Expression of activator of CREM in the testis (ACT) during normal and impaired spermatogenesis: correlation with CREM expression.
The cAMP-responsive element modulator (CREM) is involved in regulating gene expression in haploid spermatids. Transcriptional activity of the CREM protein is thought to be regulated by activator of CREM in the testis (ACT). Applying RT-PCR and in situ hybridization, cell-specific gene expression of ACT was demonstrated in man, cynomolgus monkey and mouse. During normal spermatogenesis, RT-PCR revealed a strong signal in all three species. We sequenced monkey ACT cDNA and demonstrated that the putative amino acid sequence is highly conserved between these species. In situ hybridization demonstrated ACT mRNA in mid and late pachytene spermatocytes and in round spermatids. Among four infertile men with round spermatid maturation arrest (RSMA), only one patient revealed a strong signal for ACT, while three patients displayed a weak signal for both RT-PCR and in situ hybridization, although germ cells normally expressing ACT were present in these patients. In addition, CREM knockout mice known to be infertile due to RSMA also exhibited only a weak amplification product for ACT cDNA. ACT mRNA was barely detectable in some round spermatids, but was completely absent in pachytene spermatocytes. Database search revealed two and one CRE within the putative human and mouse ACT promoters respectively. Our findings indicate a conserved function of ACT during the evolution of mammalian spermatogenesis and suggest a role for CREM in ACT transcriptional regulation.
Steger
Klaus
K
Institute of Veterinary Anatomy, Histology and Embryology, University of Giessen, Giessen, Germany. Klaus.Steger@vetmed.uni-giessen.de
Behr
Rüdiger
R
Kleiner
Ingrid
I
Weinbauer
Gerhard F
GF
Bergmann
Martin
M
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D051786:Cyclic AMP Response Element Modulator; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D017403:In Situ Hybridization; D007248:Infertility, Male / Q000235:genetics / Q000378:metabolism*; D060588:LIM Domain Proteins; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012670:Seminiferous Epithelium / Q000166:cytology / Q000378:metabolism; D016415:Sequence Alignment; D013091:Spermatogenesis / Q000502:physiology*; D013737:Testis / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics
D004268:DNA-Binding Proteins; C504656:FHL5 protein, human; C504657:Fhl5 protein, mouse; D060588:LIM Domain Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; C117930:activator of CREM in testis (ACT); D051786:Cyclic AMP Response Element Modulator