256 



HYPOPHYSIS AND GOXADOTROPHIC HORMONES 



tion of LH than is its role in the formation 

 of corpora lutea." 



B. AGE, SEX, GONADECTOMY, AND REPRODUC- 

 TIVE RHYTHMS IN RELATION TO 

 PITUITARY tiONADOTROPHINS 



1. Fetal Gonadotrophins 



Experiments cited by Smith (1939j re- 

 vealed no demonstrable gonadotrophic ac- 

 tivity in the pituitary of fetuses except in 

 the hog and horse. The amount of pooled 

 tissue available for such tests with other 

 species was often so small as to make the 

 negative findings inconclusive. The original 

 work of Smith and Dortzbach (1929) on the 

 l)ig fetus is still the most complete. Gonado- 

 trophin was detected in the late fetal stages. 



Much experimental evidence bearing on 

 the relation of the hypophysis to the devel- 

 opment of the fetal gonads has been ob- 

 tained over the past several years, princi- 

 })ally from the laboratories of Wells in 

 Minnesota and Jost in Paris. These studies 

 are admirably summarized by Jost (1953, 

 1955, 1956a) and Wells (1956). Each group 

 developed techniques for intra-uterine ab- 

 lation of fetal endocrine glands, including 

 the hypophysis; the latter being accom- 

 ])lished, in effect, by decapitation. Decapita- 

 tion of rat fetuses on day 18 did not lead to 

 abnormalities in the differentiation and de- 

 velopment of either the gonads or the ac- 

 cessory sexual structures. By contrast, re- 

 moval of the testes on day 18 led to 

 deficiencies in the development of the pros- 

 tate and coagulation glands, and a failure 

 of the Mullerian ducts to regress normally. 

 This, according to Wells, is a deficit in 

 maleness correctable by testosterone and is 

 not to be construed as a feminizing in- 

 fluence. Substitution of testosterone from 

 the time of fetal castration prevented all 

 the impairments of development except the 

 regression of the Miillerian ducts. It would 

 seem that the fetal testis exerts an influence 

 over development of the male accessory 

 structures and that this action is inde- 

 pendent of any stiiiuihis fi-oni the hy])()phy- 

 sis. 



The effects of fetal decapitation in I'abbits 

 as studied by Jost differ from those in the 

 lat in one important respect. Male fetuses 

 decapitated on the 19th. 20th, or 21st dav 



of gestation were born at term in a semi- 

 feminized state as regards the accessory 

 ducts and external genitalia. These changes 

 did not occur when decapitation was per- 

 formed after the 23rd day nor when the 

 headless fetuses were injected with gonado- 

 trophin. By way of explanation, days 22 

 and 23 were held to be a determinative 

 phase during which the prospective develop- 

 ment of the sexual ducts is established by 

 the fetal testis acting in response to the fetal 

 pituitary. Cytologic examination of the fetal 

 hypophyses during this period revealed the 

 transient presence of McManus-positive 

 cells on the 22nd and 23rd days, which 

 Jost believes may signal a transitory pro- 

 duction of gonadotrophins. That the fetal 

 rabbit pituitary actually secretes gonado- 

 trophin on days 22 to 24 would require 

 more positive documentation than is pres- 

 ently available. There are considerations 

 that urge caution. The female rabbit ovary 

 is known to be refractory, at least to exog- 

 enous gonadotrophin, throughout the entire 

 infantile period (Hertz and Hisaw, 1934), 

 a finding common to many infant mammals. 

 The fact that McManus-positive material 

 appeared in the pituitary cells is suggestive, 

 but by no means conclusive, evidence of 

 secretion of gonadotrophins. There is also 

 the possibility that maternal gonadotroph- 

 ins are available to the fetus, but the evi- 

 dence is controversial (Knobil and Briggs, 

 1955; Jost, 1956b). It seems clear that any 

 function served the fetus by maternal gon- 

 adotrophins may be of minor significance, 

 inasmuch as the maternal pituitary gland 

 has been removed quite early in gestation in 

 several mammals, including the rhesus mon- 

 key (Smith, 1954, 1955), without impair- 

 ment to the development of the fetal male or 

 female reproductive systems. Moreover, in 

 man and horse the available evidence sug- 

 gests that the pituitary gland is extremely 

 weak in gonadotrophic activity throughout 

 most of the gestation pciiod, including the 

 l)uerperiuin. 



i. Age and Sex 



Brencman and ISIason (1951 ) and Brene- 

 inan (1945, 1955) made detailed studies of 

 the gonadotrophic i)otency of cockerel and 

 pullet ]5ituitaries (using the chick testis as- 

 sav) (lnrin^ the initial 3 to 4 montiis of life 



