Absence of androgen-mediated transcriptional effects in osteoblastic cells despite presence of androgen receptors
| Autor: | J. J. Liaw, Carlos Perez-Stable, Bernard A. Roos, S. B. Liu, Kerry L. Burnstein, F. S. Czerwiec, Robert M. Grumbles, Guy A. Howard |
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| Rok vydání: | 1997 |
| Předmět: |
Male
Transcriptional Activation medicine.medical_specialty Histology Transcription Genetic Physiology medicine.drug_class Endocrinology Diabetes and Metabolism Blotting Western Bone Neoplasms Biology urologic and male genital diseases Androgen Excess Transfection Binding Competitive Cell Line Radioligand Assay Ribonucleases Genes Reporter Internal medicine Bone cell medicine Animals Humans RNA Messenger Cells Cultured Regulation of gene expression Reporter gene Osteosarcoma Osteoblasts Osteoblast Cell Differentiation DNA Androgen Blotting Northern Cell biology Androgen receptor medicine.anatomical_structure Endocrinology Gene Expression Regulation Parathyroid Hormone Receptors Androgen Dihydrotestosterone Androgens Female medicine.drug |
| Zdroj: | Bone. 21(1) |
| ISSN: | 8756-3282 |
| Popis: | Androgen excess and deficiency affect skeletal maturation and bone cell function. Understanding the molecular basis for these androgen effects could improve therapy/prevention of short stature and osteoporosis. Androgens act through binding to androgen receptors (ARs), which modulate gene transcription via interactions with DNA response elements on target genes. Because osteoblasts contain ARs at levels just below certain androgen-sensitive tissues, we sought to define the function of AR in a number of commonly used osteoblastic cell lines. Presence and quantification of AR protein and mRNA were evaluated by ligand binding assay, western blotting, and RNAse protection assay. AR-containing osteoblastic cell lines were exposed to nonaromatizable androgens and effects on gene expression were assessed. We found no evidence for direct effects of androgen on endogenous genes nor was androgen involved in modulation of parathyroid hormone effects on early gene activation. Androgen-sensitive reporter gene constructs were stimulated by androgen only when AR cDNA expression vectors were introduced into cells by cotransfection. We conclude that, in commonly used osteoblastic cell lines, the presence of AR at the levels described here does not guarantee androgen transcriptional activity. The effects of androgen on bone in vivo may involve direct stimulation of osteoblastic cells in a different setting or stage of differentiation. Alternatively, androgen may act on bone cells other than osteoblasts, or through metabolic conversion to estrogens. |
| Databáze: | OpenAIRE |
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