Response of the expression of oxytocin neurons to ghrelin in female mice.

Ghrelin is an orexigenic agonist that acts directly on neurons in the hypothalamus, controlling appetite and energy balance. Although its role in appetite-associated neurons has been described, the relationship between peripheral ghrelin stimulation and oxytocin expression in the paraventricular nucleus is not fully understood. We evaluated the suppressive function of ghrelin in oxytocin-positive paraventricular nucleus neurons in ovariectomized C57BL/6 mice 2 h after ghrelin injection. The results showed that, in intact mice, peripheral ghrelin stimulation activated estrogen receptor alpha-expressing neurons during the estrous cycle and that agouti-related peptide mRNA expression was remarkably increased. Agouti-related peptide neuron axons co-localized with oxytocin neurons in the paraventricular nucleus. Moreover, the response of oxytocin-positive paraventricular nucleus neurons to ghrelin was suppressed in the proestrus period, while ghrelin decreased the serum concentration of estradiol in the proestrus phase. These data suggest that ghrelin may suppress oxytocin-positive neuron expression via the arcuate nucleus agouti-related peptide circuit, with the possible influence of estradiol in the murine estrous cycle. Unraveling the mechanism of ghrelin-induced oxytocin expression in the hypothalamus paraventricular nucleus broadens the horizon for ghrelin-related appetite research.