Prolactin regulates liver growth during postnatal development in mice

Area of Science:

• Developmental biology
• Endocrinology
• Hepatology

Background:

• The liver-to-body weight ratio (LBW) is a key indicator of liver health and undergoes significant changes during early postnatal development.
• Prolactin (PRL), a hormone known to stimulate adult liver growth and regeneration, is present at high levels in newborns, but its role in neonatal liver growth remains unclear.

Purpose of the Study:

• To investigate the role of prolactin (PRL) and its receptor in regulating liver growth during the early postnatal period in mice.
• To determine whether local and systemic PRL signaling influences the liver-to-body weight ratio (LBW) and associated gene expression.

Main Methods:

• Analysis of liver and body growth rates, liver-to-body weight ratio (LBW), and PRL/PRL receptor expression in mice during the first 10 postnatal weeks.
• Comparison of PRL receptor null mice (Prlr-/-) with wild-type mice (Prlr+/+) to assess the impact of PRL signaling.
• Measurement of gene expression for proliferation (cyclin D1), angiogenesis (platelet/endothelial cell adhesion molecule 1), and signaling pathways (Igf-1, Socs2, Socs3) in liver tissues.

Main Results:

• Liver produces PRL and upregulates its receptor in early postnatal weeks, coinciding with slower liver growth relative to body growth.
• PRL receptor null mice exhibit reduced LBW and lower expression of proliferation and angiogenesis markers.
• At postnatal week 2, PRL receptor null mice show increased LBW with altered expression of Igf-1, Socs2, and Socs3, suggesting complex regulatory mechanisms.

Conclusions:

• Prolactin (PRL) acts both locally and systemically to modulate postnatal liver growth, exhibiting inhibitory effects early on and potentially stimulatory effects later.
• PRL influences liver growth by interacting with growth hormone signaling pathways, likely through Socs2 and Socs3, to regulate Igf-1 expression.
• These findings reveal a novel regulatory mechanism for postnatal liver development involving prolactin signaling.