Signal Transduction Mechanisms — MCQs

10 questions

Which of the following statements best describes the mechanism of action of insulin on target cells?

All the following hormones have receptors on the plasma membrane of target tissues except:

A primigravida at 38 weeks of gestation has gone into labor. Oxytocin was started to augment labor. The second messenger system through which oxytocin acts is:

Absolute refractoriness of a neuron is due to?

Which of these is true about the highlighted transporter?

Which of these hormones activate catalytic receptors?

All the following mediate their action using cAMP as second messenger except:

Which of the following is correct about the feedback hormone marked as $X$ ?

Serum prolactin levels are highest

Q10

Thyroid hormone binds to which receptor ?

Signal Transduction Mechanisms Indian Medical PG Practice Questions and MCQs

Question 1: Which of the following statements best describes the mechanism of action of insulin on target cells?

A. Insulin binds to a receptor on the outer surface of the plasma membrane, activating adenylate cyclase through the Gs protein.
B. Insulin binds to a cytoplasmic receptor and is transferred as a hormone receptor complex to the nucleus to modulate gene expression.
C. Insulin enters the cell and causes the release of calcium ions from intracellular stores.
D. Insulin binds to a transmembrane receptor on the outer surface of the plasma membrane, activating the tyrosine kinase in the cytosolic domain of the receptor. (Correct Answer)

Explanation: ***Insulin binds to a transmembrane receptor on the outer surface of the plasma membrane, activating the tyrosine kinase in the cytosolic domain of the receptor.*** - **Insulin** is a **peptide hormone** and cannot freely pass through the lipid bilayer, thus it binds to a **transmembrane receptor** on the cell surface. - This binding leads to the activation of the receptor's intrinsic **tyrosine kinase activity** in the intracellular domain, initiating a signaling cascade. *Insulin binds to a cytoplasmic receptor and is transferred as a hormone receptor complex to the nucleus to modulate gene expression.* - This mechanism describes the action of **steroid hormones**, which are lipid-soluble and can cross the cell membrane, binding to **intracellular receptors**. - **Insulin** acts via a **cell surface receptor** and its downstream effects are mediated through signal transduction pathways, not direct nuclear translocation. *Insulin binds to a receptor on the outer surface of the plasma membrane, activating adenylate cyclase through the Gs protein.* - This mechanism is characteristic of **G-protein coupled receptors (GPCRs)**, which activate or inhibit enzymes like adenylate cyclase via G-proteins to produce second messengers like cyclic AMP. - The **insulin receptor** is a **receptor tyrosine kinase**, not a GPCR, and does not directly activate adenylate cyclase via Gs protein. *Insulin enters the cell and causes the release of calcium ions from intracellular stores.* - While some hormones and neurotransmitters can trigger the release of intracellular **calcium ions**, this is typically mediated by specific pathways (e.g., GPCRs linked to phospholipase C). - **Insulin** does not directly enter target cells to cause calcium release; its actions are primarily mediated through receptor tyrosine kinase signaling pathways.

Question 2: All the following hormones have receptors on the plasma membrane of target tissues except:

A. Epinephrine
B. Glucagon
C. Estradiol (Correct Answer)
D. Thyrotropin

Explanation: ***Estradiol*** - **Estradiol** is a **steroid hormone** derived from cholesterol, making it **lipid-soluble**. - Due to its lipid solubility, estradiol can readily pass through the **plasma membrane** and bind to **intracellular receptors** in the cytoplasm or nucleus. *Epinephrine* - **Epinephrine** is a **catecholamine hormone** and is **water-soluble**. - Water-soluble hormones cannot cross the lipid bilayer of the plasma membrane and thus bind to **receptors located on the cell surface**. *Glucagon* - **Glucagon** is a **peptide hormone** and is **water-soluble**. - Like other peptide hormones, it binds to **specific receptors embedded in the plasma membrane** to elicit its cellular effects via second messenger systems. *Thyrotropin* - **Thyrotropin**, also known as **Thyroid-Stimulating Hormone (TSH)**, is a **glycoprotein hormone** and is **water-soluble**. - TSH exerts its action by binding to **receptors on the plasma membrane** of thyroid follicular cells.

