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Corticotropin-releasing hormone (CRH) mRNA is the messenger RNA transcript encoded by the CRH gene, located on chromosome 8q13 in humans (NCBI Gene ID: 1392). It serves as the template for the synthesis of the CRH preprohormone, which is subsequently processed into the 41-amino acid CRH peptide, the primary driver of the hypothalamic-pituitary-adrenal (HPA) axis (UniProt P06850). CRH mRNA is highly expressed in the paraventricular nucleus (PVN) of the hypothalamus, where its transcription is regulated by stress and glucocorticoid feedback (PubMed: 10435395). Overexpression of CRH mRNA is associated with various psychiatric and endocrine disorders, including major depressive disorder and Cushing's syndrome, due to the resulting hypercortisolemia (PubMed: 16291435). While most pharmacological interventions target CRH receptors (CRHR1 and CRHR2), CRH mRNA is a target for experimental gene-silencing strategies such as antisense oligonucleotides (ASOs) and RNA interference (RNAi) to reduce CRH production at the source (PubMed: 7963515). Therapeutic challenges include the blood-brain barrier penetration for RNA-based drugs and the risk of inducing adrenal insufficiency through excessive HPA axis suppression.
Antisense inhibition of translation or RNA interference-mediated degradation of the mRNA transcript, leading to reduced synthesis of the corticotropin-releasing hormone peptide.
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