Role of a pituitary-specific transcription factor (pit-1/GHF-1) or a closely related protein in cAMP regulation of human thyrotropin-beta subunit gene expression.

Abstract

(-128 to -61 bp) formed five specific DNA-protein complexes with mouse thyrotropic tumor (MTT) nuclear extract and two specific complexes with in vitro translated Pit-l/GHF-1. Four of the five MTT complexes and both in vitro Pit-l/GHF-1 complexes were reduced or eliminated by excess of an unlabeled Pit-1/ GHF-1 DNA-binding site from the rat growth hormone gene, but not a mutated version of the same DNA fragment, suggesting that Pit-l/GHF-1 or a closely related thyrotroph protein binds to these DNA sequences. In 293 cells, co-transfection of an expression vector containing the Pit-l/GHF-1 cDNA restored cAMP-responsiveness to the human TSH,6 promoter (5.2-and 6.6-fold maximal stimulation by 8-Br-cAMP and forskolin, respectively) but not the herpes virus thymidine kinase promoter (1.2-fold maximal stimulation by either agent).Thus we conclude that the human TSH(3 gene is positively regulated by cAMP in GH3 but not 293 cells. Since the human TSH(3 gene contains at least one high-affinity binding site for Pit-1/GHF-1 in a region necessary for cAMP stimulation and cAMP stimulation could be restored to the human TSH(6 promoter in a previously nonresponsive cell line by the addition of Pit-l/GHF-1, this suggests that Pit-l/GHF-1, or a closely related protein in the thyrotroph, may be a trans-acting factor for

The chicken pituitary-specific transcription factor pit-1 is involved in the hypothalamic regulation of pituitary hormones

“…Other data demonstrated that the promoter region of the TSHβ gene contains several regions which regulate the responsiveness to TRH [chicken: Gregory and Porter (1997); duck: Hsieh et al (2000)]. In addition, several studies have revealed that Pit-1 gene expression is stimulated by the PKC pathway, and indicated that Pit-1 is involved in the TRH-stimulated TSHβ gene expression and TSH release (Steinfelder et al, 1992). Therefore, TRH has a direct effect on the regulation of TSHβ gene expression with the involvement of Pit-1.…”

“…This was visible in the non-treated aggregates and the increase was significantly higher in the TRHtreated aggregates. Several studies pointed to the involvement of Pit-1 in the TRH-stimulated TSHβ gene expression, TSH synthesis and release (Steinfelder et al, 1992). A sharp and significant increase was observed between 60 min and 120 min and was due to new TSH synthesis and release.…”

“…promoters of growth hormone-(GH), prolactin-(PRL) and thyroid stimulating hormone-β-(TSHβ) encoding genes (Steinfelder et al, 1992). Pit-1 gene expression is autoregulated and its initial activation is under the control of the Prophet of Pit-1 (PROP-1) gene.…”

Expression of Pituitary Homeo Box 1 (Ptx1) in Human Non-Neoplastic Pituitaries and Pituitary Adenomas

“…In addition, Pit-1 was found to activate transcription of the gene for TSH␤ (31)(32)(33) and to play a role in the functional differentiation of these cells as well as in the maintenance of their viability and proliferation (34 -36). There have been several studies on the expression of Pit-1 in human pituitary adenomas (1-6).…”

Negative Regulation of the Thyrotropin β Gene by Thyroid Hormone

“…Although serum TSH levels are reduced in patient with CPHD who have mutations in the Pit1 gene (Cohen and Radovick, 2002), the involvement of Pit1 downstream of TRH signaling has been controversial (Ohba et al, 2011;Steinfelder et al, 1992a;Steinfelder et al, 1992b). Unfortunately, previous analyses have been performed without consideration of GATA2.…”