Michael S. Freemark, MD



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Professor of Pediatrics
Division Chief, Pediatric Endocrinology
Robert C. Atkins, MD, and Veronica Atkins Professor of Pediatrics
Vice Chair of Pediatric Research
Department / Division:
Pediatrics / Pediatrics-Endocrinology
DUMC 102820
Durham, NC 27710
Appointment Telephone:
Office Telephone:
  • MD, Duke University School of Medicine, 1976
  • Pediatrics, Duke University Medical Center, 1976-1979
  • Pediatric Endocrinology, Duke University Medical Center, 1980-1984
  • Molecular Endocrinology, Lineberger Cancer Center, University of North Carolina, 1990
  • Molecular Endocrinology, Necker Hospital for Sick Children (France), 1993, 2006
Other Training:
  • BA, Brandeis University (Massachusetts), 1972
Clinical Interests:
Pediatric endocrinology; hypothalamic-pituitary dysfunction; disorders of growth, thyroid function, and sexual development; diabetes mellitus; insulin resistance; celiac disease in diabetic children, hyperlipidemia
Research Interests:
The primary objective of my basic research has been to elucidate the roles of placental and fetal hormones in the regulation of maternal metabolism and fetal growth. My work has focused on the lactogenic hormones produced by the pituitary gland and placenta. In recent studies we have used targeted knockout mice to explore the molecular mechanisms by which prolactin and placental lactogen regulate pancreatic beta cell mass and insulin production during pregnancy and postnatal life.
I also have a clinical research interest in the pathogenesis and treatment of obesity and hyperlipidemia and the prevention of type 2 diabetes. In previous studies we showed that the drug metformin reduces fat stores and blood glucose and insulin levels in obese adolescents and may reduce the risk of progression to diabetes in selected patients. We have also examined the unique metabolic characteristics of Prader Willi syndrome, a genetic obesity disorder. Finally, we have recently completed a detailed study of metabolism in malnourished children in Uganda and characterized the effects of concurrent HIV infection on nutritional recovery.
Representative Publications:
  • Haqq, AM; Muehlbauer, MJ; Newgard, CB; Grambow, S; Freemark, M. The metabolic phenotype of Prader-Willi syndrome (PWS) in childhood: heightened insulin sensitivity relative to body mass index. Journal of Clinical Endocrinology and Metabolism. 2011;96:E225-E232.  Abstract
  • Arumugam, R; Horowitz, E; Noland, RC; Lu, D; Fleenor, D; Freemark, M. Regulation of islet beta-cell pyruvate metabolism: interactions of prolactin, glucose, and dexamethasone. Endocrinology. 2010;151:3074-3083.  Abstract
  • Brown, WV; Wilson, DP; Freemark, M; Kwiterovich, PO. The use of lipid-lowering drugs in children. Journal of Clinical Lipidology. 2010;4:449-461.  Abstract
  • Freemark, M. Placental hormones and the control of fetal growth. Journal of Clinical Endocrinology and Metabolism. 2010;95:2054-2057.  Abstract
  • Artz, E; Warren-Ulanch, J; Becker, D; Greenspan, S; Freemark, M. Seropositivity to celiac antigens in asymptomatic children with type 1 diabetes mellitus: association with weight, height, and bone mineralization. Pediatric Diabetes. 2008;9:277-284.  Abstract
  • Arumugam, R; Horowitz, E; Lu, D; Collier, JJ; Ronnebaum, S; Fleenor, D; Freemark, M. The interplay of prolactin and the glucocorticoids in the regulation of beta-cell gene expression, fatty acid oxidation, and glucose-stimulated insulin secretion: implications for carbohydrate metabolism in pregnancy. Endocrinology. 2008;149:5401-5414.  Abstract
