Michael S. Freemark, MD

Professor of Pediatrics

Division Chief, Pediatric Endocrinology

Department:
Pediatrics

Division:
Endocrinology

Mailing Address:
DUMC 3080 Durham, NC 27710

Appointment Telephone:
919-684-3772

Office Telephone:
919-684-3772

Fax:
919-684-8613

Training:
MD, Duke University School of Medicine, 1976

Fellowship:
Pediatric Endocrinology, Duke University Medical Center, 1980-1984
Lineberger Cancer Center, University of North Carolina, 1990
Hopital Necker Enfants Malades (Paris), 1993, 2006

Residency:
Pediatrics, Duke University Medical Center, 1976-1979

Clinical Interests:
Pediatric endocrinology; hypothalamic-pituitary dysfunction; disorders of growth, thyroid function, and sexual development; diabetes mellitus; insulin resistance

Research Interests:
The primary objective of my basic research effort is to elucidate the roles of fetal and placental hormones in the regulation of maternal metabolism and fetal growth.  My studies have focused on the lactogenic hormones produced by the pituitary gland and placenta.  In recent studies we have explored  the molecular mechanisms by which prolactin and placental lactogen regulate pancreatic insulin production and control lipid metabolism during pregnancy and postnatal life.  
   I also have a clinical research interest in the pathogenesis and treatment of obesity and the prevention of type 2 diabetes.  Recent studies show 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.  Finally, we are exploring the clinical course of diabetic children with celiac disease, an intestinal disorder that affects nutrient absorption.

Publications:
Freemark, M.  Childhood obesity: pathogenesis, complications, and management.  In Brook, C.  Clinical Pediatric Endocrinology, Oxford University Press, 2009



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(2):e1535.

Russell A and Freemark M.  Roles of race and ethnicity in the treatment of childhood obesity. Rev Endocrinol 2008; 2: 25-28, 2008

Higgins SP, Freemark M, Prose NS. Acanthosis nigricans: a practical approach to evaluation and management. Dermatol Online J. 2008;14(9):2.

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. Clin Endocrinol (Oxf). 2008 Dec;69(6):911-20.

August GP, Caprio S, Fennoy I, Freemark M, Kaufman FR, Lustig RH, Silverstein JH, Speiser PW, Styne DM, Montori VM, . Prevention and treatment of pediatric obesity: an endocrine society clinical practice guideline based on expert opinion. J Clin Endocrinol Metab. 2008 Dec;93(12):4576-99.

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 Nov;149(11):5401-14.

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. Pediatr Diabetes. 2008 Jul 28;9(4 Pt 1):277-84.

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. Clin Endocrinol (Oxf). 2007 Dec;67(6):944-51.

Freemark M. Pharmacotherapy of childhood obesity: an evidence-based, conceptual approach. Diabetes Care. 2007 Feb;30(2):395-402.

Freemark M. Liver dysfunction in paediatric obesity: a randomized, controlled trial of metformin. Acta Paediatr. 2007 Sep;96(9):1326-32.

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 Jan;148(1):258-67.

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 Oct;32(2):182-91.

Freemark M. Regulation of maternal metabolism by pituitary and placental hormones: roles in fetal development and metabolic programming. Horm Res. 2006;65 Suppl 3:41-9.

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. Horm Res. 2006;66(3):101-10.

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, . Childhood obesity. J Clin Endocrinol Metab. 2005 Mar;90(3):1871-87.

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 Jan;146(1):103-12.

Artz E, Haqq A, Freemark M. Hormonal and metabolic consequences of childhood obesity. Endocrinol Metab Clin North Am. 2005 Sep;34(3):643-58, ix.

Freemark M. Editorial: Growth hormone treatment of "idiopathic short stature": not so fast. J Clin Endocrinol Metab. 2004 Jul;89(7):3138-9.

Freemark M, Kiess W. Anti-obesity medication use in adolescents: risks and benefits. Pediatr Endocrinol Rev. 2004 Nov;2 Suppl 1:168-70.

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. Pediatr Endocrinol Rev. 2004 Mar;1(3):296-309.

