2. Endocrines and Populations 259 



if the females do become pregnant, there may be a marked increase in fetal 

 mortality with increased resorption of the embryos (Christian, 1959a, b) . 



The causes of fetal mortality in these circumstances have not been 

 explored in detail, but a number of factors may be involved. It is well 

 known that cortisone and hydrocortisone have serious effects on the fetus, 

 apparently by inhibiting growth and development (Glaubach, 1952; Fraser 

 et al, 1953; Davis and Plotz, 1954; Kalter, 1954). The resultant defect 

 probably depends to a large extent on the developmental stage of the fetus 

 when these hormones are active, as is the case with nutritional deficiencies 

 (Lutwak-Mann, 1958) . A variety of congenital defects have been produced 

 experimentally by the injection of these hormones. However, high doses are 

 required to produce these effects; furthermore, with chronic injection of 

 cortisone some fetuses do not seem to be affected (Seifter et al, 1951). 

 Hydrocortisone and cortisone increase the incidence of fetal mortality in 

 rats during the second half of pregnancy. The mechanism is unknown, but 

 it has been suggested that it may be due in part to premature ''aging" of 

 the vasculature of the placenta (Seifter et al, 1951). Increased mortality 

 may reflect fatal defects in the growth of the embryos due to the action of 

 these hormones. In other words, there may be time-dosage relationships 

 which determine whether the effects of these glucocorticoids will be fatal or 

 will result in "congenital defects," such as cleft palate or cardiac anomalies. 

 However, these explanations leave unanswered the question why many 

 embryos subjected to the same influences are born viable and free of de- 

 fects, even from the same pregnancies. However, there are many other 

 factors to consider when discussing intrauterine mortality resulting from 

 activation of physiological adaptive systems. One must consider the in- 

 creased secretion of adrenal androgens by those species in which androgens 

 or proandrogens constitute a major secretory product. These compounds 

 possibly may directly inhibit the action of estrogens and progestins. For 

 example, it has been shown that testosterone can completely inhibit the 

 feminizing action of estrogens on developing rat embryos (Greene et al, 

 1941). More importantly, the adrenal androgens can inhibit the secretion 

 of gonadotropins, especially of FSH (Byrnes and Shipley, 1950; Byrnes 

 and Meyer, 1951 ; Dorfman and Shipley, 1956). Whether the decline in the 

 secretion of gonadotropins with increased ACTH secretion is due to inhibi- 

 tion by increased circulatory levels of adrenal androgens or whether it is 

 independent of the androgens, cannot be said. However, it seems probable 

 that the androgens are not important or, if so, only in a limited number of 

 species. The adrenal secretion of androgens or their precursors in many 

 species does not appear to be sufficient to account for the effects seen. For 

 example, in humans pituitary blockage requires much higher doses of 

 testosterone than is required to produce overt androgenic responses. Very 