  • August, GP; Caprio, S; Fennoy, I; Freemark, M; Kaufman, FR; Lustig, RH; Silverstein, JH; Speiser, PW; Styne, DM; Montori, VM; Endocrine Society. Prevention and treatment of pediatric obesity: an endocrine society clinical practice guideline based on expert opinion. Journal of Clinical Endocrinology and Metabolism. 2008;93:4576-4599.  Abstract
  • Haqq, AM; Grambow, SC; Muehlbauer, M; Newgard, CB; Svetkey, LP; Carrel, AL; Yanovski, JA; Purnell, JQ; Freemark, M. Ghrelin concentrations in Prader-Willi syndrome (PWS) infants and children: changes during development. Clinical Endocrinology. 2008;69:911-920.  Abstract
  • Higgins, SP; Freemark, M; Prose, NS. Acanthosis nigricans: a practical approach to evaluation and management. Dermatology online journal. 2008;14:2.  Abstract
  • Viengchareun, S; Servel, N; Fève, B; Freemark, M; Lombès, M; Binart, N. Prolactin receptor signaling is essential for perinatal brown adipocyte function: a role for insulin-like growth factor-2. PloS one. 2008;3:e1535.  Abstract
  • Arumugam, R; Fleenor, D; Freemark, M. Effects of lactogen resistance and GH deficiency on mouse metabolism: pancreatic hormones, adipocytokines, and expression of adiponectin and insulin receptors. Endocrine. 2007;32:182-191.  Abstract
  • Arumugam, R; Fleenor, D; Freemark, M. Lactogenic and somatogenic hormones regulate the expression of neuropeptide Y and cocaine- and amphetamine-regulated transcript in rat insulinoma (INS-1) cells: interactions with glucose and glucocorticoids. Endocrinology. 2007;148:258-267.  Abstract
  • Freemark, M. Liver dysfunction in paediatric obesity: a randomized, controlled trial of metformin. Acta Paediatrica. 2007;96:1326-1332.  Abstract
  • Freemark, M. Pharmacotherapy of childhood obesity: an evidence-based, conceptual approach. Diabetes Care. 2007;30:395-402.  Abstract
  • Haqq, AM; Muehlbauer, M; Svetkey, LP; Newgard, CB; Purnell, JQ; Grambow, SC; Freemark, MS. Altered distribution of adiponectin isoforms in children with Prader-Willi syndrome (PWS): association with insulin sensitivity and circulating satiety peptide hormones. Clinical Endocrinology. 2007;67:944-951.  Abstract
  • Fleenor, D; Arumugam, R; Freemark, M. Growth hormone and prolactin receptors in adipogenesis: STAT-5 activation, suppressors of cytokine signaling, and regulation of insulin-like growth factor I. Hormone research. 2006;66:101-110.  Abstract
  • Freemark, M. Regulation of maternal metabolism by pituitary and placental hormones: roles in fetal development and metabolic programming. Hormone research. 2006;65 Suppl 3:41-49.  Abstract
  • Artz, E; Haqq, A; Freemark, M. Hormonal and metabolic consequences of childhood obesity. Endocrinology & Metabolism Clinics of North America. 2005;34:643-ix.  Abstract
  • Fleenor, D; Oden, J; Kelly, PA; Mohan, S; Alliouachene, S; Pende, M; Wentz, S; Kerr, J; Freemark, M. 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. Endocrinology. 2005;146:103-112.  Abstract
  • Speiser, PW; Rudolf, MC; Anhalt, H; Camacho-Hubner, C; Chiarelli, F; Eliakim, A; Freemark, M; Gruters, A; Hershkovitz, E; Iughetti, L; Krude, H; Latzer, Y; Lustig, RH; Pescovitz, OH; Pinhas-Hamiel, O; Rogol, AD; Shalitin, S; Sultan, C; Stein, D; Vardi, P; Werther, GA; Zadik, Z; Zuckerman-Levin, N; Hochberg, Z; Obesity Consensus Working Group. Childhood obesity. Journal of Clinical Endocrinology and Metabolism. 2005;90:1871-1887.  Abstract
  • Artz, E; Freemark, M. The pathogenesis of insulin resistance in children: metabolic complications and the roles of diet, exercise and pharmacotherapy in the prevention of type 2 diabetes. Pediatric endocrinology reviews : PER. 2004;1:296-309.  Abstract
