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Intrafetal Insulin-Like Growth Factor-I Infusion Stimulates Adrenal Growth But Not Steroidogenesis in the Sheep Fetus during Late Gestation

Discipline of Physiology (J.T.R., I.C.M., A.G.T., J.A.O., C.L.C.) and School of Molecular and Biomedical Sciences and Discipline of Obstetrics and Gynecology (F.L., J.A.O.), School of Heath Sciences, University of Adelaide, Adelaide, South Australia 5005, Australia

Address all correspondence and requests for reprints to: Dr. Catherine L. Coulter, Department of Pediatrics, Division of Neonatalogy, University of Washington, Seattle, Washington 98195-6320. E-mail: ccoulter{at}u.washington.edu.

We investigated the effects of an intrafetal infusion of IGF-I on adrenal growth and expression of the adrenal steroidogenic and catecholamine-synthetic enzyme mRNAs in the sheep fetus during late gestation. Fetal sheep were infused for 10 d with either IGF-I (26 µg/kg·h; n = 14) or saline (n = 10) between 120 and 130 d gestation, and adrenal glands were collected for morphological analysis and determination of the mRNA expression of steroidogenic and catecholamine-synthetic enzymes. Fetal body weight was not altered by IGF-I infusion; however, adrenal weight was significantly increased by 145% after IGF-I infusion. The density of cell nuclei within the fetal adrenal cortex (the zona glomerulosa and zona fasciculata), and within the adrenaline synthesizing zone of the adrenal medulla, was significantly less in the IGF-I-infused fetuses compared with the saline-infused group. Thus, based on cell-density measurements, there was a significant increase in cell size in the zona glomerulosa and zona fasciculata of the adrenal cortex and in the adrenaline-synthesizing zone of the adrenal medulla. There was no effect of IGF-I infusion on the adrenal mRNA expression of the steroidogenic or catecholamine-synthetic enzymes or on fetal plasma cortisol concentrations. In summary, infusion of IGF-I in late gestation resulted in a marked hypertrophy of the steroidogenic and adrenaline-containing cells of the fetal adrenal in the absence of changes in the mRNA levels of adrenal steroidogenic or catecholamine-synthetic enzymes or in fetal plasma cortisol concentrations. Thus, IGF-I infusion results in a dissociation of adrenal growth and function during late gestation.