DEVELOPMENTAL REGULATION OF THE THYROID-HORMONE RECEPTOR ALPHA-1 MESSENGER-RNA EXPRESSION IN THE RAT TESTIS

The multiplicity of thyroid hormone (TH) effects appears to be mediated,by two TH receptors (THRs) encoded by two genes, alpha and beta, and, perhaps, by their various isoforms. The expression of THR beta is correlated with the presence of high affinity binding sites for TH, and all the mutations which cause the syndrome of generalized thyroid hormone resistance occur in THR beta. The function of THR alpha has not been clearly defined as yet. Another enigma in TH action is the effect on the testis. It has been shown that the testis of the adult rat does not respond to TH as measured by an increase in oxygen consumption. Furthermore, it has not been possible to demonstrate the presence of a nuclear high affinity binding site for TH in adult testis. To resolve these problems we measured the levels of THR alpha, its nonhormone binding variant, and THR beta mRNA in the testis at various stages of development. We discovered that the beta-message is absent at all times, whereas the alpha-message is expressed only from fetal through prepubertal stages and is absent in adult testis. THR alpha, but not the beta-mRNA, was detected in immature Sertoli cells in culture, and neither was found in adult Sertoli cell-enriched cultures. Furthermore, THR alpha and its variant mRNA was found, using in situ hybridization, in the seminiferous cords and seminiferous tubules of fetal and prepubertal testis. Functionally, TH was able to suppress androgen binding protein mRNA in in vitro preparations enriched in immature Sertoli cells but not in adult cells, while the level of another marker of Sertoli cell differentiation, transferrin mRNA, was unaffected in both stages. Thus the alpha-form of the THR is ontologically regulated and ontologically regulates gene expression in the testis.