Expression of Thyrotropin-Releasing Hormone (TRH) Receptor mRNA in Somatotrophs in the Rat Anterior Pituitary

Abstract

A response of growth hormone (GH) to thyrotropin-releasing hormone (TRH) is observed in lower mammals and patients with diseases such as a cromegaly, but not in normal subjects. We have previously demonstrated the existence of intact TRH receptor mRNA in GH-secreting adenoma. To examine whether intact somatotrophs in the anterior pituitary also express TRH receptor, we attempted to localize both TRHR mRNA and GH immunoreactivity simultaneously. In situ hybridization analysis revealed TRHR mRNAs specifically in the anterior pituitary, and 61.1% of the anterior pituitary cells expressed this transcript. Staining for GH and PRL on the same samples showed that the somatotrophs apparently expressed TRHR mRNA and approximately 62.3% and 30.9% of hybridization-positive cells were somatotorophs and mammotrophs, respectively. Moreover, TRHR mRNA level in the somatotrophs expressed as the number of silver grains per cell was equivalent to that in the mammotrophs. These findings demonstrated expression of the TRHR mRNA in somatotrophs in the rat anterior pituitary, and also showed that more than 50% of the TRHR mRNA detected in the anterior pituitary was derived from these cells.

Multiple aberrant hormone receptors in Cushing's syndrome

“…Similar results were seen with the use of GHRH antagonist MZ-4-71 and LHRH antagonist Cetrorelix (132). In acromegaly the presence of ectopic TRH, GnRH or GIP receptors explains the frequently observed paradoxical increase in GH after administration of TRH, GnRH or oral glucose respectively (133,134,135,136,137,138). GIPR expression was investigated in 43 somatotropinomas and 12 normal pituitary glands by quantitative RT-PCR, western blotting and immunohistochemistry.…”

Loss of Basal and TRH-StimulatedTshbExpression in Dispersed Pituitary Cells

“…Two of these genes are expressed in other cell types as well, Cga in gonadotrophs and Trhr in lactotrophs and a fraction of somatotrophs (1,22), meaning that the observed mRNA expression patterns were also related to cell populations expressing these genes. In contrast, the expression of Tshb is thyrotroph specific.…”

“…TSH controls thyroid functions by stimulating the synthesis and secretion of thyroid hormones, which in turn exert a negative feedback by transcriptional and posttranscriptional mechanisms, rapidly reducing Cga and Tshb expression, synthesis of two subunits, and TSH release (10,18,19). The main positive regulator of TSH release is hypothalamic TRH (20), which activates the G q/11 -coupled TRH receptor-1 (TRHR1), also expressed in lactotrophs and a fraction of somatotrophs (21,22). TRH not only stimulates the release of prestored TSH and accounts for pulsatile and circadian patterns of TSH secretion but also stimulates Cga, Tshb, and Trhr expression and contributes to the posttranslational maturation of the TSH oligosaccharide chains, which guarantee the full biological activity of TSH (23)(24)(25)(26)(27)(28).…”