Persistent alterations in hormonal sensitivities of mammary glands from parous mice.

Mammary gland explants from virgin mice required supraphysiological concentrations of insulin, cortisol, and PRL for the induction of casein synthesis and lactose synthetase activity; dose-response curves for any one hormone were identical for each parameter of differentiation. Tissue from midpregnant mice was 5-7 times more sensitive to hormonal induction, responding to near-physiological concentrations of insulin, cortisol, and PRL; again, both casein synthesis and lactose synthetase activity required the same amounts of any individual hormone. Induction of lactose synthetase activity in glands from nonlactating nonpregnant parous mice required as little hormone as tissue from pregnant animals; however, induction of casein synthesis required a higher concentration of hormones, as was observed with glands from virgins, leading to a discrepancy between the optimal hormonal concentrations required for these two markers of differentiation in parous mice. Similar data were found in the time courses. Induction in explants from midpregnant animals was 1-2 days faster than that in virgins; in parous mice, induction of lactose synthetase activity was as rapid as in midpregnant mice, but induction of casein synthesis was slower and shifted toward that for the tissue from virgins. These data suggest that those mechanisms responsible for the rapid induction and increased hormonal sensitivity of the mammary gland during pregnancy are still operative after involution of the gland with respect to at least one parameter of differentiation.