title: 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.
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 eIF4E and eIF4G. 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.
authors.affiliation: United States Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas 77030, USA. dhadsell@bcm.tmc.edu.
authors.forename: Darryl L
authors.initials: DL
authors.lastname: Hadsell
authors.forename: Sharon
authors.initials: S
authors.lastname: Bonnette
authors.forename: Jessy
authors.initials: J
authors.lastname: George
authors.forename: Daniel
authors.initials: D
authors.lastname: Torres
authors.forename: Yann
authors.initials: Y
authors.lastname: Klimentidis
authors.forename: Yann
authors.initials: Y
authors.lastname: Klementidis
authors.forename: Shan
authors.initials: S
authors.lastname: Gao
authors.forename: Peter M
authors.initials: PM
authors.lastname: Haney
authors.forename: Joan
authors.initials: J
authors.lastname: Summy-Long
authors.forename: Melvyn S
authors.initials: MS
authors.lastname: Soloff
authors.forename: Albert F
authors.initials: AF
authors.lastname: Parlow
authors.forename: Mario
authors.initials: M
authors.lastname: Sirito
authors.forename: Michele
authors.initials: M
authors.lastname: Sawadogo
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism*; D039603:Eukaryotic Initiation Factor-4G / Q000378:metabolism*; D005260:Female; D007774:Lactation; D008321:Mammary Glands, Animal / Q000378:metabolism*; D008425:Maternal Behavior; D051379:Mice; D008822:Mice, Transgenic; D008892:Milk / Q000737:chemistry / Q000378:metabolism*; D008894:Milk Proteins / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009929:Organ Size; D010121:Oxytocin / Q000097:blood*; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D051720:Upstream Stimulatory Factors
chemical_list: D004268:DNA-Binding Proteins; D039561:Eukaryotic Initiation Factor-4E; D039603:Eukaryotic Initiation Factor-4G; D008894:Milk Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D051720:Upstream Stimulatory Factors; C497183:Usf1 protein, mouse; C497186:Usf2 protein, mouse; D010121:Oxytocin