title: Deficiency of CDKN1A or both CDKN1A and CDKN1B affects the pubertal development of mouse Leydig cells.
abstract: Cyclin-dependent kinase inhibitors p21(Cip1) (CDKN1A) and p27(Kip1) (CDKN1B) are expressed in Leydig cells. Previously, we reported that Cdkn1b knockout in the mouse led to increased Leydig cell proliferative capacity and lower steroidogenesis. However, the relative importance of CDKN1A and CDKN1B in these regulations was unclear. In the present study, we examined the relative importance of CDKN1A and CDKN1B in regulation of Leydig cell proliferation and steroidogenesis by whole-body knockout of CDKN1A (Cdkn1a(-/-)) and CDKN1A/CDKN1B double knockout (DBKO). The cell number, 5-bromo-2-deoxyuridine incorporation rate, steroidogenesis, and steroidogenic enzyme mRNA levels and activities of Leydig cells were compared among wild-type (WT), Cdkn1a(-/-), and DBKO mice. Relative to WT mice, Leydig cell number per testis was doubled in the DBKO and unchanged in the Cdkn1a(-/-) mice. Testicular testosterone levels and mRNA levels for luteinizing hormone receptor (Lhcgr), steroidogenic acute regulatory protein (Star), cholesterol side-chain cleavage enzyme (Cyp11a1), 17alpha-hydroxylase/17,20-lyase (Cyp17a1), and 17beta-hydroxysteroid dehydrogenase 3 (Hsd17b3) and their respective proteins were significantly lower in the DBKO mice. However, testicular testosterone level was unchanged in the Cdkn1a(-/-) mice, although Lhcgr mRNA levels were significantly lower relative to those in the WT control. We conclude that Cdkn1a(-/-) did not increase Leydig cell numbers (although a defect of Leydig cell function was noted), whereas DBKO caused a significant increase of Leydig cell numbers but a decrease of steroidogenesis.
authors.affiliation: The 2nd Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China.
authors.forename: Han
authors.initials: H
authors.lastname: Lin
authors.affiliation: Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan University, Guangzhou, Guangdong, P.R. China.
authors.forename: Yadong
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan University, Guangzhou, Guangdong, P.R. China.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Su
authors.affiliation: The 2nd Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China.
authors.forename: Qiqi
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Population Council & Rockefeller University, New York, New York.
authors.forename: Yufei
authors.initials: Y
authors.lastname: Ge
authors.affiliation: The 2nd Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China.
authors.forename: Guimin
authors.initials: G
authors.lastname: Wang
authors.affiliation: The 2nd Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China.
authors.forename: Claire Q F
authors.initials: CQ
authors.lastname: Wang
authors.affiliation: Department of Veterinary Biosciences, University of Illinois, Urbana, Illinois.
authors.forename: Motoko
authors.initials: M
authors.lastname: Mukai
authors.affiliation: Department of Veterinary Biosciences, University of Illinois, Urbana, Illinois.
authors.forename: Denise R
authors.initials: DR
authors.lastname: Holsberger
authors.affiliation: Department of Veterinary Biosciences, University of Illinois, Urbana, Illinois Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Cooke
authors.affiliation: The 2nd Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China lianqingquanmz@163.com.
authors.forename: Qing-Quan
authors.initials: QQ
authors.lastname: Lian
authors.affiliation: The 2nd Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China Population Council & Rockefeller University, New York, New York r_ge@yahoo.com.
authors.forename: Ren-Shan
authors.initials: RS
authors.lastname: Ge
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology*; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D007985:Leydig Cells / Q000166:cytology* / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D010750:Phosphoproteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011974:Receptors, LH / Q000378:metabolism; D012741:Sexual Maturation / Q000235:genetics / Q000502:physiology*; D013256:Steroids / Q000378:metabolism; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: C493957:Cdkn1a protein, mouse; C493961:Cdkn1b protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D010750:Phosphoproteins; D012333:RNA, Messenger; D011974:Receptors, LH; D013256:Steroids; D000098682:Steroidogenic Acute Regulatory Protein; D050760:Cyclin-Dependent Kinase Inhibitor p27; D002786:Cholesterol Side-Chain Cleavage Enzyme
keywords: Leydig cells; cell cycle; cyclin-dependent kinase inhibitor; developmental biology; mitogenesis; steroid hormones/steroid hormone receptors; testosterone