Thyroid hormone status correlates inversely with expression of the growth hormone receptor gene in rats immediately after birth

To investigate the role of thyroid hormone in the expression of the gene encoding the growth hormone receptor (GHR) and growth hormone binding protein (GHBP), fetal rats were made hypothyroid through the administration of the goitrogen methimazole to the mother. Euthyroidism was maintained in the mother by concurrent administration of L-thyroxine, which crosses the placenta poorly. Methimazole and L-thyroxine were continued in the mothers until weaning. After birth, groups of methimazole-treated or control pups were sacrificed immediately and at one, two, three, four, five, or six weeks after birth. In each group, weight was recorded, blood was obtained for measurement of T₄, thyroid stimulating hormone (TSH), and growth hormone (GH), and liver tissue was obtained for quantitation of GHR and GHBP mRNA. The methimazole-treated pups were demonstrated to be hypothyroid, with markedly higher TSH and lower T₄ concentrations, until weaning occurred between weeks three and four, after which they transiently became hyperthyroid at week five (T₄ = 17 ± 5 μg/dL vs. 6 ± 0.5 μg/dL for controls) but returned to an euthyroid state at week six. In control pups the relative abundance of GHR and GHBP mRNA increased abruptly in week one, and increased three to four fold over the ensuing six weeks. Immediately after birth, the hypothyroid pups expressed significantly more GHR and GHBP mRNA than did the controls (P < 0.01). The steady state levels of both GHR and GHBP mRNA then decreased to the level of the controls by week three, but GHR and GHBP expression was lower for the experimental pups than for the control pups at week five, coincident with the state of transient hyperthyroidism. Thus, expression of GHR and GHBP mRNA was inversely related to prevailing thyroid status. Growth hormone concentrations were not lower in the methimazole-treated group relative to controls, but the experimental pups had lower weights throughout. We conclude that thyroid hormone is involved in the growth regulation of neonatal rat pups in part by regulating the expression of the mRNA's for GHR and GHBP.