PRL Mutation Causing Alactogenesis: Insights Into Prolactin Structure and Function Relationships.

Area of Science:

• Endocrinology
• Genetics
• Reproductive Biology

Background:

• Isolated prolactin deficiency is a rare condition characterized by the absence of milk production after childbirth.
• This disorder, known as alactogenesis, can significantly impact maternal-infant bonding and infant nutrition.

Observation:

• A two-generation family presented with three women experiencing puerperal alactogenesis.
• These women exhibited significantly low prolactin levels, ranging from 0.618 to 1.4 ng/mL.
• Early menopause and fertility issues were noted in affected family members.

Findings:

• A heterozygous mutation (c.658C>T, p.Arg220Ter) was identified in exon 5 of the prolactin gene (PRL).
• This mutation resulted in impaired prolactin secretion, with minimal detectable immunoactive or bioactive prolactin.
• Further experiments with a PRL stop gain mutation deleting terminal cysteines also demonstrated impaired secretion.

Implications:

• This is the first report linking a specific PRL gene mutation to familial prolactin deficiency and alactogenesis.
• The C-terminal region of prolactin, particularly the cysteine residues, is critical for proper protein secretion.
• These findings advance our understanding of the genetic basis of prolactin deficiency and its impact on lactation.