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Expression of the Thyroid-Stimulating Hormone Receptor in the Folliculo-Stellate Cells of the Human Anterior Pituitary

Department of Endocrinology, Academic Medical Center, University of Amsterdam (M.F.P., L.J.S.B., O.B., W.M.W.), 1105 AZ Amsterdam, The Netherlands; and Unité de Recherches Hormones et Reproduction, INSERM, U-135, Hopital de Bicêtre (G.M., M.M.), Le Kremlin- Bicêtre, France

Address all correspondence and requests for reprints to: Mark F. Prummel, M.D., Ph.D., Department of Endocrinology, F5-171, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. E-mail: m.f.prummel{at}amc.uva.nl

TSH secretion from the anterior pituitary is mainly regulated by TRH and thyroid hormones. We hypothesized that in addition the pituitary itself could modulate TSH production by sensing its own TSH release, enabling fine-tuning of TSH secretion. For such an ultra-short loop control, the pituitary should contain a TSH receptor (TSH-R). To find evidence for this we screened a human pituitary complementary DNA library with a digoxigenin-labeled TSH-R probe and found 2 positive clones of 32,000 plaques. One clone was sequenced and found to be completely identical to the thyroid TSH-R. Further proof was obtained by RT-PCR on a human anterior pituitary obtained at autopsy. In situ hybridization and immunohistochemistry confirmed the presence of TSH-R in the anterior pituitary at the messenger ribonucleic acid level as well as the protein level. Moreover, double labeling experiments revealed that TSH-R messenger ribonucleic acid as well as TSH-R protein colocalize with major histocompatibility complex class II expression of folliculo-stellate cells. We conclude that TSH-R is expressed in a subpopulation of folliculo-stellate cells in the human anterior pituitary. This finding suggests ultra-short loop regulation of TSH secretion. Putative recognition of the pituitary TSH-R by TSH-R antibodies might have clinical relevance in Graves’ disease.

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