Kinase-mediated transcription, activators of nongenotropic estrogen-like signaling (ANGELS), and osteoporosis: A different perspective on the HRT dilemma

Stavros C. Manolagas, Stavroula Kousteni, Jin Ran Chen, Maria Schuller, Lilian Plotkin, Teresita Bellido

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Studies in bone, as well as other nonreproductive target tissues of sex steroid, like the cardiovascular and the central nervous system (CNS), have elucidated a previously unappreciated mechanism of sex steroid action involving the rapid activation of mitogen-activated protein kinases and/or phosphatidyl inositol 3 kinase, and consequent potent regulatory affects on the transcription of a set of genes that is distinct from that regulated through classic (genotropic) control of transcription. These actions stem from an unexpected function of the classic nuclear receptors outside the nucleus, most probably from receptor interactions within distinct signal transduction pathways in preassembled scaffolds. Importantly, these nongenotropic actions are mediated by the ligand-binding domain of the receptor and can be functionally dissociated from classic transcriptional activation with synthetic ligands, termed activators of nongenotropic estrogen-like signaling (ANGELS). We highlight this evidence and discuss its pharmacotherapeutic implications vis a vis the dilemmas posed by the recently appreciated shortfalls of postmenopausal hormone replacement therapy.

Original languageEnglish (US)
JournalKidney international. Supplement
Volume66
Issue number91
StatePublished - Oct 2004
Externally publishedYes

Fingerprint

Osteoporosis
Estrogens
Phosphotransferases
Steroids
Ligands
Estrogen Replacement Therapy
Cytoplasmic and Nuclear Receptors
Phosphatidylinositols
Mitogen-Activated Protein Kinases
Transcriptional Activation
Signal Transduction
Central Nervous System
Bone and Bones
Genes

Keywords

  • Androgens
  • Apoptosis
  • Bone
  • Estrogens
  • MAP kinases
  • Osteoporosis
  • PI3 kinases
  • Therapy

ASJC Scopus subject areas

  • Nephrology

Cite this

Kinase-mediated transcription, activators of nongenotropic estrogen-like signaling (ANGELS), and osteoporosis : A different perspective on the HRT dilemma. / Manolagas, Stavros C.; Kousteni, Stavroula; Chen, Jin Ran; Schuller, Maria; Plotkin, Lilian; Bellido, Teresita.

In: Kidney international. Supplement, Vol. 66, No. 91, 10.2004.

Research output: Contribution to journalArticle

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