  • Freemark, M. Editorial: Growth hormone treatment of "idiopathic short stature": not so fast. Journal of Clinical Endocrinology and Metabolism. 2004;89:3138-3139.  Abstract
  • Freemark, M; Kiess, W. Anti-obesity medication use in adolescents: risks and benefits. Pediatric endocrinology reviews : PER. 2004;2 Suppl 1:168-170.  Abstract
  • Freemark, M. Pharmacologic approaches to the prevention of type 2 diabetes in high risk pediatric patients. Journal of Clinical Endocrinology and Metabolism. 2003;88:3-13.  Abstract
  • Freemark, M; Levitsky, LL. Screening for celiac disease in children with type 1 diabetes: two views of the controversy. Diabetes Care. 2003;26:1932-1939.  Abstract
  • Freemark, M; Avril, I; Fleenor, D; Driscoll, P; Petro, A; Opara, E; Kendall, W; Oden, J; Bridges, S; Binart, N; Breant, B; Kelly, PA. Targeted deletion of the PRL receptor: effects on islet development, insulin production, and glucose tolerance. Endocrinology. 2002;143:1378-1385.  Abstract
  • Litton, J; Rice, A; Friedman, N; Oden, J; Lee, MM; Freemark, M. Insulin pump therapy in toddlers and preschool children with type 1 diabetes mellitus. The Journal of Pediatrics. 2002;141:490-495.  Abstract
  • Oden, J; Fleenor, D; Driscoll, P; Freemark, M. Leptin in the newborn mouse. Plasma concentrations, characterization of the circulating hormone, and tissue source. Biology of the neonate. 2002;82:109-116.  Abstract
  • Oden, J; Freemark, M. Thyroxine supplementation in preterm infants: critical analysis. Current Opinion in Pediatrics. 2002;14:447-452.  Abstract
  • Fleenor, DE; Freemark, M. Prolactin induction of insulin gene transcription: roles of glucose and signal transducer and activator of transcription 5. Endocrinology. 2001;142:2805-2810.  Abstract
  • Freemark, M. Ontogenesis of prolactin receptors in the human fetus: roles in fetal development. Biochemical Society transactions. 2001;29:38-41.  Abstract
  • Freemark, M; Bursey, D. The effects of metformin on body mass index and glucose tolerance in obese adolescents with fasting hyperinsulinemia and a family history of type 2 diabetes. Pediatrics. 2001;107:E55.  Abstract
  • Freemark, M; Fleenor, D; Driscoll, P; Binart, N; Kelly, P. Body weight and fat deposition in prolactin receptor-deficient mice. Endocrinology. 2001;142:532-537.  Abstract
  • Kelly, PA; Binart, N; Freemark, M; Lucas, B; Goffin, V; Bouchard, B. Prolactin receptor signal transduction pathways and actions determined in prolactin receptor knockout mice. Biochemical Society transactions. 2001;29:48-52.  Abstract
  • Rapaport, R; Rose, SR; Freemark, M. Hypothyroxinemia in the preterm infant: the benefits and risks of thyroxine treatment. The Journal of Pediatrics. 2001;139:182-188.  Abstract
  • Fleenor, D; Petryk, A; Driscoll, P; Freemark, M. Constitutive expression of placental lactogen in pancreatic beta cells: effects on cell morphology, growth, and gene expression. Pediatric Research. 2000;47:136-142.  Abstract
  • Handwerger, S; Freemark, M. The roles of placental growth hormone and placental lactogen in the regulation of human fetal growth and development. The Journal of pediatric endocrinology. 2000;13:343-356.  Abstract
  • Petryk, A; Fleenor, D; Driscoll, P; Freemark, M. Prolactin induction of insulin gene expression: the roles of glucose and glucose transporter-2. Journal of Endocrinology. 2000;164:277-286.  Abstract
  • Freemark, M. The fetal adrenal and the maturation of the growth hormone and prolactin axes. Endocrinology. 1999;140:1963-1965.  Abstract
  • Rivkees, SA; Sklar, C; Freemark, M. Clinical review 99: The management of Graves' disease in children, with special emphasis on radioiodine treatment. Journal of Clinical Endocrinology and Metabolism. 1998;83:3767-3776.  Abstract
