PRLR

PRLR, or prolactin receptor, is a member of the type I cytokine receptor family that binds the peptide hormone prolactin and placental lactogens. The PRLR gene produces multiple receptor isoforms through alternative splicing, resulting in transmembrane forms and soluble variants. In humans, PRLR is expressed in the mammary gland and in a broad range of tissues, including brain, immune cells, liver, pancreas, ovary, and placenta.

Structure and signaling: The receptor has an extracellular ligand-binding domain, a single transmembrane helix, and an intracellular tail that recruits signaling molecules. Ligand binding promotes receptor dimerization and activation of associated Janus kinases, chiefly JAK2, which phosphorylates STAT transcription factors (notably STAT5) and initiates downstream pathways such as MAPK and PI3K. Long and short intracellular isoforms differ in cytoplasmic length and signaling capacity. Soluble PRLR forms, produced by alternative splicing or cleavage, can act as decoys by binding circulating prolactin.

Functions: PRLR signaling is essential for mammary gland development and lactation in mammals. It also participates in reproductive regulation, metabolism, osmoregulation, and immune modulation, and plays roles in placental function during pregnancy. In the nervous system, prolactin signaling may influence various neural processes, though outcomes are context-dependent.

Clinical significance: Altered PRLR signaling has been studied in relation to lactation disorders, reproductive dysfunction, and metabolic conditions. Hyperprolactinemia is commonly managed by reducing prolactin levels rather than directly targeting the receptor. Research continues to clarify the role of PRLR signaling in cancer risk and other diseases, with therapeutic modulation of the receptor being explored in experimental settings.