Testosterone mediates expression of the selenoprotein PHGPx by induction of spermatogenesis and not by direct transcriptional gene activation.
Selenium deficiency is known to be associated with male infertility, and the selenoprotein PHGPx has been shown to increase in rat testis after puberty and to depend on gonadotropin stimulation in hypophysectomized rats [Roveri et al. (1992) J. Biol. Chem. 267, 6142 6146]. Exposure of decapsulated whole testis, however, failed to reveal any transcriptional activation or inhibition of the PHGPx gene by testosterone, human chorionic gonadotropin, or forskolin. Nevertheless, it was verified that the specific activity of PHGPx in testis, but not of cGPx, correlated with sexual maturation. Leydig cell destruction in vivo by ethane dimethane sulfonate (EDS) resulted in a delayed decrease in PHGPx activity and mRNA that could be completely prevented by testosterone substitution. cGPx transiently increased upon EDS treatment, probably as a result of reactive macrophage augmentation. In situ mRNA hybridization studies demonstrated an uncharacteristic low level of cGPx transcription in testis, whereas PHGPx mRNA was abundantly and preferentially expressed in round spermatids. The data show that the age or gonadotropin-dependent expression of PHGPx in testis does not result from direct transcriptional gene activation by testosterone, but is due to differentiation stage-specific expression in late spermatids, which are under the control of Leydig cell-derived testosterone. The striking burst of PHGPx expression at the transition of round to elongated spermatids suggests an involvement of this selenoprotein in sperm maturation.
Dipartimento di Chimica Biologica, I-35121 Padova, Italy. mmaior@civ.bio.unipd.it
M
M
Maiorino
J B
JB
Wissing
R
R
Brigelius-Flohé
F
F
Calabrese
A
A
Roveri
P
P
Steinert
F
F
Ursini
L
L
Flohé
D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000096:biosynthesis* / Q000235:genetics; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D007985:Leydig Cells / Q000201:enzymology; D008297:Male; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D012643:Selenium / Q000008:administration & dosage; D051140:Selenoproteins; D012741:Sexual Maturation / Q000235:genetics; D013087:Spermatids / Q000201:enzymology; D013091:Spermatogenesis / Q000187:drug effects / Q000235:genetics*; D013737:Testis / Q000166:cytology / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development; D013739:Testosterone / Q000494:pharmacology / Q000502:physiology*; D014158:Transcription, Genetic
D006063:Chorionic Gonadotropin; D007527:Isoenzymes; D011506:Proteins; D051140:Selenoproteins; D005576:Colforsin; D013739:Testosterone; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D005979:Glutathione Peroxidase; D012643:Selenium