Variant Prolactin Receptor in Agalactia and Hyperprolactinemia

Area of Science:

• Endocrinology
• Genetics
• Reproductive Biology

Background:

• The prolactin receptor (PRLR) mediates prolactin signaling, essential for lactation.
• Previous studies identified a loss-of-function PRLR variant associated with postpartum galactorrhea, a paradoxical presentation.
• The precise role of PRLR in human lactation requires further elucidation.

Observation:

• A 35-year-old woman presented with idiopathic hyperprolactinemia.
• She experienced a complete absence of lactation following two deliveries.
• Genetic analysis revealed she is a compound heterozygote for loss-of-function PRLR variants.

Findings:

• The patient's phenotype, characterized by hyperprolactinemia and an inability to lactate, was directly linked to biallelic loss-of-function variants in the PRLR gene.
• Her unaffected parents were heterozygous carriers of these variants.
• These human genetic findings corroborate observations in Prlr-deficient mice, which also exhibit impaired lactation.

Implications:

• This study provides definitive genetic evidence for the essential role of functional prolactin receptors in human lactation.
• Understanding PRLR function is critical for diagnosing and managing disorders of prolactin signaling and lactation.
• Further research into PRLR variants may reveal new therapeutic targets for lactation-associated conditions.