2G6 



HYPOPHYSIS AND GOXADOTROPHIC HORMONES 



adolescent (55-day-old) rats, intact and 

 spayed, for 10 days. The amounts given 

 were estimated to be within physiologic 

 limits. In the immature animals more estro- 

 gen was required to produce positive stimu- 

 lation of the uterus than to inhibit the pitui- 

 tary; the evidence for a similar differential 

 in the adolescent group was equivocal. 

 Greep and Chester Jones (1950b), using 

 adolescent rats, observed that a dose of 



estradiol benzoate which would inhibit ovar- 

 ian development in intact rats was adecjuate 

 for uterine maintenance in coetaneous cas- 

 trates. Byrnes and Meyer (1951b) observed 

 further that the quantity of estrogen re- 

 quired to inhibit the pituitary increased 

 from the immature to the adolescent rats 

 by a factor of 2.77. Although dilution of 

 hormone is involved because of the greater 

 size of the older animals, this did not seem 

 to invalidate the conclusion that the an- 

 terior pituitary becomes increasingly less 

 sensitive to the suppressing action of estro- 

 gen as sexual maturation progresses. 



These data indicate that FSH secretion 

 and estrogen bear a reciprocal relationship 

 and emphasize that FSH secretion is not a 

 pituitary property sui generis but depends 



*on the concomitant secretion of steroids. 

 This idea has an important bearing on how 

 a state of sexual maturity is attained. If we 

 consider that the evidence is in favor of a 

 prepubertal gonad-pituitary interaction, we 

 must assume that the immature gonad has 

 some capacity to secrete estrogen. In an un- 

 confirmed report, Zephiroff, Drosdovsky and 

 Dobrovolskaya-Zavadskaya (1940) have 



, claimed that immature rat ovaries have 

 a significant estrogen content. Byrnes and 

 Meyer (1951b) have postulated that re- 

 fractoriness of the adolescent rat pituitary 

 to estrogen permits higher levels of FSH 

 secretion and thus allows the attainment of 

 l)uberty. It seems clear that future progress 

 in this area will depend on the development 

 of satisfactory methods for measuring the 

 blood level of pituitary and ovarian hor- 

 mones. Until such information is available 

 it would be helpful merely to have some of 

 the present evidence confirmed. If, for in- 

 stance, it were firmly established that the 

 pituitary of the immature animal is more 

 sensitive to estrogen than is the uterus, this 



would form an excellent starting point for 

 future investigations. 



Exceptionally valuable information con- 

 cerning the effect of administered steroids 

 on pituitary function has been gained from 

 studies of parabiotic rats. The preparation 

 which has been most commonly employed 

 has consisted of immature rats, one of which 

 is castrated at the time of or following the 

 surgical union. Given no treatment, as in 

 control pairs, the castrated animal's pitui- 

 tary steps up the output of gonadotrophins, 

 thereby stimulating the gonads of the ad- 

 joined intact member. The resulting ovarian 

 secretions do not reach the pituitary of the 

 castrated partner and hence exert no in- 

 hibitory influence on it. Using substitute 

 steroids administered from the time of spay- 

 ing, it has thus been possible to ascertain 

 their ability to inhibit the castration-in- 

 duced hypersecretion of gonadotrophins. 

 The uterus of the castrate provides an index 

 of the estrogenicity of the administered 

 steroid. 



Meyer and Hertz (1937) demonstrated 

 convincingly that larger doses of estrogen 

 or androgen are required to inhibit the pi- 

 tuitary of a male than of a female rat. In 

 each the degree of gonadal inhibition in 

 the intact member was roughly propor- 

 tional to the dose of sex steroid administered 

 to the conjoined castrate. Biddulph, Meyer 

 and Gumbreck (1940) observed that the 

 minimal amounts of sex hormones required 

 for complete inhibition of the postcastration 

 rise in secretion of pituitary gonadotrophins 

 were in females: 0.025 fxg. estradiol, 1.5 /xg. 

 estriol, 1000 /xg. progesterone; and in males: 

 0.15 fxg. estradiol, 10 ^g. estriol, and 1000 /xg. 

 progesterone. These workers also noted that 

 the order of effectiveness of estrogens in 

 suppressing gonadotrophin secretion paral- 

 leled the order of their capacity to i)roduce 

 vaginal cornification in rats, viz., estradiol, 

 estrone, and estriol. 



In male animals estrogen damages the 

 spermatogenic epithelium of the testes to 

 the point that spermatogenesis is completely 

 interrupted and the testes shrink to infantile 

 size. At the same time the basophils of the 

 pituitary are severely degranulated and re- 

 duced in numbers relative to other cell 

 types, and the gonadotrophic potency of 



