Effects of perinatal testosterone on mouse mammary duct morphology and lobule induction in vitro.

The effects of several hormone supplements to the chem ically defined medium were assessed in mammary explants from C57BL/Crgl mice that had been given injections of 25 l.Lg testosterone on each of the first 5 days of life and in mammary tissues of uninjected controls. Tissues were or gan cultured the fourth week of life after 4, 6, and 9 days of pretreatment with1 j.tg 17/.3-estradiol plus1 mg progester one. Alveolar and lobular development were similar in tissues of perinatally testosterone-injected (T) mice and their controls after in vivo pretreatment and after 4 or 9 days of pretreatmentfollowedby culturein allmedia tested. Both alveolar and lobular development were inhibited in tissues from T mice after 6 days of pretreatment followed by culture with optimal medium for lobular differentiation (17/3-estradiol , progesterone , aldosterone , growth hor mone, prolactin, insulin, and thyroxine). After 6 days of pretreatment, explants from T mice responded similarly to controls after culture with suboptimal media (insulin and thyroxine, or estrogen , progesterone, aldosterone, insulin, and thyroxine).Peninatalinjectionof testosterone,a treat ment which has been reported to promote mammary tumor genesis, did not promote in vitro differentiation of mam mary lobules; indeed, significant inhibition of lobule for mation was noted at 6 days of pretreatment. A 6-day minimal threshold effect for expression of pretreatment may be involved. Duct diameter increased in explants from T mice after culture in several medium and pretreatment groups. Differ ences in duct responses were markedly uniform throughout the explant in cultured tissues of T mice. In view of the fact that mammary ducts have been implicated as sites of origin of preneoplastic and neoplastic change, duct responses are of particular interest in relation to subsequent promotion by various endogenous and exogenous factors of the neo plastic potential of mammary tissues of perinatally testos terone-injected mice.