148 



BIOLOGIC BASIS OF SEX 



in the case of one structure may be quite 

 discordant for others, resulting in serious 

 disharmonies or even in paradoxical reac- 

 tions. Nevertheless, much can be learned 

 analytically of the processes involved in 

 sex differentiation without requiring per- 

 fectly integrated results. 



XIII. Embryonic Hormones and 

 Inductor Substances 



According to generally accepted theory, 

 the normal differentiation of the gonads is 

 the result of an antagonistic interaction be- 

 tween the cortical and medullary compo- 

 nents, in which one element (as prescribed 

 by sex genotype) gradually becomes pre- 

 dominant while the other retrogresses. It 

 has been previously emphasized that in ex- 

 perimental sex transformation no new prin- 

 ciples or processes are involved ; the normal 

 mechanism is simply set in reverse. The 

 transformation process as it appears at vari- 

 ous stages presents essentially the same his- 

 tologic picture, whether the impulse to re- 

 versal comes from a developing gonad of 

 opposite sex or from an administered hor- 

 mone. It has been shown further that steroid 

 hormones are capable in many cases of re- 

 directing the differentiation process from its 

 inception, leaving but slight histologic traces 

 of reversal. Thus the processes of sex differ- 

 entiation in the gonads are amenable to 

 control by hormones at least over a consid- 

 erable range of the developmental period. 



The cjuestion then arises as to the manner 

 in which the antagonistic interactions be- 

 tween cortex and medulla are mediated in 

 normal development, and the nature and 

 relationships of the physiologic agents in- 

 volved. On this subject differences of opin- 

 ion have long existed. The well known the- 

 ory of Witschi^ postulates special inductor 

 substances elaborated by the cortical and 

 medullary tissues. Because the special sphere 

 of the inductor substances is presumed to 

 be the regulation of gonad differentiation, 

 their field of action is thus topographically 

 restricted; when at later stages the gonads 

 begin to exercise control over the develop- 

 ing accessory sex structures, frequently over 

 considerable distances, the action of embry- 

 onic hormones is presumed. However, since 

 steroid hormones also may influence, or 



even completely control, the mechanism of 

 gonad differentiation, it is important to 

 know whether such control is exerted sec- 

 ondarily, i.e., by regulating the inductor sys- 

 tems, or whether hormones are capable of 

 playing the role of inductors. It must be re- 

 membered that the inductor substances have 

 not as yet been isolated or directly identi- 

 fied; their existence and their character are 

 postulated from the nature of the effects 

 attributed to them. Consequently, this prob- 

 lem can only be approached indirectly by 

 comparing the effects of sex hormones un- 

 der as many conditions as possible with 

 those ascribed to the inductor substances. 



Although the activities of the inductor 

 substances are ordinarily confined to the 

 gonads, it is held that under favorable con- 

 ditions their influence may extend some- 

 what further, but only within a limited 

 range. This view was originally based on 

 observations in certain parabiosis experi- 

 ments (Witschi, 1932) and involves the 

 manner in which inductor substances are 

 supposedly transported. In parabiotic pairs 

 of frogs, so closely united that the gonads 

 lie within in a common body cavity, gonads 

 of different sex do not influence each other 

 significantly except when they are in con- 

 tact or in very close -proximity. The action 

 of the inductor substances, that is to say 

 the intensity of their effects, seems to be 

 roughly proportional to the distance be- 

 tween the interacting gonads (Fig. 2.2B). 

 This observation suggested that the induc- 

 tor substance is transmitted only by dif- 

 fusion through the tissues, the concentration 

 declining steadily with distance from the 

 point of origin. Failure to be effective at 

 greater distances presumably indicates that 

 the agent is not distributed through the 

 blood in the manner of a hormone. This, 

 however, may mean only that in early 

 stages of development the humoral sub- 

 stances, whatever their nature, are not pro- 

 duced in sufficient quantity to reach or 

 maintain an adequate level in the blood- 

 stream. In parabiotic salamanders, on the 

 other hand, typical sex reversal also occurs, 

 although the interacting gonads as a rule 

 are widely separated (Fig. 2.2.4). In this 

 case the inducing agent must be blood- 

 borne; nevertheless, the changes in the re- 



