Thyroid hormones and the mRNA of the GH receptor and IGFs in skeletal muscle of fetal sheep

• Published in: American journal of physiology: endocrinology and metabolism Vol. 282; no. 1; pp. E80 - E86
• Main Authors: Forhead, A. J, Li, J, Gilmour, R. S, Dauncey, M. J, Fowden, A. L
• Format: Journal Article
• Language: English
• Published: United States 01.01.2002
• Subjects: Animals; Fetus - drug effects; Fetus - metabolism; Gestational Age; Hydrocortisone - pharmacology; Insulin-Like Growth Factor I - genetics; Insulin-Like Growth Factor II - genetics; Muscle, Skeletal - drug effects; Muscle, Skeletal - embryology; Receptors, Somatotropin - genetics; RNA, Messenger - metabolism; Sheep; Thyroid Hormones - physiology; Thyroidectomy; Triiodothyronine - pharmacology
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00284.2001

1  Department of Physiology, University of Cambridge, Cambridge, CB2 3EG; 2  Biotechnology and Biological Sciences Research Council, Babraham Institute, Cambridge, CB2 4AT, United Kingdom; and 3  Department of Molecular Medicine, Auckland University Medical School, Auckland, New Zealand Thyroid hormones are required for the normal development of skeletal muscle in utero, although their mechanism of action is poorly understood. The present study examined the effects of the thyroid hormones on the gene expression of the growth hormone receptor (GHR) and the insulin-like growth factors (IGFs) IGF-I and IGF-II, in skeletal muscle of fetal sheep during late gestation (term 145 ± 2 days) and after manipulation of plasma thyroid hormone concentration. Thyroidectomy at 105-110 days of gestation suppressed muscle GHR and IGF-I gene expression in fetuses studied at 127-130 and 142-145 days. Muscle GHR mRNA abundance remained unchanged with increasing gestational age in intact and thyroidectomized fetuses. In the intact fetuses, a decrease in muscle IGF-I gene expression was observed between 127-130 and 142-145 days, which coincided with the normal prepartum surges in plasma cortisol and triiodothyronine (T 3 ). At 127-130 days, downregulation of muscle IGF-I mRNA abundance was induced prematurely in intact fetuses by an infusion of cortisol for 5 days (2-3 mg · kg 1 · day 1 iv), which increased plasma cortisol and T 3 concentrations to values seen near term. However, increasing plasma T 3 alone by an infusion of T 3 for 5 days (8-12 µg · kg 1 · day 1 iv) in intact fetuses at this age had no effect on GHR or IGF-I gene expression in skeletal muscle. In the thyroidectomized fetuses, no additional change in the low level of muscle IGF-I mRNA abundance was seen with increasing gestational age, but at 127-130 days, IGF-I gene expression was reduced further when plasma cortisol and T 3 concentrations were increased by exogenous cortisol infusion. Muscle IGF-II mRNA abundance was not affected by thyroidectomy, gestational age, or exogenous hormone infusion. These findings show, in the sheep fetus, that thyroid hormones may influence the growth and development of skeletal muscle via changes in the local activity of the somatotrophic axis. growth hormone receptor; cortisol; fetus; insulin-like growth factors; thyroxine; triiodothyronine