scholarly journals The Thyrotrope-Restricted Isoform of the Retinoid-X Receptor-γ1 Mediates 9-cis-Retinoic Acid Suppression of Thyrotropin-β Promoter Activity

1997 ◽  
Vol 11 (4) ◽  
pp. 481-489 ◽  
Author(s):  
Bryan R. Haugen ◽  
Nicole S. Brown ◽  
William M. Wood ◽  
David F. Gordon ◽  
E. Chester Ridgway

Abstract TSHβ is a subunit of TSH that is uniquely expressed and regulated in the thyrotrope cells of the anterior pituitary gland. Thyroid hormone receptors (TR) are known to mediate T3 suppression of TSHβ gene expression at the level of promoter activity. The role of other nuclear receptors in regulation of this gene is less clearly defined. Retinoid X receptors (RXR) are a family of nuclear transcription factors that function both as 9-cis-retinoic acid (RA) ligand-dependent receptors and heterodimeric partners with TR and other nuclear receptors. Recently, the RXR isoform, RXRγ, has been identified in the anterior pituitary gland and found to be restricted to thyrotrope cells within the pitutiary. In this report, we have further characterized the distribution of RXRγ1, the thyrotrope-restricted isoform of RXRγ, in murine tissues and different cell types. We have found that RXRγ1 mRNA and protein are expressed in the TtT-97 thyrotropic tumor, but not the thyrotrope-variant αTSH cells or somatotrope-derived GH3 cells. Furthermore, we have studied the effects of RXRγ1 on TSHβ promoter activity and hormone regulation in these pituitary-derived cell types. Both T3 and 9-cis-RA independently suppressed promoter activity in the TtT-97 thyrotropes. Interestingly, the combination of ligands suppressed promoter activity more than either alone, indicating that these hormones may act cooperatively to regulate TSHβ gene expression in thyrotropes. The RXRγ1 isoform was necessary for the 9-cis-RA-mediated suppression of TSHβ promoter activity in αTSH and GH3 cells, both of which lack this isoform. RXRβ, a more widely distributed isoform, did not mediate these effects. Finally, we showed that the murine TSHβ promoter region between −200 and −149 mediated a majority of the 9-cis-RA suppression of promoter activity in thyrotropes. This region is distinct from the T3-mediated response region near the transcription start site. These data suggest that retinoids can mediate TSHβ gene regulation in thyrotropes and the thyrotrope-restricted isoform, RXRγ1, is required for this effect.

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Ko-Ting Lu ◽  
Eric T Weatherford ◽  
Pimonrat Ketsawatsomkron ◽  
Justin L Grobe ◽  
Curt D Sigmund

Expression of the renin gene is required to maintain normal morphological and physiological identity of renal juxtaglomerular (JG) cells, yet the mechanisms regulating renin gene transcription remain elusive. We re-examined data from Brunskill et. al (JASN 22:2213, 2011), investigating genome-wide gene expression in JG and other renal cell types. Based on our previous data implicating nuclear receptors (RAR, RXR, VDR, PPARG, Nr2f2 and Nr2f6) in the regulation of mouse and human renin gene expression, we focused our analysis on the expression of genes encoding the 48 nuclear hormone receptors and their co-regulation with renin. Several nuclear receptors have an expression pattern emulating that of renin, that is, they were similarly enriched in JG cells but not in other cell types. These include Esr1, Nr1h4, Ppara, VDR, Nr1i2, Ppard, Hnf4g, Nr1h3, Thrb, Hnf4a, Esrrg, Nr4a3, Nr3c2, and Ar. We tested the hypothesis that a nuclear receptor that is co-regulated with renin may participate in renin gene regulation. To accomplish this, endogenous renin expression was evaluated in renin-expressing As4.1 cells after siRNA-mediated knock down of selected nuclear receptors. Each experiment included a negative control siRNA duplex (NC) that does not target any known genes. By way of example, siRNA-mediated inhibition of estrogen receptor alpha (Esr1) by 70-80% resulted in a 2-fold decrease in renin mRNA (fold change ± SEM: siEsr1: 0.4±0.2, p<0.001 vs NC). Similar results were obtained with a different siRNA targeting Esr1. Interestingly, loss of Esr1 also caused up-regulation of vitamin D receptor (VDR, 2.8±0.7 fold, p<0.001 vs NC) and Nr2f6 (2.0±0.2 fold, p<0.05 vs NC), both of which are known to be negative regulators of renin. Similarly, both renin (0.1±0.02, p<0.001 vs untreated) and Esr1 (0.3±0.1, p<0.05 vs untreated) mRNA were reduced in the kidney from mice treated with deoxycorticosterone acetate (50mg) and receiving 0.15 M NaCl in drinking water for 21 days (DOCA-salt). These data suggest Esr1 may regulate renin expression. Studies are in progress to assess if Esr1 stimulates renin expression on its own or acts by affecting the level of other nuclear receptors; and to determine if other co-regulated nuclear receptors also regulate expression of the renin gene.


1972 ◽  
Vol 20 (1) ◽  
pp. 1-12 ◽  
Author(s):  
GEORGES PELLETIER ◽  
ALEX B. NOVIKOFF

All five known secretory cell types of the rat anterior pituitary gland display nucleoside diphosphatase (NDPase) activity throughout the endoplasmic reticulum (ER), including the nuclear envelope but not the specialized region of ER at the inner aspect of the Golgi apparatus known as GERL. The functions of the ER diphosphatase are currently unknown. However, speculations concerning its association with glucuronyl transferase may focus on the metabolic roles of the ER in pituitary cells other than those directly related to secretory protein transport. The gonadotrophs have been studied for thiamine pyrophosphatase and acid phosphatase activities as well as NDPase activity. The results suggest that the secretory granules of gonadotrophs arise from GERL and not from the inner element of the Golgi apparatus. The innermost Golgi element of this cell type shows NDPase and thiamine pyrophosphatase activities and appears to be composed, in part at least, of anastomosing tubules. Nucleoside phosphatase activity is also present at the surfaces of all five secretory cell types and between the cells and adjacent blood capillaries.


1992 ◽  
Vol 579 (2) ◽  
pp. 303-308 ◽  
Author(s):  
Toshihiro Suda ◽  
Yoriko Nakano ◽  
Fumiko Tozawa ◽  
Takashi Sumitomo ◽  
Yuji Sato ◽  
...  

2007 ◽  
Vol 38 (1) ◽  
pp. 65-77 ◽  
Author(s):  
Claudius Luziga ◽  
Masaru Usui ◽  
Horii Yoichiro ◽  
Rudovick Kazwala ◽  
Yoshimi Yamamoto ◽  
...  

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