Endocrine Abstracts

Antioxidants enhance the adrenocortical response to stress in the fetus

AS Thakor & DA Giussani

University of Cambridge. Cambridge. United Kingdom.

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Introduction

Human clinical trials are currently evaluating the protective effects of antioxidants against pre-eclampsia in threatened pregnancy (Poston et al. Ann.N.Y.Acad.Sci. 1031:242.2004). While there has been increased awareness about the modulating effects on pituitary-adrenal responses to stress by antioxidants in adult life (Brody et al. Psychopharmacology. 159:319.2001). nothing is known about the effects of antioxidant treatment on stress responses during fetal life. Here. we investigate the effects of two antioxidants. vitamin C and melatonin. on basal and stimulated pituitary-adrenocortical function in the fetus.

Methods

Under halothane anaesthesia. 12 fetal sheep (0.8 gestation) were instrumented with vascular catheters. Five days later. fetuses were randomly allocated into 2 groups and subjected to 1.5 h normoxia. 0.5 h hypoxia and 1 h recovery during fetal i.v. infusion with saline or vitamin C (25 mg.min⁻¹; n=6) or saline or melatonin (0.15 μg.min⁻¹; n=6) in randomised order. on separate days. Fetal arterial blood was taken for measurement of blood gases and plasma concentrations of ACTH and cortisol (RIA).

Results

Basal plasma ACTH and cortisol concentrations were similar in all fetuses and were not affected by saline. vitamin C or melatonin infusion. Hypoxia produced similar falls in P_aO₂ in all fetuses (∼21 to 10 mmHg). During saline infusion. hypoxia induced significant increments in plasma ACTH and cortisol concentrations. In contrast. hypoxia-induced increments in plasma ACTH and cortisol were diminished and enhanced. respectively. during both vitamin C and melatonin infusion (P<0.05). Correlation analysis of individual ACTH and cortisol values for all fetuses showed an enhanced adrenocortical sensitivity to ACTH. during both vitamin C (slope of relationship: 0.19±0.04 vs. 0.05±0.02) and melatonin (slope of relationship: 0.07±0.01 vs. 0.02±0.01) infusion relative to saline infusion (P<0.05).

Conclusion

Fetal antioxidant treatment results in enhanced adrenocortical sensitivity to ACTH during fetal stress.

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Endocrine Abstracts (2005) 10 OC22