title: Alterations of gene profiles in Leydig-cell-regenerating adult rat testis after ethane dimethane sulfonate-treatment.
abstract: Only occupying about 1%-5% of total testicular cells, the adult Leydig cell (ALC) is a unique endocrine cell that produces androgens. Rat Leydig cells regenerate after these cells in the testis are eliminated with ethane dimethane sulfonate (EDS). In this study, we have characterized Leydig cell regeneration and messenger ribonucleic acids (mRNA) profiles of EDS treated rat testes. Serum testosterone, testicular gene profiling and some steroidogenesis-related proteins were analyzed at 7, 21, 35 and 90 days after EDS treatment. Testicular testosterone levels declined to undetectable levels until 7 days after treatment and then started to recover. Seven days after treatment, 81 mRNAs were down-regulated greater than or equal to two-fold, with 48 becoming undetectable. These genes increased their expression 21 days and completely returned to normal levels 90 days after treatment. The undetectable genes include steroidogenic pathway proteins: steroidogenic acute regulatory protein, Scarb1, Cyp11a1, Cyp17a1, Hsd3b1, Cyp1b1 and Cyp2a1. Seven days after treatment, there were 89 mRNAs up-regulated two-fold or more including Pkib. These up-regulated mRNAs returned to normal 90 days after treatment. Cyp2a1 did not start to recover until 35 days after treatment, indicating that this gene is only expressed in ALCs not in the precursor cells. Quantitative polymerase chain reaction, western blotting and semi-quantitative immunohistochemical staining using tissue array confirmed the changes of several randomly picked genes and their proteins.
authors.forename: Yu-Fei
authors.initials: YF
authors.lastname: Zhang
authors.forename: Kai-Ming
authors.initials: KM
authors.lastname: Yuan
authors.forename: Yong
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Heilongjiang Key Laboratory of Anti-fibrosis Biotherapy, Mudanjiang Medical University, Mudanjiang 157011, China, .
authors.forename: Yan-Hui
authors.initials: YH
authors.lastname: Chu
authors.forename: Qing-Quan
authors.initials: QQ
authors.lastname: Lian
authors.forename: Yu-Fei
authors.initials: YF
authors.lastname: Ge
authors.forename: Wei
authors.initials: W
authors.lastname: Zhen
authors.forename: Chantal M
authors.initials: CM
authors.lastname: Sottas
authors.forename: Zhi-Jian
authors.initials: ZJ
authors.lastname: Su
authors.affiliation: The 2nd Affiliated Hospital, Wenzhou Medical College, Wenzhou 325000, China; The Population Council, New York 10065, USA, .
authors.forename: Ren-Shan
authors.initials: RS
authors.lastname: Ge
mesh_terms: D000818:Animals; D000988:Antispermatogenic Agents / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D000072467:Cytochrome P450 Family 2; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D007985:Leydig Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008698:Mesylates / Q000494:pharmacology*; D046228:Microarray Analysis; D023421:Models, Animal; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000187:drug effects* / Q000502:physiology; D013250:Steroid Hydroxylases / Q000235:genetics / Q000378:metabolism; D013737:Testis / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013739:Testosterone / Q000235:genetics / Q000378:metabolism
chemical_list: D000988:Antispermatogenic Agents; D047908:Intracellular Signaling Peptides and Proteins; D008698:Mesylates; C498433:Pkib protein, rat; D012333:RNA, Messenger; D013739:Testosterone; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C456179:Cyp2a1 protein, rat; D000072467:Cytochrome P450 Family 2; C002994:ethylene dimethanesulfonate