Question 3: A primigravida at 38 weeks of gestation has gone into labor. Oxytocin was started to augment labor. The second messenger system through which oxytocin acts is:

A. Tyrosine kinase
B. Phospholipase C (IP3/DAG pathway) (Correct Answer)
C. cGMP
D. cAMP

Explanation: ***Phospholipase C (IP3/DAG pathway)*** - Oxytocin binds to its receptor, which is a **Gq protein-coupled receptor**. This activates **phospholipase C**. - **Phospholipase C** then hydrolyzes **phosphatidylinositol 4,5-bisphosphate (PIP2)** into **inositol triphosphate (IP3)** and **diacylglycerol (DAG)**, which act as second messengers to increase intracellular calcium and mediate myometrial contraction. *Tyrosine kinase* - **Tyrosine kinase receptors** are typically activated by growth factors (e.g., insulin, epidermal growth factor) and lead to phosphorylation cascades. - This mechanism is not primarily associated with the downstream signaling of **oxytocin receptors**. *cGMP* - **Cyclic guanosine monophosphate (cGMP)** is a second messenger primarily involved in signaling pathways initiated by **nitric oxide** and some peptide hormones. - It often acts to cause smooth muscle relaxation, which is contrary to oxytocin's role in uterine contraction. *cAMP* - **Cyclic adenosine monophosphate (cAMP)** is a common second messenger for many hormones that bind to **Gs protein-coupled receptors**. - Hormones such as **epinephrine (beta-adrenergic receptors)** and **glucagon** utilize cAMP, typically leading to different cellular responses than those of oxytocin.

Question 4: Absolute refractoriness of a neuron is due to?

A. Hyperpolarization of Cl channels
B. Opening of rectifier K+ channels
C. Closure of activated Na channels
D. Inactivation of Na channels (Correct Answer)

Explanation: ***Inactivation of Na channels*** - During the **absolute refractory period**, voltage-gated **Na+ channels** enter an inactivated state, making them unresponsive to further stimulation. - This inactivation prevents another action potential from being generated, regardless of the stimulus intensity, ensuring unidirectional propagation. *Hyperpolarization of Cl channels* - While **Cl- channels** can cause hyperpolarization, this typically leads to **inhibition** rather than absolute refractoriness. - Their activity doesn't directly prevent the generation of a new action potential by blocking Na+ channel function. *Opening of rectifier K+ channels* - The opening of **rectifier K+ channels** is involved in **repolarization** and the **relative refractory period**, by increasing K+ efflux. - While it contributes to making the neuron less excitable, it doesn't cause the absolute inability to fire associated with Na+ channel inactivation. *Closure of activated Na channels* - The **closure of activated Na+ channels** occurs as part of the repolarization process, but the critical mechanism for absolute refractoriness is their transition into an **inactivated state**, not simply closure. - **Inactivation** locks the channels in a non-responsive configuration, whereas simple closure would allow them to reopen quickly with sufficient depolarization.

Question 5: Which of these is true about the highlighted transporter?

A. Both molecules go in
B. One molecule goes in, other molecule goes out (Correct Answer)
C. Both molecules go out
D. One molecule goes in and two exit

Explanation: ***One molecule goes in, other molecule goes out*** - The highlighted transporter is the **Na+/K+ ATPase**, which actively pumps 3 **Na+ ions out** of the cell and 2 **K+ ions into** the cell, maintaining an electrochemical gradient. - This counter-transport (one molecule type going in and another going out) is characteristic of an **antiporter** pump. *Both molecules go in* - This option would describe a **symporter** mechanism where two different molecules move in the **same direction** across the membrane. - The Na+/K+ ATPase explicitly shows Na+ moving out and K+ moving in, which contradicts simultaneous inward movement. *Both molecules go out* - This would mean two molecules are expelled from the cell. The Na+/K+ ATPase, however, has K+ entering the cell. - While Na+ is pumped out by this transporter, K+ is actively transported inward. *One molecule goes in and two exit* - The Na+/K+ ATPase transports three Na+ ions out of the cell and two K+ ions into the cell, which is a 3:2 ratio and not one in and two out. - This option incorrectly describes the stoichiometry and directionality of ions for the Na+/K+ ATPase.

