Nongenotropic, sex-nonspecific signaling through the estrogen or androgen receptors

Dissociation from transcriptional activity

S. Kousteni, Teresita Bellido, Lilian Plotkin, C. A. O'Brien, D. L. Bodenner, L. Han, K. Han, G. B. DiGregorio, J. A. Katzenellenbogen, B. S. Katzenellenbogen, P. K. Roberson, R. S. Weinstein, R. L. Jilka, S. C. Manolagas

Research output: Contribution to journalArticle

960 Citations (Scopus)

Abstract

The relationship of the classical receptors and their transcriptional activity to nongenotropic effects of steroid hormones is unknown. We demonstrate herein a novel paradigm of sex steroid action on osteoblasts, osteocytes, embryonic fibroblasts, and HeLa cells involving activation of a Src/Shc/ERK signaling pathway and attenuating apoptosis. This action is mediated by the ligand binding domain and eliminated by nuclear targeting of the receptor protein; ERα, ERβ, or AR can transmit it with similar efficiency irrespective of whether the ligand is an estrogen or an androgen. This antiapoptotic action can be dissociated from the transcriptional activity of the receptor with synthetic ligands, providing proof of principle for the development of function-specific - as opposed to tissue-selective - and gender-neutral pharmacotherapeutics.

Original languageEnglish (US)
Pages (from-to)719-730
Number of pages12
JournalCell
Volume104
Issue number5
StatePublished - Mar 9 2001
Externally publishedYes

Fingerprint

Androgen Receptors
Estrogen Receptors
Ligands
Steroid hormones
Steroids
Artificial Receptors
Osteocytes
MAP Kinase Signaling System
Osteoblasts
Protein Transport
Fibroblasts
Cytoplasmic and Nuclear Receptors
HeLa Cells
Androgens
Estrogens
Chemical activation
Hormones
Tissue
Apoptosis
Proteins

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Kousteni, S., Bellido, T., Plotkin, L., O'Brien, C. A., Bodenner, D. L., Han, L., ... Manolagas, S. C. (2001). Nongenotropic, sex-nonspecific signaling through the estrogen or androgen receptors: Dissociation from transcriptional activity. Cell, 104(5), 719-730.

Nongenotropic, sex-nonspecific signaling through the estrogen or androgen receptors : Dissociation from transcriptional activity. / Kousteni, S.; Bellido, Teresita; Plotkin, Lilian; O'Brien, C. A.; Bodenner, D. L.; Han, L.; Han, K.; DiGregorio, G. B.; Katzenellenbogen, J. A.; Katzenellenbogen, B. S.; Roberson, P. K.; Weinstein, R. S.; Jilka, R. L.; Manolagas, S. C.

In: Cell, Vol. 104, No. 5, 09.03.2001, p. 719-730.

Research output: Contribution to journalArticle

Kousteni, S, Bellido, T, Plotkin, L, O'Brien, CA, Bodenner, DL, Han, L, Han, K, DiGregorio, GB, Katzenellenbogen, JA, Katzenellenbogen, BS, Roberson, PK, Weinstein, RS, Jilka, RL & Manolagas, SC 2001, 'Nongenotropic, sex-nonspecific signaling through the estrogen or androgen receptors: Dissociation from transcriptional activity', Cell, vol. 104, no. 5, pp. 719-730.
Kousteni, S. ; Bellido, Teresita ; Plotkin, Lilian ; O'Brien, C. A. ; Bodenner, D. L. ; Han, L. ; Han, K. ; DiGregorio, G. B. ; Katzenellenbogen, J. A. ; Katzenellenbogen, B. S. ; Roberson, P. K. ; Weinstein, R. S. ; Jilka, R. L. ; Manolagas, S. C. / Nongenotropic, sex-nonspecific signaling through the estrogen or androgen receptors : Dissociation from transcriptional activity. In: Cell. 2001 ; Vol. 104, No. 5. pp. 719-730.
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