Localization of thyrotropin-releasing hormone receptor and thyrotroph embryonic factor on mouse chromosome 15.

Abstract

We report the localization of two genes expressed in anterior pituitary thyrotrope cells, thyrotropin- releasing hormone receptor (Trhr) and thyrotroph em- bryonic factor (Tey'), on mouse Chr 15. Trhr is a G-pro- tein-coupled receptor that activates the inositol phos- pholipid-calcium-protein kinase C transduction pathway upon the binding of the hypothalamic factor, thyrotropin-releasing hormone (TRH; Straub et al. 1990). TRH increases the production and secretion of thyroid stimulating hormone (TSH) by anterior pitu- itary thyrotrope cells. TSH is necessary for growth because of its role in the development of the thyroid gland and the production of thyroid hormone. Tefis a leucine zipper transcription factor that is related to the bZIP family (Drolet et al. 1991). While Tefis expressed broadly in the adult, expression in the embryo is con- fined to the developing thyrotrope cells of the anterior pituitary (Drolet et al. 1991). This expression follows the same temporal and spatial pattern of the beta sub- unit of TSH (Tshb). Moreover, Tefhas been shown to bind three sites in the mouse TSHb promoter and stim- ulate Tshb promoter activity in transiently transfected CV-1 cells (Drolet et al. 1991). Using an interspecific backcross provided by The Jackson Laboratory, (C57BL/6J x M. spretus)F1 x M. spretus, we localized Trhr and Tel on mouse Chr 15. We first linked Trhr and Tefto mouse Chr 15 by hap- lotype analysis with two simple sequence repeat mark- ers that were previously characterized on this cross, D15Mit3 and D15Mit16 (The Jackson Laboratory, un- published results). We then confirmed the localization of Trhr and Tef with D15Mit10. Trhr and Tef were typed with RFLPs that were detected by Southern blot analysis, performed as pre- viously described (Lossie et al. 1993). A 980-bp EcoRV to BstXII fragment, which corresponds to amino acids 371 to 393 plus 900 bp of 3' untranslated