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Other factors including IGF1, GH itself, ghrelin and synthetic GH secretagogs (GHSs) can modulate the synthesis and/or release of GH by somatotrophs in vertebrates ( Figure 1 ) (96, 97), birds (98, 99) and mammals (87, 92, 100), through a longloop negative feedback (by acting on the pituitary and/or on GHRH in the brain, Figure 1 ), but also indirectly by enhancing the hypothalamic release of somatostatin (101), and is considered the other major endocrine and local effector of the GH/IGF axis