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Title: Short-term administration of rhGH increases markers of cellular proliferation, but not milk protein gene expression in normal lactating women.

Author
item MANINGAT, PATRICIA - Baylor College Of Medicine
item SEN, PARTHA - Children'S Nutrition Research Center (CNRC)
item RIJNKELS, MONIQUE - Children'S Nutrition Research Center (CNRC)
item HADSELL, DARRYL - Children'S Nutrition Research Center (CNRC)
item BRAY, MOLLY - Children'S Nutrition Research Center (CNRC)
item HAYMOND, MOREY - Children'S Nutrition Research Center (CNRC)

Submitted to: Physiological Genomics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/3/2011
Publication Date: 1/3/2011
Citation: Maningat, P.D., Sen, P., Rijnkels, M., Hadsell, D.L., Bray, M.S., Haymond, M.W. 2011. Short-term administration of rhGH increases markers of cellular proliferation, but not milk protein gene expression in normal lactating women. Physiological Genomics. 43:381-391.

Interpretive Summary: Growth hormone (GH) is one of the few pharmacologic agents known to increase milk production in humans. We undertook studies to determine how growth hormone increases milk production in normal lactating women. We previously developed the methodology to measure messenger RNA (mRNA, the signal produced by genes have been turned on) in human milk reflects the genes in the cells producing milk. Our results showed that the growth hormone did not increase the activity of any of the genes directly relating to the production of milk products, but did increase genes which affect cell growth and division (cell cycling genes). We conclude that the human growth hormone increases milk production by the activation of genes that control cellular growth and metabolism, but not those directly controlling the product of milk sugar, protein or fat.

Technical Abstract: Growth hormone is one of few pharmacologic agents known to augment milk production in humans. We hypothesized that recombinant human GH (rhGH) increases the expression of cell proliferation and milk protein synthesis genes. Sequential milk and blood samples collected over four days were obtained from five normal lactating women. Following 24 h of baseline milk and blood sampling, rhGH (0.1 mg/kg/day) was administered subcutaneously once daily for 3 days. Gene expression changes were determined by microarray studies utilizing milk fat globule RNA isolated from each milk sample. Following rhGH administration, DNA synthesis and cell cycle genes were induced, while no significant changes were observed in the expression of milk synthesis genes. Expression of glycolysis and citric acid cycle genes were increased by day 4 compared with day 1, while lipid synthesis genes displayed a circadian-like pattern. Cell cycle gene upregulation occurred after a lag of approximately 2 days, likely explaining the failure to increase milk production after only 3 days of rhGH treatment. We conclude that rhGH induces expression of cellular proliferation and metabolism genes, but does not induce milk protein gene expression, as potential mechanisms for increasing milk production and could account for the known effect of rhGH to increase milk production following 7-10 days.