Functional Development of the Mammary Gland: Use of Expression Profiling and Trajectory Clustering to Reveal Changes in Gene Expression During Pregnancy, Lactation, and Involution

Overview

Journal J Mammary Gland Biol Neoplasia

Date 2004 Feb 20

PMID 14973374

Citations 109

Authors

Michael C Rudolph

James L McManaman

Larry Hunter

Tzulip Phang

Margaret C Neville

Affiliations

Soon will be listed here.

Abstract

To characterize the molecular mechanisms by which progesterone withdrawal initiates milk secretion, we examined global gene expression during pregnancy and lactation in mice, focusing on the period around parturition. Trajectory clustering was used to profile the expression of 1358 genes that changed significantly between pregnancy day 12 and lactation day 9. Predominantly downward trajectories included stromal and proteasomal genes and genes for the enzymes of fatty acid degradation. Milk protein gene expression increased throughout pregnancy, whereas the expression of genes for lipid synthesis increased sharply at the onset of lactation. Examination of regulatory genes with profiles similar or complementary to those of lipid synthesis genes led to a model in which progesterone stimulates synthesis of TGF-beta, Wnt 5b, and IGFBP-5 during pregnancy. These factors are suggested to repress secretion by interfering with PRL and IGF-1 signaling. With progesterone withdrawal, PRL and IGF-1 signaling are activated, in turn activating Akt/PKB and the SREBPs, leading to increased lipid synthesis.

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