title: Enhancement of maternal lactation performance during prolonged lactation in the mouse by mouse GH and long-R3-IGF-I is linked to changes in mammary signaling and gene expression.
abstract: GH, prolactin (PRL), and IGF-I stimulate lactation-related metabolic processes in mammary epithelial cells. However, the ability of these factors to stimulate milk production in animals varies depending on species and experimental variables. Previous work in our laboratory demonstrated that transgenic overexpression of des(1-3)IGF-I within the mammary glands of lactating mouse dams increased lactation capacity during prolonged lactation. This work also suggested that some of the effects of the overexpressed IGF-I may have been mediated through elevated concentrations of IGF-I or PRL in the systemic circulation. In the present study, murine GH and PRL, and a human IGF-I analog, long-R3-IGF-I (LR3), were administered as s.c. injections to compare their ability to enhance milk production, and alter mammary gland signaling and gene expression. Lactation capacity, as measured by litter gain, was increased (P<0.05) by GH, but not by PRL. LR3 increased (P<0.05) mammary phospho-Akt and suppressors of cytokines signaling 3 (SOCS3) gene expression, and had a modest ability to increase (P<0.05) lactation capacity. GH both increased (P<0.05) mammary SOCS1 expression and decreased (P<0.05) mammary expression of tryptophan hydroxylase 1, the rate-limiting enzyme in the synthesis of serotonin and a potential feedback inhibitor of lactation. These results suggest that while both GH and IGF-I stimulate milk production in the lactating mouse, the effect of GH may be additionally mediated through IGF-I-independent effects associated with repression of mammary serotonin synthesis.
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, USDA/ARS Children's Nutrition Research Center, Houston, Texas 77030, USA. dhadsell@bcm.tmc.edu
authors.forename: Darryl L
authors.initials: DL
authors.lastname: Hadsell
authors.forename: Albert F
authors.initials: AF
authors.lastname: Parlow
authors.forename: Daniel
authors.initials: D
authors.lastname: Torres
authors.forename: Jessy
authors.initials: J
authors.lastname: George
authors.forename: Walter
authors.initials: W
authors.lastname: Olea
mesh_terms: D000818:Animals; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D013006:Growth Hormone / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000031:analogs & derivatives* / Q000494:pharmacology; D007774:Lactation / Q000187:drug effects*; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D011247:Pregnancy; D011388:Prolactin / Q000494:pharmacology; D015398:Signal Transduction; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics
chemical_list: C084339:LR(3)IGF-I; D050826:Suppressor of Cytokine Signaling Proteins; D007334:Insulin-Like Growth Factor I; D011388:Prolactin; D013006:Growth Hormone; D048049:Extracellular Signal-Regulated MAP Kinases