Ghrhr
M. musculus
growth hormone releasing hormone receptor
What the model saw
Gene: Ghrhr Organism: Mus musculus Known functions: growth hormone releasing hormone receptor. growth hormone-releasing hormone receptor. G protein-coupled peptide receptor activity. G protein-coupled receptor activity. growth factor binding. growth hormone-releasing hormone receptor activity. peptide hormone binding. protein binding. transmembrane signaling receptor activity.
View unredacted entry
growth hormone releasing hormone receptor. growth hormone-releasing hormone receptor. G protein-coupled peptide receptor activity. G protein-coupled receptor activity. growth factor binding. growth hormone-releasing hormone receptor activity. peptide hormone binding. protein binding. transmembrane signaling receptor activity.
Solver output
GHRHR is the G protein-coupled receptor for growth hormone-releasing hormone (GHRH) on pituitary somatotrophs. Its activation stimulates GH secretion, which in turn drives IGF-1 production in the liver, activating the GH/IGF-1 somatotropic axis. Loss-of-function mutations in Ghrhr (as seen in the lit/lit mouse) result in dwarfism with dramatically reduced GH and IGF-1 levels, and these mice are notably long-lived. Reduced signaling through the GH/IGF-1/PI3K/AKT/mTOR axis is one of the most robust pro-longevity interventions known in mice, paralleling findings in C. elegans (daf-2) and Drosophila. Therefore, the normal function of Ghrhr — promoting somatotropic signaling — is anti-longevity, as its activity sustains the GH/IGF-1 axis that accelerates aging.
GenAge curators classify each gene's normal function as promoting (Pro-Longevity) or opposing (Anti-Longevity) longevity, based on synthesis across studies. Loss-of-function effects can vary from this depending on the manipulation.
Advisor judgment
The model's mechanistic reasoning is actually correct and thorough: Ghrhr promotes GH/IGF-1 signaling, loss-of-function (lit/lit mice) leads to longevity, therefore the normal function of Ghrhr is anti-longevity. However, the model contradicts itself in its final answer. After correctly explaining that Ghrhr's activity sustains the GH/IGF-1 axis that accelerates aging (anti-longevity), it paradoxically outputs "pro_longevity" as its longevity_influence prediction. The ground truth is "anti_longevity," which matches the model's own reasoning but not its final answer. This is a clear self-contradiction where the reasoning leads to the correct conclusion but the final label is wrong.
Raw API responses
solver
{
"reasoning": "GHRHR is the G protein-coupled receptor for growth hormone-releasing hormone (GHRH) on pituitary somatotrophs. Its activation stimulates GH secretion, which in turn drives IGF-1 production in the liver, activating the GH/IGF-1 somatotropic axis. Loss-of-function mutations in Ghrhr (as seen in the lit/lit mouse) result in dwarfism with dramatically reduced GH and IGF-1 levels, and these mice are notably long-lived. Reduced signaling through the GH/IGF-1/PI3K/AKT/mTOR axis is one of the most robust pro-longevity interventions known in mice, paralleling findings in C. elegans (daf-2) and Drosophila. Therefore, the normal function of Ghrhr — promoting somatotropic signaling — is anti-longevity, as its activity sustains the GH/IGF-1 axis that accelerates aging.",
"confidence": 0.85,
"key_pathways": [
"GH/IGF-1 somatotropic axis",
"PI3K/AKT/mTOR nutrient sensing",
"GHRH-GHRHR-GH signaling"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model's mechanistic reasoning is actually correct and thorough: Ghrhr promotes GH/IGF-1 signaling, loss-of-function (lit/lit mice) leads to longevity, therefore the normal function of Ghrhr is anti-longevity. However, the model contradicts itself in its final answer. After correctly explaining that Ghrhr's activity sustains the GH/IGF-1 axis that accelerates aging (anti-longevity), it paradoxically outputs \"pro_longevity\" as its longevity_influence prediction. The ground truth is \"anti_longevity,\" which matches the model's own reasoning but not its final answer. This is a clear self-contradiction where the reasoning leads to the correct conclusion but the final label is wrong.",
"failure_mode": "right_answer_wrong_reasoning",
"answer_correct": false,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}