Q.90 A typical receptor senses extracellular stimuli by virtue of its localization on plasma membrane.
The receptor to which of the following ligands is an exception to this rule?
(A) γ-amino butyric acid (B) Acetylcholine
(C) Estrogen (D) Luteinizing hormone
Steroid hormones like estrogen bind intracellular receptors in the cytoplasm or nucleus, not plasma membrane receptors, making it the exception among the options.
Typical receptors for neurotransmitters and peptide hormones localize to the cell surface.
Correct Answer
(C) Estrogen
Option Analysis
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(A) γ-amino butyric acid (GABA): GABA receptors (GABA_A ionotropic, GABA_B metabotropic) are ligand-gated ion channels or G-protein coupled receptors (GPCRs) embedded in the plasma membrane, sensing extracellular GABA to mediate inhibition.
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(B) Acetylcholine: Nicotinic receptors are pentameric ligand-gated ion channels on the plasma membrane; muscarinic are GPCRs also membrane-localized, responding to synaptic acetylcholine release.
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(C) Estrogen: Estrogen receptors (ERα/ERβ) are nuclear receptors primarily intracellular (cytosol/nucleus). Lipophilic estrogen diffuses across the membrane, binds ER, forms dimers, and translocates to DNA for transcription; a minor membrane fraction exists via palmitoylation but isn’t the “typical” sensing mechanism.
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(D) Luteinizing hormone (LH): LH binds G-protein coupled receptors (LHCGR) on the plasma membrane of gonadal cells, activating cAMP signaling for steroidogenesis and gametogenesis.
Receptor Localization Principles
Hydrophilic ligands (GABA, ACh, LH) cannot cross membranes, requiring plasma membrane receptors with extracellular binding domains. Lipophilic steroids (estrogen) freely diffuse, binding intracellular nuclear receptors that function as ligand-activated transcription factors.
Receptor Plasma Membrane Exception Estrogen: Key Mechanism
The receptor plasma membrane exception estrogen highlights steroid hormone signaling. Unlike typical receptors sensing extracellular stimuli at the plasma membrane, estrogen receptors reside intracellularly, enabling gene regulation after diffusion.
Ligand-Receptor Localization Compared
| Ligand | Receptor Type | Localization |
|---|---|---|
| Estrogen | Nuclear (ERα/β) | Cytoplasm/Nucleus – exception |
| GABA | Ionotropic GPCR | Plasma membrane |
| Acetylcholine | nAChR, mAChR | Plasma membrane |
| LH | GPCR (LHCGR) | Plasma membrane |
Receptor plasma membrane exception estrogen underscores GATE Life Sciences cell signaling: hydrophilic ligands need surface receptors; steroids act intracellularly.
GATE Prep Insights
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Nuclear receptors: Steroids, thyroid hormones, retinoids.
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Mechanism: Ligand diffusion → HSP release → dimer-DNA binding.
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Test focus: Estrogen as intracellular exception vs. membrane GPCRs.
