Thyroid hormone excess targeted to oxytocin neurons disrupts oxytocin physiology without impacting behavior.
Excess thyroid hormone targeted to oxytocin neurons disrupts oxytocin levels but does not appear to affect behavior in mice.
Where it sits
this study against the rest of the oxytocin corpusSummary and findings
This study measured the impact of thyroid hormone excess targeted to oxytocin neurons in a mouse model. It found that T3 excess led to significant deficits in oxytocin physiology without affecting behavior. The study highlights the relationship between thyroid hormone and oxytocin gene regulation.
Abstract
Deficiencies in oxytocin are associated with neurodevelopmental and behavioral disorders, and the oxytocin gene (Oxt) can be regulated by thyroid hormone. We have previously shown that a systemic excess of thyroid hormone during development causes deficits in oxytocin that are associated with major abnormalities in mood-related and social behaviors. To determine whether the disruption in oxytocin physiology is responsible for these aberrant behaviors we targeted thyroid hormone excess to oxytocin neurons using a mouse model of conditional deficiency of the type 3 deiodinase (DIO3), the neuronal enzyme responsible for the clearance of thyroid hormones and the modulation of thyroid hormone action. We observed that mice of both sexes with T3 excess in oxytocin neurons largely recapitulated the oxytocin deficits of systemic thyrotoxicosis, and exhibited reduced neonatal and adult hypothalamic expression of Oxt mRNA, markedly blunted pituitary Oxt expression and lower serum levels of oxytocin. However, these mice did not show any significant abnormality in physical activity levels, depression- and anxiety-like behaviors, aggression, sociability or maternal behavior. We conclude that T3 excess in mouse oxytocin neurons is sufficient to cause significant oxytocin deficits, but insufficient per se to cause detectable abnormalities in behavioral profiles. Our results suggest that the profound behavioral syndrome previously observed in mice with systemic developmental thyrotoxicosis likely involves other brain neural circuits affected by developmental T3 excess that remain to be identified.
Background
This paper investigates the relationship between thyroid hormone excess and oxytocin physiology, particularly in the context of neurodevelopmental and behavioral disorders. Previous studies indicated that systemic thyroid hormone excess during development leads to deficits in oxytocin and associated behavioral abnormalities. Understanding the specific role of oxytocin neurons in this context is crucial for elucidating the underlying mechanisms of these disorders.
Methods
The study utilized a mouse model with conditional deficiency of the type 3 deiodinase (DIO3) to target thyroid hormone excess specifically to oxytocin neurons. The population included mice of both sexes, and the primary outcome measures focused on oxytocin expression levels in the hypothalamus and pituitary, as well as serum oxytocin levels. Behavioral assessments were also conducted to evaluate physical activity, depression, anxiety, aggression, sociability, and maternal behavior.
Results
Mice with T3 excess in oxytocin neurons exhibited reduced neonatal and adult hypothalamic expression of Oxt mRNA, markedly blunted pituitary Oxt expression, and lower serum levels of oxytocin. However, these mice did not show any significant abnormalities in physical activity levels, depression- and anxiety-like behaviors, aggression, sociability, or maternal behavior.
Interpretation
The findings suggest that while T3 excess in oxytocin neurons leads to significant deficits in oxytocin, it does not directly cause detectable behavioral abnormalities. This contrasts with previous observations of behavioral syndromes associated with systemic developmental thyrotoxicosis, indicating that other neural circuits may be involved. The small sample size and reliance on a rodent model limit the generalizability of these results to human conditions.
Key findings
- Reduced hypothalamic expression of Oxt mRNA in T3 excess mice.
- Markedly blunted pituitary Oxt expression.
- Lower serum levels of oxytocin in T3 excess mice.
- No significant abnormalities in physical activity levels, depression- and anxiety-like behaviors, aggression, sociability or maternal behavior.
Limitations
- Rodent model may not directly translate to humans.
- No significant behavioral abnormalities despite hormonal changes.
- Small sample size not reported.
- Single-site study limits generalizability.