Question 6: Which of these hormones activate catalytic receptors?

A. All of these
B. Leptin
C. GH
D. IGF1 (Correct Answer)

Explanation: ***Correct: IGF1*** - **IGF-1** binds to the **IGF-1 receptor (IGF-1R)**, which is a **receptor tyrosine kinase (RTK)** with **intrinsic catalytic activity** [1]. - Upon IGF-1 binding, the receptor undergoes **autophosphorylation** and directly phosphorylates intracellular substrates through its own tyrosine kinase domain [2]. - This qualifies as a **true catalytic receptor** because the enzymatic activity is intrinsic to the receptor itself [3]. *Incorrect: Leptin* - Leptin binds to the **leptin receptor (Ob-R)**, which is a member of the **cytokine receptor family**. - This receptor **lacks intrinsic enzymatic activity** and instead signals through **associated Janus kinases (JAKs)** via the JAK-STAT pathway. - Since the catalytic activity comes from associated proteins (JAKs) rather than the receptor itself, this is **not classified as a catalytic receptor**. *Incorrect: GH* - **Growth Hormone (GH)** binds to the **GH receptor**, another member of the cytokine receptor superfamily. - Like the leptin receptor, the GH receptor **does not have intrinsic catalytic activity** but relies on associated JAKs for signal transduction via the JAK-STAT pathway. - This is **not a catalytic receptor** because the enzymatic function is provided by associated kinases, not the receptor itself. **Key Distinction:** - **Catalytic receptors** = Receptors with intrinsic enzymatic activity (e.g., receptor tyrosine kinases, receptor serine/threonine kinases) [1], [3] - **Cytokine receptors** = Receptors that recruit associated kinases but lack intrinsic catalytic domains

Question 7: All the following mediate their action using cAMP as second messenger except:

A. Glucagon
B. Dopamine
C. Corticotropin
D. Vasopressin (Correct Answer)

Explanation: ***Vasopressin (ADH)*** - Vasopressin has **dual signaling mechanisms** depending on receptor type: - **V2 receptors** (kidney collecting duct): Use **Gs-protein → cAMP pathway** for water reabsorption via aquaporin-2 insertion - **V1 receptors** (vascular smooth muscle): Use **Gq-protein → IP3/DAG pathway** for vasoconstriction - In the context of this question, vasopressin is considered the exception because it has **significant non-cAMP mediated actions** through V1 receptors, unlike the other hormones listed which **predominantly or exclusively** use cAMP - **Note**: This is a teaching point about receptor subtypes; vasopressin DOES use cAMP at V2 receptors *Glucagon* - **Exclusively uses cAMP pathway** in hepatocytes and adipocytes - Binds to **glucagon receptor** (GPCR) → **Gs-protein** → adenylyl cyclase activation → **increased cAMP** → PKA activation - Promotes glycogenolysis, gluconeogenesis, and lipolysis *Dopamine* - **D1 and D5 receptors** are **Gs-coupled** → **stimulate adenylyl cyclase** → **increase cAMP** - Important for neurotransmission (motor control, reward) and renal vasodilation - D2-family receptors (D2, D3, D4) inhibit cAMP but D1-family predominates in many physiological contexts *Corticotropin (ACTH)* - Binds to **melanocortin-2 receptor (MC2R)** on adrenal cortex - **Gs-protein coupled** → adenylyl cyclase activation → **increased cAMP** → PKA activation - Stimulates steroidogenesis and cortisol secretion - **Exclusively cAMP-dependent mechanism**

Question 8: Which of the following is correct about the feedback hormone marked as $X$ ?

