114 



BIOLOGIC BASIS OF SEX 



react in an opposite way to the same treat- 

 ment. 



In chick embryos also, early treatment 

 with male hormone may completely sup- 

 press development of the Miillerian ducts 

 (Figs. 2.23 and 2.12; see also Gaarenstroom, 

 1939; Stoll, 1948, 1950) and a similar effect 

 is produced by grafts of the embryonic 

 testis (Wolff, 1946; Huijbers, 1951). Again, 

 however, suppression of the ducts depends 

 on certain rather precise conditions, the 

 dose must be adequate and the hormone 

 must act at the proper stage of development. 

 They can be suppressed completely before 

 the 6th or 7th day of development (Stoll, 

 1948; Huijbers, 1951) but later treatment is 

 ineffective. Thus (as was found also for the 

 ''stabilizing effect" of female hormone on 

 the Miillerian ducts of male embryos) there 

 is a limited period of development during 

 which the ducts are susceptible to inhibition 

 by male hormones. In contrast with these 

 clear-cut results, however, a paradoxical 

 hypertrophic effect of certain male hormones 

 (androsterone, dehydro-androsterone and 

 related compounds) has been reported on 

 the ^Miillerian ducts of chick embryos after 

 rather large doses (Willier, 1939; Wolff. 

 1938; Wolff, Strudel and Wolff, 1948). 



In the embryos of mammals effective in- 

 hibition of the Miillerian ducts by male hor- 

 mones has not been found, but suppression 

 of regional parts of the duct sometimes oc- 

 curs. The ostial portion is suppressed in the 

 hedge-hog (Mombaerts, 1944) and the vagi- 

 nal segment (the last part to be laid down) 

 is frequently inhibited in female opossums 

 (Burns, 1942a, b) and in mice (Raynaud, 

 1942). In the mouse and in the rabbit fail- 

 ure of the posterior ends of the ducts to 

 unite to form vagina and corpus uteri has 

 been reported (Raynaud, 1942; .lost, 1947a). 

 In female opossum embryos treated with 

 testosterone propionate the vaginal canals 

 are absent in about half of all cases and 

 arc always absent in males (in which, as 

 noted earlier, the terminal portion of the 

 Miillerian duct is lacking) . However, a para- 

 doxical stimulation of the Miillerian duct 

 and its derivatives also takes place in opos- 

 sums of both sexes when large doses (25 to 

 100 ^g. per day) are employed (Fig. 2.24; 

 see also Moore, 1941, 1947; Burns, 1939a. 

 1955b) an effect which completely disa]^)- 



pears when the dose is lowered to ±5 /xg. or 

 less (Burns, 1942a, b). 



In contrast with the failure of androgenic 

 hormones to inhibit effectively the Miillerian 

 ducts of mammalian embryos it is known 

 that they are normally inhibited by the 

 hormone of the fetal testis. In castrated 

 male fetuses of the rabbit the ducts persist 

 instead of regressing and develop almost as 

 well as in normal females; conversely, the 

 embryonic testis when grafted into a female 

 fetus inhibits the Miillerian duct in the 

 vicinity of the graft (Jost, 1953, 1955). On 

 the other hand, a crystal of testosterone pro- 

 pionate implanted in the same manner lacks 

 this inhibiting power. Testosterone also fails 

 to inhibit development of the Miillerian 

 ducts in castrate males although in all other 

 respects it fully compensates for the ab- 

 sence of the testis (Jost, 1947b, 1953, 1955). 

 This discrepancy has led to the suggestion 

 (Jost) that in mammals another substance 

 may be required for the inhibition of the 

 Miillerian ducts. In the fetal rat, on the 

 other hand (Price, 1956), neither testoster- 

 one nor the presence of the fetal testis in- 

 fluences the differentiation of the ]\Iiillerian 

 ducts in genital tracts when isolated at an 

 age of 17.5 days and cultured in vitro. In 

 this case, however (as suggested by Price), 

 it is likely that development of the Miille- 

 rian ducts has already been irreversibly de- 

 termined before the time of explantation. 

 This question will come up again in a dis- 

 cussion of the stage at which irreversible 

 determination occurs in the rat. 



The effects of castration on development 

 of the Miillerian ducts. Although the effects 

 of steroid hormones on the development of 

 the Miillerian ducts are on the whole con- 

 sistent with theory (failure of the ducts of 

 mammalian embryos to be inhibited by male 

 hormone is a notable exception) such results 

 do not constitute evidence that sex hor- 

 mones are present and active in the normal 

 differentiation of sex. A direct test of this 

 question is provided by castration of the 

 eni])ryo. The effects of castration in am- 

 phibian larvae have been previously men- 

 tioned (p. 112); after removal of the gon- 

 ads both sex ducts fail to differentiate 

 fui'tluM-, ]X'rsisting indefinitely in the condi- 

 tion in which they were at operation. In re- 

 cent years this difficult operation lias been 



