134 



BIOLOGIC BASIS OF SEX 



to the 24th clay of development thus falls 

 within the period during which testis ac- 

 tivity is most essential for normal morpho- 

 genesis (p. 125). 



In the light of these results the anterior 

 hypophysis was studied cytologically for 

 direct evidences of secretory activity, using 

 the MacManus periodic acid-Schiff (PAS) 

 test (Jost and Gonse, 1953; Jost and Ta- 

 vernier, 1956). PAS-positive cells are first 

 seen in small numbers, and faintly stained, 

 on the 19th day of development. Thereafter 

 they increase in numbers and in staining 

 reaction, reaching a maximal development 

 during the 22nd and 23rd days; on the 24th 

 day these cells abruptly decrease in number 

 and stainability and almost disappear. The 

 peak of gonadotrophic activity, as indicated 

 by the cytologic evidence, falls again dur- 

 ing the 2-day period when the secretory ac- 

 tivity of the testis is at its height, as judged 

 by the conseciuences of castration, a re- 

 markable example of endocrine correlation 

 (for a fuller account see Jost, 1953, 1955). 



It was once widely believed that in hu- 

 man anencephalic monsters the pituitary is 

 absent or vestigial in character ; more recent 

 studies have revealed, however, that al- 

 though difficult to identify grossly, anterior 

 lobe tissue can usually be demonstrated by 

 careful histologic examination {e.g., Ange- 

 vine, 1938). Nevertheless, cases are known 

 in which apparently no anterior lobe tissue 

 is present, and such cases are pertinent to 

 the present discussion. Barr and Grumbacli 

 (1958, and personal communication of Dr. 

 Grumbach) have described such a case in a 

 newborn male infant, in which no malforma- 

 tion of the genital system was evident ex- 

 cept that the testes were somewhat smaller 

 than usual. They were not otherwise abnor- 

 mal, however, and interstitial tissue was 

 present. In a similar case, also a male, re- 

 ported by Blizzard and Alberts (1956), the 

 external genitalia were small but normal in 

 structure. The testes also were small and 

 undescended, lying in a pelvic position, the 

 tubules were somewhat atrophic and no 

 interstitial tissue was present. No other ab- 

 normalities were noted. It is perhaps sig- 

 nificant in this case that absence of the 

 interstitial cells is correlated with under- 

 development of the external genitalia and 



failure of the testes to descend. In two cases 

 of congenital absence of the hypophysis, a 

 male and a female (Brewer, 1957), develop- 

 ment of the gonads and genital system was 

 apparently normal. 



Cases in which complete absence of the 

 pituitary has been demonstrated are un- 

 fortunately few but of great value since 

 they represent in humans the closest ap- 

 proach to hypophysectomy in experimental 

 animals. The consequences of the deficiency 

 and the conclusions to be drawn in the two 

 cases are similar; the primary differentia- 

 tion of the gonads is evidently independent 

 of the pituitary but secondary defects may 

 appear later, both in the gonads and in the 

 genital tract. The testes may be underde- 

 veloped, the tubules may show secondary 

 atrophy or degenerative changes, and the 

 interstitial tissue may be reduced or lack- 

 ing, but in some cases it appears to be well 

 develoj^ed. There is need for a careful cor- 

 relation of the status of the interstitial tis- 

 sue in such cases with the presence or ab- 

 sence of defects of the accessory organs. 

 The consequences to the gonad of absence 

 of the pituitary may hinge on whether a 

 secondary source of gonadotrophin is avail- 

 able to the fetus (Jost, 1953). This is a 

 matter which may be expected to vary in 

 different groups or species. As yet too few 

 species have been studied to clarify the 

 point. 



VII. Group Differences in the Relations 

 of Hormones to Sex Differentiation 



The extensive experimental data reviewed 

 in the foregoing pages show clearly that the 

 embryonic gonads produce sex specific sub- 

 stances which must be regarded as hormones 

 and which act as physiologic agents in the 

 differentiation of sex, controlling not only 

 the development of the various accessory 

 sex structures but in many cases the differ- 

 entiation of the gonads themselves. That the 

 substances are hormones in the usual sense 

 is shown by the fact that they regulate the 

 development of distant structures in such 

 fashion that they can only be distributed by 

 way of the circulating blood. This, however, 

 does not preclude a sharply localized action 

 under jiroper circumstances. That they are 

 ('hib<)iat('(l in the gonads is demonstrated bv 



