Reversal of bone loss in mice by nongenotropic signaling of sex steroids

S. Kousteni, J. R. Chen, Teresita Bellido, L. Han, A. A. Ali, C. A. O'Brien, Lilian Plotkin, Q. Fu, A. T. Mancino, Y. Wen, A. M. Vertino, C. C. Powers, S. A. Stewart, R. Ebert, A. M. Parfitt, R. S. Weinstein, R. L. Jilka, S. C. Manolagas

Research output: Contribution to journalArticle

349 Citations (Scopus)

Abstract

We show that sex steroids protect the adult murine skeleton through a mechanism that is distinct from that used to preserve the mass and function of reproductive organs. The classical genotropic actions of sex steroid receptors are dispensable for their bone protective effects, but essential for their effects on reproductive tissues. A synthetic ligand (4-estren-3α,17β-diol) that reproduces the nongenotropic effects of sex steroids, without affecting classical transcription, increases bone mass and strength in ovariectomized females above the level of the estrogen-replete state and is at least as effective as dihydrotestosterone in orchidectomized males, without affecting reproductive organs. Such ligands merit investigation as potential therapeutic alternatives to hormone replacement for osteoporosis of bone mass in both women and men.

Original languageEnglish (US)
Pages (from-to)843-846
Number of pages4
JournalScience
Volume298
Issue number5594
DOIs
StatePublished - Oct 25 2002
Externally publishedYes

Fingerprint

Steroids
Bone and Bones
Ligands
Dihydrotestosterone
Steroid Receptors
Skeleton
Osteoporosis
Estrogens
Hormones
Therapeutics
4-estren-3,17-diol

ASJC Scopus subject areas

  • General

Cite this

Kousteni, S., Chen, J. R., Bellido, T., Han, L., Ali, A. A., O'Brien, C. A., ... Manolagas, S. C. (2002). Reversal of bone loss in mice by nongenotropic signaling of sex steroids. Science, 298(5594), 843-846. https://doi.org/10.1126/science.1074935

Reversal of bone loss in mice by nongenotropic signaling of sex steroids. / Kousteni, S.; Chen, J. R.; Bellido, Teresita; Han, L.; Ali, A. A.; O'Brien, C. A.; Plotkin, Lilian; Fu, Q.; Mancino, A. T.; Wen, Y.; Vertino, A. M.; Powers, C. C.; Stewart, S. A.; Ebert, R.; Parfitt, A. M.; Weinstein, R. S.; Jilka, R. L.; Manolagas, S. C.

In: Science, Vol. 298, No. 5594, 25.10.2002, p. 843-846.

