens, at or near the naturally 

 occurring levels, have been given. Here, 

 however, there is not agreement with respect 

 to the meaning of the results. It has often 

 l)een claimed that maturity may be* 

 achieved by pituitary function independent 

 of estrogen secretion. In the development of 

 a broader concept. Heller and his co-workers 

 were the first to take the position that 

 amounts of estrogen falling within physio- 

 logic limits have no suppressive action on pi- 

 tuitary potency in rats nor on the secretion 

 of gonadotrophins as measured by urinary 



excretion (of F8H> in women. Thus Lauson, 

 Heller and Sevringhaus (1938) reported that 

 ovarian development and sexual maturation 

 in rats were not altered by chronic treatment 

 with what they considered to be physiologic 

 quantities of estrogen, nor did the pitui- 

 taries exhibit any significant decrease in 

 gonadotrophin content. Heller and Heller 

 (1939) and Heller, Heller and Sevringhaus 

 (1942) found that amounts of estrogen 

 which inhibited ovarian compensatory hy- 

 pertrophy in rats following unilateral cas- 

 tration did not decrease pituitary potency; 

 and in women doses of estrogen, adequate 

 to control clinical symptoms at the meno- 

 pause, did not diminish the excretion of gon- 

 adotrophin. Heller, Chandler and jMyers 

 (1944) also reported that whereas physio- 

 logic doses of estradiol failed to prevent the 

 typical rise in the titer of urinary gonadotro- 

 phin following ovariectomy in women, larger 

 doses were completely effective. This series 

 of papers by Heller and his associates has 

 long been puzzling in the interpretation of 

 pituitary-gonadal relationships. It is a weak 

 point in their evidence that they used uter- 

 ine stimulation in recipient immature intact 

 rats as the end point for the assay of pitui- 

 tary gonadotrophin potency. It is doubtful 

 if this procedure is sufficiently reliable for 

 the establishment of this important concept. 

 It is to be noted that in the domestic fowl 

 Breneman (1955) likewise has observed no 

 suppressive effects on gonadal maturation 

 using doses of estrogen that are wathin the 

 upper limits of normal blood estrogen levels. 

 Heller's observations have been contra- 

 dicted by later observations based on more 

 critical assay procedures. Biddulph, Meyer 

 and Gumbreck (1940) suggested that gon- 

 adotrophic functions in rats are inhibited 

 by doses of estrogen well below the 

 threshold dose for the estrous reaction of the 

 vagina. Of greatest interest and pertinence, 

 Byrnes and Meyer (1951a) found that the 

 minimal amount of estradiol or estrone re- 

 quired to stimulate the uterus in the spayed 

 member of spayed-intact parabionts was 

 3 to 4 times that needed to inhibit the pi- 

 tuitary of the same animal as judged by the 

 ovaries of the adjoined twin. In an extension 

 of this study Byrnes and Meyer (1951b) 

 administered estradiol in closely graded 

 doses to single immature (30-dav-old) and 



