Figure 2.

Schematic representation about the possible relationships between GH, Insulin growth factor (IGF-I) and Klotho, and its actions on the vascular endothelium. (1) Pituitary GH induces the hepatic expression of IGF-I (2) and acts on the repair of the damaged vascular endothelium (DVE), although it is also possible that the hormone enhances the production of Klotho by this damaged tissue. (3) Besides, its inhibitory effects on pituitary GH release, IGF-I also contributes to repair DVE, and, as in the case of GH, it could enhance Klotho production in DVE. (4) DVE secretes Klotho and it inhibits the negative effect of IGF-I on pituitary GH release, but plasma Klotho may also proceed from kidneys (7), contributing or being responsible for the inhibition of IGF-I effects on GH secretion. (5) The possibility exists that Klotho released from DVE stimulates GH secretion for repairing DVE. (6) GH plays an important role on the physiology of kidneys, being particularly important when there is a chronic kidney disease; since in this pathology there is a state of systemic Klotho deficiency, it is possible that GH tries to correct this problem associated to cardiovascular diseases. Some of these concepts are merely speculative, but existing data lead to think that there is a feedback regulation circuit between GH, IGF-I and Klotho. Blue arrows indicate stimulation and red arrows indicate inhibition.