Farnesoid X Receptor Alpha (FXRα) is a Critical Actor of the Development and Pathologies of the Male Reproductive System

Overview

Journal Cell Mol Life Sci

Publisher Springer

Specialty Biology

Date 2019 Aug 14

PMID 31407019

Citations 2

Authors

Manon Garcia

Laura Thirouard

Melusine Monrose

Helene Holota

Angelique De Haze

Francoise Caira

Claude Beaudoin

David H Volle

Affiliations

Soon will be listed here.

Abstract

The farnesoid-X-receptorα (FXRα; NR1H4) is one of the main bile acid (BA) receptors. During the last decades, through the use of pharmalogical approaches and transgenic mouse models, it has been demonstrated that the nuclear receptor FXRα controls numerous physiological functions such as glucose or energy metabolisms. It is also involved in the etiology or the development of several pathologies. Here, we will review the unexpected roles of FXRα on the male reproductive tract. FXRα has been demonstrated to play functions in the regulation of testicular and prostate homeostasis. Even though additional studies are needed to confirm these findings in humans, the reviewed reports open new field of research to better define the effects of bile acid-FXRα signaling pathways on fertility disorders and cancers.

Citing Articles

Genetic alterations and molecular mechanisms underlying hereditary intrahepatic cholestasis.

Xie S, Wei S, Ma X, Wang R, He T, Zhang Z Front Pharmacol. 2023; 14:1173542.

PMID: 37324459 PMC: 10264785. DOI: 10.3389/fphar.2023.1173542.

The Gut Microbial Bile Acid Modulation and Its Relevance to Digestive Health and Diseases.

Fogelson K, Dorrestein P, Zarrinpar A, Knight R Gastroenterology. 2023; 164(7):1069-1085.

PMID: 36841488 PMC: 10205675. DOI: 10.1053/j.gastro.2023.02.022.

References

Volle D, Duggavathi R, Magnier B, Houten S, Cummins C, Lobaccaro J . The small heterodimer partner is a gonadal gatekeeper of sexual maturation in male mice. Genes Dev. 2007; 21(3):303-15. PMC: 1785120. DOI: 10.1101/gad.409307. View

Tabarin A, Achermann J, Recan D, Bex V, Bertagna X, Christin-Maitre S . A novel mutation in DAX1 causes delayed-onset adrenal insufficiency and incomplete hypogonadotropic hypogonadism. J Clin Invest. 2000; 105(3):321-8. PMC: 377437. DOI: 10.1172/JCI7212. View

Maloney P, Parks D, Haffner C, Fivush A, Chandra G, Plunket K . Identification of a chemical tool for the orphan nuclear receptor FXR. J Med Chem. 2000; 43(16):2971-4. DOI: 10.1021/jm0002127. View

Volzke H, Aumann N, Krebs A, Nauck M, Steveling A, Lerch M . Hepatic steatosis is associated with low serum testosterone and high serum DHEAS levels in men. Int J Androl. 2009; 33(1):45-53. DOI: 10.1111/j.1365-2605.2009.00953.x. View

Baptissart M, Martinot E, Vega A, Sedes L, Rouaisnel B, De Haze A . Bile acid-FXRα pathways regulate male sexual maturation in mice. Oncotarget. 2016; 7(15):19468-82. PMC: 4991395. DOI: 10.18632/oncotarget.7153. View

Rust C, Wild N, Bernt C, Vennegeerts T, Wimmer R, Beuers U . Bile acid-induced apoptosis in hepatocytes is caspase-6-dependent. J Biol Chem. 2008; 284(5):2908-2916. DOI: 10.1074/jbc.M804585200. View

Wang H, He Q, Wang G, Xu X, Hao H . FXR modulators for enterohepatic and metabolic diseases. Expert Opin Ther Pat. 2018; 28(11):765-782. DOI: 10.1080/13543776.2018.1527906. View

