HORMONES IN DIFFERENTIATION OF SEX 



105 



to determine whether hormones or other 

 diffusible substances might be produced, 

 capable of modifying the differentiation 

 process. As a control procedure, ovaries were 

 transplanted alone, or in association with 

 nongonadal tissues, into noncastrate male 

 hosts. 



The results in most respects correspond 

 with those already described. The testis was 

 found to develop normally regardless of the 

 sex of the host or the presence of a contigu- 

 ous ovary. The behavior of grafted ovaries 

 differed, however, according to whether they 

 were associated with an embryonic testis, 

 or developed alone or with other tissues 

 (control operations). In the jEirst case the 

 ovaries were strongly modified along the 

 lines previously described. Some differenti- 

 ated poorly or hardly at all, others showed 

 fairly good development of the cortex with 

 some primary follicles, but in the medullary 

 area tubular structures resembling testis 

 tubules were found. Still others had a few 

 well formed follicles in the cortex, but again 

 tubular structures were present in the me- 

 dulla which sometimes contained ovocytes. 

 The two last mentioned categories would 

 seem to correspond to the "ovotestes," or 

 ovaries with "transformed medullary cords" 

 described by previous writers. In contrast, 

 however, ovaries grafted alone, or with non- 

 gonadal tissues, were found to differentiate 

 in an almost normal fashion. It is at this 

 point that the findings depart from those 

 of other investigators. The conclusion was 

 reached that the modifications observed in 

 ovaries associated with embryonic testes are 

 due to a substance produced by the testis, 

 and considered to be of the nature of a 

 medullary inductor. 



However, both with respect to the sever- 

 ity of cortical inhibition and the degree of 

 masculinization of medullary structures, 

 these modified ovaries do not appear to 

 differ significantly from those described by 

 previous investigators when ovaries were 

 grafted alone. The significance of the results 

 rests then upon failure to obtain similar 

 changes in the control ovaries. The age and 

 state of differentiation of the control gonads 

 at the time of transplantation is important. 

 They were from donor fetuses of 15 days 

 development, and although older than any 

 used by Buyse they were still within the 



period during which Torrey found the ovary 

 to be extremely labile in its differentiation. 

 According to Torrey only a small proportion 

 of ovaries aged 15 to 16 days developed as 

 such (5 of 17 cases) whereas at an age of 

 17 days — after the cortical zone is estab- 

 lished — ovaries are obtained almost without 

 exception (10 of 11 cases). Further experi- 

 ments are needed to clarify this matter. 



In all of the foregoing experiments there 

 was general agreement (for a partial ex- 

 ception see Holyoke) that the hormonal en- 

 vironment provided by adult hosts of both 

 sexes, intact or castrate, has no important 

 influence on the sexual differentiation of the 

 transplanted gonads, even in the case of 

 ovaries which are still in a labile state. The 

 reason for this is not clear. Possibly it is a 

 matter of insufficient concentration of the 

 host hormone (compare the case of the 

 chick, p. 99), or it may be that after trans- 

 plantation a certain interval, perhaps a crit- 

 ical one, elapses before vascularization 

 makes the graft accessible to the hormones 

 of the host. On the other hand, it has been 

 pointed out that in the embryos of placental 

 mamtnals pure hormones thus far have pro- 

 duced no significant changes in the dif- 

 ferentiation of the gonads. The cjuestion 

 remains whether there is an essential differ- 

 ence between the sex hormones of adults and 

 the hormones or sex-differentiating sub- 

 stances elaborated by embryonic gonads. 



3. Experimental Transjormation of the Tes- 

 tis in the Opossum 



Up to now the clearest experimental dem- 

 onstration of sex reversal in the gonad of 

 any mammal, and the only one to be pro- 

 duced by a steroid hormone, has been ob- 

 tained in the gonads of young opossums 

 (Didelphis virginiana) . In this species the 

 embryonic testes, if taken in time, are read- 

 ily transformed into ovotestes or even into 

 "ovaries" of remarkably normal histologic 

 structure by the action of estradiol dipro- 

 pionate (Burns, 1950, 1955a, 1956b). The 

 hormone is administered at short intervals, 

 beginning at a stage of development corre- 

 sponding to stage B in Figure 2.16. This is 

 the condition found at birth in litters born 

 at stage 34 of McCrady's series (McCrady, 

 1938). It is characterized by the presence 

 of well developed primary sex cords which 



