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United States Department of Agriculture

Agricultural Research Service

Title: Overexpression of Des(1-3) Insulin-Like Growth Factor 1 in the Mammary Glands of Transgenic Mice Delays the Loss of Milk Production with Prolonged Lactation

Authors
item Hadsell, D - BAYLOR COLLEGE MED
item Torres, D - BAYLOR COLLEGE MED
item Lawrence, N - BAYLOR COLLEGE MED
item George, J - BAYLOR COLLEGE MED
item Parlow, A - HARBOR-UCLA, CA
item Lee, A - BAYLOR COLLEGE MED
item Fiorotto, M - BAYLOR COLLEGE MED

Submitted to: Biology of Reproduction
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: August 2, 2005
Publication Date: December 1, 2005
Citation: Hadsell, D.L., Torres, D.T., Lawrence, N.A., George, J., Parlow, A.F., Lee, A.V., Fiorotto, M.L. 2005. Overexpression of des(1-3) insulin-like growth factor 1 in the mammary glands of transgenic mice delays the loss of milk production with prolonged lactation. Biology of Reproduction. 73:1116-1125.

Interpretive Summary: During prolonged lactation, milk production rates declines through a process we refer to as secretory diminution. The goal of this study was to determine if insulin-like growth factor I, a hormone known to support mammary secretory cell survival and metabolism, could delay secretory diminution during prolonged lactation. For this study we used genetically engineered mice that overexpress insulin-like growth factor I in their mammary glands during lactation. The overexpression of the hormone allowed these mice to maintain greater milk production than that found in normal mice. These studies may help us understand why milk production rates decrease during the declining phase of lactation.

Technical Abstract: During prolonged lactation, the mammary gland gradually loses the capacity to produce milk. In agricultural species, this decline can be slowed by administration of exogenous growth hormone (GH), which is believed to act through insulin-like growth factor 1 (IGF1). Our previous work demonstrated delayed natural mammary gland involution in des(1-3)IGF1-overexpressing transgenic mice (Tg[Wap-des{1-3}IGF1]8266 Jmr), hereafter referred to as WAP-DES mice. The present study tested the hypothesis that overexpressed des(1-3)IGF1 would delay the loss of milk production during prolonged lactation. Accordingly, we examined lactational performance in WAP-DES mice by artificially prolonging lactation with continual litter cross-fostering. Over time, lactational capacity and mammary development declined in both WAP-DES and control mice. However, the rate of decline was 40% slower in WAP-DES mice. Mammary cell apoptosis increased by 3-fold in both groups during prolonged lactation but was not different between genotypes. Plasma concentrations of murine IGF1 were decreased in WAP-DES mice, while those of the transgenic human IGF1 were elevated during prolonged lactation. Phosphorylation of the mammary IGF1 receptor was increased in the WAP-DES mice, but only during prolonged lactation. Plasma prolactin decreased with prolonged lactation in nontransgenic mice but remained high in WAP-DES mice. The WAP-DES mice maintained a higher body mass and a greater lean body mass during prolonged lactation. These data support the conclusion that overexpressed des(1-3)IGF1 enhanced milk synthesis and mammary development during prolonged lactation through localized and direct activation of the mammary gland IGF1 receptor and through systemic effects on prolactin secretion and possibly nutrient balance.

Last Modified: 7/31/2014
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