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Fetal Plasma Insulin and Thyroid Hormone Levels during Acute in Utero Ethanol Exposure in a Maternal-Fetal Sheep Model^*

Departments of Physiology and Pharmacology and Comparative Medicine, Bowman Gray School of Medicine of Wake Forest University Winston-Salem, North Carolina 07103

Address all correspondence and requests for reprints to: Dr. Maria I. Castro, Division of Endocrinology and Metabolism, University of Massachusetts Medical Center, 55 Lake Avenue North, Worcester, Massachusetts 01605–2397.

Abstract

The effects of acute in utero ethanol (ETOH) treatment on basal and stimulated thyroid and insulin levels in fetal plasma were studied in chronically cannulated fetal sheep. In test situations, pregnant ewes (0.78–0.88 gestation) which were chronically cannulated received 2 g/kg ETOH [25% (vol/vol) in isotonic saline] for 2 h; this was followed by a maintenance iv infusion of 0.13 g/kg ETOH. Control animals received isovolemic infusions of isotonic saline. Fetal arterial plasma samples were obtained after the 2-h infusion, and basal levels of T₃, T₄, glucose, and insulin were measured. The 2-h ETOH infusion did not influence fetal basal plasma T₃, T₄, insulin, or glucose. Fetal thyroid responses to an intraarterial injection of 0.01,0.10,1.00, or 10.00 µg/kg TRH or of 5 mU/kg TSH through the fetal catheters were studied in the presence or absence of high plasma ETOH concentrations. Fetal T₄ or T₃ levels during the 4 h following any of these stimuli were not significantly different in ethanol-treated and control animals. The effects of acute ETOH exposure on insulin responses to a glucose challenge challenge were studied in six chronically cannulated ewes and their fetuses using a cross-over experimental design. After the 2-h ETOH infusion, ewes received a bolus injection of 600 mg/kg 50% glucose, followed by a 1-h infusion of 624 mg/kg 50% glucose and 0.13 g/kg ETOH. In control situations, ewes received saline plus glucose. Acute ETOH treatment did not influence maternal or fetal plasma glucose levels at any time, but enhanced both maternal and fetal insulin responses to glucose. Total insulin release, as measured by the area under the insulin response curve, was greater during ETOH exposure in both mother (ETOH, 4740 ± 1475 µU/ml·min; control, 2807 ± 766 µU/ml·min; P = 0.05) and fetus (ETOH, 562 ± 94 µU/ml·min; control, 363 ± 46 µU/ml·min; P < 0.05). Thus acute in utero ETOH exposure does not diminish plasma levels of either thyroid hormones or insulin, two important hormones for fetal growth and development. However, ethanol exposure enhances the insulin response to increases in blood glucose in both mother and fetus. (Endocrinology 118: 1735–1742, 1986)

Footnotes

^* This work was supported by NC Alcoholism Research Authority Grants 7904 and 8101.

Received June 27, 1985.