ABSTRACT The pituitary gland plays a pivotal role in regulating puberty and reproductive physiology; however, the precise cellular and molecular mechanisms driving the pubertal transition in large animal, such as ewes, remain poorly understood. Here, we generated a comprehensive single‐cell transcriptomic atlas of the ovine anterior pituitary, specifically comparing the pre‐pubertal (3 month) and post‐pubertal (6 month) stages. We identified 30 335 cells classified into ten distinct clusters. Comparative analysis revealed a global transcriptional reprogramming during puberty, characterized by a marked upregulation of genes associated with ribosome biogenesis, unfolded protein response, and hormone secretion across endocrine cells, reflecting an expanded biosynthetic capacity. Specifically, we identified SCG2 as a critical regulator of gonadotroph maturation. Functional validation demonstrated that SCG2 facilitates the biogenesis of secretory granules, thereby promoting FSH synthesis and secretion. Furthermore, intercellular communication analysis uncovered a distinct shift in the pituitary microenvironment: the 6 month pituitary exhibited enhanced regulatory networks, including IGF signaling mediated by non‐endocrine cells and NT signaling (e.g., BDNF–NTRK2) driven by multiple cell types. These findings suggest that the onset of puberty relies on a coordinated “endocrine‐to‐endocrine” and “non‐endocrine‐to‐endocrine” crosstalk. This study provides a high‐resolution molecular blueprint of the pubertal transition, highlighting the key roles of biosynthetic machinery upgrades and microenvironmental remodeling in establishing the high reproductive performance of Hu sheep.
Li et al. (Thu,) studied this question.