HORMONES IN DIFFERENTIATION OF SEX 



147 



tosterone propionate in maintaining tlie 

 male accessory glands has been shown in 

 castrated rat embryos (Wells, 1950; Wells 

 and Fralick, 1951 ) . In opossum and other 

 mammalian embryos synthetic androgens 

 readily induce in females prostatic glands 

 which are histologically indistinguishable 

 from those of normal males although the 

 latter are known to be conditioned in cer- 

 tain species by the hormone of the embry- 

 onic testes. Also, with proper timing, syn- 

 thetic androgens induce involution of chick 

 Miillerian ducts, either in vivo or in vitro, 

 in a manner not histologically distinguish- 

 able from the effects of the embryonic testis 

 (p. 114). Examples of this kind could be 

 multiplied. Furthermore, the female hor- 

 mone estradiol controls the sex type of vari- 

 ous avian sex primordia, even when admin- 

 istered in vitro, closely simulating the 

 normal action of the embryonic ovary. Wlien 

 it is added to the culture medium, testes are 

 transformed into ovotestes in the same fash- 

 ion as when cultured in association with 

 an embryonic ovary (Wolff and Haffen, 

 1952b) , and it produces a typical female 

 syrinx or genital tubercle in vitro regardless 

 of the sex of the donor embryo (Wolff and 

 Wolff, 1952a; Wolff, 1953a). 



Conversely, an example of an embryonic 

 hormone substituting for an adult sex hor- 

 mone is seen in the effect of a graft of the 

 embryonic testis on the epithelium of the 

 seminal vesicle in an adult castrate rat 

 (Jost, 1948b, 1953; Jost and Colonge, 19491. 

 Within a few days the vesicle epithelium in 

 the vicinity of the graft is completely re- 

 stored. Although the interstitial tissue of the 

 grafted testis is somewhat hypertrophied 

 under the influence of the host's hypophysis, 

 it is improbable that a radical change in 

 the character of the testicular secretion 

 could be induced so quickly. That the hor- 

 mone of the graft must be attributed to in- 

 terstitial cells which cytologically are like 

 those of the adult testis is also significant. 

 It should be noted further that both estro- 

 gens and androgens (which can be detected 

 by standard methods of assaying adult sex 

 hormones) have been extracted from chick 

 embryos in the latter half of the incubation 

 period (Leroy, 1948) and from fetal mam- 

 malian gonads as well {e.g.. Cole, Hart, Ly- 



ons and Catchpole, 1933). If special em- 

 bryonic hormones are necessary for the 

 control of sex differentiation, it would seem 

 that hormones of adult type are also being 

 produced during the same period. 



Many minor inconsistencies can be 

 pointed out in comparing the effects of the 

 two types of hormone, but experimental 

 conditions are usually too dissimilar to 

 justify such detailed comparisons. It is note- 

 worthy that the most "normal" results from 

 the use of steroid hormones have been ob- 

 tained under conditions which most closely 

 approach the ideal, as when larval amphib- 

 ians absorb the hormone continuously but 

 in low concentration from the surrounding 

 water. In many such experiments involving 

 many species (Table 2.1) all individuals 

 develop in accordance with, the type of lior- 

 mone used, and without obvious histologic 

 abnormalities. Under similar conditions, 

 however, if the concentration is increased, 

 all gonads become intersexual and very 

 strong doses may actually produce effects 

 exactly opposite to those obtained at very 

 low levels (p. 94). 



It is nevertheless too simple to suppose 

 that all difficulties may be avoided simply 

 by empirically arriving at the proper dose. 

 What constitutes the optimal dose is not 

 easy to determine from one species to an- 

 other for, regardless of absolute concentra- 

 tion, the hormone level in the internal en- 

 vironment of the experimental organism 

 may be greatly affected by such factors as 

 the rates of absorption, utilization, and in- 

 activation. These are factors which vary 

 widely with different hormone preparations, 

 different methods of administration, and 

 also no doubt from one organism to another. 

 In the second place, it is difficult or impos- 

 sible to adjust the dosage accurately and 

 flexibly from stage to stage, to correspond 

 with the changing conditions of develop- 

 ment and the state of the reacting struc- 

 tures; however, a continuing equilibrium is 

 doubtless more nearly approached when 

 doses are relatively low and the hormone 

 enters continuously through the gills or by 

 infusion from a graft. In comparison with 

 normal development experimental condi- 

 tions must always be arbitrary and inflexi- 

 ble; a dose which permits a normal re^^jionsc 



