HORMONES IN DIFFERENTIATION OF SEX 



119 



ferentiation, and testis grafts inhibit the 

 Miillerian ducts of females; on the other 

 hand, male hormones of adult type fail to 

 inhibit the ducts, or produce only a limited 

 and localized involution in a few species. 



c. The time factor is critical in the hor- 

 monal control of the jNIiillerian ducts. To 

 suppress primary differentiation of the ducts 

 in birds and amphibians, male hormone 

 must be administered before or during the 

 formative stage of development. However, 

 the fully formed duct remains sensitive to 

 hormones up to the onset of sex differentia- 

 tion. Female hormone administered before 

 this stage insures retention and develop- 

 ment of the ducts in males, and during the 

 same period they are subject to inhibition 

 by male hormone or by the embryonic testis. 

 Beyond this point the final development or 

 the involution of the ducts has been irre- 

 versibly determined and hormones are with- 

 out effect. 



d. In the absence of previous hormonal 

 conditioning, as after early castration or 

 early isolation in vitro, the Miillerian ducts 

 of either sex are capable of an autonomous 

 differentiation, comparable to development 

 in normal females; this development can 

 be prevented, however, and involution in- 

 duced, by introduction in vitro of an em- 

 bryonic testis, or (in birds) by the ad- 

 dition of male hormone to the medium. 



e. In amniote embryos the testis hormone 

 is the controlling factor in the differentiation 

 of the Miillerian ducts. The involution of 

 the ducts in males is conditioned by the 

 testes, whereas in the absence of gonads 

 there is an almost normal development of 

 the ducts in embryos of either sex. This 

 does not mean, however, that the embryonic 

 Miillerian ducts are insensitive to female 

 hormone; in sufficient concentration it pro- 

 duces hypertrophic de^'elopment in both 

 sexes. 



f. The evidence from cultivation in vitro 

 shows that the effects of hormones on the 

 Miillerian ducts are exerted directly and 

 are independent of the organism as a whole. 



3. The Male Duct System 



The male sex duct, or Wolffian duct, de- 

 velops first as the duct of the pronephros 

 (primary nephric duct) and subsequently 



serves as the mesonephric duct in both sexes. 

 As the mesonephros is replaced by the 

 metanephros in amniote embryos, the Wolf- 

 fian duct loses its excretory function and its 

 fate in the two sexes is different. In the fe- 

 male it disappears entirely or survives only 

 as vestiges, but in males it acquires a new 

 status as the male sex duct. At the same time 

 a certain number of mesonephric tubules, 

 which connect the duct with the rete canals 

 of the testis, become a part of the epididy- 

 mis, and the seminal vesicle develops as a 

 diverticulum of the duct near its junction 

 with the urinogenital sinus. During its early 

 history as the duct of the mesonephros the 

 Wolffian duct is unresponsive to sex hor- 

 mones, but with the onset of sex differentia- 

 tion it becomes responsive to the male hor- 

 mone. 



The role of male hormone in the differen- 

 tiation of the Wolffian ducts. In the female 

 of amphibians experimental transformation 

 of ovaries into testes is followed by hyper- 

 tro])hy and masculinization of the AVolffian 

 ducts (Humphrey, 1942), and transplanta- 

 tion of testes into larval castrates of either 

 sex has the same effects (de Beaumont, 

 1933). Administration of male hormones 

 produces marked hypertrophy of the Wolff- 

 ian ducts in larval amphibians of either 

 sex [e.g., Burns, 1939c; Foote, 1941; for 

 summary see Gallien, 1955). A similar re- 

 sponse occurs in the embryos of birds and 

 has also been reported in many species of 

 mammals (Figs. 2.23, 2.24). ^^ This is the 

 case in female embryos as well as in males. 

 Development of epididymal tubules (from 

 the epoophoron) also takes place in females 

 (Fig. 2.24D) which also commonly develop 

 seminal vesicles (Greene, 1942; Raynaud, 

 1942; Wells and van Wagenen, 1954 L With 

 higher dosages all these structures undergo 

 extreme hypertrophy. 



Female hormones, on the contrary, appear 

 to have little influence on the development 

 of the Wolffian ducts, although in a few 

 cases a jiartial involution of the ducts has 



^" This effect has been widely reported : see Wil- 

 lier (1939), Wolff (1938, 1950) for the chick; Greene 

 (1942) for the rat; Raynaud (1942), Turner (1940) 

 for the mouse; Jost (1947a) for the rabbit; Godet 

 (1949) for the mole; Burns (1939a and b, 1945a); 

 and Moore (1941) for the opossum. 



