Transcriptional up-regulation of the human androgen receptor by androgen in bone cells

Kristine Wiren, Xiaowei Zhang, Chawnshang Chang, Edward Keenan, Eric Orwoll

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

Androgen regulation of androgen receptor (AR) expression has been observed in a variety of tissues, generally as inhibition, and is thought to attenuate cellular responses to androgen. AR is expressed in osteoblasts, the bone-forming cell, suggesting direct actions of androgens on bone. Here we characterized the effect of androgen exposure on AR gene expression in human osteoblastic SaOS-2 and U-2 OS cells. Treatment of osteoblastic cells with the nonaromatizable androgen 5α-dihydrotestosterone increased AR steady state messenger RNA revels in a time- and dose-dependent fashion. Reporter assays with 2.3 kilobases of the proximal 5'-flanking region of the human AR promoter linked to the chloramphenicol acetyltransferase gene in transfected cultures showed that up-regulation of AR promoter activity by androgen was time and dose dependent. Treatment with other steroid hormones, including progesterone, 17 β-estradiol, and dexamethasone, was without effect. The antiandrogen hydroxyflutamide completely antagonized androgen up-regulation. Thus, in contrast to many other androgen target tissues, androgen exposure increases steady state AR messenger RNA levels in osteoblasts. This regulation occurs at least partially at the level of transcription, is mediated by the 5'-promoter region of the AR gene, and is dependent on functional AR. These results suggest that physiological concentrations of androgens have significant effects on AR expression in skeletal tissue.

Original languageEnglish (US)
Pages (from-to)2291-2300
Number of pages10
JournalEndocrinology
Volume138
Issue number6
DOIs
StatePublished - 1997

Fingerprint

Androgen Receptors
Androgens
Up-Regulation
Bone and Bones
Osteoblasts
human AR protein
Androgen Antagonists
Messenger RNA
Chloramphenicol O-Acetyltransferase
Dihydrotestosterone
5' Flanking Region
Genetic Promoter Regions
Dexamethasone
Genes
Progesterone
Estradiol
Steroids
Hormones
Gene Expression

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Transcriptional up-regulation of the human androgen receptor by androgen in bone cells. / Wiren, Kristine; Zhang, Xiaowei; Chang, Chawnshang; Keenan, Edward; Orwoll, Eric.

In: Endocrinology, Vol. 138, No. 6, 1997, p. 2291-2300.

Research output: Contribution to journalArticle

Wiren, Kristine ; Zhang, Xiaowei ; Chang, Chawnshang ; Keenan, Edward ; Orwoll, Eric. / Transcriptional up-regulation of the human androgen receptor by androgen in bone cells. In: Endocrinology. 1997 ; Vol. 138, No. 6. pp. 2291-2300.
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