Intestinal steroidogenesis controls PPARγ expression in the colon and is impaired during ulcerative colitis

Bouguen, Guillaume; Langlois, Audrey; Djouina, Madjid; Branche, Julien; Koriche, Dine; Dewaeles, Edmone; Mongy, Alice; Auwerx, Johan; Colombel, Jean–Frédéric; Desreumaux, Pierre; Dubuquoy, Laurent; Bertin, Benjamin

doi:10.1136/gutjnl-2014-307618

Cited by 50 publications

(76 citation statements)

References 35 publications

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“…In human tissue, CYP11A1 and CYP11B1 were detected in colonic biopsies suggesting that in physiological state the human mucosa is able to produce GC [29]. We recently confirmed and detailed this finding by showing expression of steroidogenic enzymes (3bHSD 1, 3bHSD 2, 11bHSD1) and cortisol production in colonic epithelial cells isolated from human surgical specimens [19].…”

Section: Evidence Of Intestinal Gc Productionmentioning

confidence: 59%

“…Indeed, this was first demonstrated in vitro by Mueller and colleagues who showed that LRH 1 induces the CYP11A1 and CYP11B1 expression as well as corticosterone production in the murine intestinal epithelial cell line [40,42]. In human colon cancer cell lines, the down regulation of LRH 1 by small interfering RNA leads to the reduction of steroidogenic enzyme expression and cortisol synthesis [18,19]. In normal human colonic epithelial cells, the expression level of the mRNA encoding LRH 1 strongly correlates with the expression levels of 3bHSD and 11bHSD [19], suggesting that LRH 1 regulates intestinal GC synthesis under physiological state.…”

Section: Regulation Of Gc Production: From Adrenal To the Intestinementioning

confidence: 92%

“…More recently, CYP11A1, CYP17 and CYP11B1 and a production of cortisol were observed in colorec tal cancer cell lines (Caco 2, HT 29) as well as in primary human intestinal tissue and colorectal tumors [18]. Caco 2 cells were also found to constitutionally express 3bHSD1 and 2 [19], as well as the cholesterol transporter StAR, CYP21 and 11bHSD1 (B. Bertin, unpublished data). In human tissue, CYP11A1 and CYP11B1 were detected in colonic biopsies suggesting that in physiological state the human mucosa is able to produce GC [29].…”

Section: Evidence Of Intestinal Gc Productionmentioning

confidence: 93%

“…The expression of 11bHSD2 (11 beta hydroxysteroid dehydrogenase 2), which converts active GCs to inactive metabolites, was also detected in the intestine of rodents and humans [25,26]. Subse quent studies demonstrated steroidogenic enzyme expression as well as intestinal steroid metabolism in various species such as frog [27], fish [28], mouse [17], and human [18,19,29]. Most of the comprehensive studies on intestinal steroidogenesis have been undertaken using mouse models.…”

Section: Evidence Of Intestinal Gc Productionmentioning

confidence: 99%

“…In human colon cancer cell lines, the down regulation of LRH 1 by small interfering RNA leads to the reduction of steroidogenic enzyme expression and cortisol synthesis [18,19]. In normal human colonic epithelial cells, the expression level of the mRNA encoding LRH 1 strongly correlates with the expression levels of 3bHSD and 11bHSD [19], suggesting that LRH 1 regulates intestinal GC synthesis under physiological state. In vivo, LRH 1 haploinsufficiency in mice con firmed the critical role of LRH 1 in controlling intestinal corticoste rone production.…”

Section: Regulation Of Gc Production: From Adrenal To the Intestinementioning

confidence: 99%

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Intestinal steroidogenesis

et al. 2015

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a b s t r a c tSteroids are fundamental hormones that control a wide variety of physiological processes such as metabolism, immune functions, and sexual characteristics. Historically, steroid synthesis was considered a function restricted to the adrenals and the gonads. In the past 20 years, a significant number of studies have demonstrated that steroids could also be synthesized or metabolized by other organs. According to these studies, the intestine appears to be a major source of de novo produced glucocorticoids as well as a tissue capable of producing and metabolizing sex steroids. This finding is based on the detection of ste roidogenic enzyme expression as well as the presence of bioactive steroids in both the rodent and human gut. Within the intestinal mucosa, the intestinal epithelial cell layer is one of the main cellular sources of steroids. Glucocorticoid synthesis regulation in the intestinal epithelial cells is unique in that it does not involve the classical positive regulator steroidogenic factor 1 (SF 1) but a closely related homolog, namely the liver receptor homolog 1 (LRH 1). This local production of immunoregulatory glucocorticoids contributes to intestinal homeostasis and has been linked to pathophysiology of inflammatory bowel dis eases. Intestinal epithelial cells also possess the ability to metabolize sex steroids, notably estrogen; this mechanism may impact colorectal cancer development. In this review, we contextualize and discuss what is known about intestinal steroidogenesis and regulation as well as the key role these functions play both in physiological and pathological conditions.

