HORMONES IN DIFFERENTIATION OF SEX 



87 



ferentiation process is experimentally dis- 

 turbed — does it respond readily by growth 

 and differentiation or is it relatively inert 

 and refractory? In particular cases the ca- 

 pacity of a gonad for reversal under experi- 

 mental conditions obviously depends on 

 which of the various situations prevails. An- 

 other variable concerns the humoral activity 

 of the gonad, as regards the time of onset 

 and the factors of quantity or rate of pro- 

 duction. Species differ widely in this respect 

 and marked sex differences are also found. 

 Presumably all such characteristics exist as 

 predispositions within the gonad primor- 

 dium, but they are not as a rule irreversibly 

 determined. 



In addition the process of reversal, as seen 

 histologically, may be influenced by experi- 

 mental conditions such as the procedure em- 

 ployed, the stage of development at which 

 reversal is initiated and the duration of the 

 experiment. If conditions are favorable at 

 the beginning of sex differentiation, reversal 

 may take place directly without leaving ob- 

 vious histologic traces, i.e., an individual of 

 one sex may adopt the developmental pat- 

 tern of the other virtually from the start. 

 If, on the other hand, transformation is not 

 initiated until sex differentiation is well ad- 

 vanced, various stages of intersexuality will 

 appear in the transforming gonads, until 

 one sex component finally establishes com- 

 plete dominance and the other disappears. 

 The first situation commonly occurs when 

 larvae are reared in optimal concentrations 

 of hormone dissolved in the aquarium wa- 

 ter; exposure to the hormone is continuous 

 from a stage long antedating the appearance 

 of morphologic sex differentiation, and all 

 embryos regardless of sex genotype develop 

 as one sex. However, the same result may 

 occur also in grafting experiments (parabio- 

 sis or gonad transplantation) in which het- 

 eroplastic combinations of different species 

 assure decisive predominance of one sex 

 from the beginning by virtue of great in- 

 equality in size and in rate of development. 

 The second situation is encountered when 

 the conditions of the experiment do not lead 

 to establishment of dominance at an early 

 stage. Reversal sets in late, intersexual 

 stages may be prolonged, and complete 

 transformation mav never occur. 



2. Parabiosis and Grajting of the Gonad or 

 the Gonad Primordium 



Experiments of this kind involve the in- 

 teraction of embryonic or larval gonads 

 through the agency of substances of a hu- 

 moral nature but of unknown chemical con- 

 stitution. In some species, or under certain 

 experimental conditions, the effects may be 

 limited and highly localized, appearing only 

 when the interacting gonads are in contact 

 or in close proximity. Transport of the hu- 

 moral agent takes place apparently by dif- 

 fusion through the intervening tissues (Figs. 

 2.25 and 2.3 j . In other cases the effects are 

 exerted over great distances and the sub- 

 stances must of necessity be carried in the 

 blood. This does not necessarily mean, how- 

 ever, that different substances are involved 

 in the two cases. As will be shown, hor- 

 mones in low concentrations may have only 

 local effects and, given a sufficient concen- 

 tration in the blood stream, there is no rea- 

 son to suppose that the so-called "inductor 

 substances" could not act at a distance. The 

 mode of transport does not seem to be cru- 

 cial for the definition of these substances 

 (for discussions see Willier, 1939, page 134, 

 and Burns 1949, 1955b). 



In most species of amphibians which have 

 been investigated the male is the dominant 

 sex. In grafting experiments, whether the 

 method is parabiosis or transplantation of 

 embryonic gonads, testes as a rule induce sex 

 reversal in ovaries without being greatly 

 modified themselves. In some cases domi- 

 nance of the testis is so extreme that no real 

 reversal of the ovary occurs, only an almost 

 complete suppression and sterility. This 

 type of response is seen, for example, in 

 parabiotic pairs of the wood frog (Witschi, 

 1927) and in the newt Triturus (Witschi 

 and McCurdy, 1929), and is probably cor- 

 related with a constitutional inadequacy of 

 the medullary component in the embryonic 

 ovaries of the species in question. In other 

 species, on the other hand, a severe initial 

 repression of the ovary is followed by a de- 

 layed reversal, which may have a prolonged 

 course but which eventuall}^ may be quite 

 complete. In parabiotic pairs of certain spe- 

 cies of Ambystoma (Fig. 2.7) there is a se- 

 vere inhibition of the ovary before active 

 transformation is initiated, and when rcver- 



