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 TRα1, TRβ1 and TRα2, but expression of TRβ2, a pituitary specific isoform of TR, was only detected in MtT/S cells. However, the deficiency of TRβ2 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 TRβ2 and RXRα 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.

Rapid induction of the Growth Hormone Gene Transcription by Glucocorticoids In Vitro: Possible Involvement of Membrane Glucocorticoid Receptors and Phosphatidylinositol 3‐Kinase Activation

“…The results of the previous studies are inconsistent with respect to whether or not glucocorticoids alone stimulate GH transcription . The results of the present study showed that DEX stimulates GH hnRNA levels in a serum‐free condition, suggesting that DEX alone can stimulate the GH gene transcription.…”

“…Previous studies conducted in rat pituitary tumour cell lines have shown that the transcriptional effect of glucocorticoids alone is minimal, undetectable or even inhibitory (10)(11)(12)(13)(14)(15). By contrast, other studies have demonstrated the stimulatory effects of glucocorticoids on GH transcription in clonal pituitary cells (16)(17)(18)(19)(20) or in a primary culture of rat pituitary cells (21).…”

Expression of retinaldehyde dehydrogenase 1 in the anterior pituitary glands of adult rats

“…Both all-trans-RA and 9-cis-RA might regulate adult pituitary functions. All-trans-RA and 9-cis-RA stimulate the expression of mRNA for GH-releasing hormone receptor synergistically with dexamethasone (Nogami et al 2000) and activate the GH promoter in GH-producing cells (Nogami et al 2006). However, the difference between the functions of all-trans-RA and 9-cis-RA on pituitary cells is not clearly understood.…”