Regulation of 5'-promoter activity of the rat growth hormone and growth hormone-releasing hormone receptor genes in the MtT/S and MtT/E cells.

Abstract

The MtT/E and MtT/S cells have been established from a mammotrophic pituitary tumor, and postulated to be progenitor and premature growth hormone (GH) cells, respectively. The difference in the regulation of GH and GH-releasing hormone (GHRH) receptor gene transcription in relation to the developmental stage of GH cells were examined in these two cell lines. In MtT/S cells, triiodothyronine (T3), all-trans retinoic acid (RA) and 9-cis retinoic acid (9cRA) stimulated GH promoter activity but dexamethasone (DEX) did not. On the other hand, DEX stimulated GHRH-receptor promoter alone. T3, RA and 9cRA showed little effect alone but each of them augmented the effect of DEX when used together with DEX. In MtT/E cells, DEX, RA and 9cRA showed similar effect as observed in MtT/S cells on both GH and GHRH-receptor promoter activity. However, T3 neither stimulated GH promoter activity nor augmented the DEX-induced GHRH-receptor gene transcription in MtT/E cells. RT-PCR analyses revealed that both cell types expressed TRalpha1, TRbeta1 and TRalpha2, but expression of TRbeta2, a pituitary specific isoform of TR, was only detected in MtT/S cells. However, the deficiency of TRbeta2 for its own sake does not appear to be a reason why T3 action was not observed in MtT/E cells, because co-transfection of expression plasmids for TRbeta2 and RXRalpha failed in conferring on the cells an ability to respond to T3 by increased GH or GHRH-receptor promoter activity. These results suggest that the acquisition of mechanisms responsible for the regulation of GH or GHRH-receptor transcription by T3 may be involved in the process of functional development of GH cells.

• Authors: Haruo Nogami, Yoshiki Hiraoka, Kinji Inoue, Sadakazu Aiso, Setsuji Hisano
• Journal: Neuroendocrinology (Neuroendocrinology) Vol. 84 Issue 1 Pg. 31-41 ( 2006) ISSN: 0028-3835 [Print] Switzerland
• PMID: 17090972 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2006 S. Karger AG, Basel.

Chemical References

• Receptors, Neuropeptide
• Receptors, Pituitary Hormone-Regulating Hormone
• Receptors, Somatotropin
• Triiodothyronine
• 9,13-retinoic acid
• Tretinoin
• Growth Hormone
• somatotropin releasing hormone receptor

Topics

• Animals
• COS Cells
• Cell Line, Tumor
• Chlorocebus aethiops
• Gene Expression Regulation (drug effects)
• Gene Expression Regulation, Neoplastic
• Growth Hormone (metabolism)
• Pituitary Neoplasms (genetics, metabolism, pathology)
• Promoter Regions, Genetic (genetics)
• Rats
• Receptors, Neuropeptide (genetics, metabolism)
• Receptors, Pituitary Hormone-Regulating Hormone (genetics, metabolism)
• Receptors, Somatotropin (genetics, metabolism)
• Tretinoin (analogs & derivatives, pharmacology)
• Triiodothyronine (pharmacology)