HORMONES IN DIFFERENTIATION OF SEX 



131 



Treatment with sex hormones during the 

 latter half of gestation shows that the proc- 

 esses described above are readily controlled 

 or reversed experimentally. In female fe- 

 tuses of mothers injected with male hor- 

 mone, development of the mammary gland 

 follows the male pattern; the mammary 

 buds separate from the epidermis and per- 

 sist only as nodular rudiments, the nipple 

 fold does not appear and nipples fail to de- 

 velop. The female pattern of differentiation 

 is converted completely to the male type. 

 The use of female hormones, on the other 

 hand, leads to a somew^hat paradoxical re- 

 sult ; there is an inhibition of the mammary 

 buds rather similar to that exerted by an- 

 drogen, but nipple development on the con- 

 trary is strongly stimulated (Fig. 2.34D). 

 The dosages were large, however, and the 

 effects of female hormones under more phys- 

 iologic conditions have not as yet been de- 

 termined. With respect to development of 

 the nipple similar results have been reported 

 in the laboratory mouse (Greene, 1942); 

 male hormone completely inhibits the nijv 

 ples in females whereas female hormone in- 

 duces typical development in males. 



Of particular interest are the effects of 

 castration on mammary development in 

 mice. When the embryonic gonads are de- 

 stroyed by irradiation the mammary glands 

 continue to develop in both sexes according 

 to the normal female pattern (Raynaud, 

 1950). This pattern obviously does not de- 

 pend on the ovary but represents the asexual 

 or anhormonal type of development. Its ap- 

 pearance in castrate males indicates that the 

 regression of the mammary glands in the 

 male is normally determined by the testis. 

 This is in agreement with the results of ad- 

 ministering male hormone, as described 

 above. Once more the predominant role of 

 the male hormone in mammalian sex differ- 

 entiation is demonstrated. 



An entirely different type of sex character, 

 and one which exhibits sexual dimorphism 

 in a striking way, is the syrinx of birds. This 

 organ has received special study in the duck 

 (Wolff, Em., 1950) . The syrinx makes it ap- 

 pearance as a vesicular dilatation at the 

 junction of the trachea and bronchial tubes, 

 and at first it is small and symmetrical in 

 form in both sexes. This is the permanent 



condition of the syrinx in the female but in 

 males a pronounced asymmetry soon ap- 

 pears, involving an enlargement of the left 

 side of the vesicle with corresponding modi- 

 fications of the cartilaginous rings. By the 

 10th day of incubation the asymmetry is 

 extreme (Fig. 2.25). The appearance of di- 

 morphism follows closely the beginning of 

 sex differentiation in the gonads. 



Experimental studies have shown that the 

 dimorphism of the avian syrinx is condi- 

 tioned by the ovary, or by the female hor- 

 mone (Wolff, Em., 1950). Estradiol ben- 

 zoate, introduced into incubating eggs, 

 inhibits the development of the male syrinx 

 and the female form appears. However, if 

 large doses are used, or if treatment is too 

 long delayed, a paradoxical result appears, 

 consisting in the development of atypical 

 and intermediate forms (Lewis and Domm, 

 1948). ]Male hormone (testosterone propio- 

 nate) in moderate dosages has little effect on 

 the syrinx (a slight enlargement may occur) 

 but with large doses a paradoxical tendency 

 is again found; the male syrinx is inhibited 

 and may actually be reduced in size, resem- 

 bling somewhat the female form. 



Castration again reveals the dominant 

 role of the female hormone in birds. In cas- 

 trates of both sexes the form of the syrinx is 

 male, both in size and in its asymmetry (Fig. 

 2.25) ; absence of the ovary is critical but 

 the presence or absence of the testis is of no 

 consequence in the sexual differentiation of 

 this structure. In its response to castration 

 the syrinx thus behaves like the genital tu- 

 bercle. 



The differentiation of the syrinx has also 

 been studied in vitro (Wolff and Wolff, 

 1952a; Wolff, 1953a) with similar results. 

 When explanted before the onset of sex dif- 

 ferentiation, the result is the same as after 

 castration; in an anhormonal environment 

 the male form develops without regard to 

 the sex of the donor. When explanted after 

 the beginning of sex differentiation, how- 

 ever, development proceeds always in ac- 

 cordance wuth genotype. At this stage the 

 form of the female syrinx has already been 

 irreversibly determined. The syrinx develop- 

 ing in vitro responds directly to sex hor- 

 mones introduced experimentally. Addition 

 of estradiol benzoate to the culture medium 



