title: Insulin resistance elicited in postpubertal primate offspring deprived of estrogen in utero.
abstract: We recently demonstrated that offspring delivered to baboons deprived of estrogen during the second half of gestation exhibited insulin resistance prior to onset of puberty. Because gonadal hormones have a profound effect on insulin action and secretion in adults, we determined whether insulin resistance is retained after initiation of gonadal secretion of testosterone and estradiol. Glucose tolerance tests were performed in postpubertal baboon offspring of untreated and letrozole-treated animals (serum estradiol reduced >95 %). Basal fasting levels of insulin (P < 0.05) and peak 1 min and 1 + 3 + 5 min levels of glucose after glucose tolerance tests challenge (P < 0.03) were greater in offspring delivered to letrozole-treated, estrogen-deprived baboons than untreated animals. Moreover, the value for the HOMA-IR, an accepted index of insulin resistance, was 2-fold greater (P < 0.05) in offspring delivered to baboons treated with letrozole than in untreated animals. Collectively these results support the proposal that estrogen normally has an important role in programming mechanisms in utero within the developing fetus that lead to insulin sensitivity after birth.
authors: Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, VA, USA. PEPEGJ@EVMS.EDU.
authors: Gerald J
authors: GJ
authors: Pepe
authors: Department of Obstetrics/Gynecology/Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.
authors: Adina
authors: A
authors: Maniu
authors: Department of Obstetrics/Gynecology/Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.
authors: Graham
authors: G
authors: Aberdeen
authors: Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, VA, USA.
authors: Terrie J
authors: TJ
authors: Lynch
authors: Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, VA, USA.
authors: Soon Ok
authors: SO
authors: Kim
authors: Department of Internal Medicine, Eastern Virginia Medical School, Norfolk, VA, USA.
authors: Jerry
authors: J
authors: Nadler
authors: Departments of Obstetrics/Gynecology/Reproductive Sciences and Physiology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors: Eugene D
authors: ED
authors: Albrecht
mesh_terms: D000818:Animals; D047072:Aromatase Inhibitors; D004958:Estradiol / Q000097:blood / Q000172:deficiency*; D005260:Female; D005951:Glucose Tolerance Test; D007333:Insulin Resistance; D000077289:Letrozole; D009570:Nitriles; D048530:Papio anubis / Q000502:physiology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012741:Sexual Maturation; D014230:Triazoles
chemical_list: D047072:Aromatase Inhibitors; D009570:Nitriles; D014230:Triazoles; D004958:Estradiol; D000077289:Letrozole
keywords: Estrogen; Insulin sensitivity; Offspring; Primate