MAMMARY GLAND MPA RESPONSIVENESS IS STRAIN SPECIFIC AND INFLUENCED BY THE STROMAL BACKGROUND

J.P. CERLIANI, M.C. BOTTINO, J. BOLADO, G. MONTERO GIRARD*, M. A GOROSTIAGA, A. MOLINOLO**, S.I. VANZULLI*, AND C. LANARI

Seefeld, Austria

Congreso; Meeting of the Journal of Steroid Biochemistry and Molecular Biology; 2006

JSBMB

We have previously demonstrated that medroxyprogesterone acetate (MPA) induces in BALB/c female mice invasive ductal mammary carcinomas and that C57BL/6 mice are resistant to MPA-induced carcinogenesis.  The aim of this study was to evaluate mammary glands’ MPA responsiveness in both strains. Short term experiments were designed to compare Pg and MPA effects on mammary glands. Two month old female mice of both strains were sc implanted with 40 mg silastic pellets of MPA, progesterone (Pg) or placebo (4/group). After 2 months mammary glands were either fixed for histological evaluation or used in WM studies. MPA induced an increase in ductal branching and Pg induced a higher lobular differentiation mainly in BALB/c mice. Hormone receptors were evaluated by immunohistochemistry using validated antibodies. ERa and PR A expression were higher (p<0.05) in control BALB/c mice than in C57BL/6 mice and their expression was down regulated in progestin treated mice. PR B levels were low in control mice of both strains and increased mainly in MPA-treated mice of both strains. To determine if the differences between strains were mainly of the epithelial cells or from the microenvironment, purified epithelial cells from both strains were implanted in the left and right cleared fat pads respectively of Swiss nude female mice implanted with silastic hormone pellets (estradiol:0.02mg;-MPA:20mg). After one month mammary glands were excised and microscopically examined. Syngeneic transplantations and cleared mammary fat pads of hormone treated animals were used as controls. Surprisingly, mammary glands generated from C57BL/6 mice were histologically similar to those from BALB/c mice. In summary, in this study we have demonstrated that a) the mammary glands of C57BL/6 mice respond very poorly to progestins, b) they show lower levels of ERa and PR A than those of BALB/c mice c) MPA and Pg have early different effects in mammary gland morphology d) progestins down regulate PR A but upregulate PR B, e) stromal differences between strains may be responsible for the different hormone responsiveness.