Research output: Contribution to journalArticle

Kousteni, S, Chen, JR, Bellido, T, Han, L, Ali, AA, O'Brien, CA, Plotkin, L, Fu, Q, Mancino, AT, Wen, Y, Vertino, AM, Powers, CC, Stewart, SA, Ebert, R, Parfitt, AM, Weinstein, RS, Jilka, RL & Manolagas, SC 2002, 'Reversal of bone loss in mice by nongenotropic signaling of sex steroids', Science, vol. 298, no. 5594, pp. 843-846. https://doi.org/10.1126/science.1074935
Kousteni S, Chen JR, Bellido T, Han L, Ali AA, O'Brien CA et al. Reversal of bone loss in mice by nongenotropic signaling of sex steroids. Science. 2002 Oct 25;298(5594):843-846. https://doi.org/10.1126/science.1074935
Kousteni, S. ; Chen, J. R. ; Bellido, Teresita ; Han, L. ; Ali, A. A. ; O'Brien, C. A. ; Plotkin, Lilian ; Fu, Q. ; Mancino, A. T. ; Wen, Y. ; Vertino, A. M. ; Powers, C. C. ; Stewart, S. A. ; Ebert, R. ; Parfitt, A. M. ; Weinstein, R. S. ; Jilka, R. L. ; Manolagas, S. C. / Reversal of bone loss in mice by nongenotropic signaling of sex steroids. In: Science. 2002 ; Vol. 298, No. 5594. pp. 843-846.
@article{23bf469179094f4f8b5ddab8a7f0dc0a,
title = "Reversal of bone loss in mice by nongenotropic signaling of sex steroids",
abstract = "We show that sex steroids protect the adult murine skeleton through a mechanism that is distinct from that used to preserve the mass and function of reproductive organs. The classical genotropic actions of sex steroid receptors are dispensable for their bone protective effects, but essential for their effects on reproductive tissues. A synthetic ligand (4-estren-3α,17β-diol) that reproduces the nongenotropic effects of sex steroids, without affecting classical transcription, increases bone mass and strength in ovariectomized females above the level of the estrogen-replete state and is at least as effective as dihydrotestosterone in orchidectomized males, without affecting reproductive organs. Such ligands merit investigation as potential therapeutic alternatives to hormone replacement for osteoporosis of bone mass in both women and men.",
author = "S. Kousteni and Chen, {J. R.} and Teresita Bellido and L. Han and Ali, {A. A.} and O'Brien, {C. A.} and Lilian Plotkin and Q. Fu and Mancino, {A. T.} and Y. Wen and Vertino, {A. M.} and Powers, {C. C.} and Stewart, {S. A.} and R. Ebert and Parfitt, {A. M.} and Weinstein, {R. S.} and Jilka, {R. L.} and Manolagas, {S. C.}",
year = "2002",
month = "10",
day = "25",
doi = "10.1126/science.1074935",
language = "English (US)",
volume = "298",
pages = "843--846",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "5594",

}

TY - JOUR

T1 - Reversal of bone loss in mice by nongenotropic signaling of sex steroids

AU - Kousteni, S.

AU - Chen, J. R.

AU - Bellido, Teresita

AU - Han, L.

AU - Ali, A. A.

AU - O'Brien, C. A.

AU - Plotkin, Lilian

AU - Fu, Q.

AU - Mancino, A. T.

AU - Wen, Y.

AU - Vertino, A. M.

AU - Powers, C. C.

AU - Stewart, S. A.

AU - Ebert, R.

AU - Parfitt, A. M.

AU - Weinstein, R. S.

AU - Jilka, R. L.

AU - Manolagas, S. C.

PY - 2002/10/25

Y1 - 2002/10/25

N2 - We show that sex steroids protect the adult murine skeleton through a mechanism that is distinct from that used to preserve the mass and function of reproductive organs. The classical genotropic actions of sex steroid receptors are dispensable for their bone protective effects, but essential for their effects on reproductive tissues. A synthetic ligand (4-estren-3α,17β-diol) that reproduces the nongenotropic effects of sex steroids, without affecting classical transcription, increases bone mass and strength in ovariectomized females above the level of the estrogen-replete state and is at least as effective as dihydrotestosterone in orchidectomized males, without affecting reproductive organs. Such ligands merit investigation as potential therapeutic alternatives to hormone replacement for osteoporosis of bone mass in both women and men.

AB - We show that sex steroids protect the adult murine skeleton through a mechanism that is distinct from that used to preserve the mass and function of reproductive organs. The classical genotropic actions of sex steroid receptors are dispensable for their bone protective effects, but essential for their effects on reproductive tissues. A synthetic ligand (4-estren-3α,17β-diol) that reproduces the nongenotropic effects of sex steroids, without affecting classical transcription, increases bone mass and strength in ovariectomized females above the level of the estrogen-replete state and is at least as effective as dihydrotestosterone in orchidectomized males, without affecting reproductive organs. Such ligands merit investigation as potential therapeutic alternatives to hormone replacement for osteoporosis of bone mass in both women and men.

UR - http://www.scopus.com/inward/record.url?scp=0037174675&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037174675&partnerID=8YFLogxK

U2 - 10.1126/science.1074935

DO - 10.1126/science.1074935

M3 - Article

C2 - 12399595

AN - SCOPUS:0037174675

VL - 298

SP - 843

EP - 846

JO - Science

JF - Science

SN - 0036-8075

IS - 5594

ER -