ARS | Publication request: Overexpression of des(1-3)hIGF-I in the mammary gland during prolonged lactation enhances milk yield and elevates prolactin secretion

Submitted to: Endocrine Society Meeting
Publication Type: Abstract Only
Publication Acceptance Date: March 1, 2005
Publication Date: June 1, 2005
Citation: Hadsell, D.L., Torres, D., George, J., Shelton, G.S., Parlow, A.F., Fiorotto, M.L. 2005. Overexpression of des(1-3)hIGF-I in the mammary gland during prolonged lactation enhances milk yield and elevates prolactin secretion [abstract]. In: The 87th Annual Meeting of the Endocrine Society, June 4-7, 2005, San Diego, California. p. 531.

Technical Abstract: During prolonged lactation, the mammary gland loses the capacity to synthesize and secrete the large amounts of milk that are produced during early lactation. This loss occurs despite the continued presence of a suckling stimulus and complete removal of mammary secretions. The decline in milk synthesis during prolonged lactation is believed to result from apoptotic loss of secretory epithelial cells and can be slowed by administration of exogenous growth hormone. Our previous work has demonstrated that overepression of des(1-3)hIGF-I in the mammary glands of transgenic mice (WAP-DES) inhibited apoptosis during natural mammary gland involution. The present study tests the hypothesis that overexpressed IGF-I delays the loss of milk synthesis that occurs during prolonged lactation. Accordingly, lactation capacity, mammary gland development, and milk composition were compared in nontransgenic and WAP-DES dams during a single lactation that was artificially prolonged for up to 42 days. Lactation performance, measured as the weekly gain of cross-fostered litters, and mammary epithelial cell content declined in both groups, but were 40% faster (P<0.05) in nontransgenic than WAP-DES dams. Milk composition was similar between nontrangenic and WAP-DES dams. Mammary cell apoptosis, increased (P<0.05) threefold in both groups during prolonged lactation, but was similar in nontransgenic and WAP-DES dams. Blood concentration of murine IGF-I was decreased in WAP-DES dams while those of human IGF-I were dramatically elevated during prolonged lactation, so that total blood IGF-I concentration was higher than in nontransgenic dams. Blood prolactin, and the phosphorylation of STAT5 within the mammary gland, decreased with prolonged lactation. However, in WAP-DES dams, blood prolactin was significantly higher (P<0.05) than that of nontransgenic dams. In addition the WAP-DES mice maintained a higher body mass and a greater lean body mass than their nontransgenic littermates. These data support the conclusion that overexpression of des(1-3)hIGF-I enhanced milk synthesis and mammary development during prolonged lactation through a mechanism that involves improved maternal nutrient balance and increased prolactin secretion.