Endocrine pharmacology: molecular and cellular mechanisms of hormone action MCQs With Answer

Introduction:
This MCQ set focuses on molecular and cellular mechanisms of hormone action, tailored for M.Pharm students studying Advanced Pharmacology-II. It covers receptor classes (GPCRs, RTKs, nuclear receptors), second messenger systems (cAMP, IP3/DAG, Ca2+), intracellular signaling cascades (JAK–STAT, PI3K–Akt, MAPK), receptor regulation (desensitization, internalization, ubiquitination), transcriptional control (coactivators/corepressors, chromatin modification), and pharmacological concepts such as biased agonism, receptor reserve, and competitive antagonism. Questions emphasize mechanistic understanding and clinical relevance to pharmacotherapy and drug development, helping students integrate molecular detail with therapeutic strategy and experimental interpretation.

Q1. Which class of hormone receptor acts primarily by direct regulation of gene transcription through binding to DNA hormone response elements?

• G protein–coupled receptor
• Receptor tyrosine kinase
• Nuclear (intracellular) receptor
• Ligand-gated ion channel

Correct Answer: Nuclear (intracellular) receptor

Q2. Activation of the vasopressin V2 receptor in renal collecting duct cells increases water reabsorption mainly through which second messenger?

• Inositol 1,4,5‑trisphosphate (IP3)
• Diacylglycerol (DAG)
• cAMP
• Intracellular calcium release via ryanodine receptors

Correct Answer: cAMP

Q3. Which receptor family signals predominantly via associated Janus kinases (JAKs) and activates STAT transcription factors?

• Receptor tyrosine kinases (RTKs)
• G protein–coupled receptors (GPCRs)
• Ligand-gated ion channels
• Cytokine receptor family (Type I/II, e.g., growth hormone, erythropoietin receptors)

Correct Answer: Cytokine receptor family (Type I/II, e.g., growth hormone, erythropoietin receptors)

Q4. Heat shock protein 90 (HSP90) associated with steroid hormone receptors in the cytoplasm primarily functions to:

• Promote immediate DNA binding before ligand binding
• Maintain the receptor in an inactive, ligand‑ready conformation and assist folding
• Target the receptor for proteasomal degradation
• Direct the receptor to the plasma membrane for rapid signaling

Correct Answer: Maintain the receptor in an inactive, ligand‑ready conformation and assist folding

Q5. Which nuclear coactivator has intrinsic histone acetyltransferase (HAT) activity and is commonly recruited by activated nuclear hormone receptors to enhance transcription?

• HDAC1
• p300/CBP
• GRK2
• β‑arrestin

Correct Answer: p300/CBP

Q6. “Biased agonism” at a GPCR refers to a ligand’s ability to:

• Bind irreversibly to the orthosteric site
• Preferentially stabilize receptor conformations that activate specific downstream pathways (e.g., G protein vs β‑arrestin)
• Increase receptor expression on the cell surface
• Completely block all receptor signaling equally

Correct Answer: Preferentially stabilize receptor conformations that activate specific downstream pathways (e.g., G protein vs β‑arrestin)

Q7. Agonist‑induced desensitization of many GPCRs is initiated by which sequence of events?

• Ubiquitination → proteasomal degradation → decreased receptor synthesis
• GRK phosphorylation of receptor → β‑arrestin binding → receptor internalization
• Receptor dimerization → increased G protein coupling → prolonged signaling
• Phosphatase recruitment → dephosphorylation → enhanced signaling

Correct Answer: GRK phosphorylation of receptor → β‑arrestin binding → receptor internalization

Q8. The genomic (classical) mechanism of steroid hormone action typically requires which of the following steps?

• Immediate opening of ligand‑gated ion channels
• Dimerization of ligand‑bound receptor and binding to specific hormone response elements (HREs) on DNA
• Activation of membrane tyrosine kinases within seconds
• Direct phosphorylation of cytosolic enzymes without nuclear entry

Correct Answer: Dimerization of ligand‑bound receptor and binding to specific hormone response elements (HREs) on DNA

Q9. Which cellular process most directly targets activated membrane receptors for degradation and thereby decreases receptor number (downregulation)?

