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

被引：332

作者：

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 ^{[1
]}

机构：

[1] Univ Arkansas Med Sci, Dept Internal Med, Div Endocrinol & Metab, Little Rock, AR 72205 USA

[2] Univ Arkansas Med Sci, Ctr Osteoporosis & Metab Bone Dis, Little Rock, AR 72205 USA

[3] Univ Arkansas Med Sci, Dept Surg, Little Rock, AR 72205 USA

[4] Univ Arkansas Med Sci, Dept Pathol, Little Rock, AR 72205 USA

[5] Univ Arkansas Med Sci, Div Biometry, Little Rock, AR 72205 USA

[6] Cent Arkansas Vet Hlth Care Syst, Little Rock, AR 72205 USA

来源：

SCIENCE | 2002年 / 298卷 / 5594期

关键词：

D O I：

10.1126/science.1074935

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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-3alpha, 17beta-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.

引用

页码：843 / 846

页数：5

共 21 条

[11] Birth and death of bone cells: Basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis [J].