602 



PHYSIOLOGY OF CIOXADS 



lar epithelium. Recently, Mizuno, lida and 

 Naito (1955) and Mizuno and Naito (19561 

 have confirmed Lyons' observations on the 

 mammogenic effect of intracluct injections 

 of prolactin in the rabbit both by histologic 

 and biochemical means (DNA estimations) 

 and there seems little doubt that the pro- 

 lactin is capable of exerting a direct effect 

 on the growth of the mammary parenchyma, 

 at least in the rabbit whose pituitary is in- 

 tact. 



In the last 18 years much information on 

 the role of the anterior pituitary in mam- 

 mary growth has been obtained by Lyons 

 and his colleagues in studies on hypophy- 

 sectomized, hypophysectomized-ovariecto- 

 mized, and hypophysectomized-ovariecto- 

 mized-adrenalectomized (triply operated) 

 rats of the Long-Evans strain. In 1943 

 Lyons showed that in the hypophysecto- 

 mized-ovariectomized rat, estrogen + pro- 

 gesterone + prolactin induced lobule- 

 alveolar development, but the degree of 

 development was less than that obtained 

 in the ovariectomized rat with intact pitui- 

 tary receiving estrogen and progesterone. 

 When supplies of purified anterior-pitui- 

 tary hormones became available the experi- 

 ments were extended (Lyons, Li and 

 Johnson, 1952) and it was shown that if 

 somatotrophin (STH) was added to the 

 hormone combination of estrogen -f pro- 

 gesterone + prolactin, the degree of lobule- 

 alveolar development obtained in the hy- 

 pophysectomized-ovariectomized rat was 

 much enhanced. The omission of prolactin 

 from the hormonal tetrad prevented lobule- 

 alveolar development from occurring. In 

 the hypophysectomized-ovariectomized-ad- 

 renalectomized rat the above hormonal tet- 

 rad could also evoke lobule-alveolar devel- 

 opment, provided the animals were given 

 saline to drink (Lyons, Li, Cole and John- 

 son, 1953). In yet more recent experiments 

 Lyons, Li and Johnson (1958) observed that 

 somatotrophin has a direct stimulatory ef- 

 fect on duct growth, but in the hypophysec- 

 tomized-ovariectomized rat, the presence of 

 estrogen is also necessary to evoke normal 

 duct development (Fig. 10.6a, b, c) ; Like- 

 wise, in the triply operated rat, STH plus 

 estrogen is mammogenic, but the presence of 

 a corticoid is r('([ui]'ed to o])tain full duct de- 



velopment (Fig. 10.6r/). Lyons and his col- 

 leagues were able to build up the mammary 

 glands of triply operated rats from the state 

 of bare regressed ducts to full prolactational 

 lobule-alveolar development by giving es- 

 trogen + STH + corticoids for a period of 

 10 days to obtain duct proliferation fol- 

 lowed by a further treatment (for 10 to 20 

 days) with estrone + progesterone -I- STH 

 -I- prolactin + corticoid to induce lobule- 

 alveolar development. Alilk secretion could 

 then be induced by a third course of treat- 

 ment lasting about 6 days in which only 

 prolactin and corticoids were given (Fig. 

 10. 6e, /). Essentially similar results have 

 been obtained in studies with the hooded 

 Norway rat (Cowie and Lyons, 1959). 



Studies on mammogenesis in the hypo- 

 physectomized mouse have revealed some 

 differences in the response of the mammary 

 gland of this species in comparison with 

 that of the rat and indications of strain 

 differences within the species. The mam- 

 mary gland of the hypophysectomized male 

 weanling mouse of the Strong A2G strain 

 shows no response to the ovarian steroids 

 alone, to prolactin, or to STH alone, but it 

 responds with vigorous duct proliferation 

 to combinations of estrogen + progesterone 

 + prolactin, or of estrogen 4- progesterone 

 + STH (Hadfield, 1957; Hadfield and 

 Young, 1958). In the hypophysectomized 

 male mouse of the CHI strain slight duct 

 growth occurs in response to estrogen + 

 jirogesterone and this is much enhanced 

 when STH is also given; the further addi- 

 tion of prolactin then results in alveolar 

 development (Flux, 1958). Extensive studies 

 in triply operated mice of the C3H 'HeCrgl 

 strain have been reported by Nandi (1958a, 

 b). In this strain some duct growth was ob- 

 served in triply operated animals in re- 

 sponse to steroids alone (estrogen -I- pro- 

 gesterone + corticoids), but normal duct 

 develojmient was believed to be due to the 

 action of estrogen + STH + corticoids, a 

 conclusion in agreement with Lyons' ob- 

 servations in the rat. Extensive lobule- 

 ahcohii' development could be induced by 

 a number of hormone coml)inations, one 

 of the most effective being estrogen + pro- 

 gesterone + corticoids + prolactin + STH, 

 milk secretion occurring when the ovarian 



