RESUMO
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.
Assuntos
Androgênios/farmacologia , Proteínas de Caenorhabditis elegans , Proteínas de Drosophila , Proteínas de Ligação a RNA/genética , Ribonucleoproteínas/genética , Processos de Determinação Sexual , Sequência de Aminoácidos , Animais , Sequência de Bases , Linhagem Celular , Primers do DNA/genética , Humanos , Masculino , Metribolona/farmacologia , Camundongos , Dados de Sequência Molecular , Neurônios Motores/efeitos dos fármacos , Neurônios Motores/metabolismo , Processamento Pós-Transcricional do RNA/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Homologia de Sequência de Aminoácidos , Congêneres da Testosterona/farmacologia , Transfecção , Regulação para Cima/efeitos dos fármacosRESUMO
OBJECT: The workforce demand for neurosurgeons was quantified by a review and an analysis of journal recruitment advertisements published over the past 13 years. METHODS: A retrospective analysis of recruitment advertisements from July 1985 through June 1998 was performed by examining issues of the Journal of Neurosurgery and Neurosurgery. Advertisement information that appeared in each journal during the last 3 years was collected from alternating months (July to May); information that appeared prior to that time was collected from alternating recruitment years back to 1985. The authors examined the following workforce parameters: practice venue, subspecialization, and practice size. They found no significant decrease in neurosurgical recruitment advertisements. There was an average of 102.7+/-22.4 (standard deviation) advertised positions per year during the most recent 3 years compared with 92.6+/-17.9 advertised positions per year during the preceding decade. Similarly, there has been no decline in advertised positions either in academic (33+/-6.1/year for the most recent 3 years compared with 32.8+/-5.9/year for 1985-1995) or private practice (69.7+/-21.6/year for the most recent 3 years compared with 59.8+/-13.4/year for 1985-1995). A shift in demand toward subspecialty neurosurgery was observed. During the past 3 years, 31.2+/-5.9% of advertised positions called for subspecialty expertise, compared with 18.5+/-2.8% for the preceding decade (p < 0.05). The largest number of subspecialty advertisements designated positions for spine and pediatric neurosurgeons. Private practice advertisements increasingly sought to add neurosurgeons to group practices. CONCLUSIONS: Contrary to previous reports and a prevailing myth, our data show no decrease in workforce demand for neurosurgeons in the United States over the past 3 years compared with the prior decade. A shift toward subspecialist recruitment, particularly for spine neurosurgeons, has been demonstrated in both academic and private practice venues.