This Article Full Text Full Text (PDF) All Versions of this Article: 146/1/103    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fleenor, D. Articles by Freemark, M. Search for Related Content PubMed PubMed Citation Articles by Fleenor, D. Articles by Freemark, M. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB GLUCOSE

Roles of the Lactogens and Somatogens in Perinatal and Postnatal Metabolism and Growth: Studies of a Novel Mouse Model Combining Lactogen Resistance and Growth Hormone Deficiency

Division of Pediatric Endocrinology and Diabetes (D.F., J.O., S.W., J.K., M.F.), Duke University Medical Center, Durham North Carolina 27710; Institut National de la Santé et de la Recherche Médicale Unité 584-Hormone Targets (P.A.K., S.A., M.P.), Faculte de Medecine Necker, Paris, France 75015; and Musculoskeletal Diseases Center (S.M.), Jerry L. Pettis Veterans Affairs Medical Center, Loma Linda, California 92357

Address all correspondence and requests for reprints to: Dr. Michael Freemark, Division of Pediatric Endocrinology and Diabetes, Box 3080, Duke University Medical Center, Durham, North Carolina 27710. E-mail: freem001{at}mc.duke.edu.

To delineate the roles of the lactogens and GH in the control of perinatal and postnatal growth, fat deposition, insulin production, and insulin action, we generated a novel mouse model that combines resistance to all lactogenic hormones with a severe deficiency of pituitary GH. The model was created by breeding PRL receptor (PRLR)-deficient (knockout) males with GH-deficient (little) females. In contrast to mice with isolated GH or PRLR deficiencies, double-mutant (lactogen-resistant and GH-deficient) mice on d 7 of life had growth failure and hypoglycemia. These findings suggest that lactogens and GH act in concert to facilitate weight gain and glucose homeostasis during the perinatal period. Plasma insulin and IGF-I and IGF-II concentrations were decreased in both GH-deficient and double-mutant neonates but were normal in PRLR-deficient mice. Body weights of the double mutants were reduced markedly during the first 3–4 months of age, and adults had striking reductions in femur length, plasma IGF-I and IGF binding protein-3 concentrations, and femoral bone mineral density. By age 6–12 months, however, the double-mutant mice developed obesity, hyperleptinemia, fasting hyperglycemia, relative hypoinsulinemia, insulin resistance, and glucose intolerance; males were affected to a greater degree than females. The combination of perinatal growth failure and late-onset obesity and insulin resistance suggests that the lactogen-resistant/GH-deficient mouse may serve as a model for the development of the metabolic syndrome.

This article has been cited by other articles:

				N. Ben-Jonathan, C. R. LaPensee, and E. W. LaPensee What Can We Learn from Rodents about Prolactin in Humans? Endocr. Rev., February 1, 2008; 29(1): 1 - 41. [Abstract] [Full Text] [PDF]

				J.-P. del Rincon, K. Iida, B. D. Gaylinn, C. E. McCurdy, J. W. Leitner, L. A. Barbour, J. J. Kopchick, J. E. Friedman, B. Draznin, and M. O. Thorner Growth Hormone Regulation of p85{alpha} Expression and Phosphoinositide 3-Kinase Activity in Adipose Tissue: Mechanism for Growth Hormone-Mediated Insulin Resistance Diabetes, June 1, 2007; 56(6): 1638 - 1646. [Abstract] [Full Text] [PDF]

				C. R. LaPensee, N. D. Horseman, P. Tso, T. D. Brandebourg, E. R. Hugo, and N. Ben-Jonathan The Prolactin-Deficient Mouse Has an Unaltered Metabolic Phenotype Endocrinology, October 1, 2006; 147(10): 4638 - 4645. [Abstract] [Full Text] [PDF]

				A. Bartke Minireview: Role of the Growth Hormone/Insulin-Like Growth Factor System in Mammalian Aging Endocrinology, September 1, 2005; 146(9): 3718 - 3723. [Abstract] [Full Text] [PDF]