PHYSIOLOGY OF ANTERIOR HYPOPHYSIS 



269 



The early idea that the gonadal hormones 

 were sex specific has been abandoned and 

 the possibility of abnormal functioning is 

 hardly considered when androgens are stud- 

 ied in the female. Perhaps it should be, be- 

 cause in many females among the Mam- 

 malia androgens are not known to have a 

 physiologic role. There is much doubt also 

 as to how importantly androgens contribute 

 to the regulation of the pituitary in the fe- 

 male. For the most part, injection of andro- 

 gen into female mammals produces a dele- 

 terious effect on ovarian development, 

 structure, and cyclic functions. Two excep- 

 tions may be noted: van Wagenen (1949) 

 injected sexually immature female monkeys 

 with androgen for long periods and obtained 

 a remarkable hastening of the appearance 

 of puberty. The age at first menses was, in 

 fact, reduced by nearly one-half. Androgen 

 injections have also been used successfully 

 to promote ovulation in persistent-estrous 

 rats (Marvin, 1948). 



Very soon after the pure androgenic ster- 

 oids became available, it was established 

 that these substances in adequate dosage 

 (which varied according to the androgenic- 

 ity of the compound) (1) caused a partial 

 reduction of the pituitary gonadotrophic 

 potency in castrated rats (Heller, Segaloff 

 and Nelson, 1943), and (2) prevented the 

 appearance of castration cells in the pitui- 

 tary (Nelson, 1935; Nelson and Merckel, 

 1937a; Wolfe and Hamilton, 1937). The 

 work of Hertz and Meyer (1937) and Nel- 

 son (1937i^ placed androgen-pituitary rela- 

 tionships onlTijuantitative basis. The rela- 

 tive efficiency of testosterone propionate 

 and dehydroandrosterone in restricting the 

 secretion of gonadotrophins by gonadec- 

 tomized parabionts was determined by 

 Hertz and Meyer (1937). Each compound 

 in adequate dosage completely suppressed 

 secretion of pituitary gonadotrophins as 

 shown by absence of ovarian stimulation 

 in the intact partner. Using these compounds 

 in dosages less than that required to pro- 

 duce complete ovarian suppression, the de- 

 gree of inhibition was found to be roughly 

 proportional to the dose. 



The androgens evoke clear-cut alterations 

 in pituitary FSH and LH potency and no 

 doubt are in part responsible for the quan- 

 titative sex differences in the pituitary 



content and level of secretion of these gon- 

 adotrophins. On a comparative basis the pi- 

 tuitaries of adult males are distinctly richer 

 in FSH than those of adult females (Hell- 

 baum and Greep, 1938; Greep and Chester 

 Jones, 1950b; Hoogstra and Paesi, 1955; 

 Paesi, de Jongh, Hoogstra and Engelbregt, 

 1955), yet in the absence of androgen, as 

 after castration, FSH increases as though 

 an inhibiting influence had been removed. 

 Long-term castrates given large doses of 

 testosterone showed only a partial (Heller, 

 Segaloff and Nelson, 1943) or no reduction 

 in gonadotrophic potency. Examining the 

 effect of androgens on the pituitary gonado- 

 trophins of adult intact female rats, Greep 

 and Chester Jones (1950b) found unex- 

 pectedly that within a specified range of 

 dosage (0.1 to 0.5 mg. of testosterone pro- 

 pionate per day) , FSH potency was elevated 

 over that of untreated controls. Similar 

 findings have been reported by Pincus 

 (1950), Hoogstra and Paesi (1957), and 

 Paesi, de Jongh and Willemse (1958) . Hoog- 

 stra and Paesi made the additional observa- 

 tion that the increase of pituitary FSH 

 with androgen treatment (2 mg. of testos- 

 terone propionate daily) is not limited to 

 intact females, but occurs in intact males 

 and gonadectomized males and females as 

 well. Furthermore, the response was not 

 modified by simultaneous administration of 

 2 fxg. of estradiol benzoate. 



Interest in the androgen-LH relationship 

 is stimulated by the consideration that LH 

 acting independently evokes androgen se- 

 cretion by the testis, whereas its ability to 

 elicit the secretion of estrogen by the ovary 

 necessarily involves other factors, notably 

 FSH. It would be expected then that the 

 LH-testicular androgen relationship might 

 be subject to somewhat more precise analy- 

 sis on the basis of experimental data, but 

 this has not been fully realized. There is 

 some evidence that a push-pull mechanism 

 is operative. The injection of testosterone 

 for more than 30 days results in the elimina- 

 tion of LH potency from the pituitary 

 glands of long-term gonadectomized rats 

 (Hellbaum and Greep, 1943; Paesi, de 

 Jongh and Willemse, 1958). The latter au- 

 thors concluded that testosterone depressed 

 the LH content to lower levels in intact rats 



