# A long-lasting prolactin stimulates galactopoiesis in mice

## TL;DR

Scientists created a long-lasting version of prolactin that improves milk production in mice and could help study lactation.

## Contribution

A long-acting prolactin variant (Prolactin-XL) was engineered to sustain lactation with reduced infant exposure.

## Key findings

- Prolactin-XL has a 2,625-fold longer serum half-life in mice compared to natural prolactin.
- Prolactin-XL restores lactation in mice with pharmacologically ablated lactation.
- Prolactin-XL has low oral bioavailability, reducing the risk of infant drug exposure.

## Abstract

Prolactin is the main hormonal driver of mammalian lactation. To sustain milk production, basal prolactin levels must remain elevated compared to nonpregnant states. However, prolactin (23 kDa) is short-lived in circulation due to rapid renal excretion. Here, we design and test the galactopoietic effects of an engineered long-lasting prolactin in mice. The engineered variant, prolactin-extra long-acting (Prolactin-XL), is comprised of endogenously active human prolactin fused to an engineered human immunoglobulin G1 (IgG1) Fc domain. Prolactin-XL has a serum half-life of 70.9 h in mice, 2,625-fold longer than endogenously active human prolactin alone (70.9 h vs. 0.02 h). Prolactin-XL is engineered to be more susceptible to gastrointestinal proteases to reduce its uptake by nursing neonates. We demonstrate that Prolactin-XL increases lactation and restores growth of pups fed by dams with pharmacologically ablated lactation. We propose that Prolactin-XL is a potential tool for the study and pharmacologic stimulation of galactopoiesis.

•Prolactin-XL was engineered to be breastfeeding-compatible•Prolactin-XL has a 2,625-fold longer half-life than endogenously active prolactin in mice•Prolactin-XL has low oral bioavailability to limit infant drug exposure•Prolactin-XL restores lactation in a mouse model of pharmacologically ablated lactation

Prolactin-XL was engineered to be breastfeeding-compatible

Prolactin-XL has a 2,625-fold longer half-life than endogenously active prolactin in mice

Prolactin-XL has low oral bioavailability to limit infant drug exposure

Prolactin-XL restores lactation in a mouse model of pharmacologically ablated lactation

Biochemistry; Physiology; Biochemical engineering; Pharmaceutical Engineering