• Glycosylation in the Golgi apparatus
• Ubiquitination followed by lysosomal or proteasomal degradation
• Palmitoylation enhancing membrane anchoring
• Increased transcription of receptor mRNA

Correct Answer: Ubiquitination followed by lysosomal or proteasomal degradation

Q10. A reversible competitive antagonist at a receptor will, under classical pharmacological assumptions, cause which effect on the agonist dose–response curve?

• Leftward shift and increased maximal response
• Rightward shift without change in maximal response (surmountable antagonism)
• Nonparallel downward shift that reduces Emax irreversibly
• Complete blockade regardless of agonist concentration

Correct Answer: Rightward shift without change in maximal response (surmountable antagonism)

Q11. Phospholipase C activation by many peptide hormones generates IP3 and DAG; which of these primarily activates protein kinase C (PKC)?

• Inositol 1,4,5‑trisphosphate (IP3)
• Diacylglycerol (DAG)
• cGMP
• Adenylyl cyclase

Correct Answer: Diacylglycerol (DAG)

Q12. Thyroid hormone receptors regulate gene transcription most commonly by forming heterodimers with which partner nuclear receptor?

• Glucocorticoid receptor (GR)
• Retinoid X receptor (RXR)
• Peroxisome proliferator‑activated receptor α (PPARα)
• Vitamin D receptor (VDR)

Correct Answer: Retinoid X receptor (RXR)

Q13. A positive allosteric modulator of a GPCR differs from an orthosteric agonist because it:

• Binds to the same site as the endogenous ligand and activates the receptor directly
• Binds to a distinct site and enhances the response to the endogenous ligand
• Irreversibly blocks receptor internalization
• Causes receptor ubiquitination and degradation

Correct Answer: Binds to a distinct site and enhances the response to the endogenous ligand

Q14. Dimerization of STAT transcription factors requires which post‑translational modification after JAK activation?

• Serine methylation
• Tryptophan glycosylation
• Tyr‑phosphorylation and SH2 domain–mediated reciprocal binding
• Proteolytic cleavage at the N‑terminus

Correct Answer: Tyr‑phosphorylation and SH2 domain–mediated reciprocal binding

Q15. In receptor–ligand binding kinetics, a lower equilibrium dissociation constant (Kd) indicates:

• Lower affinity of the ligand for the receptor
• Higher affinity of the ligand for the receptor
• Faster receptor internalization rate
• Higher concentration of receptor required for effect

Correct Answer: Higher affinity of the ligand for the receptor

Q16. The concept of ‘receptor reserve’ (spare receptors) explains which pharmacological observation?

• Maximal tissue response can be achieved when only a fraction of receptors are occupied by agonist
• Agonists always require full receptor occupancy to elicit maximal effect
• Competitive antagonists reduce the number of receptors available irreversibly
• Receptor reserve prevents any desensitization from occurring

Correct Answer: Maximal tissue response can be achieved when only a fraction of receptors are occupied by agonist

Q17. Rapid, non‑genomic effects of steroid hormones are typically mediated by:

• Nuclear receptor homodimers binding to HREs over hours
• Membrane‑associated steroid receptors or signaling via G proteins and kinases producing effects within seconds to minutes
• Transcriptional coactivator recruitment only
• Inhibition of mitochondrial electron transport chain exclusively

Correct Answer: Membrane‑associated steroid receptors or signaling via G proteins and kinases producing effects within seconds to minutes

Q18. Insulin receptor activation leads to metabolic actions primarily through which downstream signaling branch?

• JAK–STAT pathway
• PI3K–Akt pathway via IRS proteins
• cAMP–PKA pathway
• Notch signaling cascade

Correct Answer: PI3K–Akt pathway via IRS proteins

Q19. Nuclear receptor corepressors such as NCoR and SMRT repress transcription by recruiting which enzymatic activity?

• Histone acetyltransferase (HAT)
• Histone deacetylase (HDAC)
• DNA methyltransferase exclusively
• RNA polymerase II activating kinase

Correct Answer: Histone deacetylase (HDAC)

Q20. Which component of the ubiquitination cascade confers substrate specificity, often determining which receptor proteins are targeted for ubiquitin tagging?

• E1 ubiquitin‑activating enzyme
• E2 ubiquitin‑conjugating enzyme
• E3 ubiquitin ligase
• Proteasome 19S regulatory particle

Correct Answer: E3 ubiquitin ligase

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