Glucocorticoid receptor is involved in the breed-dependent transcriptional regulation of 3β-hydroxysteroid dehydrogenase in the liver of preweaning piglets

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background

Hepatic 3β-hydroxysteroid dehydrogenase (3β-HSD) plays an important role in steroid inactivation and catabolism. Serum concentrations of steroid hormones differ significantly between breeds in pigs, however the molecular mechanism regulating hepatic 3β-HSD expression in different breeds of pigs is poorly understood. In the present study, we used preweaning purebred male Large White (LW) and Erhualian (EHL) piglets as model to investigate the breed difference in the expression and regulation of 3β-HSD gene in porcine liver.

Results

The hepatic expression of 3β-HSD mRNA was significantly lower ( P < 0.01) in EHL piglets compared to that in LW piglets. Significant breed differences were detected for the hepatic expression of transcription factors such as androgen receptor (AR), glucocorticoid receptor (GR), and CCAAT/enhancer binding protein β (C/EBPβ). The nucleoprotein contents of AR ( P < 0.05), GR ( P < 0.01) and phospho-Ser ²¹¹GR ( P < 0.01) were significantly higher in the liver of EHL piglets. Chromatin immunoprecipitation (ChIP) assay demonstrated significantly lower binding of GR, but not AR or C/EBPβ, to 3β-HSD gene promoter in EHL piglets ( P < 0.05). GR was not detected to interact with C/EBPβ or AR in the co-immunoprecipitation analysis.

Conclusions

These results indicate that GR binding to 3β-HSD promoter is involved in the breed-dependent 3β-HSD expression in the liver of piglets.

Related collections

Most cited references 43

Record: found
Abstract: found
Article: not found

Overview of steroidogenic enzymes in the pathway from cholesterol to active steroid hormones.

Anita Payne, Dale B Hales (2004)

Significant advances have taken place in our knowledge of the enzymes involved in steroid hormone biosynthesis since the last comprehensive review in 1988. Major developments include the cloning, identification, and characterization of multiple isoforms of 3beta-hydroxysteroid dehydrogenase, which play a critical role in the biosynthesis of all steroid hormones and 17beta-hydroxysteroid dehydrogenase where specific isoforms are essential for the final step in active steroid hormone biosynthesis. Advances have taken place in our understanding of the unique manner that determines tissue-specific expression of P450aromatase through the utilization of alternative promoters. In recent years, evidence has been obtained for the expression of steroidogenic enzymes in the nervous system and in cardiac tissue, indicating that these tissues may be involved in the biosynthesis of steroid hormones acting in an autocrine or paracrine manner. This review presents a detailed description of the enzymes involved in the biosynthesis of active steroid hormones, with emphasis on the human and mouse enzymes and their expression in gonads, adrenal glands, and placenta.

0 comments Cited 354 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Molecular biology of the 3beta-hydroxysteroid dehydrogenase/delta5-delta4 isomerase gene family.

Jacques Simard, Marie-Louise Ricketts, Sebastien Gingras … (2005)

The 3beta-hydroxysteroid dehydrogenase/Delta(5)-Delta(4) isomerase (3beta-HSD) isoenzymes are responsible for the oxidation and isomerization of Delta(5)-3beta-hydroxysteroid precursors into Delta(4)-ketosteroids, thus catalyzing an essential step in the formation of all classes of active steroid hormones. In humans, expression of the type I isoenzyme accounts for the 3beta-HSD activity found in placenta and peripheral tissues, whereas the type II 3beta-HSD isoenzyme is predominantly expressed in the adrenal gland, ovary, and testis, and its deficiency is responsible for a rare form of congenital adrenal hyperplasia. Phylogeny analyses of the 3beta-HSD gene family strongly suggest that the need for different 3beta-HSD genes occurred very late in mammals, with subsequent evolution in a similar manner in other lineages. Therefore, to a large extent, the 3beta-HSD gene family should have evolved to facilitate differential patterns of tissue- and cell-specific expression and regulation involving multiple signal transduction pathways, which are activated by several growth factors, steroids, and cytokines. Recent studies indicate that HSD3B2 gene regulation involves the orphan nuclear receptors steroidogenic factor-1 and dosage-sensitive sex reversal adrenal hypoplasia congenita critical region on the X chromosome gene 1 (DAX-1). Other findings suggest a potential regulatory role for STAT5 and STAT6 in transcriptional activation of HSD3B2 promoter. It was shown that epidermal growth factor (EGF) requires intact STAT5; on the other hand IL-4 induces HSD3B1 gene expression, along with IL-13, through STAT 6 activation. However, evidence suggests that multiple signal transduction pathways are involved in IL-4 mediated HSD3B1 gene expression. Indeed, a better understanding of the transcriptional factors responsible for the fine control of 3beta-HSD gene expression may provide insight into mechanisms involved in the functional cooperation between STATs and nuclear receptors as well as their potential interaction with other signaling transduction pathways such as GATA proteins. Finally, the elucidation of the molecular basis of 3beta-HSD deficiency has highlighted the fact that mutations in the HSD3B2 gene can result in a wide spectrum of molecular repercussions, which are associated with the different phenotypic manifestations of classical 3beta-HSD deficiency and also provide valuable information concerning the structure-function relationships of the 3beta-HSD superfamily. Furthermore, several recent studies using type I and type II purified enzymes have elegantly further characterized structure-function relationships responsible for kinetic differences and coenzyme specificity.

