The ability to reproduce depends on metabolic status. In rodents, the ventral premammillary
nucleus (PMv) integrates metabolic and reproductive signals. While leptin (adiposity-related)
signaling in the PMv is critical for female fertility, male reproductive functions
are strongly influenced by glucose homeostasis. The anorexigenic peptide nesfatin-1
is a leptin-independent central regulator of blood glucose. Therefore, its integrative
role in male rats can be assumed. To investigate this, we mapped the distribution
of nesfatin-1 mRNA- and protein-producing cells in the PMv during postnatal development
via in situ hybridization and immunohistochemistry, respectively. Fos-nesfatin-1,
double immunostaining was used to determine the combined effect of heterosexual pheromone
challenge and insulin-induced hypoglycemia on neuronal activation in adults. We found
that ~75% of the pheromone-activated neurons were nesfatin-1 cells. Hypoglycemia reduced
pheromone-induced cell activation, particularly in nesfatin-1 neurons. Immuno-electron
microscopy revealed innervation of PMv nesfatin-1 neurons by urocortin3-immunoreactive
terminals, reportedly originating from the medial amygdala. Nesfatin-1 immunopositive
neurons expressed GPR10 mRNA, a receptor associated with metabolic signaling, but
did not respond with accumulation of phosphorylated STAT3 immunopositivity, a marker
of leptin receptor signaling, in response to intracerebroventricular leptin treatment.
Our results suggest that PMv nesfatin-1 neurons are primarily responsible for integrating
reproductive and metabolic signaling in male rats.
