HORMONES IX DIFFERENTIATION OF SEX 



133 



of the hypophyseal region (Wolff and Stoll, 

 1937) . After excision of the forebrain, histo- 

 logic differentiation of the gonads proceeds 

 normally. Later, however, the interstitial 

 tissue of the testis fails to develop or is de- 

 ficient in quantity, and the cortex of the 

 left ovary remains rather thin through fail- 

 ure of secondary sex cords to develop in the 

 usual numbers. The development of the 

 gonaducts, on the other hand, is normal in 

 both sexes. Wolff and Stoll reported that, 

 after destruction of the hypophysis by ir- 

 radiation, differentiation of the gonads con- 

 tinued in a normal manner to the end of 

 incubation and again the gonaducts were 

 found to develop normally. Such embryos, 

 moreover, undergo sex reversal in the usual 

 manner when treated with sex hormones 

 (Wolff, 1937). The available experimental 

 evidence indicates, then, that the hypophy- 

 sis has no appreciable part in the primary 

 differentiation of sex, a conclusion which is 

 supported by van Deth, van Limborgh and 

 van Faassen (1956). 



In mammalian embryos and fetuses, hy- 

 pophysectomy has been carried out by pro- 

 cedures similar to those described for the 

 chick, namely, partial or total decapitation 

 and irradiation with x-rays. The former 

 method was used on embryos of the rat 

 (Wells, 1947, 1950) and the rabbit (Jost, 

 1947d, 1950, 1951a), and the latter on the 

 embryos of the mouse (Raynaud and Fril- 

 ley, 1947; for a summary see Raynaud 

 1950) . In the case of the rabbit and the rat, 

 the operation was not performed early 

 enough to affect the primary differentiation 

 of the gonads; in the mouse, however, ir- 

 radiation on the 12th day of gestation, just 

 at the beginning of differentiation, was 

 without effect except for a certain reduction 

 in the number of germ cells when the hy- 

 pophysis was entirely destroyed. The re- 

 sults differed sharply, however, with refer- 

 ence to the condition of the genital tracts 

 in hypophysectomized male rabbit fetuses, 

 as opposed to those of the rat and the mouse. 

 In the two latter species no significant 

 changes in the development of the accessory 

 genital structures were observed. It may be 

 that in these species the entire process of 

 sexual differentiation is independent of pi- 

 tuitary function, although the possibility is 



perhaps not excluded that an extraneous 

 gonadotrophin, of maternal or placental ori- 

 gin, may be substituted. In the rabbit, on 

 the other hand, definite defects were found 

 in the development of certain accessory 

 genital structures, resembling those which 

 follow embryonic castration but somewhat 

 less severe. However, if gonadotrophin is 

 administered following decapitation these 

 deficiencies do not appear; they may there- 

 fore be ascribed to lack of gonadotrophic 

 activity (Jost, 1951a, 1953). The defects 

 observed vary in severit}^ according to po- 

 sition ; the anterior regions of the gonaducts 

 and the epididymides, which are near the 

 testes, develop normally, whereas distant 

 structures such as the prostatic glands and 

 external genitalia may be almost as se- 

 verely affected as in castrate fetuses. This 

 observation indicates that the testis is act- 

 ing in an intermediary capacity. In the ab- 

 sence of the pituitary its humoral activity 

 is diminished to a level adequate for normal 

 differentiation of nearby structures but in- 

 sufficient to maintain the development of 

 more distant parts. The point has been pre- 

 viously established that after decapitation 

 there is a decrease in the amount of inter- 

 stitial tissue. 



The problem of the time of onset of gon- 

 adotrophic function in its relation to gonad 

 secretion and the dift'erentiation of the geni- 

 tal tract has been studied in the rabbit by 

 Jost (1951a). By examining the genital 

 tracts of decapitated male fetuses at short 

 intervals to determine when the first signs of 

 abnormal development appear, and by vary- 

 ing also the age at which decapitation was 

 performed, he was able to define rather 

 closely the beginning of gonadotrophic func- 

 tion and the period during which it is criti- 

 cal for normal development of the genital 

 structures. Following decapitation on the 

 19th day of gestation no marked defects in 

 the genital structures appear until about 

 the 22nd day, after which abnormalities be- 

 come more and more pronounced until the 

 24th day. If decapitation is delayed until 

 the 24th day no important anomalies are 

 subsequently found. It should be recalled 

 that the latter date coincides with the stage 

 after which castration likewise has no effect 

 on development. The interval from the 22nd 



