EXPRESSION OF GROWTH-HORMONE IN CANINE MAMMARY TISSUE AND MAMMARY-TUMORS - EVIDENCE FOR A POTENTIAL AUTOCRINE PARACRINE STIMULATORY LOOP/

The role of progestins in the pathogenesis of breast cancer in women r emains controversial, To advance this discussion, we report the demons tration and localization of progestin-induced biosynthesis of growth h ormone (GH) in canine mammary gland tissue. Nontumorous mammary tissue s and tumors, both benign and malignant, were obtained from private ho usehold dogs. Immunoreactive GH tons localized in mammary epithelial c ells and correlated with the presence of GH mRNA. Local synthesis of G H tons also proven immunoelectron microscopically by demonstrating GH- containing secretory granules. Cellular GH production in nontumorous t issues was more extensive during the progesterone-dominated luteal pha se of the ovarian cycle or during exposure to synthetic progestins tha n during anestrus, GH was also associated with areas of hyperplastic m ammary epithelium, which may indicate that locally produced GH enhance s proliferation, acting in an autocrine and/or paracrine manner In 41 of 44 tumors, GH was present, Of 3 GH-negative tumor samples, 2 were f rom progestin-depleted, castrated bitches, In nonmalignant mammary tis sues, GH production is stimulated by progesterone and synthetic proges tins interacting with progesterone receptors. In some progesterone-rec eptor-negative malignant tumors, GH expression was found, indicating l oss of this control, Progestin-induced GH probably participates in the cyclic development of the mammary gland but may promote mammary tumor igenesis by stimulating proliferation of susceptible, and sometimes tr ansformed, mammary epithelial cells.