Theprolactin receptor (PRLR) is atype I cytokine receptor^[1] encoded in humans by thePRLR gene on chromosome 5p13-14. It is the receptor forprolactin (PRL). The PRLR can also bind to and be activated bygrowth hormone (GH) andhuman placental lactogen (hPL). The PRLR is expressed in themammary glands,pituitary gland, and othertissues. It plays an important role inlobuloalveolar development of the mammary glands duringpregnancy and inlactation.

The prolactin receptor (PRLR) is amembrane-bound protein of thecytokine receptor superfamily. In humans, it is encoded by a single gene that contains 11exons and is located onchromosome 5.^[2] PRLR expression can be found in several tissues such as thegonads,breast,uterus,heart,liver,kidney,brain,immune cells, as well asadrenal and pituitary glands.

Several PRLRisoforms have been described in different tissues. These have varying lengths and cytoplasmic domain composition, but share identicalextracellular domains, which are the regions binding to PRLR.

Diversity of PRLR is a result of transcription initiation in different sites of the PRLRpromoter region. Additionally, post-translational modifications, like alternativesplicing are the events that result in the different isoforms that allow for all the different actions of prolactin in the body.^[3]

The PRLR is a class 1 cytokine receptor that uses messenger pathways to controlcell proliferation,migration, intracellular ion concentration and inhibit programmed cell death (apoptosis).^[4][5] PRLRs also have functions in thesecond messenger cascades, including:

• JAK-STAT pathway – theSTAT protein family has been shown to have a key transduction role in cytokine receptor signalling; this pathway is initiated following the activation of PRLRs.^[6] Although there have been 4 STAT proteins identified as transducer molecules of PRLR,STAT5 is recognised as the most important transducer of PRLR isoforms, with a role in inhibiting the regulation ofgene transcription.
• Ras-Raf-MAPK – initiated by PRLR activation.Phosphotyrosine residues on PRLR act as binding sites for adapter proteins – these connect PRLR to the Ras/Raf/MAP kinase cascade
• JAK-RUSH pathway^[7][8]
• PI3K/AKT/mTOR pathway^[9]

Expression of the PRLR protein is found within cells of the mammary glands^[10] in accordance with its role in lactation, but also is the subject of attention for its diverse and emerging roles by its expression in adipose tissue,^[11] pancreatic islet cell proliferation,^[12] and immune responses.^[13] The PRLR it essential forlobuloalveolar maturation of the mammary glands during pregnancy, as evidenced by the fact that PRLRknockout mice show severely impaired development of lobuloalveolar structures.^[14][15] Disruption of PRLR signaling pathways has been linked to tumorigenesis andbreast cancer development.^[16]

• Prolactin
• Growth hormone
• Human placental lactogen
• Placental growth hormone
• S179D-hPRL^[17]

Prolactin receptor antagonists such asDel1-9-G129R-hPRL have been developed.^{[18][19][20][21][22]}

Dopamine agonists are currently the most common method used for treatinghyperprolactinemia. However, since dopamine agonists only negatively regulate prolactin production from the pituitary gland, a few studies have tried to develop prolactin receptor antagonists for potentially treating the dopamine-resistant local hyperprolactinemia.^[18][23]Δ1–9-G129R-hPRL is one of the prolactin receptor antagonists been studied. Δ1–9-G129R-hPRL as a mutant (inactivated) form of prolactin which exerts its antagonist effect by competing with prolactin to bind with prolactin receptors; thereby, inhibiting the agonist effects of prolactin on prolactin receptors.^[18] Besides molecular antagonists,antibodies can also potentially be used to inhibit prolactin receptor signaling. LFA102 is amonoclonal antibody that has been studied and tested for disrupting prolactin receptor's signaling inbreast cancers andprostate cancers.^[24] Although LFA102 has been proven sufficient to reduce prolactin receptor signaling based onin vitro andin vivo (mouse) studies, LFA102 likely has low effects on limiting tumor growth (breast and prostate cancer) as shown in phase I clinical trials.^[24][25]

• ABS-201
• BAY-1158061 (HMI-115)

PRLR dysfunction has been seen to positively regulate the proliferation of malignant cells in breast cancer. Defects in prolactin receptor signalling can trigger tumour activity, rather than suppress it. Signal control is monitored by a variety of genes, and thePRLR gene has been identified in the tissue ofmetastatic primary breast cancer cells.^[26] The defect in the gene is thought to have built a resistance tochemotherapy, and has lost the ability to regulate the apoptosis of cells with mutated DNA.^[27] This signalling defect then fails to promote cellular differentiation and promotes the upstream survival of the cancerous cells. In breast cancer, the survival of the breast epithelial cells resembles the malignant cells, characteristically known to have an increased proliferative rate.^[28]

• Prolactin modulator
• Hypothalamic–pituitary–prolactin axis

• Prolactin+receptor at the U.S. National Library of MedicineMedical Subject Headings (MeSH)

• Genes on human chromosome 5

• Articles with short description
• Short description is different from Wikidata
• Protein pages needing a picture
• Human gene pages with Wikidata item