Androgens regulate the mammalian homologues of invertebrate sex determination genes tra-2 and fox-1.
Androgens, like other steroid hormones, exert profound effects on cell growth and survival by modulating the expression of target genes. In vertebrates, androgens play a critical role downstream of the testis determination pathway, influencing the expression of sexually dimorphic traits. Among cells of the nervous system, motor neurons respond to trophic effects of androgen stimulation, with a subpopulation of spinal motor neurons exhibiting sexually dimorphic survival. To study the mechanisms of androgen action in these cells, we performed a subtractive screen for genes upregulated by androgen in a motor neuron cell line. We show androgen-inducible expression of two RNA-binding proteins that are the mammalian homologues of invertebrate sex determination genes. Androgens upregulate the expression of tra-2alpha, an enhancer of RNA splicing homologous to Drosophila tra-2, and promote redistribution of the protein from a diffuse to a speckled pattern within the nucleus. Similarly, androgens upregulate the expression of a novel gene homologous to Caenorhabditis elegans fox-1. These data indicate that androgens exert their effects, in part, by modulating the expression and function of genes involved in RNA processing, and identify homologues of invertebrate sex determination genes as androgen-responsive genes in mammals.
Lieberman
A P
AP
Neurogenetics Branch, National Institutes of Health, Bethesda, Maryland 20892, USA. lieberman@ninds.nih.gov
Friedlich
D L
DL
Harmison
G
G
Howell
B W
BW
Jordan
C L
CL
Breedlove
S M
SM
Fischbeck
K H
KH
D000595:Amino Acid Sequence; D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D029742:Caenorhabditis elegans Proteins; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D029721:Drosophila Proteins; D006801:Humans; D008297:Male; D015741:Metribolone / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics*; D012261:Ribonucleoproteins / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D019849:Sex Determination Processes; D045165:Testosterone Congeners / Q000494:pharmacology; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects
D000728:Androgens; D029742:Caenorhabditis elegans Proteins; D017931:DNA Primers; D029721:Drosophila Proteins; C117552:FOX-1 protein, C elegans; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D045165:Testosterone Congeners; C066174:tra2 protein, Drosophila; D015741:Metribolone