94 



BIOLOGIC BASIS OF SEX 



sex-differentiating agents. Anomalous or 

 paradoxical results of this kind have ap- 

 peared in experiments with both types of 

 hormone, and involve not only the gonads 

 but other sex structures as well. 



Such a result was first reported by Padoa 

 (1936) who found that a crystalline form of 

 female hormone (Crystallovar) had a strong 

 masculinizing effect on the sexual differen- 

 tiation of tadpoles of Bana esculenta, all 

 gonads developing as testes. This unex- 

 pected result (the so-called "paradoxical 

 effect") was confirmed by others and has 

 been found to be usually associated with 

 the use of high dosages. In the course of time 

 it was shown in this and in two other spe- 

 cies [Rana temporaria, Rana sijlvatica) 

 that the same hormone (estradiol) may 

 have diametrically opposite effects when 

 administered in different dosages. As was 

 emphasized earlier, low doses have a proper 

 feminizing action, producing all female in- 

 dividuals according to theoretical expecta- 

 tion; with high dosages, on the contrary, 

 only males are obtained, and at intermedi- 

 ate levels all individuals become intersexual 

 (Padoa, 1938, 1942; Gallien, 1941, 1955; 

 Witschi, 1952, 1953). Indeed, identical 

 amounts of the same substance may have 

 opposite effects when different solvents are 

 employed. Administered in oil the effect on 

 the gonads is feminizing but in aqueous so- 

 lution complete masculinization occurs 

 (Gallien, 1941). This also would appear to 

 be a dosage effect since in aqueous solution 

 the rate of uptake is presumably much 

 faster than in oil. There are no histologic 

 indications in the above experiments as to 

 how the paradoxical effect is mediated. But, 

 although such effects are found in various 

 ranid species, they do not occur in Dis- 

 coglossus regardless of dosage, thus empha- 

 sizing the importance of species differences 

 in the phenomenon (Gallien, 1955). 



Male hormones also produce paradoxical 

 effects on the gonads and, although the 

 doses employed have generally been high, 

 it again appears that the result often de- 

 pends on the species tested. The same dose 

 of the same substance may have opposite 

 effects in different species. Testosterone or 

 cthinyl-testostcrone in large doses have 

 strong feminizing effects on the testes of the 

 salamander Pleurodeles, whereas the devel- 



o])ment of the ovaries is retarded but other- 

 wise unaffected, a typical paradoxical effect 

 (Gallien, 1950, 1955). Ethinyl-testosterone 

 has the same effect in Discoglossus, but in 

 Rana temporaria this hormone has only the 

 expected masculinizing action. Such differ- 

 ences in response may arise from differences 

 in sensitivity on the part of the gonads or 

 gonad components; a dose which is rela- 

 tively large for one species may not be so in 

 the case of another. 



The effects of sex hormones in urodele am- 

 phibians. In urodele amphibians the effects 

 of sex hormones on the differentiation of the 

 gonads are perhaps even more variable; 

 however, as opposed to the situation in the 

 Anura, it is the female hormones which are 

 more effective in producing reversal than 

 the male (Gallien, 1955). In only one in- 

 stance, the newt Pleurodeles, has a func- 

 tional transformation of sex been achieved 

 (Gallien, 1954). In this species prolonged 

 treatment with estradiol benzoate com- 

 pletely reverses the differentiation of all 

 males, some of which become capable of 

 laying eggs. Varying degrees of transforma- 

 tion have been reported in other urodele 

 genera after shorter periods of treatment, in 

 Amby stoma (Burns, 1938a; Ackart and 

 Leavy, 1939; Foote, 1941) and in Hynobius 

 (Hanaoka 1941a). There was great varia- 

 tion in the timing of treatment and in the 

 dosages employed in these experiments; the 

 incomplete character of the reversal may be 

 due in part to such factors, but the role of 

 species variability must also be great. 



On the other hand the male hormone, in 

 marked contrast to its dominating role in 

 the Anura, has but a limited transforming 

 action in Urodeles. Indeed, it frequently, but 

 not always, produces paradoxical effects 

 icf. Burns, 1939c; Foote, 1941; Bruner, 

 1952). In Pleurodeles, in which the males 

 arc completely transformed by estradiol, the 

 effect of testosterone is limited to a severe 

 inhibition, which affects the gonads of both 

 sexes but is more extreme in males (Gallien, 

 1955). Medullary development is almost 

 completely suppressed, and after an interval 

 of recovery the vestigial gonads give rise 

 almost exclusively to rudimentary ovaries, 

 a result mentioned pi'e\-i()usly in discussing 

 paradoxical effects. In tliis case, however, 

 there is clear histologic evidence as to how 



