LIN28B affects gene expression at the hypothalamic-pituitary axis and serum testosterone levels

Area of Science:

• Genetics and Developmental Biology
• Endocrinology

Background:

• Genome-wide association studies (GWAS) link LIN28B gene variations to pubertal timing, growth, and disease.
• The precise biological mechanisms connecting LIN28B to these traits remain largely unknown.

Purpose of the Study:

• To investigate the functional role of LIN28B in the hypothalamic-pituitary (HP) axis.
• To elucidate the molecular mechanisms underlying LIN28B's association with pubertal timing and growth.

Main Methods:

• Generated CRISPR-Cas9-mediated lin28b knockout (KO) zebrafish models.
• Analyzed gene expression in KO zebrafish, focusing on the HP axis.
• Correlated genetic variants near LIN28B with hormone levels using UK Biobank data.

Main Results:

• lin28b KO zebrafish exhibited accelerated growth, reduced adult size, and altered mitochondrial gene expression.
• LIN28B expression positively correlates with ESR1 in the hypothalamus and POMC in the pituitary.
• The rs7759938 T allele near LIN28B is associated with elevated testosterone levels.

Conclusions:

• LIN28B plays a role in regulating sex hormone pathways.
• Findings suggest LIN28B influences pubertal timing and growth via the HP axis.
• This research provides a biological basis for LIN28B's association with diverse traits.