Puberty Blocker, Leuprolide, Reduces Sex Differences in Rough-and-Tumble Play and Anxiety-like Behavior in Juvenile...

Area of Science:

• Neuroendocrinology
• Behavioral Neuroscience
• Developmental Biology

Background:

• Puberty involves significant hormonal and behavioral changes, including the emergence of sex differences.
• The gonadotropin-releasing hormone (GnRH) system plays a critical role in pubertal maturation and is implicated in anxiety.
• Understanding the impact of hormonal shifts during puberty on behavior is crucial for addressing developmental and mental health concerns.

Purpose of the Study:

• To investigate the effects of the GnRH agonist leuprolide acetate on sex differences in juvenile behavior and neuroendocrine parameters in adolescent rats.
• To explore the potential of leuprolide acetate as a tool to modulate sex differences during development and its impact on anxiety-like behavior.
• To provide a preclinical model for understanding the role of pubertal hormone maturation in anxiety development.

Main Methods:

• Administration of leuprolide acetate to adolescent male and female rats.
• Assessment of rough-and-tumble play behavior and anxiety-like behavior.
• Measurement of gonadal and pituitary hormone levels (e.g., testosterone, FSH, LH, GH, TSH, corticosterone).
• Analysis of activity-regulated cytoskeleton-protein (Arc) mRNA levels in the amygdala.

Main Results:

• Leuprolide acetate treatment significantly lowered anxiety-like behavior in adolescent rats.
• The treatment reduced masculinized rough-and-tumble play behavior and lowered follicle-stimulating hormone levels.
• Leuprolide acetate attenuated sex differences in various hormone levels, including testosterone, growth hormone, thyrotropin, and corticosterone.
• Hormonal changes correlated with reduced sex differences in behavior and amygdala gene expression.

Conclusions:

• Leuprolide acetate effectively pauses pubertal development and reduces sex differences in hormones, brain, and behavior.
• The findings suggest that GnRH system maturation is linked to increased anxiety during puberty.
• Leuprolide acetate may offer a potential therapeutic strategy to mitigate anxiety associated with puberty and support gender-affirming care by harmonizing developmental trajectories.