Enhanced endocrine sensitivity in mouse mammary glands: hormonal requirements for induction and maintenance.

This laboratory has previously shown that mammary epithelium from pregnant and parous mice are 5-7 times more sensitive in vitro to insulin, cortisol, and PRL than tissue from virgins, with respect to lactose synthetase activity. In the present studies, virgin mice were treated for 2 weeks with either progesterone or a pituitary allograft to increase PRL levels, and the mammary explants exhibited the same heightened sensitivity to all three hormones that was noted in pregnant animals. Treatment with estradiol or T4 was without effect. However, this effect was transient, since the tissue lost its elevated hormonal responsiveness 4 weeks after progesterone withdrawal, suggesting that the permanent effect seen in nonpregnant nonlactating parous mice involves a more complex series of events than simply elevated progesterone or PRL levels. Even tissue from parous mice reverted to a reduced insulin and PRL sensitivity, if the tissue was initially cultured in the absence of any hormones. Although the increased sensitivity to cortisol did appear to be permanent under the culture conditions used, the maintenance of a heightened insulin responsiveness required the continuous presence of insulin, cortisol, and PRL, while that for PRL needed at least two of these three hormones. In summary, progesterone and/or PRL may be partly responsible for the increased hormonal sensitivity first manifest during pregnancy, but a normal endocrine milieu is required to maintain this responsiveness in vitro.