Prolactin receptor

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Prolactin Receptor
Identifiers
SymbolPRLR
lobuloalveolar development of the mammary glands during pregnancy and in lactation
.

Structure

The prolactin receptor (PRLR) is a

immune cells, as well as adrenal
and pituitary glands.

Several PRLR

extracellular domains
, which are the regions binding to PRLR.

Diversity of PRLR is a result of transcription initiation in different sites of the PRLR

promoter region. Additionally, post-translational modifications, like alternative splicing are the events that result in the different isoforms that allow for all the different actions of prolactin in the body.[3]

Signaling

The PRLR is a class 1 cytokine receptor that uses messenger pathways to control

second messenger cascades
, including:

Function

Expression of the PRLR protein is found within cells of the mammary glands

knockout mice show severely impaired development of lobuloalveolar structures.[14][15] Disruption of PRLR signaling pathways have been linked to tumorigenesis and breast cancer development.[16]

Ligands

Agonists

Antagonists

Prolactin receptor antagonists such as Del1-9-G129R-hPRL have been developed.[18][19][20][21][22]

Dopamine agonists are currently the most common methods used for treating hyperprolactinemia. 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 a monoclonal antibody that has been studied and tested for disrupting prolactin receptor's signaling in breast cancers and prostate cancers.[24] Although LFA102 has been proved sufficient to reduce prolactin receptor signaling based on in vitro and in 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]

Prolactin receptor dysfunction

PRLR dysfunction has been seen to positively regulate the proliferation of malignant cells in breast cancer. Defects on prolactin receptor signalling can trigger tumour activity, rather than suppress. Signal control is monitored by a variety of genes, and the

PRLR gene has been identified in the tissue of metastatic primary breast cancer cells.[26] The defect in the gene is thought to have built a resistance to chemotherapy, and has lost the ability to regulate the apoptosis of cells with mutated DNA.[27] This signalling defect then fails to promote the cellular differentiation, and promotes the upstream survival of the cancerous cells. In breast cancer, the survival of the breast epithelial cells resemble the malignant cells, characteristically known to have an increased proliferative rate.[28]

See also

References

External links