TY - JOUR
T1 - Lanosterol metabolism and sterol regulatory element binding protein (SREBP) expression in male germ cell maturation
AU - Fon Tacer, Klementina
AU - Kalanj-Bognar, Svjetlana
AU - Waterman, Michael R.
AU - Rozman, Damjana
N1 - Funding Information:
We wish to thank Dr. Davorin Ježek, School of Medicine, University of Zagreb, Croatia, for support to the project and helpful suggestions. Thanks also to Dr. Mogens Baltsen, Rikhospitalitet, University of Copenhagen, for the sterol standards. This work was supported by the SLO-CRO bilateral collaborative grant from Ministries of Science of Slovenia and Croatia, by the grants J1-3438 from Ministry of Science of Slovenia, by FIRCA/NIH grant 1 RO3 TW01174-01, and by the ICGEB grant CRP/SLO00-01. K. Fon Tacer is supported by a graduate fellowship from the Ministry of Science of Slovenia.
PY - 2003/6
Y1 - 2003/6
N2 - Expression of genes involved in cholesterol biosynthesis in male germ cells is insensitive to the negative cholesterol feedback regulation, in contrast to cholesterol level-sensitive/sterol regulatory element binding protein (SREBP)-dependent gene regulation in somatic cells. The role of sterol regulatory element binding proteins in spermatogenic cells was an enigma until recently, when a soluble, 55kDa cholesterol-insensitive form of SREBP2 (SREBP2gc) was discovered [Mol. Cell. Endocrinol. 22 (2002) 8478], being translated from a germ cell-specific SREBP2 mRNA. Our RT-PCR results also show that SREBP2 as well as SREBP1c mRNAs are detectable in prepubertal and postpubertal male germ cells while SREBP1a is not detected. Surprisingly, three SREBP2 immunoreactive proteins (72, 63 and 55kDa), that are not present in mouse liver nuclei, reside in testis nuclei of prepubertal and adult mice. The 55kDa protein is likely SREBP2gc, the other two isoforms are novel. HPLC measurements in liver and testes of fasted prepubertal and postpubertal mice showed no significant difference in cholesterol level. However, FF-MAS and lanosterol/testis-meiosis activating sterol (T-MAS) intermediates that are detectable mainly in testes, increase in fasted postpubertal mice which coincides well with the elevated level of 68kDa SREBP2. Similar to SREBP2gc, the two novel SREBP2 immunoreactive proteins seem to be insensitive to the level of cholesterol.
AB - Expression of genes involved in cholesterol biosynthesis in male germ cells is insensitive to the negative cholesterol feedback regulation, in contrast to cholesterol level-sensitive/sterol regulatory element binding protein (SREBP)-dependent gene regulation in somatic cells. The role of sterol regulatory element binding proteins in spermatogenic cells was an enigma until recently, when a soluble, 55kDa cholesterol-insensitive form of SREBP2 (SREBP2gc) was discovered [Mol. Cell. Endocrinol. 22 (2002) 8478], being translated from a germ cell-specific SREBP2 mRNA. Our RT-PCR results also show that SREBP2 as well as SREBP1c mRNAs are detectable in prepubertal and postpubertal male germ cells while SREBP1a is not detected. Surprisingly, three SREBP2 immunoreactive proteins (72, 63 and 55kDa), that are not present in mouse liver nuclei, reside in testis nuclei of prepubertal and adult mice. The 55kDa protein is likely SREBP2gc, the other two isoforms are novel. HPLC measurements in liver and testes of fasted prepubertal and postpubertal mice showed no significant difference in cholesterol level. However, FF-MAS and lanosterol/testis-meiosis activating sterol (T-MAS) intermediates that are detectable mainly in testes, increase in fasted postpubertal mice which coincides well with the elevated level of 68kDa SREBP2. Similar to SREBP2gc, the two novel SREBP2 immunoreactive proteins seem to be insensitive to the level of cholesterol.
KW - Cholesterol
KW - MAS
KW - Male germ cell
KW - SREBP
KW - Testis
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U2 - 10.1016/S0960-0760(03)00191-2
DO - 10.1016/S0960-0760(03)00191-2
M3 - Article
C2 - 12943732
AN - SCOPUS:0041977056
VL - 85
SP - 429
EP - 438
JO - Journal of Steroid Biochemistry and Molecular Biology
JF - Journal of Steroid Biochemistry and Molecular Biology
SN - 0960-0760
IS - 2-5
ER -