The GH/IGF axis in the mouse kidney

Growth hormone (GH) is a protein hormone synthesized and secreted by somatotroph cells within the anterior pituitary predominantly under regulation of hypothalamic peptides, GH releasing hormone (GHRH) and somatostatin (SS) (1-3) (Figure 1). Further, production of GH is modulated by various neuronal and endocrine factors. Genetic predisposition, nutrition, stress, exercise and sleep pattern are all known to influence GH release. GH itself can regulate its own production at the hypothalamic level, where it modulates the release of GHRH and SS (2), and at pituitary level where it has autocrine inhibitory effect on secretion from the somatotroph (4) (Figure 1). GH secretion is also regulated through a negative feedback loop involving the principal mediator of GH activity, insulin-like growth factor (IGF-I) (5) (Figure 1). High serum levels of IGF-I are believed to decrease GH secretion not only by directly suppressing the somatotroph, but also by stimulating release of somatostatin from the hypothalamus. However, recent results from liverspecific IGF-I KO mouse suggest that IGF-I feedback regulates GH secretion at the pituitary rather than at the hypothalamic level (6). Integration of all the factors that affect GH synthesis and secretion results in a pulsatile pattern of release.

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