592 



PHYSIOLOGY OF GONADS 



this Balinsky ( 1950b j found that addition 

 of estrogens or mouse pituitary extract to 

 the culture medium had no effect on the 

 growth of the mammary rudiment in vitro. 



On the other hand, extensive studies by 

 Raynaud (1947c, 1949b) of the sex dif- 

 ference in the histogenesis of the mammary 

 gland in the mouse, first described by Tur- 

 ner and Gomez (1933), indicate that the 

 mammary rudiment is sensitive to the in- 

 fluence of exogenous gonadal steroids during 

 the prenatal stages. The mammary bud in 

 the strain of mouse studied by Raynaud 

 shows no sex differences in development un- 

 til the 15th to 16th day at which time the 

 genital tract, hitherto indifferent, begins to 

 differentiate. Coincident with this the mam- 

 mary bud in the male becomes surrounded 

 by a condensation of special mesenchymal 

 cells the action of which constricts the bud 

 at its junction with the epidermis from 

 which it ultimately becomes completely 

 detached (Fig. 10.1). The inguinal glands 

 seem particularly susceptible to this in- 

 fluence because they exhibit this effect 

 earlier than the thoracic glands and in some 

 strains the second inguinal bud in the male 

 tends to disappear completely. Sex differ- 

 ences in the prenatal development of the 

 mammary rudiment in certain species of 

 wild mouse were also described by Raynaud 

 (1949b). 



The fact that, after x-ray desti'uction of 

 the gonad in the 13-day male mouse embryo, 

 the mammary bud remains attached to the 

 epidermis and the duct primordia ramify 

 in a manner similar to the primordia in the 

 female shows that this phenomenon of de- 

 tachment of the mammary bud is due to the 

 action of the fetal testis (Raynaud and 

 Frilley, 1947, 1949). That the masculiniz- 

 ing action of the fetal testis seems to be 

 due to the hormonal secretion of a sub- 

 stance having the same effect as testosterone 

 is suggested by the fact that injection of tes- 

 tosterone into the pregnant mother causes 

 the mammary buds in the female embryo to 

 undergo the male type of development (Fig. 

 10.1). Here again the inguinal glands seem 

 most sensitive because sufficiently high 

 doses in many cases cause complete dis- 

 appearance of the primordia of the second 

 inguinal glands (Raynaud, 1947a. 1949a). 



On the other hand, destruction of the fetal 

 gonad in the female has no effect on the 

 development of the mammary bud (Ray- 

 naud and Frilley, 1947, 1949), yet the lattW 

 is not completely indifferent to the action 

 of estrogen because high doses of estrogen 

 administered to the mother, or lower doses 

 injected early into the embryo itself inhibit 

 the growth of the mammary bud (Raynaud. 

 1947b, 1952; Raynaud and Raynaud, 1956, 

 1957), an effect reminiscent of the well 

 known action of excessive doses of estrogen 

 on the adult mammary duct system (for 

 reference see Folley, 1952a) . In pouch young 

 of the opossum, on the other hand, Plagge 

 (1942) found that estrogen treatment stim- 

 ulated growth of the mammary duct pri- 

 mordia. Similarly in the fetal male mouse 

 low doses of estrogen stimulate growth 

 of the mammary bud (Raynaud, 1947d), 

 but this may be an indirect effect ascrib- 

 able to estrogen's antagonizing the inhibi- 

 tory action of the fetal testis. 



The problem of the histogenesis of the 

 teat has also come under experimental at- 

 tack. Raynaud and Frilley (1949) showed 

 that the formation of the ''epithelial hood," 

 the circular invagination of the epidermis 

 surrounding tlie mammary bud which con- 

 stitutes the teat anlage in the mouse, is not 

 hormonally determined since its appearance 

 was not prevented by the irradiation of the 

 fetal ovary at the 13th day of life. In the 

 male mouse the epithelial hood does not 

 normally appear and the male is born with- 

 out teats. This is undoubtedly due to the 

 action of the fetal testis inasmuch as the 

 teat anlagen develop in the male embryos 

 whose testes are irradiated at 13 days (Ray- 

 naud and Frilley, 1949). 



The foregoing observations jioint to an 

 ahormonal type of development for the teat 

 and mammary bud in the female fetus, at 

 least in the mouse, although the mammary 

 bud is specifically susceptible to the action 

 of excess exogenous estrogen which can in- 

 liibit its development without affecting that 

 of other skin gland ])rimordia. The mam- 

 mary hud is a'so sus('ei)tible to the action 

 of anch'ogen which in the normal male fetus 

 not only dii-ects its development along char- 

 act(M-istic lines, but also suppresses the for- 

 mation of the teat. 