Vega A, Baptissart M, Martinot E, Saru J, Baron S, Schoonjans K . Hepatotoxicity induced by neonatal exposure to diethylstilbestrol is maintained throughout adulthood via the nuclear receptor SHP. Expert Opin Ther Targets. 2014; 18(12):1367-76. DOI: 10.1517/14728222.2014.964209. View

Catalano S, Malivindi R, Giordano C, Gu G, Panza S, Bonofiglio D . Farnesoid X receptor, through the binding with steroidogenic factor 1-responsive element, inhibits aromatase expression in tumor Leydig cells. J Biol Chem. 2009; 285(8):5581-93. PMC: 2820785. DOI: 10.1074/jbc.M109.052670. View

10.

Mooradian A, SHAMMAA M, Salti I, Cortas N . Hypophyseal-gonadal dysfunction in men with non-alcoholic liver cirrhosis. Andrologia. 1985; 17(1):72-9. DOI: 10.1111/j.1439-0272.1985.tb00961.x. View

11.

Martinot E, Baptissart M, Vega A, Sedes L, Rouaisnel B, Vaz F . Bile acid homeostasis controls CAR signaling pathways in mouse testis through FXRalpha. Sci Rep. 2017; 7:42182. PMC: 5299845. DOI: 10.1038/srep42182. View

12.

Catalano S, Panza S, Malivindi R, Giordano C, Barone I, Bossi G . Inhibition of Leydig tumor growth by farnesoid X receptor activation: the in vitro and in vivo basis for a novel therapeutic strategy. Int J Cancer. 2012; 132(10):2237-47. DOI: 10.1002/ijc.27915. View

13.

Sedes L, Martinot E, Baptissart M, Baron S, Caira F, Beaudoin C . Bile acids and male fertility: From mouse to human?. Mol Aspects Med. 2017; 56:101-109. DOI: 10.1016/j.mam.2017.05.004. View

14.

Houten S, Volle D, Cummins C, Mangelsdorf D, Auwerx J . In vivo imaging of farnesoid X receptor activity reveals the ileum as the primary bile acid signaling tissue. Mol Endocrinol. 2007; 21(6):1312-23. DOI: 10.1210/me.2007-0113. View

15.

Schoeters G, Den Hond E, Dhooge W, Van Larebeke N, Leijs M . Endocrine disruptors and abnormalities of pubertal development. Basic Clin Pharmacol Toxicol. 2008; 102(2):168-75. DOI: 10.1111/j.1742-7843.2007.00180.x. View

16.

Morelli A, Comeglio P, Filippi S, Sarchielli E, Cellai I, Vignozzi L . Testosterone and farnesoid X receptor agonist INT-747 counteract high fat diet-induced bladder alterations in a rabbit model of metabolic syndrome. J Steroid Biochem Mol Biol. 2012; 132(1-2):80-92. DOI: 10.1016/j.jsbmb.2012.02.007. View

17.

Hsu C, Zhao J, Huang R, Hsieh J, Hamm J, Chang X . Quantitative high-throughput profiling of environmental chemicals and drugs that modulate farnesoid X receptor. Sci Rep. 2014; 4:6437. PMC: 4894417. DOI: 10.1038/srep06437. View

18.

Teodoro J, Rolo A, Palmeira C . Hepatic FXR: key regulator of whole-body energy metabolism. Trends Endocrinol Metab. 2011; 22(11):458-66. DOI: 10.1016/j.tem.2011.07.002. View

19.

Agbaje I, McVicar C, Schock B, McClure N, Atkinson A, Rogers D . Increased concentrations of the oxidative DNA adduct 7,8-dihydro-8-oxo-2-deoxyguanosine in the germ-line of men with type 1 diabetes. Reprod Biomed Online. 2008; 16(3):401-9. DOI: 10.1016/s1472-6483(10)60602-5. View

20.

Casals-Casas C, Desvergne B . Endocrine disruptors: from endocrine to metabolic disruption. Annu Rev Physiol. 2010; 73:135-62. DOI: 10.1146/annurev-physiol-012110-142200. View