Lanosterol 14α-demethylase and MAS sterols in mammalian gametogenesis

Rozman, Damjana; Cotman, Marko; Frangež, Robert

doi:10.1016/s0303-7207(01)00693-1

Cited by 49 publications

(30 citation statements)

References 34 publications

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“…Granulosa cells in all developing stages showed background level of expression. 7) But in eCG stimulated mouse, our lab showed a similar results to that of eCG stimulated rats 21) that a high expression of the CYP51 protein in primordial and primary oocytes, and reduced but detectable staining in more mature oocyte stages. Granulosa cells in primordial and primary follicles showed background level of expression and become higher in Graafian follicles.…”

Section: Discussionsupporting

confidence: 65%

“…Expression of the CYP51 protein in bovine testis showed leydig cells express high levels as well as that in rat, 6) mouse, 7) pig, human and marmoset (Majdič et al, and Rozman, unpublished). The highest expression in all mammalian leydig cells of testis may be related to its function of the large amount synthesis of cholesterol and hormone.…”

Section: Discussionmentioning

confidence: 99%

“…CYP51 protein is highly expressed in mammalian testis leydig cell and round, elongating spermatids. 6,7) It resides in the endoplasmatic reticulum of most cells and also in acrosomal membranes of spermatids where transport through the Golgi apparatus is suggested. 8) But the role of MAS in the spermatogenesis is not well known.…”

mentioning

confidence: 99%

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cDNA Cloning, Genomic Structure and Expression Analysis of the Bovine Lanosterol 14.ALPHA.-Demethylase (CYP51) in Gonads

Wang

Shen

Song

et al. 2006

Biological & Pharmaceutical Bulletin

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Sterol biosynthesis is an essential metabolic pathway in all eukaryotic organisms. Lanosterol 14a-demethylase (CYP51) is a cytochrome P450 enzyme of the sterol biosynthesis pathway belonging to the CYP51 gene family which is the most evolutionarily conserved member of the CYP superfamily and the only cytochrome P450 family present in all kingdoms of biology.1,2) CYP51 protein catalyzes the oxidative removal of the 14a-methyl group (C32) of lanosterol and 24-methylene-24,25-dihydrolanosterol in yeast and fungi, lanosterol and 24,25-dihydrolanosterol in mammals, and obtusifoliol in plants.In mammalian gonads, CYP51 enzyme is not only important to the synthesis of cholesterol, but also has a role in overproducing meiosis activating sterol (MAS), an intermediate of the postsqualene part of cholesterol biosynthesis, including follicular fluid meiosis activating sterol (FF-MAS) and testis meiosis activating sterol (T-MAS) accumulating mainly in ovaries and testis respectively. MAS was proved to have the ability to trigger resumption of oocytes meiosis, 3) which can promote not only the nuclear but also plasma maturation and preimplantation development of mouse oocytes and fertilized oocytes in vitro. 4,5) Our lab recently have proved MAS also can promote the formation of follicle in fetal mouse ovaries (Xie, unpublished, 2005). CYP51 protein is highly expressed in mammalian testis leydig cell and round, elongating spermatids.6,7) It resides in the endoplasmatic reticulum of most cells and also in acrosomal membranes of spermatids where transport through the Golgi apparatus is suggested.8) But the role of MAS in the spermatogenesis is not well known.The mammalian CYP51 cDNA and the gene have previously been characterized in mouse, 9) rat, 10) human, 11,12) and pig. 13) CYP51 mRNAs are widely expressed in those mammalian tissues with the highest level in haploid male germ cells spermatids. Two different types of CYP51 transcripts somatic transcripts and additional testis-specific transcripts are observed for differential polyadenylation site usage. CYP51 genes have several common characteristics: ten exons and nine introns, highly conserved exon/intron borders and proximal promoter structures.14) The promoter region is TATA-less and contains several highly conserved regulatory elements, such as GC-box, cAMP-responsive elements (CRE), sterol regulatory element (SRE), suggesting an evolutionary conserved mechanism of CYP51 transcriptional regulation in mammals. In somatic cells CYP51 expression is regulated by sterol regulatory element binding proteins (SREBPs), 14) while the germ-cell-specific cAMP/CREMtdependent upregulation of CYP51 expression might contribute to increase the production of MAS in testis. 14,15) Although T-MAS was first found and purified from bovine testis, the information of bovine CYP51 is little. In the present study, we characterized the bovine CYP51 gene and its expression and discussed the probable role of CYP51 and MAS in reproduction. MATERIALS AND METHODS RNA ExtractionBovine tissues were coll...

