Steroid hormone receptors, when unliganded, are retained in the cytoplasm by heat shock proteins. Upon ligand binding, the receptor undergoes which sequence of events to regulate gene transcription?

• A Ligand binding → receptor dimerization → HSP dissociation → nuclear translocation → DNA binding at HRE ✓
• B Ligand binding → cAMP production → PKA activation → receptor phosphorylation → nuclear entry
• C Ligand binding → PLC activation → IP3 release → calcium-calmodulin → gene activation
• D Ligand binding → JAK activation → STAT phosphorylation → nuclear translocation

Explanation

Steroid hormones (glucocorticoids, sex steroids, mineralocorticoids) are lipophilic and diffuse through the plasma membrane to bind intracellular receptors. In the unliganded state, these receptors are kept in the cytoplasm by inhibitory heat shock proteins (especially Hsp90). Ligand binding causes conformational change, Hsp90 dissociation, receptor homodimerization, nuclear translocation, and binding to hormone response elements (HREs) in gene promoters to modulate transcription. This is entirely distinct from the cAMP (option B), IP3/calcium (option C), or JAK-STAT (option D) pathways used by peptide hormones.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.