RESUMO
Loss of mechanical loading, or disuse, rapidly precipitates locally mediated bone resorption. However, the pathway by which this process is initiated and mediated is poorly understood. In this study, we used a complementary in vivo and in vitro approach to determine whether disuse-induced osteocyte hypoxia resulted in upregulation of the hypoxia-dependent transcription factor HIF-1alpha. We found that acute disuse (1-5 days) resulted in a significant increase in the percentage of osteocytes staining positive for HIF-1alpha vs. normal bone (30.9 +/- 6.1 vs. 14.1 +/- 3.8%) and that this response was uniform around the cortex. In addition, we found that acute oxygen deprivation (4-12 h of 2% O2) resulted in a 2.1- to 3.7-fold upregulation of HIF-1alpha protein expression in MLO-Y4 osteocyte-like cells compared with cells cultured in parallel under normal oxygen conditions. Given known HIF-1alpha targets genes, we suggest that osteocyte hypoxia and subsequent upregulation of hypoxia-dependent pathways may serve to initiate and mediate disuse-induced bone resorption.
Assuntos
Reabsorção Óssea/patologia , Proteínas de Ligação a DNA/biossíntese , Hipóxia/fisiopatologia , Proteínas Nucleares/biossíntese , Osteócitos/fisiologia , Fatores de Transcrição/biossíntese , Perus/fisiologia , Animais , Atrofia , Western Blotting , Reabsorção Óssea/metabolismo , Células Cultivadas , Hipóxia/metabolismo , Fator 1 Induzível por Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia , Processamento de Imagem Assistida por Computador , Imuno-Histoquímica , Masculino , Microscopia Confocal , Regulação para Cima/fisiologiaRESUMO
This study was undertaken to determine if hormone receptor activity in breast cancers changes during different phases of the menstrual cycle. Estrogen (ER) and progesterone (PgR) receptors in seventy-eight primary breast carcinomas from premenopausal women were compared with the phase of the menstrual cycle at the time of biopsy. The frequency of ER positivity did not change, but PgR positivity became significantly higher after the early follicular phase. An increase in mean ER and PgR concentration was found (p less than .05) in the late luteal phase. The results indicate that tumor ER and PgR values change during the menstrual cycle, probably in response to endogenous hormonal fluctuations, and this may account for some vicissitudes in establishing hormone dependence.