|Hadsell, D - BAYLOR COLLEGE MED|
|Parlow, A - HARBOR-UCLA MED CTR|
|Torres, D - BAYLOR COLLEGE MED|
|George, J - BAYLOR COLLEGE MED|
|Olea, W - BAYLOR COLLEGE MED|
Submitted to: Journal of Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: April 8, 2008
Publication Date: July 1, 2008
Citation: Hadsell, D.L., Parlow, A.F., Torres, D., George, J., Olea, W. 2008. 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. Journal of Endocrinology. 198:61-70. Interpretive Summary: Treatment of lactating females with growth hormone increases milk production through a mechanism that is not fully defined. Previous studies suggest that the hormone IGF-I may mediate some of these effects. This study compared the effect of growth hormone and insulin-like growth factor I on milk production in lactating mice. The study also measured the effects of these two hormones on the activation of mammary cell signaling pathways. Both growth hormone and insulin-like growth factor I increased milk production in the mice. However, the two hormones activated different signaling pathways, suggesting that their effect may occur through unique mechanisms. Understanding how these two hormones increase milk production may lead to a further understanding of the control of lactation, which could help breastfeeding mothers with insufficient milk supply.
Technical 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 to 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.