Development of transgenic mice overexpressing GH and GHR-KO mice with GH resistance provided novel animal models for study of the somatotropic axis and for identifying GH actions that may be relevant to its current and contemplated use in medicine and agriculture. Studies of phenotypic characteristics of these animals revealed previously unsuspected actions of GH and IGF-I on neuroendocrine functions related to reproduction and to the release of "stress hormones" (glucocorticoids and prolactin). These studies also provided novel and still-disputed evidence for involvement of somatotropic axis in the control of aging and life span and in mediating the actions of longevity genes.