Androgen Receptors in Bone-Forming TissueNoble B.a · Routledge J.b · Stevens H.a · Hughes I.b · Jacobson W.b
aUniversity of Cambridge School of Clinical Medicine (Bone Research Group), Level 4, and bUniversity Department of Paediatrics, Level 8, Addenbrooke’s Hospital, Cambridge, UK
Do you have an account?
- Rent for 48h to view
- Buy Cloud Access for unlimited viewing via different devices
- Synchronizing in the ReadCube Cloud
- Printing and saving restrictions apply
Rental: USD 8.50
Cloud: USD 20.00
Androgen receptors (AR) were stained in sections of normal human growth plate of the costo sternal junction obtained at postmortem from one 4-day-old and two 5-day-old male infants, and in osteoblasts, grown in culture obtained from the femora of 3 male patients undergoing orthopaedic surgery for osteoarthritis. In the growth plate AR were found mostly in a narrow band of chondrocytes occupying an area about midway between the proximal and distal end of the epiphysis. Nearly all AR were in the cytoplasm and appeared in a granular form; there was no diffuse staining and the nuclei were either completely devoid of AR or only contained a few. Less-differentiated chondroblasts, perichondrial cells and hypertrophic chondrocytes contained few or no AR. Osteoblasts (and osteocytes) contained numerous AR and almost all were in the cytoplasm. Normal human osteoblasts, in their second or third passage, were grown on coverslips either in a medium with no added androgen or in the presence of 5α-dihydrotestosterone or methyltrienolone for a period of 24 h or longer. In control cultures, with vehicle and no added androgen, nearly all AR were found in the cytoplasm, with hardly any in the nucleus. In the presence of added androgen some osteoblasts from two of the specimens demonstrated a clear translocation of AR into the nucleus, whilst osteoblasts from a third specimen failed to translocate. These preliminary results indicate that AR translocation to the nucleus occurs in osteoblastic cells derived from osteoarthritic subjects. However, the ability to translocate may depend on the state of differentiation of the osteoblast and on culture conditions.
Orwoll ES: Androgens; in Bilezikian JP, Raisz LG, Rodan GA (eds): Principles of Bone Biology. Boston, Academic Press, 1996, pp 563–580.
- Colvard DS, Eriksen EF, Keeting PE, Wilson EM, Lubahn DB, French FS, Riggs BL, Spelsberg TC: Identification of androgen receptors in normal human osteoblast-like cells. Proc Natl Acad Sci USA 1989;86:854–857.
- Orwoll ES, Stribrska L, Ramsey EE, Keenan EJ: Androgen receptors in osteoblast-like cell lines. Calcif Tissue Int 1991;49:183–187.
- Kasperk CH, Wergedal JE, Farley JR, Linkhart TA, Turner RT, Baylink DJ: Androgens directly stimulate proliferation of bone cells in vitro. Endocrinology 1989;124:1576–1578.
- Kasperk CH, Wakely GK, Hierl T, Ziegler R: Gonadal and adrenal androgens are potent regulators of human bone cell metabolism in vitro. J Bone Miner Res 1997;12:464–471.
- Wiren KM, Zhang X, Chang C, Keenan E, Orwoll ES: Transcriptional up-regulation of the human androgen receptor by androgen in bone cells. Endocrinology 1997;138:2291–2300.
- Benz DJ, Haussler MR, Thomas MA, Speelman B, Komm BS: High affinity androgen binding and androgenic regulation of alpha 1(1)-procollagen and transforming growth factor-beta steady state messenger ribonucleic acid levels in human osteoblast-like sarcoma cells. Endocrinology 1991;128:2723–2730.
- Czerwiec FS, Liaw JJ, Liu S-B, Perez-Stable C, Grumbles R, Howard GA, Roos BA, Burnstein KL: Absence of androgen-mediated transcriptional effects in osteoblastic cells despite presence of androgen receptors. Bone 1997;21:49–56.
- Abu EO, Horner V, Kusec JT, Compston JE: The localisation of androgen receptors in human bone. J Clin Endocrinol Metabol 1997;82:3493–3497.
- Jacobson W, Routledge J, Davies H, Saich T, Hughes I, Brinkmann A, Brown B, Clarkson P: Localisation of androgen receptors in dermal fibroblasts, grown in vitro, from normal subjects and from patients with androgen insensitivity syndrome. Horm Res 1995;44:75–84.
- Beresford JN, Gallagher JA, Poser JW, Russell RG: Production of osteocalcin by human bone cells in vitro: Effects of 1,25 (OH)2 D3, 24, 25 (OH)2 D3, parathyroid hormone and glucocorticoids. Metab Bone Dis Relat Res 1984;5:229–234.
- Griffin JE, Punyashthiti K, Wilson JD: Dihydrotestosterone binding by cultured human fibroblasts. J Clin Invest 1976;57:1342–1351.
- Collier ME, Griffin JE, Wilson JD: Intranuclear binding of [3H]dihydrotestosterone by cultured human fibroblasts. Endocrinology 1978;103:1499–1505.
- Kaufman M, Pinsky L, Kubski A, Straisfield C, Dobrenis K, Shiroky J, Chan T, Macgibbon B: Some properties of the specific androgen-binding activities in cultured human genital skin fibroblasts. J Clin Endocrinol Metabol 1978;47:738–745.
- Gyorkin S, Warne GL, Khalid BAK, Funder JW: Defective nuclear accumulation of androgen receptors in disorders of sexual differentiation. J Clin Invest 1983;72:819–825.
- Hughes IA, Evans BAJ, Ismail R, Matthews J: Complete androgen insensitivity syndrome characterised by increased concentration of a normal androgen receptor in genital skin fibroblasts. J Clin Endocrinol Metabol 1986;63:309–315.
- Georget V, Lobaccaro JM, Terouanne B, Mangeat P, Nicolas J-C, Sultan C: Trafficking of the androgen receptor in living cells with fused green fluorescent protein-androgen receptor. Mol Cell Endocrinol 1997;129:17–26.
Article / Publication Details
Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.