Differential expression and regulation of thyrotropin (TSH) in T cell lines

Abstract

The immune system's production of and response to thyrotropin (TSH) suggests the existence of a hypothalamic-lymphoid-thyroid regulatory axis (HLT). To evaluate the possible roles of lymphocyte-derived TSH we characterized its structure and regulation of production. Using an in vitro system, we screened T cell lines for the production of TSH in response to thyrotropin-releasing hormone (TRH). We identified MOLT 4 T cells as producers of intact TSH based on TSH radioimmunoassay (RIA) displacement and de novo synthesized protein structure similar to pituitary TSH. Northern blot analysis using a cDNA probe to TSH beta showed the existence of an mRNA species similar in molecular size to pituitary mRNA of TSH beta. The MOLT 4-derived TSH is induced in a dose-dependent fashion by TRH and that induction is significantly inhibited by the thyroid hormone, triiodothyronine (T3). HUT 78 T cells express an mRNA species similar to TSH beta but do not express detectable protein suggesting a lack of translation of the mRNA species. The evidence suggests that the MOLT 4 T cells serve as an in vitro model for TSH production and may be used to study differential expression of the genes for TSH in the immune system. Elucidation of this in vitro system will provide information on mechanisms of regulation of an HLT axis that are unique to the immune system as well as pathways common to the immune and neuroendocrine systems.