132 



BIOLOGIC BASIS OF SEX 



has the expected result; regardless of sex 

 constitution, only the female type of syrinx 

 develops. But male hormone (testosterone 

 proprionate) under the same conditions pro- 

 duces, paradoxically, organs of female or of 

 intermediate form. The dosages employed, 

 however, were extremely large (5 mg. and 

 40 mg. per cc. solvent) ^^ and in the light of 

 the effects of large doses of androgen on the 

 gonads and other structures the anomalous 

 result is not surprising. 



VI. The Pituitary and the Diiferentiation 



of Sex 



It does not appear that the anterior lobe 

 of the pituitary is concerned in the primary 

 differentiation of sex, i.e., in the morpho- 

 genesis of the gonads themselves. Early hy- 

 pophysectomy does not interfere with their 

 histologic differentiation, up to the stage at 

 least where they are fully characterized as 

 ovaries or testes; neither is the process of 

 differentiation appreciably delayed. Later, 

 however, deficiencies of a secondary order 

 may appear in the genital tracts of hypo- 

 physectomized animals; the development of 

 various accessory sex structures may be 

 considerably retarded but without any es- 

 sential change in character. This effect is 

 explainable as the result of diminished se- 

 cretory activity on the part of the gonads 

 through lack of adequate gonadotrophic 

 stimulation. The question of when the func- 

 tional interrelation between the gonads and 

 the anterior pituitary is established has been 

 reviewed by Willier (1952, 1955) with spe- 

 cial reference to the chick, and .lost (1953, 

 1955) has dealt with this problem in mam- 

 malian embryos and fetuses. In each case 

 gonadotrophic activity is evident shortly 

 after the period of gonad differentiation and 

 covers the period when the sex ducts and 

 other accessory structures are differentiat- 

 ing. Some of the evidence on which these 

 statements are based will be briefly re- 

 viewed. 



In amj)hibian embryos or early larvae, 



^* Under the conditions of culture the exphints 

 develop in close contact with droplets of the hor- 

 mone solution, and may actually be exposed to 

 extremely high concentrations. Culture with the 

 oil solvent alone, however, shows that the solvent 

 is not the disturbing factor. 



hypophysectomized long before the time of 

 sex differentiation, the development of ova- 

 ries and testes proceeds normally and with- 

 out appreciable delay until toward the end 

 of the larval period (Smith, 1932, p. 752; 

 Chang and Witschi, 1955; Chang, 1955). It 

 is also well known that during larval life 

 the gonads are capable of responding readily 

 to gonadotrophic substances by rapid 

 growth and precocious maturation of the 

 germinal elements (e.g., Burns and Buyse, 

 1931; Burns, 1934). During this period 

 pituitary stimulation merely accelerates the 

 normal processes of development and matu- 

 ration. It has been shown previously that 

 in many amphibian species administration 

 of steroid sex hormones during the larval 

 period induces transformation of the gon- 

 ads; however, an interesting case is known 

 in which sex hormones appear to be without 

 effect unless a gonadotrophin is also adminis- 

 tered (Puckett, 1939, 1940). The tadpoles 

 of a so-called "undifferentiated race" of 

 Rana catesbiana all have gonads w^iich 

 structurally resemble young ovaries until 

 late in larval life, when differentiation of 

 the males occurs rather abruptly. The ad- 

 ministration of gonadotrophin alone to the 

 undifferentiated tadpoles initiates sex dif- 

 ferentiation precociously, the two sexes ap- 

 pearing in the usual 50:50 ratio. The ad- 

 ministration of sex hormones of either type 

 to tadpoles during the indifferent period is 

 without effect; the gonads are apparently 

 incapable of responding at this stage of de- 

 velopment. However, when the sex hor- 

 mone and gonadotrophin are administered 

 concurrently a striking response occurs; 

 not only is sex differentiation precipitated, 

 as when gonadotrophin was administered 

 alone, but a complete transformation of sex 

 takes place, resulting in all males or all fe- 

 males, according to the type of sex hormone 

 employed. The gonadotrophin is evidently 

 necessary to initiate sexual diff(>rentiation 

 but the type of differentiation which follows 

 is determined by the type of sex hormone. 

 In chick embryos "hypophysectomy" be- 

 fore the onset of sex differentiation has been 

 accomplished in two ways, by partial de- 

 capitation, in which the forebrain area is 

 remov(>d surgically after 33 to 38 hours of 

 incubation (Futio, 1940), and bv irradiation 



