604 



PHYSIOLOGY OF GONADS 



steroids were withdrawn, while the })rohic- 

 tin, STH, and Cortisol were continued. A 

 further interesting observation made by 

 Nandi is that in the C3H/HeCrgl mouse 

 STH can replace prolactin in the stimula- 

 tion of all phases of mammary development 

 and in the induction of milk secretion; en- 

 hanced effects were obtained, however, when 

 prolactin and STH were given together. 

 Nandi also considers that progesterone 

 plays a greater role in duct development in 

 the mouse than in the rat. 



The above experiments clearly indicate 

 that both in the triply operated rat and 

 mouse, it is possible to build up the mam- 

 mary gland to the full prolactational state 

 by injecting the known ovarian, adrenal 

 cortical, and anterior pituitary hormones. 

 There would thus seem to be no necessity 

 to postulate the existence of other uniden- 

 tified pituitary mammogens. It must be 

 recognized, however, that in normal preg- 

 nancy the placenta may be an important 

 source of mammogenic hormones. The pla- 

 centa of the rat contains a substance or sub- 

 stances possessing luteotrophic, mammo- 

 genic, lactogenic, and crop-sac stimulating 

 properties, but it is uncertain whether this 

 material is identical with pituitary prolactin 

 (Averill, Ray and Lyons, 1950; Canivenc, 

 1952; Canivenc and Mayer, 1953; Ray, 

 Averill, Lyons and Johnson, 1955). There 

 is also some evidence of the presence of a 

 somatotrophin-like principle in rat placenta 

 (Ray, Averill, Lyons and Johnson, 19551. 



3. Metabolic Hormones {Corticoids, Insulin, 

 and Thyroid Hormones) 



We have already noted that Lyons and 

 his colleagues were able to obtain full duct 

 development in the triply operated rat only 

 when corticoids were given. Early studies 

 of the role of the adrenals in mammary de- 

 velopment have given conflicting and un- 

 certain results (see review by Folley, 

 1952a). Recent studies have not entirely 

 clarified the position. Flux (1954b) tested 

 a number of 11 -oxygenated corticoids, and 

 found that not only were they devoid of 

 mammogenic activity in the ovariectomized 

 virgin mouse, but that they inhibited the 

 gi'owth-promoting effects of estrogen on the 

 mammary ducts, whereas 11-desoxycorti- 

 costerone acted synergistically with estro- 



gen in promoting duct growth. In subsequent 

 studies it was shown that injections of ad- 

 renocorticotrophin (ACTH) into intact 

 female mice did not influence mammary 

 growth (Flux and ]\lunford, 1957), but 

 that Cortisol acetate in low doses (12.5 /^g. 

 l)er day) stimulated mammary develop- 

 ment in ovariectomized and in ovariec- 

 tomized estrone-treated mice, whereas at 

 higher levels (25 and 50 ftg. per day) it was 

 without effect (Munford, 1957). In the vir- 

 gin rat, on the other hand, glucocorticoids 

 are said to stimulate mammary growth and 

 to induce milk secretion (Selye, 1954; John- 

 son and Meites, 1955). Some light on these 

 conflicting results has been shed by the 

 studies of Ahren and Jacobsohn (1957) 

 who investigated the effects of cortisone on 

 the mammary glands of ovariectomized 

 and of ovariectomized-hypophysectomized 

 rats, both in the presence and absence of 

 exogenous ovarian hormones. In the hypo- 

 physectomized animals, cortisone promoted 

 enlargement and proliferation of the epi- 

 thelial cells lining the duct walls, but nor- 

 mal growth and differentiation did not oc- 

 cur, nor did the addition of estrogen and 

 progesterone appreciably alter these effects ; 

 in rats with intact pituitaries, however, 

 cortisone stimulated secretion but not 

 mammary growth, whereas the addition of 

 estrogen and progesterone promoted both 

 growth and al)undant secretion. Ahren and 

 Jacobsohn concluded that "the effect elic- 

 ited by cortisone in the mammary gland 

 should be analysed with due regard to the 

 endocrine state of the animal both as to its 

 effects on the structures of the mammary 

 gland and to the consequences resulting 

 from an eventual upset of the general meta- 

 bolic equilibrium." They consider that in 

 circumstances optimal for mammary gland 

 growth and maintenance of homeostasis 

 the predominant actions of cortisone are en- 

 hancement of alveolar growth and stimula- 

 tion of secretion, whereas under conditions 

 ill which the metabolic actions of cortisone 

 are not efficiently counteracted, gland 

 growth is either inhibited or an abnormal 

 development of certain iiianimaiy cells 

 may be e^■()ked. 



That the general metabolic milieu may 

 indeed profoundly influence the response 

 of the iiuuiimarv gland to hormones has 



