Diminished Milk Synthesis in Upstream Stimulatory Factor 2 Null Mice Is Associated with Decreased Circulating Oxytocin and Decreased Mammary Gland Expression of Eukaryotic Initiation Factors 4E and 4G

Darryl L. Hadsell, Sharon Bonnette, Jessy George, Daniel Torres, Yann Klementidis, Shan Gao, Peter M. Haney, Joan Summy-Long, Melvyn S. Soloff, Albert F. Parlow, Mario Sirito, Michele Sawadogo

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Previous studies have suggested that upstream stimulatory factors (USFs) regulate genes involved with cell cycle progression. Because of the relationship of USFs to an important oncogene in breast cancer, c-myc, we chose to determine the importance of USF to normal mammary gland development in the mouse. Expression of USF in the mammary gland throughout development demonstrated only modest changes. Mutation of the Usf2 gene was associated with reduced fertility in females, but had no effect on prepartum mammary gland development. However, lactation performance in Usf2-/- females was only half of that observed in Usf2+/+ females, and both lactose and nitrogen were decreased in milk from Usf2-/- dams. This decrease was associated with diminished mammary tissue wet weight and luminal area by d 9 of lactation and with a decreased protein-DNA ratio. This decrease was associated with reduced abundance of the eukaryotic initiation factors elF4E and elF4G. Blood oxytocin concentrations on d 9 postpartum were also lower in Usf2 -/- mice than Usf2+/+ mice. In contrast, the mutation had no effect on blood prolactin concentrations, mammary cell proliferation or apoptosis, mammary tissue oxytocin receptors, or milk protein gene expression. The mutation had only modest effects on maternal behavior. These data support the idea that USF is important to physiological processes necessary for the establishment and maintenance of normal lactation and suggest that USF-2 may impact lactation through both systemic and mammary cell-specific mechanisms.

Original languageEnglish (US)
Pages (from-to)2251-2267
Number of pages17
JournalMolecular Endocrinology
Volume17
Issue number11
DOIs
StatePublished - Nov 2003

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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