Renal LRP2 expression in man and chicken is estrogen-responsive

Area of Science:

• Molecular biology
• Endocrinology
• Comparative genomics

Background:

• Low-density lipoprotein receptor-related protein-2 (LRP2) is a crucial endocytic receptor in mammals.
• Understanding LRP2's evolutionary conservation and regulation offers insights into physiological processes.

Purpose of the Study:

• To characterize the chicken LRP2 homolog and investigate its gene expression regulation.
• To explore potential sex-specific differences in LRP2 expression and its hormonal control.

Main Methods:

• Molecular cloning and sequencing of chicken LRP2 cDNA.
• Quantitative analysis of LRP2 transcript and protein levels in chicken kidneys.
• Bioinformatic analysis of LRP2 gene promoter regions for regulatory elements (ERE, Sp1 sites).
• Estrogen induction studies in primary chicken kidney cells and human kidney cell lines.

Main Results:

• Chicken LRP2 shares high sequence identity (73%) with human LRP2, indicating strong conservation.
• Avian LRP2 expression is significantly higher in females and estrogen-treated males compared to untreated males.
• Potential estrogen-responsive elements and Sp1 sites were identified in the LRP2 gene promoter.
• Estrogen treatment induced LRP2 expression in both chicken and human kidney cells.

Conclusions:

• The LRP2 gene exhibits novel regulatory features leading to sex-specific expression.
• Estrogen plays a key role in regulating LRP2 expression, potentially through direct and indirect pathways.
• These findings contribute to understanding LRP2's role in lipoprotein metabolism and its evolutionary regulation.