POU1F1, also known as POU Class 1 Homeobox1, is a pituitary-specific transcription factor. It plays a crucial role in the development and function of the anterior pituitary gland, regulating the expression of genes encoding growth hormone (GH), thyroid-stimulating hormone (TSH), and prolactin. It is involved in pathways related to growth, metabolism, and endocrine regulation, and its normal function is essential for overall physiological homeostasis. Genetic models, such as mouse models, are valuable for studying its functions [2,3,4,5,6].

Mice carrying the Pou1f1 c.143-83A>G substitution, which recapitulates a human intronic variant, showed postnatal growth failure, anterior pituitary hypoplasia, and deficiencies in circulating insulin-like growth factor 1 and thyroxine. RNA-seq and immunohistochemical analyses confirmed a reduction in somatotrophs. Reverse transcription polymerase chain reaction of pituitary Pou1f1 mRNA showed abnormal splicing, with changes in the ratios of alpha and beta isoforms and the emergence of an exon-skipped transcript [2]. In humans, POU1F1 mutations are prevalent in Indian combined pituitary hormone deficiency (CPHD) cohorts. Patients with these mutations often have severe GH, TSH, and prolactin deficiencies. Phenotype-genotype analysis revealed that patients with heterozygous mutations have milder phenotypes, including higher mean peak-GH levels and lower prevalence of anterior-pituitary hypoplasia compared to those with homozygous and compound heterozygous mutations [1]. Some patients with POU1F1 mutations also present with central precocious puberty or early puberty, although the relationship between the genotype and these pubertal phenotypes has not been firmly established. Animal studies suggest that the Pou1f1 gene may affect GnRH receptor function and the Gata2 gene, and control gonadotrope evolution [3].

In conclusion, POU1F1 is essential for the normal development and function of the anterior pituitary gland, regulating key hormones involved in growth and metabolism. Mouse models with specific Pou1f1 mutations have provided insights into the role of this gene in postnatal growth, pituitary development, and endocrine function. In humans, POU1F1 mutations are associated with CPHD and some pubertal abnormalities, highlighting the gene's significance in understanding these disease conditions [1,2,3].