Deficiency of CDKN1A or both CDKN1A and CDKN1B affects the pubertal development of mouse Leydig cells.

Autor:	Lin H; The 2nd Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China., Huang Y; Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan University, Guangzhou, Guangdong, P.R. China., Su Z; Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan University, Guangzhou, Guangdong, P.R. China., Zhu Q; The 2nd Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China., Ge Y; Population Council & Rockefeller University, New York, New York., Wang G; The 2nd Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China., Wang CQ; The 2nd Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China., Mukai M; Department of Veterinary Biosciences, University of Illinois, Urbana, Illinois., Holsberger DR; Department of Veterinary Biosciences, University of Illinois, Urbana, Illinois., Cooke PS; Department of Veterinary Biosciences, University of Illinois, Urbana, Illinois Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida., Lian QQ; The 2nd Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China lianqingquanmz@163.com., Ge RS; 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.
Jazyk:	angličtina
Zdroj:	Biology of reproduction [Biol Reprod] 2015 Mar; Vol. 92 (3), pp. 77. Date of Electronic Publication: 2015 Jan 21.
DOI:	10.1095/biolreprod.114.118463
Abstrakt:	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. (© 2015 by the Society for the Study of Reproduction, Inc.)
Databáze:	MEDLINE
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