Mechanism of steroid (sex) hormone action: How do these hormones activate transcription of specific genes?

Introduction / Context:
Steroid (sex) hormones are lipid-soluble ligands that enter cells and modulate gene expression. Their primary mode of action is via ligand-activated transcription factors known as nuclear hormone receptors.

Given Data / Assumptions:

• Hormone molecules diffuse across membranes.
• Intracellular receptors (e.g., estrogen receptor, androgen receptor) bind hormone.
• Ligand binding converts receptors into active transcription factors.

Concept / Approach:
Hormones do not bind DNA or RNA polymerase directly. Instead, they bind their receptors, causing conformational changes, receptor dimerization, co-activator recruitment, and binding to specific DNA response elements (enhancers) to regulate transcription.

Step-by-Step Solution:
Identify the direct binding partner of the hormone: the receptor (a TF).Activated receptor binds DNA at hormone response elements.Transcription is modulated through co-activators and the basal transcriptional machinery.

Verification / Alternative check:
ChIP assays show receptor occupancy at response elements only in the presence of ligand; polymerase recruitment increases subsequently.

Why Other Options Are Wrong:

• RNA polymerase binding: No direct hormone–polymerase interaction.
• Direct DNA binding by hormone: The receptor, not the small-molecule hormone, binds DNA.
• Promoter-only binding: Receptors often target enhancer elements as well.
• Histone phosphorylation without receptor: Not the canonical mechanism.

Common Pitfalls:
Confusing ligand (hormone) with its receptor; the receptor is the DNA-binding TF.

Final Answer:
By binding to a transcription factor (nuclear hormone receptor), activating it.