0 comments Cited 108 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Ligand-induced repression of the glucocorticoid receptor gene is mediated by an NCoR1 repression complex formed by long-range chromatin interactions with intragenic glucocorticoid response elements.

J Cidlowski, Sivapriya Ramamoorthy (2013)

Glucocorticoids are among the most potent and effective agents for treating inflammatory diseases and hematological cancers. However, subpopulations of patients are often resistant to steroid therapy, and determining the molecular mechanisms that contribute to glucocorticoid resistance is thus critical to addressing this clinical problem affecting patients with chronic inflammatory disorders. Since the cellular level of the glucocorticoid receptor (GR) is a critical determinant of glucocorticoid sensitivity and resistance, we investigated the molecular mechanisms mediating repression of glucocorticoid receptor gene expression. We show here that glucocorticoid-induced repression of GR gene expression is mediated by inhibition of transcription initiation. This process is orchestrated by the recruitment of agonist-bound GR to exon 6, followed by the assembly of a GR-NCoR1-histone deacetylase 3-containing repression complex at the transcriptional start site of the GR gene. A functional negative glucocorticoid response element (nGRE) in exon 6 of the GR gene and a long-range interaction occurring between this intragenic response element and the transcription start site appear to be instrumental in this repression. This autoregulatory mechanism of repression implies that the GR concentration can coordinate repression with excess ligand, regardless of the combinatorial associations of tissue-specific transcription factors. Consequently, the chronic nature of inflammatory conditions involving long-term glucocorticoid administration may lead to constitutive repression of GR gene transcription and thus to glucocorticoid resistance.

0 comments Cited 52 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Xian Li: lixianlovelv@163.com

Yimin Jia: jymrobin@hotmail.com

Runsheng Li: ysxlrs@163.com

Zhiyuan Sun: sunzhiyuan1984@163.com

Xi Li: 243397182@163.com

Shiyan Sui: suishiyan2005@aliyun.com

Ruqian Zhao: zhao.ruqian@gmail.com

Journal

Journal ID (nlm-ta): BMC Vet Res

Journal ID (iso-abbrev): BMC Vet. Res

Title: BMC Veterinary Research

Publisher: BioMed Central (London )

ISSN (Electronic): 1746-6148

Publication date (Electronic): 26 May 2015

Publication date PMC-release: 26 May 2015

Publication date Collection: 2015

Volume: 11

Electronic Location Identifier: 123

Affiliations

Key Laboratory of Animal Physiology and Biochemistry, Nanjing Agricultural University, Nanjing, 210095 P. R. China

Article

Publisher ID: 441

DOI: 10.1186/s12917-015-0441-6

PMC ID: 4489036

PubMed ID: 26008782

SO-VID: 5ad23565-0696-481c-ab63-8539b3f8bc77

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 18 December 2014

Date accepted : 18 May 2015

Custom metadata

ScienceOpen disciplines: Veterinary medicine

Keywords: ar,c/ebpβ,gr,liver,pig,3β-hsd

Data availability:

ScienceOpen disciplines: Veterinary medicine

Keywords: ar, c/ebpβ, gr, liver, pig, 3β-hsd

Comments

Comment on this article

scite_

Smart Citations

Citing PublicationsSupportingMentioningContrasting

View Citations

See how this article has been cited at scite.ai

scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.