Defects of the PROK2 pathway in humans affect the neuroendocrine control of reproduction by causing hypogonadotropic hypogonadism due to the GnRH deficiency, which is caused by a reduction in the number of GnRH neurons in the preoptic region of the hypothalamus [32]. This evidence concerns the gene GNRH1 and hyperinsulinemic hypoglycemia, familial, 4.