Hormone Signaling

The steroid hormone cell signaling functions in transcriptional activation and gene expression. The steroid hormone signaling pathway may be activated by steroid hormones, such as estrogen and progesterone, which bind to a steroid binding protein (SBP).

Figure 1. Steroid hormones (e.g., estrogen, androgen, progesterone) travel through the bloodstream from an endocrine gland bound by a steroid binding protein (SBP). The steroid is released from the SBP and is transported across the extracellular membrane and into the cell where is binds a nuclear receptor (e.g., ESR1, AR, PGR). The steroid also binds a heat shock protein (HSP90), a chaperone protein that aids in protein folding. HSP90 dissociates, and the steroid and nuclear receptor cross the nuclear membrane. The steroid and nuclear receptor homodimerize and bind to the hormone response element (HRE) within the promoter of a gene, which activates gene transcription and promotes cell growth and survival. Specific nodes in the pathway that are therapeutically actionable are noted. Click here to open a larger version of this image in a new window.

Downstream Pathways

• Cell cycle control

Diseases in Which Pathway is Aberrantly Activated

• Breast cancer
• Ovarian cancer
• Prostate cancer

Therapies That Target This Pathway

• Conversion enzyme inhibitors
  • Aromatase inhibitors
• HSP90 inhibitors
• Steroid receptor inhibitors
• • Androgen receptor antagonists
  • Estrogen receptor antagonists
  • Selective estrogen receptor modulators (SERMs)
  • Selective estrogen receptor degraders (SERDs)
  • Selective androgen receptor modulators (SARMs)

Genes Involved in the Pathway

• AR
• ESR1
• LRP1B
• PGR
• TSHR

Last Updated: May 24, 2016