  • Freemark, M; Driscoll, P; Maaskant, R; Petryk, A; Kelly, PA. Ontogenesis of prolactin receptors in the human fetus in early gestation. Implications for tissue differentiation and development. Journal of Clinical Investigation. 1997;99:1107-1117.  Abstract
  • Freemark, M; Driscoll, P; Andrews, J; Kelly, PA; Royster, M. Ontogenesis of prolactin receptor gene expression in the rat olfactory system: potential roles for lactogenic hormones in olfactory development. Endocrinology. 1996;137:934-942.  Abstract
  • Bridges, RS; Freemark, MS. Human placental lactogen infusions into the medial preoptic area stimulate maternal behavior in steroid-primed, nulliparous female rats. Hormones and Behavior. 1995;29:216-226.  Abstract
  • Freemark, M; Nagano, M; Edery, M; Kelly, PA. Prolactin receptor gene expression in the fetal rat. Journal of Endocrinology. 1995;144:285-292.  Abstract
  • Royster, M; Driscoll, P; Kelly, PA; Freemark, M. The prolactin receptor in the fetal rat: cellular localization of messenger ribonucleic acid, immunoreactive protein, and ligand-binding activity and induction of expression in late gestation. Endocrinology. 1995;136:3892-3900.  Abstract
  • Fowlkes, J; Freemark, M. Placental lactogen-binding sites in isolated fetal fibroblasts: characterization, processing, and regulation. Endocrinology. 1993;132:2477-2483.  Abstract
  • Freemark, M; Kirk, K; Pihoker, C; Robertson, MC; Shiu, RP; Driscoll, P. Pregnancy lactogens in the rat conceptus and fetus: circulating levels, distribution of binding, and expression of receptor messenger ribonucleic acid. Endocrinology. 1993;133:1830-1842.  Abstract
  • Pihoker, C; Robertson, MC; Freemark, M. Rat placental lactogen-I binds to the choroid plexus and hypothalamus of the pregnant rat. Journal of Endocrinology. 1993;139:235-242.  Abstract
  • Fowlkes, J; Freemark, M. Binding of placental lactogen and growth hormone to fetal sheep fibroblasts. Pediatric Research. 1992;32:200-203.  Abstract
  • Fowlkes, J; Freemark, M. Developmental regulation of insulin-like growth factor binding protein production: studies in fetal, postnatal, and pregnant sheep. Journal of Cellular Physiology. 1992;152:19-27.  Abstract
  • Fowlkes, J; Freemark, M. Evidence for a novel insulin-like growth factor (IGF)-dependent protease regulating IGF-binding protein-4 in dermal fibroblasts. Endocrinology. 1992;131:2071-2076.  Abstract
  • Freemark, M; Keen, A; Fowlkes, J; Mularoni, T; Comer, M; Grandis, A; Kodack, L. The placental lactogen receptor in maternal and fetal sheep liver: regulation by glucose and role in the pathogenesis of fasting during pregnancy. Endocrinology. 1992;130:1063-1070.  Abstract
  • Osborn, BH; Fowlkes, J; Han, VK; Freemark, M. Nutritional regulation of insulin-like growth factor-binding protein gene expression in the ovine fetus and pregnant ewe. Endocrinology. 1992;131:1743-1750.  Abstract
  • Freemark, M; Comer, M; Mularoni, T; D'Ercole, AJ; Grandis, A; Kodack, L. Placental lactogen receptors in maternal sheep liver: effects of fasting and refeeding. The American journal of physiology. 1990;258:E338-E346.  Abstract
  • Freemark, M; Comer, M. Purification of a distinct placental lactogen receptor, a new member of the growth hormone/prolactin receptor family. Journal of Clinical Investigation. 1989;83:883-889.  Abstract
  • Freemark, M; Comer, M; Mularoni, T; D'Ercole, AJ; Grandis, A; Kodack, L. Nutritional regulation of the placental lactogen receptor in fetal liver: implications for fetal metabolism and growth. Endocrinology. 1989;125:1504-1512.  Abstract