A. Inhibin A
B. Inhibin B (Correct Answer)
C. Progesterone
D. Estrone

Explanation: **Correct: Inhibin B** - The diagram shows a feedback loop where "X" is produced downstream and inhibits the anterior pituitary. This fits the role of **Inhibin B**, which is primarily secreted by the **granulosa cells** of the ovary and **Sertoli cells** of the testis. - **Inhibin B** selectively inhibits the secretion of **FSH** from the anterior pituitary, as indicated by the negative feedback arrow pointing towards the pituitary. - Inhibin B is the key hormone in the follicular phase that provides selective FSH feedback control. *Incorrect: Inhibin A* - **Inhibin A** is predominantly secreted by the **corpus luteum** during the luteal phase of the menstrual cycle and is involved in placental function during pregnancy. - Its levels peak later in the cycle compared to Inhibin B during the follicular phase, and its primary role is not the selective inhibition of FSH shown in this diagram's context for follicular development. *Incorrect: Progesterone* - **Progesterone** is a steroid hormone primarily involved in preparing the uterus for pregnancy and maintaining it during early pregnancy. - While it exerts negative feedback on GnRH and LH/FSH, it is typically secreted by the corpus luteum after ovulation, and the diagram appears to depict a more general inhibitory feedback on FSH. *Incorrect: Estrone* - **Estrone** is one of the three major naturally occurring estrogens but is less potent than estradiol. - While estrogens provide feedback on the hypothalamus and pituitary, the diagram specifically labels "Estrogen" separately, and "X" represents a distinct feedback hormone, making estrone an unlikely specific fit for "X."

Question 9: Serum prolactin levels are highest

A. 24 hrs after parturition
B. REM sleep
C. In actively lactating mothers
D. During third trimester of pregnancy (Correct Answer)

Explanation: ***Correct: During third trimester of pregnancy*** - **Serum prolactin levels reach their absolute highest** during the **third trimester of pregnancy**, rising progressively from normal levels (5-25 ng/mL) to peak values of **200-400 ng/mL** near term. - This represents the **highest physiological prolactin levels** observed in humans. - Despite these high levels, **lactation does not occur** during pregnancy because **estrogen and progesterone** block prolactin's action on mammary tissue. - The high prolactin prepares the breast for lactation but milk secretion is inhibited until delivery. *Incorrect: 24 hrs after parturition* - After delivery, prolactin levels actually begin to **decline** from their pregnancy peak, though they remain elevated (around 200 ng/mL). - While **lactogenesis II** (copious milk production) begins 24-72 hours postpartum, this is due to the **removal of estrogen/progesterone inhibition**, not because prolactin levels peak at this time. - The confusion arises from conflating **functional milk production** with **peak hormone levels**. *Incorrect: REM sleep* - Prolactin exhibits **circadian variation** with nocturnal rise during sleep, peaking in early morning hours. - However, these sleep-related peaks (typically 25-40 ng/mL) are **much lower** than pregnancy levels. - This physiological variation is unrelated to reproductive function. *Incorrect: In actively lactating mothers* - During established lactation, basal prolactin levels gradually decline over weeks to months. - Each **suckling episode** causes transient prolactin surges (2-10 fold increase), but these peaks are still **lower than third trimester levels**. - By 6 months postpartum, basal prolactin may return near pre-pregnancy levels despite continued lactation.

Question 10: Thyroid hormone binds to which receptor ?

A. Membrane
B. Cytoplasmic
C. Nuclear (Correct Answer)
D. None of the options

Explanation: ***Nuclear*** - Thyroid hormones, being **lipid-soluble**, readily diffuse across the **cell membrane** to bind to receptors located in the nucleus. - This binding directly influences **gene expression** and protein synthesis, mediating the hormone's effects. *Membrane* - Membrane receptors typically bind **water-soluble hormones** (e.g., peptide hormones, catecholamines) that cannot freely cross the cell membrane. - These interactions usually trigger a **second messenger cascade** within the cell. *Cytoplasmic* - While some **steroid hormones** bind to cytoplasmic receptors which then translocate to the nucleus, thyroid hormones bind directly to nuclear receptors. - Cytoplasmic receptors are located in the **cytosol** before their ligand-induced translocation. *None of the options* - This option is incorrect, as thyroid hormones have a specific and well-defined receptor location. - The direct action on **gene regulation** necessitates a nuclear receptor.

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