Abstract
Insulin signalling in the brain plays an important role in the central regulation of energy homeostasis and fertility, such that mice exhibiting widespread deletion of insulin receptors (InsR) throughout the brain and peripheral nervous system display diet sensitive obesity and hypothalamic hypogonadism. However, the specific cell types mediating the central effects of insulin on fertility remain largely unidentified. To date, the targeted deletion of InsR from individual neuronal populations implicated in the metabolic control of fertility has failed to recapitulate the hypogonadic and subfertile phenotype observed in brain‐specific InsR knockout mice. Because insulin and leptin share similar roles as centrally‐acting metabolic regulators of fertility, we used the Cre‐loxP system to generate mice with a selective inactivation of the Insr gene from the same widespread neuronal population previously shown to mediate the central effects of leptin on fertility by crossing Insr ‐flox mice with calcium/calmodulin‐dependent protein kinase type II α ( Camk II α )‐Cre mice. Multiple reproductive and metabolic parameters were then compared between male and female Insr ‐flox/Cre‐positive (CamK‐ IRKO ) and Insr ‐flox/Cre‐negative control mice. Consistent with brain‐specific InsR knockout mice, CamK‐ IRKO mice exhibited a mild but significant obesogenic phenotype. Unexpectedly, CamK‐ IRKO mice exhibited normal reproductive maturation and function compared to controls. No differences in the age of puberty onset, oestrous cyclicity or fecundity were observed between CamK‐ IRKO and control mice. We conclude that the central effects of insulin on the neuroendocrine reproductive axis are not critically mediated via the same neuronal populations targeted by leptin.