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Sexual Dimorphism in the Growth Hormone and Insulin-Like Growth Factor Axis at Birth

Center for Human Growth and Maturation at the London Center for Pediatric Endocrinology and Metabolism, Department of Obstetrics and Gynecology, University College (C.H.R.), London, United Kingdom W1T 3AA; and Program in Development and Fetal Health, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto (J.C.P.K.), Toronto, Canada

Address all correspondence and requests for reprints to: Dr. P. C. Hindmarsh, Center for Human Growth and Maturation, Cobbold Laboratories, Middlesex Hospital, Mortimer Street, London, United Kingdom W1T 3AA. E-mail: p.hindmarsh{at}ucl.ac.uk.

In rodents and humans there is a sexually dimorphic pattern of GH secretion that influences the serum concentration of IGF-I. Pattern differences can be identified in children, but it is not known how early this difference is established. We studied the plasma concentrations of IGF-I, IGF-II, IGF-binding protein-3 (BP-3), and GH in cord blood taken from the offspring of 1650 singleton Caucasian pregnancies born at term and related these values to birth weight, length, and head circumference. Pregnancies complicated by preterm delivery, antepartum hemorrhage, pregnancy-induced hypertension, preeclampsia, or gestational diabetes and where cigarette smoking continued were excluded, resulting in a cohort of 987. Cord plasma concentrations of IGF-I, IGF-II, and IGFBP-3 were influenced by factors influencing birth size: gestational age at delivery, mode of delivery, maternal height, and parity of the mother. Plasma GH concentrations were inversely related to the plasma concentrations of IGF-I and IGFBP-3; 10.2% of the variability in cord plasma IGF-I concentration and 2.7% for IGFBP-3 was explained by sex of the offspring and parity. None of the factors, apart from maternal height, influenced cord serum IGF-II concentrations (adjusted r² = 1%). Sex of the baby, mode of delivery, and parity influenced cord serum GH concentrations (adjusted r² = 2.6%). Birth weight, length, and head circumference measurements were greater in males than females (P < 0.001). Mean cord plasma concentrations of IGF-I (males, 66.4 ± 1.2 µg/liter; females, 74.5 ± 1.3 µg/liter; P < 0.001) and IGFBP-3 (males, 910 ± 13 µg/liter; females 978 ± 13 µg/liter; P < 0.001) were significantly lower in males than females. Cord plasma GH concentrations were higher in males than females (males, 30.0 ± 1.2 mU/liter; females, 26.9 ± 1.1 mU/liter; P = 0.05), but no difference was noted between the sexes for IGF-II (males, 508 ± 6 µg/liter; females, 519 ± 6 µg/liter; P = NS). After adjustment for gestational age, parity, and maternal height, cord plasma concentrations of IGF-I and IGFBP-3 along with sex explained 38.0% of the variability in birth weight, 25.0% in birth length, and 22.7% in head circumference. These data demonstrate that in a group of singleton Caucasian babies born at term, cord plasma IGF-I, IGFBP-3, and GH concentrations relate to birth size, with evidence for sexual dimorphism in the GH-IGF axis.

This work was supported by grants from the British Heart Foundation, Children Nationwide UK, and Pharmacia-Upjohn (to P.C.H.). J.C.P.K. is funded by the Program in Development and Fetal Health, Samuel Lunenfeld Institute, and Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto.

Abbreviations: CV, Coefficients of variance; IGFBP-3, IGF-binding protein 3; SDS, SD score.

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