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This version published online on August 15, 2002
Molecular Endocrinology, doi:10.1210/me.2002-0169
Molecular Endocrinology Vol. 0, No. 2002 200201691-
doi:10.1210/me.2002-0169
Copyright © 2002 by the Endocrine Society.
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Submitted on May 9, 2002
Accepted on July 25, 2002

A Novel LacZ Reporter Mouse Reveals Complex Regulation of the Progesterone Receptor Promoter During Mammary Gland Development

Preeti M. Ismail1, Jie Li1, Francesco J. DeMayo1, Bert W. O'Malley1, and John P. Lydon1*

1 Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030-3498

* To whom correspondence should be addressed. E-mail: jlydon{at}bcm.tmc.edu.

To further our understanding of progesterone (P) as an endocrine mammogen, a PRlacz \'knockin' mouse was generated in which the endogenous progesterone receptor (PR) promoter directly regulated lacZ reporter expression. The PRlacz mouse revealed PR promoter activity was restricted to the epithelial compartment during the pre-and post-natal stages of mammary gland development. At puberty, PR promoter activity was unexpectedly robust and restricted to the body cells within the terminal end buds and to the luminal epithelial cells in the subtending ducts. In the adult, the preferential localization of PRlacz positive cells to the distal regions of ductal side branches provided a cellular context to P's recognized mandatory role in ductal side-branching, and segregation of these cells from cells that undergo proliferation supported an intra-epithelial paracrine mode of action for P in branching morphogenesis. Toward the end of pregnancy, the PRlacz mouse disclosed a progressive attenuation in PR promoter activity, supporting the postulate that the preparturient removal of P's proliferative signal is a prerequisite for the emergence of a functional lactating mammary gland. The data suggest that PR expression before pregnancy is to ensure the specification and spatial organization of ductal and alveolar progenitor cell-lineages, whereas abrogation of PR expression before lactation is required to enable terminal differentiation of the mammary gland.
Key words: Progesterone Receptor • Mammary Gland • LacZ knockin • Mouse

NURSA Molecule Pages Link:

Nuclear Receptors:   PR
Ligands:   17β-Estradiol  |  Progesterone



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