HORMONES IX DIFFERENTIATION OF SEX 



141 



tain stage their fate can be permanently 

 conditioned by hormones administered ex- 

 perimentally (Wolff, 1938; Stoll, 1948). In 

 male embryos involution of the ducts is pre- 

 vented by administration of female hor- 

 mone at the proper stage (p. 112), and 

 once "stabilized" in this manner their sub- 

 sequent development is assured without fur- 

 ther treatment. Male hormones adminis- 

 tered before this stage induce involution of 

 the ducts in the living embryo or in vitro, 

 but beyond this point have no effect. 



The genital tubercle of the female duck 

 shows a critical stage in relation to the em- 

 bryonic ovaries during the 9th day of in- 

 cubation (Wolff and Wolff, 1952b). When 

 isolated in vitro before this stage the tu- 

 bercle always develops the male form, which 

 is also the condition found in castrated em- 

 bryos. Isolation after the 9th day, however, 

 results always in a structure of female type. 

 About the 9th day of development, then, its 

 future character becomes fixed after which 

 differentiation proceeds without further 

 need of hormonal conditioning. Similar re- 

 sults were obtained in the case of the syrinx. 

 If isolated before the stage of final deter- 

 mination the sex type of both j^-imordia can 

 be readily controlled in vitro by addition of 

 hormones to the medium. 



The Wolffian ducts of mammalian em- 

 bryos behave similarly. In this instance the 

 male hormone is necessary at a certain stage 

 to insure retention of the ducts. Castration 

 of male rabbit embryos before the 22nd day 

 is followed by involution but later castra- 

 tion has little effect; changes of an irre- 

 versible nature have occurred which insure 

 continuation of development regardless of 

 hormonal conditioning. A critical period of 

 brief duration also exists for the prostate 

 glands of young opossums, involving the 

 response to both types of sex hormone. 

 Estrogens permanently suppress prostate 

 development in males if a single dose is ad- 

 ministered just before the stage when the 

 buds should appear. Male hormones, on the 

 other hand, induce prostatic glands in fe- 

 males at this stage which thereafter con- 

 tinue to develop without further treatment. 

 The effects of castration on the prostate are 

 like those described for the Wolffian ducts. 

 In rabbit embryos the critical period falls 



from the 22nd to the 23rd day of gestation 

 after which the operation has but slight 

 effect (Table 2.2). 



It appears from much evidence of this 

 kind that sex primordia typically pass 

 through developmental phases which are 

 crucial with respect to the origin, the sur- 

 vival or the future mode of differentiation 

 of the structure in question. At such stages, 

 and for brief periods, formative or suppres- 

 sive, trophic or involutionary, responses are 

 readily induced by hormones. However, the 

 physiologic status of the primordium itself 

 prescribes the specific quality of the re- 

 sponse and the timing as well. 



X. Specificity of Hormone Action 



and the Significance of 



Paradoxical Effects 



Perhaps the objection most frequently 

 urged against steroid hormones as specific 

 agents in sexual differentiation is the com- 

 mon occurrence of paradoxical effects, in 

 which a hormone of one type stimulates the 

 differentiation of structures of the other 

 sex, sometimes in a striking manner. Such 

 responses have been encountered in all ma- 

 jor groups thus far investigated, and prac- 

 tically every type of sex character may be 

 involved. The frequency with which this 

 phenomenon is associated with high dosages 

 has been noted, with emphasis on the fact 

 that in low concentrations the effects are 

 usually sex specific. Some apparent excep- 

 tions to this general rule may, indeed, be 

 due to difficulty in defining a low dose in 

 particular cases in view of the efficiency of 

 extremely low concentrations in certain spe- 

 cies (e.g., Mintz, 1948). Specificity of action 

 obviously implies that male hormones stim- 

 ulate development of male characters in em- 

 bryos of either sex, whereas female pri- 

 mordia are inhibited or give no positive 

 response; in like manner, female hormones 

 should induce differentiation of female pri- 

 mordia while inhibiting the development of 

 male structures. Convincing examples of 

 specific action in this sense are found in the 

 complete and even functional transforma- 

 tions obtained in various amphibian species 

 with low concentrations of hormones (Ta- 

 ble 2.1) ; in the maintenance of normal dif- 

 ferentiation after castration by treatment 



