MC4R and hypogonadotropic hypogonadism: Although this is likely the first in vivo proof of principle for the action of an MC4R PC, a previous study has demonstrated that PCs targeting the GnRHR can restore the activity of a mouse model in which a mutation responsible for hypogonadotropic hypogonadism was introduced in the mouse GnRHR gene (11), illustrating the generalizability of the concept.