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Section: Evidence Of Intestinal Gc Productionmentioning

confidence: 59%

Section: Regulation Of Gc Production: From Adrenal To the Intestinementioning

confidence: 92%

Section: Evidence Of Intestinal Gc Productionmentioning

confidence: 93%

Section: Evidence Of Intestinal Gc Productionmentioning

confidence: 99%

Section: Regulation Of Gc Production: From Adrenal To the Intestinementioning

confidence: 99%

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Intestinal steroidogenesis

et al. 2015

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Aspergillus cristatus attenuates DSS‐induced intestinal barrier damage through reducing the oxidative stress, regulating short‐chain fatty acid and inhibiting MAPK signaling pathways

Wang

Zhang

et al. 2022

J Sci Food Agric

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BACKGROUND Probiotics are regarded as a promising strategy for relieving colitis caused by dextran sulfate sodium (DSS). One of the dominant probiotic fungi in Fuzhuan brick tea is identified as Aspergillus cristatus, but whether it can effectively improve colitis remains poorly understood. Here, the improving effect of A. cristatus on colitis was investigated. RESULTS Our results showed that A. cristatus intervention prominently alleviated gut damage as evidenced by the inhibition of shortened colon length, goblet cell depletion, and histological injury. Mechanistically, after administration with low concentrations of A. cristatus H‐1 and A. cristatus S‐6, the expression of interleukin‐6, tumor necrosis factor‐α, interleukin‐1β, nitric oxide, and malondialdehyde were significantly downregulated, and the content of glutathione, catalase, interleukin‐10, immunoglobulin G, claudin‐1, occludin, and zonula occludens‐1 were effectively upregulated. More importantly, live A. cristatus supplementation lightened DSS‐induced gut barrier damage by suppressing activation of the mitogen‐activated protein kinase (MAPK) signaling pathway, increasing the synthesis of short‐chain fatty acids (SCFAs) and stimulating the increase in peroxisome proliferator‐activated receptor γ expression. CONCLUSION Together, A. cristatus can attenuate DSS‐induced intestinal barrier damage through reducing the oxidative stress, regulating SCFA and inhibiting MAPK signaling pathways (P38/JNK/ERK). Our findings indicate that A. cristatus replenishment has potential as a new probiotic fungi to reduce DSS‐induced colitis. © 2022 Society of Chemical Industry.

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Wogonin regulates colonocyte metabolism via PPARγ to inhibit Enterobacteriaceae against dextran sulfate sodium‐induced colitis in mice

Liang

Zhang

et al. 2022

Phytotherapy Research

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To investigate the potential effects and mechanism of wogonin on dextran sulfate sodium (DSS)‐induced colitis, 70 male mice were administered wogonin (12.5, 25, 50 mg·kg−1·d−1, i.g.) for 10 days, meanwhile, in order to induce colitis, the mice were free to drink 3% DSS for 6 days. We found that wogonin could obviously ameliorate DSS‐induced colitis, including preventing colon shortening and inhibiting pathological damage. In addition, wogonin could increase the expression of PPARγ, which not only restores intestinal epithelial hypoxia but also inhibits iNOS protein to reduce intestinal nitrite levels. All these effects facilitated a reduction in the abundance of Enterobacteriaceae in DSS‐induced colitis mice. Therefore, compared with the DSS group, the number of Enterobacteriaceae in the intestinal flora was significantly reduced after administration of wogonin or rosiglitazone by 16s rDNA technology. We also verified that wogonin could promote the expression of PPARγ mRNA and protein in Caco‐2 cells, and this effect disappeared when PPARγ signal was inhibited. In conclusion, our study suggested that wogonin can activate the PPARγ signal of the Intestinal epithelium to ameliorate the Intestinal inflammation caused by Enterobacteriaceae bacteria expansion.

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Intestinal steroidogenesis controls PPARγ expression in the colon and is impaired during ulcerative colitis

Abstract: These results demonstrate cortisol control of PPARγ expression in CEC, highlighting cortisol production deficiency in colonocytes as a key molecular event in the pathophysiology of UC.

Cited by 50 publications

References 35 publications

Intestinal steroidogenesis

Intestinal steroidogenesis

Aspergillus cristatus attenuates DSS‐induced intestinal barrier damage through reducing the oxidative stress, regulating short‐chain fatty acid and inhibiting MAPK signaling pathways

Wogonin regulates colonocyte metabolism via PPARγ to inhibit Enterobacteriaceae against dextran sulfate sodium‐induced colitis in mice

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