Guanidinoacetate methyltransferase in the mouse: extensive expression in Sertoli cells of testis and in microvilli of caput epididymis.
Guanidinoacetate methyltransferase (GAMT) catalyzes the last step of the biosynthetic pathway to creatine (Cr), the transfer of a methyl group from S-adenosylmethionine to guanidinoactate. Despite the importance of this methylation reaction in cellular energy metabolism and in methyl group metabolism, a systematic study of the expression and cellular localization of this enzyme is lacking. As a means for determining why the testis and seminal vesicles contain high levels of Cr, we analyzed GAMT protein and mRNA levels in mouse tissues by Western and Northern blot analyses. The results show that GAMT was regulated at tissue-specific levels; the enzyme was most highly expressed in testis, caput epididymis, ovary, and liver. Differences were also noted between sexes; the levels of GAMT mRNA and protein were higher in female liver than in male liver. Furthermore, as the male mouse developed from neonatal stages through sexual maturity, the GAMT protein level increased in testis but decreased in liver. Immunohistochemical labeling showed that GAMT was localized primarily in Sertoli cells of the testis and in microvilli of the epithelial cells lining the caput epididymis. GAMT expression in Sertoli cells was confirmed by biochemical and molecular analyses of purified testicular cells, testes from prepubertal mice of different ages, and germ cell-deficient mutant mouse testes. These results indicate that Cr is synthesized extensively in the epithelia of seminiferous tubules and caput epididymis, suggesting that GAMT or metabolic pathways related to Cr biosynthesis may be important for germ cell development or function.
Lee
H
H
Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia 19104-6080.
Ogawa
H
H
Fujioka
M
M
Gerton
G L
GL
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D003401:Creatine / Q000378:metabolism; D004822:Epididymis / Q000201:enzymology*; D005260:Female; D005455:Fluorescent Antibody Technique; D005854:Germ Cells; D050937:Guanidinoacetate N-Methyltransferase; D007150:Immunohistochemistry; D008099:Liver / Q000201:enzymology; D008297:Male; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D008871:Microvilli / Q000201:enzymology*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D012708:Sertoli Cells / Q000201:enzymology*; D012741:Sexual Maturation; D013737:Testis / Q000201:enzymology*; D014018:Tissue Distribution
D012333:RNA, Messenger; D008780:Methyltransferases; C494507:Gamt protein, mouse; D050937:Guanidinoacetate N-Methyltransferase; D003401:Creatine