Endocrine Abstracts (2006) 11 P554

Developmental control of tissue deiodinases by cortisol in fetal sheep during late gestation

AJ Forhead1, K Curtis1, E Kaptein2, TJ Visser2 & AL Fowden1

1University of Cambridge, Cambridge, United Kingdom; 2Erasmus MC, Rotterdam, Netherlands.

Deiodinase enzymes have an important role in thyroid hormone metabolism. Type I 5′-monodeiodinase (D1) converts thyroxine (T4) to triiodothyronine (T3), while type III 5-monodeiodinase (D3) inactivates T3 and produces reverse-T3 (rT3) from T4. In fetal sheep, plasma T3 rises towards term in association with the prepartum cortisol surge. This study investigated the effect of cortisol on tissue deiodinase activities and plasma thyroid hormone concentrations in fetal sheep during late gestation.

Eighteen sheep fetuses were chronically-catheterised under general anaesthesia at 115–118 d of gestation (term 145±2 d) and, from 125 d, were infused intravenously for 5d with either saline (0.9% NaCl, n=8) or cortisol (3–5 mg/kg/d, n=10). Arterial blood was taken before and during infusion. On the fifth day of infusion, tissues were collected after maternal euthanasia. Tissues were also collected from 15 fetuses at 141–146 d: 7 were intact and 8 were adrenalectomised under general anaesthesia at 116–119 d. Umbilical arterial blood was taken at delivery. Plasma cortisol and thyroid hormones, and tissue deiodinase activities, were measured by radioimmunoassay and radiometric enzyme assay. Data were analysed by t-test and two-way ANOVA (P<0.05).

Exogenous cortisol infusion increased plasma cortisol and T3, but not T4 or rT3. On the fifth day of infusion, hepatic and renal D1 activities were higher, and renal and placental D3 activities were lower, in the cortisol-infused fetuses compared with the saline-infused fetuses. Fetal adrenalectomy abolished the prepartum rises in plasma cortisol and T3, without any change in T4 or rT3. At 141–146 d, hepatic and renal D1 were lower, and renal and placental D3 were higher, in the adrenalectomised fetuses compared with the intact fetuses.

Therefore, in fetal sheep, the prepartum cortisol surge stimulates hepatic and renal D1, and suppresses renal and placental D3 activities. These changes in tissue deiodinase activity may be responsible for the rise in plasma T3 concentration near term.

Supported by BBSRC and Isaac Newton Trust.

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