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Early-life exposure to testosterone programs the hypothalamic melanocortin system
Kazunari Nohara1, Yan Zhang, Rizwana S Waraich
1Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Tarry 15-761, Chicago, Illinois 60611, USA.
Endocrinology
|February 10, 2011
Summary
Neonatal testosterone (NT) programs masculinized feeding behaviors in female mice by altering proopiomelanocortin (POMC) neurons. This programming also leads to estrogen-dependent leptin resistance and obesity.
Area of Science:
- Neuroendocrinology
- Reproductive Biology
- Metabolic Regulation
Background:
- Male mammals exhibit higher food consumption, a masculinized behavior, yet the underlying mechanisms remain unclear.
- Neonatal testosterone (NT) is crucial for brain masculinization and establishing sex differences in reproductive physiology.
- Proopiomelanocortin (POMC) neurons in the arcuate nucleus (ARC) regulate energy intake, with their development significantly influenced neonatally.
Purpose of the Study:
- To investigate if neonatal testosterone (NT) programs masculinized energy intake by affecting POMC neurons.
- To compare control females, control males (CMs), and neonatally androgenized females (NTFs) to understand these mechanisms.
Main Methods:
- Comparison of feeding behavior, POMC expression, and ARC innervation in control females, CMs, and NTFs.
- Assessment of the effects of dihydrotestosterone (DHT) and estrogen on NTFs.
- Evaluation of leptin sensitivity and its downstream signaling pathways (STAT3) in relation to neonatal hormonal exposure.
Main Results:
- CMs showed increased food intake, reduced POMC expression, and decreased POMC innervation compared to control females.
- NTFs exhibited masculinized energy intake and ARC POMC characteristics, mimicked by neonatal DHT exposure.
- NTFs displayed hyperleptinemia and leptin resistance, which was estrogen-dependent and not a direct result of masculinization.
Conclusions:
- Neonatal testosterone (NT) programs sexual differentiation of POMC neurons in female mice via dihydrotestosterone (DHT).
- NT also predisposes females to leptin resistance and obesity through an estrogen-dependent pathway.
- These findings elucidate the hormonal programming of sex-specific feeding behaviors and metabolic regulation.
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