  • Freemark, M; Handwerger, S. The role of placental lactogen in the regulation of fetal metabolism and growth. Journal of Pediatric Gastroenterology and Nutrition. 1989;8:281-283.  Abstract
  • Freemark, M; Comer, M; Korner, G. Differential solubilization of placental lactogen (PL)- and growth hormone-binding sites: further evidence for a unique PL receptor in fetal and maternal liver. Endocrinology. 1988;122:2771-2779.  Abstract
  • Hill, DJ; Freemark, M; Strain, AJ; Handwerger, S; Milner, RD. Placental lactogen and growth hormone receptors in human fetal tissues: relationship to fetal plasma human placental lactogen concentrations and fetal growth. Journal of Clinical Endocrinology and Metabolism. 1988;66:1283-1290.  Abstract
  • Freemark, M; Comer, M. Epidermal growth factor (EGF)-like transforming growth factor (TGF) activity and EGF receptors in ovine fetal tissues: possible role for TGF in ovine fetal development. Pediatric Research. 1987;22:609-615.  Abstract
  • Freemark, M; Comer, M; Korner, G; Handwerger, S. A unique placental lactogen receptor: implications for fetal growth. Endocrinology. 1987;120:1865-1872.  Abstract
  • Handwerger, S; Freemark, M. Role of placental lactogen and prolactin in human pregnancy. Advances in experimental medicine and biology. 1987;219:399-420.  Abstract
  • Freemark, M. Epidermal growth factor stimulates glycogen synthesis in fetal rat hepatocytes: comparison with the glycogenic effects of insulin-like growth factor I and insulin. Endocrinology. 1986;119:522-526.  Abstract
  • Freemark, M; Comer, M; Handwerger, S. Placental lactogen and GH receptors in sheep liver: striking differences in ontogeny and function. The American journal of physiology. 1986;251:E328-E333.  Abstract
  • Freemark, M; Handwerger, S. The glycogenic effects of placental lactogen and growth hormone in ovine fetal liver are mediated through binding to specific fetal ovine placental lactogen receptors. Endocrinology. 1986;118:613-618.  Abstract
  • Freemark, M; D'Ercole, AJ; Handwerger, S. Somatomedin-C stimulates glycogen synthesis in fetal rat hepatocytes. Endocrinology. 1985;116:2578-2582.  Abstract
  • Freemark, M; Handwerger, S. Ovine placental lactogen inhibits glucagon-induced glycogenolysis in fetal rat hepatocytes. Endocrinology. 1985;116:1275-1280.  Abstract
  • Freemark, M; Handwerger, S. Glycogenolytic effects of the calcium ionophore A23187, but not of vasopressin or angiotensin, in foetal-rat hepatocytes. The Biochemical journal. 1984;220:441-445.  Abstract
  • Freemark, M; Handwerger, S. Ovine placental lactogen stimulates glycogen synthesis in fetal rat hepatocytes. The American journal of physiology. 1984;246:E21-E24.  Abstract
  • Freemark, M; Handwerger, S. Synergistic effects of oPL and insulin on glycogen metabolism in fetal rat hepatocytes. The American journal of physiology. 1984;247:E714-E718.  Abstract
  • Freemark, M; Handwerger, S. Ovine placental lactogen, but not growth hormone, stimulates amino acid transport in fetal rat diaphragm. Endocrinology. 1983;112:402-404.  Abstract
  • Freemark, M; Handwerger, S. Ovine placental lactogen stimulates amino acid transport in rat diaphragm. Endocrinology. 1982;110:2201-2203.  Abstract
  • Dubois, PJ; Freemark, M; Lewis, D; Drayer, BP; Heinz, ER; Osborne, D. Case report. Atypical findings in adrenoleukodystrophy. Journal of Computer Assisted Tomography. 1981;5:888-891.  Abstract
  • Raffin, BJ; Freemark, M. Streptobacillary rat-bite fever: a pediatric problem. Pediatrics. 1979;64:214-217.  Abstract
  • Freemark, M; Stoff, DM; Moja, EA; Gillin, JC; Wyatt, RJ. Testosterone-attenuated stereotype and hyperactivity induced by beta-phenylethylamine in pargyline-pretreated rats. Biological Psychiatry. 1978;13:455-463.  Abstract