Question

Growth hormone releasing hormone (GHRH) produced by the hypothalamus binds to its pituitary receptor and leads to the production of growth hormone (GH) because of increase in cyclic AMP. Certain pituitary tumors result in hypersecretion of GH because of a mutation that produces a \(G_{s}-\alpha\) protein with a greatly diminished GTPase activity. Low GTPase activity in the mutated protein results in consitutive activation of \(G_{s}\) and adenylate cyclase because A. GTP-bound \(\alpha\) -subunit does not reform the \(\alpha \beta \gamma\) trimer. B. GTP-bound G protein binds more strongly to the membrane receptor. C. GTP reacts directly with adenylate cyclase to activate it. D. the trimeric form of the G protein is stabilized. E. adenylate cyclase is phosphorylated more readily.

Short answer

Answer: A. GTP-bound α-subunit does not reform the αβγ trimer.

Step-by-step solution

Understand the role of G proteins in hormone signaling

G proteins play a crucial role in hormone signaling pathways. When a hormone like GHRH binds to its receptor on the cell membrane, it activates specific G proteins. G proteins usually exist as a trimer made of α, β, and γ subunits. When activated by a ligand-binding event, GDP is released from the α-subunit, and GTP takes its place. This way, the Gα-subunit with GTP attached dissociates from the β and γ subunits.

Understand the role of \(G_{s}\) and adenylate cyclase in the production of GH

The \(G_{s}\) protein is a type of G protein that stimulates the production of cAMP. When activated, the GTP-bound α-subunit of \(G_{s}\) binds to and activates an enzyme called adenylate cyclase. Adenylate cyclase then converts ATP to cyclic AMP (cAMP), which further acts as a secondary messenger to initiate the production of growth hormone (GH).

Understand the effect of low GTPase activity on G proteins

GTPase activity is essential for turning off the signaling pathway. G proteins with low GTPase activity remain in their active, GTP-bound state for a longer time, leading to prolonged activation of adenylate cyclase and increased cAMP production. This results in hypersecretion of GH.

Evaluate the given options to find the correct reason for the hypersecretion of GH

A. GTP-bound α-subunit does not reform the αβγ trimer: This option is incorrect because the dissociation of the trimer is necessary for activating adenylate cyclase. Low GTPase activity means the α-subunit remains GTP-bound and dissociated from β and γ subunits for a longer time. So, the correct answer must show what prolongs this state. B. GTP-bound G protein binds more strongly to the membrane receptor: This is incorrect because the G protein's interaction with the receptor is not altered due to low GTPase activity. The prolonged GTP-bound state of the α-subunit is the primary factor that leads to increased activation of adenylate cyclase. C. GTP reacts directly with adenylate cyclase to activate it: This statement is incorrect because GTP doesn't interact directly with adenylate cyclase. The dissociated GTP-bound α-subunit binds to and activates adenylate cyclase in the signaling pathway. D. The trimeric form of the G protein is stabilized: This statement is incorrect because low GTPase activity would instead lead to a delayed reformation of the trimeric form of the G protein due to the prolonged active state of the α-subunit. E. Adenylate cyclase is phosphorylated more readily: This option is also incorrect since the crucial factor contributing to the increased GH production in this case is the prolonged activation of the α-subunit. The analysis shows that option A is the correct answer, as it highlights the key factor of prolonged GTP-bound α-subunit dissociation from β and γ subunits due to low GTPase activity.