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Endocrinology Vol. 139, No. 5 2314-2321
Copyright © 1998 by The Endocrine Society

ARTICLES

Elevated Expression of Lanosterol 14{alpha}-Demethylase (CYP51) and the Synthesis of Oocyte Meiosis-Activating Sterols in Postmeiotic Germ Cells of Male Rats1

Maria Strömstedt2, Michael R. Waterman, Trine B. Haugen3, Kjetil Taskén, Martti Parvinen and Damjana Rozman

Department of Biochemistry, Vanderbilt University School of Medicine (M.S., M.R.W.), Nashville, Tennessee 37232-0146; the Institute of Medical Biochemistry, University of Oslo (T.B.H., K.T.), N-0317 Oslo, Norway; Department of Anatomy, University of Turku (M.P.), Kiinamyllynkatu 10, FIN-20520 Turku, Finland; and Institute of Biochemistry (D.R.), Medical Center for Molecular Biology, Medical Faculty, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia

Address all correspondence and requests for reprints to: Dr. Damjana Rozman, Institute of Biochemistry, Medical Center for Molecular Biology, Medical Faculty University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia. E-mail: rozman{at}ibmi.mf.uni-lj.si

Mammalian CYP51 encodes lanosterol 14{alpha}-demethylase (P45014DM) that is involved in the postsqualene part of cholesterol biosynthesis. This enzyme removes the 14{alpha}-methyl group from lanosterol and 24,25-dihydrolanosterol producing intermediates in cholesterol biosynthesis, the oocyte meiosis-activating sterols FF-MAS and MAS-412. Human and rat CYP51 messenger RNAs (mRNAs) are expressed in all tissues, with highest levels in the testis due to the presence of an additional shorter CYP51 transcript in this tissue. In situ hybridization shows the highest CYP51 mRNA levels in seminiferous tubules, with only background levels in Leydig cells. The rat testis-specific CYP51 mRNA arises from the use of an upstream polyadenylation site and is restricted to germ cells, being most abundant in elongating spermatids in stages VII–XIV, whereas somatic CYP51 transcripts are present in all cells. In contrast, the mRNA levels of squalene synthase are maximal in round spermatids, and no germ cell-specific transcript is observed. The rat male germ cell-specific CYP51 transcript is translated in vitro to two proteins of approximately 55 and 53.5 kDa. CYP51 activity is higher in protein extracts of testes and germ cells of sexually mature rats than in prepubertal animals, in which postmeiotic germ cells are not yet present. This shows increased capacity for the production of MAS sterols by male germ cells that have already completed meiosis, suggesting that they serve a role different from meiosis activation.




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