Endocrine Abstracts (2004) 7 OC8

Effect of maternal dexamethasone treatment on hepatic and renal type I 5'-monodeiodinase activity and plasma triiodothyronine concentration in fetal sheep

AJ Forhead, DA Giussani & AL Fowden

Department of Physiology, University of Cambridge, Cambridge, UK.

Type I 5'-monodeiodinase (5'-MDI) converts thyroxine (T4) to triiodothyronine (T3). In fetal sheep, hepatic 5'-MDI activity increases near term in association with the prepartum cortisol surge. This study investigated the effect of maternal dexamethasone treatment, in clinically relevant doses, on hepatic and renal type I 5'-MDI activity and plasma thyroid hormone concentrations in fetal sheep.

From 125 days of gestation (term 145 plus/minus 2 days), nine ewes, carrying single fetuses, were injected twice i.m. with either saline (0.9% NaCl, n=4) or dexamethasone (2x12 mg in 2 ml 0.9% NaCl, n=5) at 24 hour intervals. Ten hours after the second injection, the ewes and fetuses were euthanised, and tissues and umbilical arterial blood were collected. Plasma T4 and T3 were measured by radioimmunoassay, and tissue type I 5'-MDI activity by outer ring deiodination of iodinated reverse-T3. Data (mean plus/minus SEM) were analysed by unpaired t-test and linear regression.

Fetal plasma T3 but not T4 concentrations were increased by maternal dexamethasone treatment (p<0.001). Hepatic type I 5'-MDI activity in the dexamethasone-exposed fetuses (2308 plus/minus 112 pmoles I-/mg protein/hour) was greater than in the control fetuses (1188 plus/minus 40, p<0.001). Overall, plasma T3 correlated with hepatic type I 5'-MDI activity (r=0.96, p<0.001). There was no significant difference in renal type I 5'-MDI activity between the saline (29.1 plus/minus 4.9 pmoles I-/mg protein/hour) and dexamethasone-exposed fetuses (35.3 plus/minus 4.1).

Therefore, maternal dexamethasone treatment increases hepatic type I 5'-MDI and plasma T3 concentration in fetal sheep. Changes in T3 bioavailability may mediate some of the maturational effects of dexamethasone in the preterm fetus.

Supported by the BBSRC and Tommy's, the baby charity.

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