Freemark M. Pharmacologic approaches to the prevention of type 2 diabetes in high risk pediatric patients. J Clin Endocrinol Metab. 2003 Jan;88(1):3-13.

Freemark M, Levitsky LL. Screening for celiac disease in children with type 1 diabetes: two views of the controversy. Diabetes Care. 2003 Jun;26(6):1932-9.

Oden J, Freemark M. Thyroxine supplementation in preterm infants: critical analysis. Curr Opin Pediatr. 2002 Aug;14(4):447-52.

Oden J, Fleenor D, Driscoll P, Freemark M. Leptin in the newborn mouse. Plasma concentrations, characterization of the circulating hormone, and tissue source. Biol Neonate. 2002 Aug;82(2):109-16.

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. J Pediatr. 2002 Oct;141(4):490-5.

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 Apr;143(4):1378-85.

Rapaport R, Rose SR, Freemark M. Hypothyroxinemia in the preterm infant: the benefits and risks of thyroxine treatment. J Pediatr. 2001 Aug;139(2):182-8.

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. Biochem Soc Trans. 2001 May;29(Pt 2):48-52.

Freemark M. Ontogenesis of prolactin receptors in the human fetus: roles in fetal development. Biochem Soc Trans. 2001 May;29(Pt 2):38-41.

Freemark M, Fleenor D, Driscoll P, Binart N, Kelly P. Body weight and fat deposition in prolactin receptor-deficient mice. Endocrinology. 2001 Feb;142(2):532-7.

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 Apr;107(4):E55.

Fleenor DE, Freemark M. Prolactin induction of insulin gene transcription: roles of glucose and signal transducer and activator of transcription 5. Endocrinology. 2001 Jul;142(7):2805-10.

Petryk A, Fleenor D, Driscoll P, Freemark M. Prolactin induction of insulin gene expression: the roles of glucose and glucose transporter-2. J Endocrinol. 2000 Mar;164(3):277-86.

Handwerger S, Freemark M. The roles of placental growth hormone and placental lactogen in the regulation of human fetal growth and development. J Pediatr Endocrinol Metab. 2000 Apr;13(4):343-56.

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. Pediatr Res. 2000 Jan;47(1):136-42.

Freemark M. The fetal adrenal and the maturation of the growth hormone and prolactin axes. Endocrinology. 1999 May;140(5):1963-5.

Rivkees SA, Sklar C, Freemark M. Clinical review 99: The management of Graves' disease in children, with special emphasis on radioiodine treatment. J Clin Endocrinol Metab. 1998 Nov;83(11):3767-76.

Freemark, M.: Human Placental Lactgen (Human Chorionic Somatommotropin). In, Encyclopedia of Reproduction. E. Knobil and J.D. Neill (eds.), Academic Press, California, Vol 2, pp.694-700, 1998.

Freemark, M.:  The roles of growth hormone, prolactin and placental lactogen in human fetal development:  Critical analysis of molecular,  cellular and clinical investigations.  In, Molecular and Cellular Pediatric Endocrinology.  S. Handwerger (ed.), The Humana Press, Inc., Totowa, NJ, 1999, pp. 57-83.

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. J Clin Invest. 1997 Mar 1;99(5):1107-17.

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 Mar;137(3):934-42.

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 Sep;136(9):3892-900.

Freemark M, Nagano M, Edery M, Kelly PA. Prolactin receptor gene expression in the fetal rat. J Endocrinol. 1995 Feb;144(2):285-92.

Bridges RS, Freemark MS. Human placental lactogen infusions into the medial preoptic area stimulate maternal behavior in steroid-primed, nulliparous female rats. Horm Behav. 1995 Jun;29(2):216-26.

Freemark, M., Kirk, K. and Robertson, M.: Cellular distribution of placental lactogen II binding sites in the pregnant rat. Endocrine Journal 2: 199-205, 1994.

Pihoker C, Robertson MC, Freemark M. Rat placental lactogen-I binds to the choroid plexus and hypothalamus of the pregnant rat. J Endocrinol. 1993 Nov;139(2):235-42.

