PRLRs

PRLRs, or prolactin receptors, are a family of cell-surface receptors that bind the hormone prolactin to mediate its biological effects. They belong to the type I cytokine receptor superfamily and are encoded by the PRLR gene. In humans, a single PRLR gene gives rise to multiple receptor isoforms through alternative splicing and promoter usage, producing a long form (PRLR-L) and several shorter forms (PRLR-S). All isoforms share an extracellular ligand-binding domain and a single transmembrane helix, but differ in their intracellular tails, which influences signaling capacity.

Ligand binding induces receptor dimerization and activation of the associated Janus kinase 2 (JAK2), leading to phosphorylation of downstream signaling molecules such as STAT5, and to engagement of other pathways including STAT3, PI3K-Akt, and MAPK. Long forms generally drive robust signaling relevant to lactation and mammary gland development, while short forms may have reduced signaling or antagonistic effects and can modulate the overall response.

Expression is widespread, with high levels in the mammary gland and placenta, and notable presence in the brain, immune cells, liver, and adipose tissue. In some species, PRLRs also participate in osmoregulation or other physiological processes through tissue-specific receptor isoforms.

Clinical and research relevance includes roles in lactation disorders and hyperprolactinemia, pituitary adenomas, and potential associations with breast cancer risk or metabolic conditions. Therapeutic approaches may involve modulation of PRLR signaling, either through agonists or antagonists, depending on the disease context.

Evolutionarily, some vertebrates possess multiple PRLR genes due to gene duplication, while in humans the diversity of signaling is largely achieved through alternative splicing of a single PRLR gene.