Journal of Steroid Biochemistry & Molecular Biology 74 (2000) 149 – 155 Follicle-stimulating hormone, testosterone, and hypoxia differentially regulate UDP-glucuronosyltransferase 1 isoforms expression in rat Sertoli and peritubular myoid cells Massimo Magnanti a,1 , Laura Giuliani a,1 , Orietta Gandini a , Paola Gazzaniga a , Vittorio Santiemma b , Marco Ciotti c , Gloria Saccani d , Luigi Frati a,e , Anna Maria Agliano ` a, * a Dipartimento di Medicina Sperimentale e Patologia, Uniersita ` degli Studi di Roma ‘La Sapienza’, Viale Regina Elena, 324 -00161 Rome, Italy b Dipartimento di Fisiopatologia Medica, Uniersita ` degli Studi di Roma ‘La Sapienza’, Viale Regina Elena, 324 -00161 Rome, Italy c Section on Genetic Disorders of Drugs Metabolism, Heritable Disorders Branch, NICHD/NIH, 9000 Rockille Pike, Bethesda, MD 20892, USA d Campus Biomedico, Rome, Italy e Istituto Mediterraneo di Neuroscience, Pozzilli, Italy Received 20 July 1999; accepted 15 June 2000 Abstract Uridine diphosphoglucuronosyltransferases (UGTs) are detoxifying enzymes responsible for the metabolism of endogenous and xenobiotics compounds. UGT isoforms are widely distributed in rat tissues showing a constitutive and inducible gene expression. However, little information is available concerning UGTs expression in testis. The UGT1A1, UGT1A2, and UGT1B1 mRNAs expression in whole rat testis, in Sertoli and peritubular myoid cells in basal conditions, and after hormonal and hypoxic stimulation were investigated by reverse transcriptase-polymerase chain reaction (RT-PCR). Constitutive expression of each UGT1 isoform was present in rat testis with higher levels of UGT1A2. UGT transcripts were also detected in Sertoli and peritubular myoid cells. After FSH stimulation, Sertoli cells showed an increase in UGT1B1 mRNA expression, whereas the levels of UGT1A1 and UGT1A2 resulted unmodified. The main effect induced by testosterone was a decrease of UGT1B1 mRNA expression in peritubular myoid cells, whereas in Sertoli cells an increase in UGT1A1 and UGT1B1 was observed. In hypoxic conditions, a reduction in UGTs mRNA levels was detected in both cell types. These findings suggest that rat UGT1 isoforms are regulated in testis by hormonal and environmental factors. Thus, it was speculated that alterations in UGTs expression and/or activity may be involved in the pathogenesis of testis injury. © 2000 Elsevier Science Ltd. All rights reserved. Keywords: UGT1A1; UGT1A2; UGT1B1; Testis; Hypoxia; FSH www.elsevier.com/locate/jsbmb 1. Introduction Uridine diphosphoglucuronosyltransferases (UGTs) are a family of isoenzymes located in the endoplasmic reticulum that catalyse the transfer of the glucuronic acid from uridine diphosphoglucuronic acid to a wide variety of endogenous compounds including bilirubin, steroid hormones, fat-soluble vitamins, and thyroid hormones [1]. UGTs are also involved in the metabolism and inactivation of various xenobiotic com- pounds such as drugs, teratogens, and carcinogens [2]. Based on their aminoacid sequence similarities, two families of UGTs have been characterized, UGT1 and UGT2, consisting of drug-glucuronidating forms and steroid-glucuronidating forms, respectively. However, it has been demonstrated that UGT1 family is also able to glucoronidate steroids [3,4]. Furthermore, UGT1 family was divided in two subgroups, UGT1A and UGT1B, according to their preferential substrate spe- * Corresponding author. Tel.: +39-6-4462791; fax: +39-6- 4454820. E-mail address: annamaria.agliano@uniroma1.it (A.M. Agliano `). 1 These authors contributed equally to this manuscript. 0960-0760/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved. PII:S0960-0760(00)00095-9