Presented at the Neonatal Society 2005 Autumn Meeting.

Matthews PA, Fowden AL, Forhead AJ

Department of Physiology, University of Cambridge, Cambridge, CB2 3EG, UK

Introduction: Glycogen content in the fetal liver increases towards term in preparation for glucose homeostasis after birth. Hepatic glycogen deposition is induced by the prepartum rise in circulating cortisol concentrations in the fetus. The prepartum cortisol surge also stimulates the production of triiodothyronine (T3) from thyroxine (T4), and causes an increase in plasma T3 near term. However, the effect of thyroid hormones on glycogen content in the fetal liver is unknown. Therefore, this study investigated hepatic glycogen content in sheep fetuses after experimental manipulation of thyroid hormone concentration by T3 infusion and fetal thyroidectomy (TX).

Methods: All surgical and experimental procedures were carried out in accordance with UK Home Office legislation. Under general anaesthesia (1.5% halothane in O2-N2O), thyroid glands were removed from 13 fetuses at 105-110 days of gestation (term 145 ± 2 days), and catheters were implanted into the femoral artery and vein of a further 15 fetuses at 115-120 days. These and 10 untreated fetuses were divided into six experimental groups:
1) infused with saline i.v. for 5 days (n=5) or untreated (n=2), and tissue collection at 130 days
2) infused with cortisol i.v. for 5 days, and tissue collection at 130 days (n=5, 2-3 mg kg^-1 day^-1)
3) infused with T3 i.v. for 5 days, and tissue collection at 130 days (n=5, 8-12 μg kg^-1 day^-1)
4) TX and tissue collection at 130 days (n=7)
5) TX and tissue collection at 144 days (n=6)
6) untreated and tissue collection at 144 days (n=8)

On the day of tissue collection, all ewes and fetuses were administered a lethal dose of sodium pentobarbitone. Umbilical arterial blood and liver samples were obtained at delivery by Caesarean section. Plasma cortisol and thyroid hormone concentrations were measured by radioimmunoassay, and hepatic glycogen content was determined by amyloglucosidase assay. Data were analysed by one-way and two-way ANOVA, and unpaired t-test (p<0.05).

Results: On the fifth day of infusion, plasma T3 concentrations were significantly higher in the fetuses infused with T3 (0.93 ± 0.23 ng ml^-1) and cortisol (0.67 ± 0.07 ng ml^-1), compared with those infused with saline (0.23 ± 0.02 ng ml^-1). Plasma T3 concentrations increased with gestational age to 0.58 ± 0.05 ng ml^-1 in the intact fetuses, but were reduced to 0.13 ± 0.02 ng ml^-1 in the TX fetuses. In immature fetuses infused with T3, hepatic glycogen content was increased above that seen in the salineinfused fetuses (45.6 ± 5.4 versus 28.0 ± 4.3 mg g^-1), but not to the level seen in fetuses infused with cortisol (102.9 ± 13.2 mg g^-1).

At 130 days of gestation, hepatic glycogen in the TX fetuses (48.3 ± 5.7 mg g^-1) was significantly greater than in the intact fetuses (28.0 ± 4.3 mg g^-1). However, the normal increment in hepatic glycogen content seen between 130 and 144 days of gestation was abolished when the prepartum rise in T3, but not cortisol, was prevented by fetal TX. At 144 days, hepatic glycogen in TX fetuses (55.7 ± 4.0 mg g^-1) was significantly lower than in the intact fetuses (108.8 ± 6.6 mg g^-1).

Conclusions: Therefore, thyroid hormones have an important role in stimulating glycogen deposition in the fetal liver near term, and may mediate, in part, the maturational effect of cortisol.

Acknowledgements: Funded by the BBSRC.