Loss of differentiative potential of the mammary gland in ovariectomized mice: prevention and reversibility of the defect.

The differentiative functions, lactose synthetase activity and casein synthesis, are not expressed in vitro in mammary gland explants from female virgin mice castrated for 1-2 months. 17 beta-Estradiol (E2) treatment (3 micrograms, twice weekly) initiated immediately after ovariectomy completely preserves this ability for as long as 2 months; however, elevating serum PRL levels by either perphenazine treatment or pituitary transplantation under the renal capsule is ineffective. Therefore, the loss of differentiative potential in the mammary gland appears to be a result of E3 deprivation and not depressed serum PRL concentrations. E2 therapy for 5 weeks also partially restores this potential in animals whose mammary glands have previously lost it. Complete reversal of this defect occurs when the tissue from mice castrated for 4 weeks is transplanted into the cleared fat pads of intact virgins. These data suggest that E2 has an important role in differentiation of the mouse gland in addition to its known role in mammary epithelial growth.