HORMONES IN DIFFERENTIATION OF SEX 



85 



tiation of the medullary cord, which results 

 in a very unequal allocation of the germ 

 cells between the two components. Prob- 

 ably the sex genotype acts primarily by 

 determining the developmental pattern of 

 the medullary cord. The role of the germ 

 cells in the formation of the gonad appears 

 to be a purely passive one since the non- 

 germinal tissues are capable of producing 

 the typical structure of a testis or an ovary 

 in the absence of all germinal elements (for 

 a review of this subject see Burns, 1955b). 



The origin of the medullary component 

 of the gonad from the mesonephric blastema 

 and its dominant role in gonad formation 

 has been demonstrated in a striking experi- 

 ment by Houillon (1956). Formation of the 

 gonad is dependent on the normal develop- 

 ment of the mesonephros, and this can be 

 repressed or entirely prevented by blocking 

 the development of the primary nephric 

 duct (pronephric ductj at an early stage. 

 In the absence of the nephric duct the meso- 

 nephric blastema is reduced in quantity and 

 delayed in its appearance; typically only a 

 few mesonephric tubules develop and these 

 are poorly differentiated. In consequence of 

 the suppression of the mesonephric blas- 

 tema, medullary cords are lacking or poorly 

 developed, and the result is a vestigial gonad 

 consisting chiefly of a rudimentary cortex. 

 The essential role of the medullary cords in 

 gonadogenesis is also demonstrated in the 

 gonads of toads (Witschi, 1933) in which 

 the so-called "organ of Bidder" corresponds 

 to an anterior segment of the genital ridge 

 in which medullary cords are absent. 



The proportion of cortex to medulla as 

 laid down in embryonic gonads depends 

 primarily on genie constitution, but the 

 stage of development is a factor in the rep- 

 resentation of the two elements at any par- 

 ticular time, since during the progress of 

 sexual differentiation one component (cor- 

 responding to the genetically determined 

 sex) shows an increasing predominance from 

 stage to stage. Furthermore, the morpho- 

 logic representation of the two sex compo- 

 nents in the indifferent gonad is subject to 

 variation in different groups, species, or 

 races. In some species the recessive com- 

 ponent is weakly represented or virtually 

 absent, even in early development, or when 

 present its existence may be of brief dura- 



tion. In such cases capacity for sex reversal 

 is reduced or lacking. In other species, in 

 which the recessive sex component is well 

 developed, or when it persists over a con- 

 siderable period of time, capacity for ex- 

 perimental reversal is correspondingly in- 

 creased. 



The alternative behavior of the cortical 

 and medullary components of the gonad in 

 normal differentiation, as well as their be- 

 havior under experimental conditions, long 

 ago suggested that the physiologic mecha- 

 nism of sex differentiation consists essen- 

 tially of an antagonistic interaction between 

 the two elements, in which the genetically 

 dominant component gradually inhibits its 

 antagonist (Fig. 2.5). This concept of "cor- 

 ticomedullary antagonism" (Witschi, 1932) 

 has been generally accepted as the basic 

 mechanism in the histologic differentiation 

 of the gonad and forms the starting point 

 for the inductor theory of sex differentia- 

 tion.^ A number of seemingly unrelated ex- 

 perimental procedures which are capable of 

 inducing sex reversal all appear to have a 

 common base of action by influencing or 

 controlling this simple mechanism. For ex- 

 ample, sex reversal is in some cases readily 

 induced by external or environmental influ- 

 ences of an unspecific character, which ap- 

 parently produce their effects by depressing 

 or destroying the dominant gonad compo- 

 nent. 



Classical experiments of this type are the 



^ As originally formulated, this theory postulated 

 simply that each gonad component produces a 

 substance which specifically inhibits the differen- 

 tiation of the other. These substances, called med- 

 ullarin and corticin, were considered to be similar 

 in character and to behave like the embryonic in- 

 ductors of earlier development, being transmitted 

 by diffusion and having strictly localized effects. 

 Subsequently the theory was elaborated to allow 

 for stimulatory as well as inhibitory action, with 

 each inductor system assigned a dual role; ac- 

 cordingly, positive and negative factors were as- 

 sumed and so designated, e.g., medullarin* and 

 medullarin'. More recently it has been proposed 

 that interactions between the sex inductors are of 

 the nature of an immunologic reaction (Chang 

 and Witschi, 1956), the positive factor appearing 

 first in the role of an antigen which stimulates the 

 other system to produce an antibody, the inhibi- 

 tory factor (for the development of the inductor 

 theory see Witschi, 1934, 1939, 1942, 1950, 1957). To 

 account for the great taxonomic variability in the 

 action of the sex inductors thej' are assumed to 

 be proteins. 



