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Estrogen and Progesterone are Critical Regulators of Stat5a Expression in the Mouse Mammary Gland

Breast Cancer and the Environment Research Center, Cell and Molecular Biology Program and Departments of Physiology (S.Z.H.) and Microbiology and Molecular Genetics (S.E.C.), Michigan State University, East Lansing, Michigan 48824

Address all correspondence and requests for reprints to: Susan E. Conrad, Ph.D., Department of Microbiology and Molecular Genetics, 2209 Biomedical & Physical Sciences Building, East Lansing, Michigan 48824. E-mail: conrad{at}msu.edu.

Signal transducer and activator of transcription (Stat)5a is a well-established regulator of mammary gland development. Several pathways for activating Stat5a have been identified, but little is known about the mechanisms that regulate its expression in this tissue. In this report, we used immunofluorescent staining to examine Stat5a expression in mammary epithelial cells during normal development and in response to treatment with the ovarian hormones estrogen (E) and progesterone (P). Stat5a was present at very low levels in the prepubertal gland and was highly induced in a subset of luminal epithelial cells during puberty. The percentage of positive cells increased in adult virgin, pregnant, and lactating animals, dropped dramatically during involution, and then increased again after weaning. Ovariectomy ablated Stat5a expression in virgin animals, and treatment with both E and P was necessary to restore it. Double-labeling experiments in animals treated with E plus P for 3 d demonstrated that Stat5a was localized exclusively to cells containing both E and P receptors. Together, these results identify a novel role for E and P in inducing Stat5a expression in the virgin mammary gland and suggest that these hormones act at the cellular level through their cognate receptors.