Integrative Transcriptomics Deconstructs the H-P-M Axis: A Multi-Level Coordinated Regulatory Network Mediated by an “Interface-Relay-Hub” Architecture

The molecular architecture of the growth-regulating hypothalamus-pituitary-muscle (H-P-M) axis is poorly understood. We performed integrative transcriptomic analysis of the hypothalamus, pituitary, and longissimus dorsi muscle from Liangshan black sheep with superior growth performance to dissect this regulatory network. Analysis of 3,422 differentially expressed genes (DEGs) identified across pairwise tissue comparisons revealed a three-tiered regulatory architecture: (1) tissue-specific interfaces defining spatial hierarchy, (2) relay modules for temporal dynamics, and (3) shared core hubs (131 genes) establishing neuro-endocrine-muscle integration. This study provides a multi-level regulatory map of the H-P-M axis, identifying key pathways such as pituitary calcium signaling and hub genes (e.g., NPY), with 12 of 14 candidate genes validated by quantitative PCR. These findings deepen the understanding of neuroendocrine control over skeletal muscle growth and offer novel molecular targets for genetic improvement in livestock.