High-affinity androgen binding and androgenic regulation of α1(I)-procollagen and transforming growth factor-β steady state messenger ribonucleic acid levels in human osteoblast-like osteosarcoma cells

David J. Benz, Mark R Haussler, Mitchell A. Thomas, Becky Speelman, Barry S. Komm

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Abstract

Clinical observations have demonstrated a positive effect of estrogens and androgens on the maintenance of structural bone integrity. This study examines the direct effects of androgenic hormones on the osteoblast-like human osteosarcoma cell line, HOS TE85. Employing radiolabeled dihydrotestosterone (DHT), 2800 saturable, high-affinity (dissociation constant = 0.66 nM) androgen binding sites were detected per HOS TE85 cell. Androgen binding was specific in that DHT and testosterone (T) displayed significantly greater competition than the progestins, progesterone and medroxyprogesterone. The expression of androgen receptors in HOS TE85 cells was further substantiated by Northern analysis. A human androgen receptor complementary DNA probe revealed a 9.5 kilobase transcript which corresponds to the predominant human androgen receptor transcript detected in human male reproductive tissues. Androgens were also found to elicit biological responses in HOS TE85 cells. Physiological concentrations of DHT and T decreased HOS TE85 cell proliferation as assessed by cell count. This finding suggests that DHT may also play a role in osteoblast differentiation. In support of this hypothesis, treatment with T (24 h, 10 nM) enhanced the abundance of both α1(I)-procollagen messenger RNA (mRNA) (5-fold) and transforming growth factor-β mRNA (2.2 fold). The nonaromatizable androgen DHT (24 h, 10 nM) elicited an increase in the steady state concentration of α1(I)-procollagen mRNA similar to the increase observed with T treatment. Thus, in addition to the recent discovery of estradiol receptors and estrogenic regulation of HOS TE85 cells, it is now evident that these osteoblast-like osteosarcoma cells also express high affinity androgen binding sites and can respond biologically to androgens.

Original languageEnglish (US)
Pages (from-to)2723-2730
Number of pages8
JournalEndocrinology
Volume128
Issue number6
StatePublished - Jun 1991

Fingerprint

Procollagen
Transforming Growth Factors
Osteosarcoma
Osteoblasts
Androgens
Dihydrotestosterone
RNA
Messenger RNA
Medroxyprogesterone
Binding Sites
Estradiol Receptors
DNA Probes
Androgen Receptors
Progestins
Progesterone
Testosterone
Estrogens
Complementary DNA
Cell Count
Maintenance

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

High-affinity androgen binding and androgenic regulation of α1(I)-procollagen and transforming growth factor-β steady state messenger ribonucleic acid levels in human osteoblast-like osteosarcoma cells. / Benz, David J.; Haussler, Mark R; Thomas, Mitchell A.; Speelman, Becky; Komm, Barry S.

In: Endocrinology, Vol. 128, No. 6, 06.1991, p. 2723-2730.

Research output: Contribution to journalArticle

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abstract = "Clinical observations have demonstrated a positive effect of estrogens and androgens on the maintenance of structural bone integrity. This study examines the direct effects of androgenic hormones on the osteoblast-like human osteosarcoma cell line, HOS TE85. Employing radiolabeled dihydrotestosterone (DHT), 2800 saturable, high-affinity (dissociation constant = 0.66 nM) androgen binding sites were detected per HOS TE85 cell. Androgen binding was specific in that DHT and testosterone (T) displayed significantly greater competition than the progestins, progesterone and medroxyprogesterone. The expression of androgen receptors in HOS TE85 cells was further substantiated by Northern analysis. A human androgen receptor complementary DNA probe revealed a 9.5 kilobase transcript which corresponds to the predominant human androgen receptor transcript detected in human male reproductive tissues. Androgens were also found to elicit biological responses in HOS TE85 cells. Physiological concentrations of DHT and T decreased HOS TE85 cell proliferation as assessed by cell count. This finding suggests that DHT may also play a role in osteoblast differentiation. In support of this hypothesis, treatment with T (24 h, 10 nM) enhanced the abundance of both α1(I)-procollagen messenger RNA (mRNA) (5-fold) and transforming growth factor-β mRNA (2.2 fold). The nonaromatizable androgen DHT (24 h, 10 nM) elicited an increase in the steady state concentration of α1(I)-procollagen mRNA similar to the increase observed with T treatment. Thus, in addition to the recent discovery of estradiol receptors and estrogenic regulation of HOS TE85 cells, it is now evident that these osteoblast-like osteosarcoma cells also express high affinity androgen binding sites and can respond biologically to androgens.",
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