Cell interactions in initiation of mammary epithelial proliferation by oestradiol and progesterone in prepubertal heifers.

The acute temporal effects of exogenous oestradiol (0.1 mg/kg per day), progesterone (0.25 mg/kg per day) or both together on the proliferative response of epithelial cells, fibroblasts, adipocytes and endothelial cells in the mammary tissue of prepubertal cross-bred heifers were determined. Mammary biopsies were taken immediately before, then 24, 48 and 96 h after the initiation of daily administration of hormones to three heifers per treatment group. Incorporation of [3H]thymidine into explants prepared from biopsies was evaluated after a 1-h incubation by measuring trichloroacetic acid (TCA)-insoluble radioactivity in explant homogenates as well as by quantitative histoautoradiography. Incorporation expressed as d.p.m./mg tissue or d.p.m./microgram DNA was increased (P < or = 0.05) approximately 11-fold by 96 h in oestradiol-treated heifers. Progesterone-treated animals were unresponsive and heifers treated with both hormones were intermediate in response compared with oestradiol-treated heifers. Autoradiographic data for ductal or terminal duct epithelial cells showed similar dramatic increases in labelling by 24 h with further increased (P < 0.01) labelling by 96 h (5.1% vs 0.1%) in heifers given oestradiol. As with incorporation, tissue from progesterone-treated heifers showed no time or treatment response compared with pretreatment biopsies and tissue from heifers given both showed intermediate responses, i.e. significantly increased labelling by 96 h compared with pretreatment (P < or = 0.05) but less labelling (P < 0.05) than oestradiol-treated heifers. A proliferative response of epithelial cells in oestradiol-treated heifers occurred prior to the response of fibroblasts adjacent to epithelial cells (< or = 50 microns).(ABSTRACT TRUNCATED AT 250 WORDS)