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Glycosylation-Dependent Cell Adhesion Molecule 1 (GlyCAM 1) Is Induced by Prolactin and Suppressed by Progesterone in Mammary Epithelium¹

Department of Molecular and Cellular Physiology (Z.H., J.P.B., A.J.V., M.M., J.M., J.A.L., N.D.H.), Department of Internal Medicine, Division of Endocrinology and Metabolism (N.D.H.), University of Cincinnati, Cincinnati, Ohio 45267; Department of Biology (A.J.V.), Beaver College, Glenside, Pennsylvania 19038

Address all correspondence and requests for reprints to: Nelson D. Horseman, 231 Bethesda Avenue, Cincinnati, Ohio 45267-0576. E-mail: nelson.horseman{at}uc.edu

Glycosylation-dependent cell adhesion molecule 1 (GlyCAM 1), a mucin-like endothelial glycoprotein, was induced by PRL and suppressed by progesterone in the mammary gland of mice, and in HC11 mouse mammary epithelial cells. Complementary DNA microarray analysis revealed that expression of GlyCAM 1 was reduced in the mammary gland of PRL-gene disrupted mice (PRL^-/-) compared with control (PRL^+/-) littermates. This result was confirmed by in situ hybridization and immunostaining. The messenger RNA (mRNA) encoding GlyCAM 1 was present in mammary epithelia of PRL-stimulated mice. Immunohistochemistry indicated that GlyCAM 1 protein was detectable both in mammary epithelia and in the ductal lumen in PRL^+/- virgin mice, but not in PRL^-/- mice. GlyCAM 1 mRNA was highly induced by grafting pituitary glands from normal littermates. Trace amounts of mRNA for GlyCAM 1 were detected by RT-PCR in mammary tissue of PRL^-/- mice. Progesterone inhibited both basal and PRL-stimulated GlyCAM 1 transcription. In HC11 cells, GlyCAM 1 mRNA was induced in cells treated with insulin, dexamethasone, and PRL. Similar to the in vivo studies, progesterone inhibited the induction of GlyCAM 1 transcription. In CHO cells, PRL stimulated transcription of a luciferase reporter gene containing an 800-bp promoter fragment of GlyCAM 1, and progesterone partially suppressed the PRL effect. These data demonstrate that expression of GlyCAM 1 in mammary gland is under the control of both PRL and progesterone.

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