Thyroid glands: novel sites of growth hormone action.
Thyroid hormones inhibit the synthesis and release of GH in avian species. This may represent a feedback mechanism, since GH enhances the peripheral production of tri-iodothyronine (T3). The possibility that GH may also have direct effects on thyroidal function was therefore investigated. The basal and thyrotrophin-induced release of thyroxine (T4) from incubated chicken thyroid glands was not enhanced, however, in the presence of chicken GH. Contrarily, GH impaired T4 release in a dose-related way. These actions were probably mediated by specific receptors, since binding sites for radiolabelled GH were demonstrated on the plasma membranes of chicken thyroid glands. Expression of the GH receptor gene in these tissues was also demonstrated using a cRNA probe for the rabbit liver GH receptor, which specifically hybridized with RNA moieties of 4.4 kb, 2.7 kb and 1.0 kb. Moreover, reverse transcription of thyroidal RNA and its amplification in the presence of 3'- and 5'-oligonucleotide primers coding for the extracellular or intracellular domains of the GH receptor generated electrophoretically separable fragments of 500 bp and 800 bp respectively, as would be expected from analysis of the hepatic GH receptor cDNA sequence. Digestion of the 500 bp fragment with NcoI or EcoRI also produced moieties of expected size (350 bp and 150 bp or 325 bp and 175 bp respectively), as did BamHI or HaeIII digestion of the 800 bp fragment (yielding fragments of 550 bp and 275 bp or 469 bp and 337 bp respectively). Translation of the GH receptor mRNA was also indicated by the immunocytochemical demonstration of GH receptors in thyroid follicular and parafollicular cells, using a specific polyclonal antibody raised against the chicken GH-binding protein. These results therefore provide evidence, for the first time, of GH receptor gene expression in thyroid tissue and the translation of functional GH receptors in thyroid glands. These results also demonstrate differential effects of GH on the extracellular concentrations of T3 and T4, which may permit subtle regulation within the somatotroph-thyroid axis.