Effects of estrogen and leptin on hypothalamic Agouti‐related peptide/neuropeptide Y (Agrp/Npy) synaptic density

As humans age metabolic function decreases, causing increased body weight and adiposity, thus, also increasing predisposition to obesity. Specific populations of neurons within the hypothalamus regulate whole body metabolism. Agouti‐related peptide/neuropeptide Y (Agrp/Npy) neurons decrease energy expenditure and increase food intake by direct action on downstream neurons and inhibition of pro‐opiomelanocortin (Pomc) neurons, which promote negative energy balance. The defect in the ability of these neurons to respond to leptin, a hormone responsible for regulating energy intake and expenditure, leads to decreased metabolic function. We have previously found that as age increases, there is an increase in high density Agrp/Npy synaptic clusters (abbreviated as “rings”), found within the hypothalamus. The age‐related increase in “rings” around Pomc cells has been found to be dependent on leptin in both male and female mice. Another hormone that has an anorectic effect on energy balance, similar to leptin's effects, is estrogen. Considering estrogen levels change with age, this experiment investigated the effect of estrogen on “ring” formation in female mice. “Ring” number was compared in posterior and medial sections of the arcuate nucleus of five month old wild‐type and ovariectomized mice. As expected, estrogen‐deficient ovariectomized mice had greater body fat and adiposity when compared to wild‐type control mice. Despite the low estrogen and high leptin levels in ovariectomized mice, both groups of females have had approximately the same number of rings. Although estrogen may play a part in “ring” formation, it is not a primary determinant.