Hypothalamic Estrogen Receptor α Is Essential for Female Marmoset Sexual Behavior Without Protecting From Obesity

Area of Science:

• Neuroendocrinology
• Reproductive biology
• Metabolic regulation

Background:

• Estrogen receptor alpha (ERα) in rodents regulates sexual behavior, reproduction, and metabolism.
• The role of hypothalamic ERα in female nonhuman primates (NHPs) remains uncharacterized.
• Estradiol (E2) is crucial for these functions, but its specific hypothalamic targets in NHPs are unknown.

Purpose of the Study:

• To investigate the role of ERα in the ventromedial (VMN) and arcuate (ARC) nuclei of the female marmoset hypothalamus.
• To determine if ERα knockdown affects sexual receptivity, gonadotropic function, and metabolic homeostasis.

Main Methods:

• Adult female marmosets underwent ovariectomy and estradiol replacement.
• Diet-induced obesity was induced, followed by selective ERα knockdown (KD) using shRNA in the VMN and ARC via MRI-guided surgery.
• ERα expression was quantified using immunohistochemistry.

Main Results:

• ERα KD significantly reduced ERα expression in the VMN and ARC.
• ERα KD led to a loss of sexual receptivity and timely sexual responses.
• ERα KD resulted in elevated gonadotropin levels, hyperglycemia, and reduced calorie consumption.

Conclusions:

• ERα activation in the female NHP mediobasal hypothalamus is essential for sexual behavior.
• ERα plays a role in modulating gonadotropic and metabolic control in female NHPs.