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 ge ne encoding the growth hormone receptor (GHR) and growth hormone bindi ng protein (GHBP), fetal rats were made hypothyroid through the admini stration 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 co ntinued in the mothers until weaning. After birth, groups of methimazo le-treated or control pups were sacrificed immediately and at one, two , three, four, five, or six weeks after birth. In each group, weight w as recorded, blood was obtained for measurement of T-4, thyroid Stimul ating hormone (TSH), and growth hormone (GH), and Liver tissue was obt ained for quantitation of GHR and GHBP mRNA. The methimazole-treated p ups were demonstrated to be hypothyroid, with markedly higher TSH and lower T4 concentrations, until. weaning occurred between weeks three a nd four, after which they transiently became hyperthyroid at week five (T-4 = 17 +/- 5 mu g/dL vs. 6 +/- 0.5 mu g/dL for controls) but retur ned to an euthyroid state at week six. In control pups the relative ab undance of GHR and GHBP mRNA increased abruptly in week one, and incre ased 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 G HR and GHBP mRNA then decreased tb the level of the controls by week t hree, but GHR and GHBP expression was lower for the experimental pups than for the control pups at week five, coincident with the state of t ransient hyperthyroidism. Thus, expression of GHR and GHBP mRNA was in versely related to prevailing thyroid status. Growth hormone concentra tions were not lower in the methimazole-treated group relative to cont rols, but the experimental pups had lower weights throughout. We concl ude that thyroid hormone is involved in the growth regulation of neona tal rat pups in part by regulating the expression of the mRNA's for GH R and GHBP.