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Section: Discussionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

cDNA Cloning, Genomic Structure and Expression Analysis of the Bovine Lanosterol 14.ALPHA.-Demethylase (CYP51) in Gonads

Wang

Shen

Song

et al. 2006

Biological & Pharmaceutical Bulletin

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“…FF-MAS and T-MAS, is unknown in rat testis. These intermediates are presumed to be signaling substances that initiate meiotic division of the oocyte and spermatocyte, respectively [6][7][8][9]. The concentrations of FF-MAS and T-MAS in the testis in the GA group were significantly lower than those in the control group (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…1). Interestingly, FF-MAS and T-MAS are presumed to be signaling substances that trigger the start of meiotic division of the oocyte and spermatocyte, respectively [8]. Indeed, Grondahl et al have demonstrated that FF-MAS has the ability to reinitiate meiosis in a mouse oocyte assay in vitro [9].…”

Section: Introductionmentioning

confidence: 99%

Relationship between Garcinia cambogia-Induced Impairment of Spermatogenesis and Meiosis-Activating Sterol Production in Rat Testis

Kiyose¹,

Ogino²,

Kubo³

et al. 2006

J. Clin. Biochem. Nutr.

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Summary Dietary supplements for body fat reduction have become popular, particularly in developed countries. Garcinia cambogia (GA) is one such supplement, and its active component is (−)-hydroxycitric acid ((−)-HCA), a competitive inhibitor of ATP citrate lyase, which is responsible for producing acetyl CoA from citric acid. Recently we have found that administration of (−)-HCA-containing GA markedly reduces testis weight in male Zucker obese rats. In particular, histopathological examinations revealed testicular atrophy and impairment of spermatogenesis. In the present study, we investigated the cause of the impaired spermatogenesis after ingestion of GA containing (−)-HCA at 102 mmol / kg diet in young Fischer 344 male rats. Among hormones related to spermatogenesis, the serum level of inhibin-B was significantly lower and that of follicle-stimulating hormone (FSH) was higher in the GA group. The level of testis meiosis-activating sterol (T-MAS), which is an intermediate in cholesterol biosynthesis from acetyl CoA and is presumed to transmit a signal for spermatogenesis, was statistically lower in the testes of rats administered GA. We hypothesize from these results that (−)-HCA-mediated inhibition of ATP citrate lyase in rats fed GA leads to diminished accumulation of MAS substances, thus resulting in impairment of spermatogenesis.

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Disorders of sterol synthesis: Beyond Smith–Lemli–Opitz syndrome

Herman

Kratz

2012

American J of Med Genetics Pt C

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Since the discovery in 1993 that Smith-Lemli-Opitz syndrome (SLOS) is a disorder of cholesterol biosynthesis, human disorders associated with additional enzymes involved in the conversion of lanosterol to cholesterol have been identified. This review will focus primarily on the clinical aspects of these disorders, highlighting newly described syndromes, such as SC4MOL deficiency and CK syndrome. We will also provide clinical descriptions of additional cases for extremely rare disorders, such as desmosterolosis. We will compare and contrast the findings with those found in SLOS and briefly discuss possible mechanisms of disease pathogenesis.

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Lanosterol 14α-demethylase and MAS sterols in mammalian gametogenesis

Cited by 49 publications

References 34 publications

cDNA Cloning, Genomic Structure and Expression Analysis of the Bovine Lanosterol 14.ALPHA.-Demethylase (CYP51) in Gonads

cDNA Cloning, Genomic Structure and Expression Analysis of the Bovine Lanosterol 14.ALPHA.-Demethylase (CYP51) in Gonads

Relationship between Garcinia cambogia-Induced Impairment of Spermatogenesis and Meiosis-Activating Sterol Production in Rat Testis

Disorders of sterol synthesis: Beyond Smith–Lemli–Opitz syndrome

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