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 Oct;133(4):1830-42.

Fowlkes J, Freemark M. Placental lactogen-binding sites in isolated fetal fibroblasts: characterization, processing, and regulation. Endocrinology. 1993 Jun;132(6):2477-83.

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 Oct;131(4):1743-50.

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 Feb;130(2):1063-70.

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 Nov;131(5):2071-6.

Fowlkes J, Freemark M. Developmental regulation of insulin-like growth factor binding protein production: studies in fetal, postnatal, and pregnant sheep. J Cell Physiol. 1992 Jul;152(1):19-27.

Fowlkes J, Freemark M. Binding of placental lactogen and growth hormone to fetal sheep fibroblasts. Pediatr Res. 1992 Aug;32(2):200-3.

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. Am J Physiol. 1990 Feb;258(2 Pt 1):E338-46.

Freemark M, Handwerger S. The role of placental lactogen in the regulation of fetal metabolism and growth. J Pediatr Gastroenterol Nutr. 1989 Apr;8(3):281-3.

Freemark M, Comer M. Purification of a distinct placental lactogen receptor, a new member of the growth hormone/prolactin receptor family. J Clin Invest. 1989 Mar;83(3):883-9.

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 Sep;125(3):1504-12.

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. J Clin Endocrinol Metab. 1988 Jun;66(6):1283-90.

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 Jun;122(6):2771-9.

Handwerger S, Freemark M. Role of placental lactogen and prolactin in human pregnancy. Adv Exp Med Biol. 1987;219:399-420.

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. Pediatr Res. 1987 Nov;22(5):609-15.

Freemark M, Comer M, Korner G, Handwerger S. A unique placental lactogen receptor: implications for fetal growth. Endocrinology. 1987 May;120(5):1865-72.

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 Aug;119(2):522-6.

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 Feb;118(2):613-8.

Freemark M, Comer M, Handwerger S. Placental lactogen and GH receptors in sheep liver: striking differences in ontogeny and function. Am J Physiol. 1986 Sep;251(3 Pt 1):E328-33.

Freemark M, Handwerger S. Ovine placental lactogen inhibits glucagon-induced glycogenolysis in fetal rat hepatocytes. Endocrinology. 1985 Apr;116(4):1275-80.

Freemark M, D'Ercole AJ, Handwerger S. Somatomedin-C stimulates glycogen synthesis in fetal rat hepatocytes. Endocrinology. 1985 Jun;116(6):2578-82.

Freemark M, Handwerger S. Synergistic effects of oPL and insulin on glycogen metabolism in fetal rat hepatocytes. Am J Physiol. 1984 Dec;247(6 Pt 1):E714-8.

Freemark M, Handwerger S. Ovine placental lactogen stimulates glycogen synthesis in fetal rat hepatocytes. Am J Physiol. 1984 Jan;246(1 Pt 1):E21-4.

Freemark M, Handwerger S. Glycogenolytic effects of the calcium ionophore A23187, but not of vasopressin or angiotensin, in foetal-rat hepatocytes. Biochem J. 1984 Jun 1;220(2):441-5.

Freemark M, Handwerger S. Ovine placental lactogen, but not growth hormone, stimulates amino acid transport in fetal rat diaphragm. Endocrinology. 1983 Jan;112(1):402-4.

Freemark M, Handwerger S. Ovine placental lactogen stimulates amino acid transport in rat diaphragm. Endocrinology. 1982 Jun;110(6):2201-3.

Dubois PJ, Freemark M, Lewis D, Drayer BP, Heinz ER, Osborne D. Case report. Atypical findings in adrenoleukodystrophy. J Comput Assist Tomogr. 1981 Dec;5(6):888-91.

Raffin BJ, Freemark M. Streptobacillary rat-bite fever: a pediatric problem. Pediatrics. 1979 Aug;64(2):214-7.

Freemark M, Stoff DM, Moja EA, Gillin JC, Wyatt RJ. Testosterone-attenuated stereotype and hyperactivity induced by beta-phenylethylamine in pargyline-pretreated rats. Biol Psychiatry. 1978 Aug;13(4):455-63.