Growth Hormone, Not Simply Just a Hormone for Growth

Since its discovery almost 100 years ago, growth hormone (GH) has been extensively studied to elucidate its structural characteristics, receptor interactions and its physiologic and non-physiologic effects. These actions include but are not limited to its effects on somatic growth, substrate metabolism, body composition, bone mineral density, cardiovascular system, and cognitive function. Contextually, recombinant human GH was approved for growth promotion in children and to enhance metabolic health in adult patients with GH deficiency (GHD), along with other clinical indications. Studies involving individuals and animal models exhibiting dysregulated GH levels, ranging from complete or partial GHD to GH excess, have unveiled a spectrum of several less evident GH actions. In this review, we exclude discussing the classic GH therapeutic applications but instead focus on the interplay between GH and glucose metabolism, fibrosis, and carcinogenesis that is observed with varying GH levels and action. We also discuss clinical data derived from studies in acromegaly and GHD patients (including individuals with congenital GH and insulin-like growth factor I [IGF-I] deficiencies), and attempt to integrate findings from cellular, animal and human studies with the aim of highlighting novel characteristics and underlying molecular pathways through which both GH and IGF-I exert their more subtle actions.