Growth hormone (GH)-producing pituitary cells (somatotropes) comprise a fundamental regulator for a plethora of relevant physiological functions, including somatic growth and whole-body metabolism, by controlling the function of different endocrine/non-endocrine targets. Synthesis and release of GH has been classically thought to be primarily regulated by central, dual neuroendocrine signals: i.e. GH-releasing hormone and somatostatin. However, it is progressively becoming evident that multiple metabolic factors, from insulin and IGF-I to adipokines, ghrelin, obestatin, melatonin, cortistatin, neuronostatin, kisspeptin, etc., produced by GH-sensitive metabolic tissues (e.g. pancreas, liver, fat, stomach, etc.) can feedback directly to the pituitary to exert capital adjusts on GH synthesis and release. In this manner, somatotrope cells serve as metabolic sensors of the organism to integrate central and peripheral signals in order to fine-tune whole-body homeostasis, although it is clear that pituitary cell regulation is species-, age- and sex-dependent. The purpose of this presentation is to provide a comprehensive, general overview of our current knowledge on: 1) Central and peripheral metabolic regulators that directly control somatotrope cell function, and their associated intracellular mechanisms, as elucidated by using primary pituitary cell cultures from different species as well as in vivo mouse model treated with different metabolic factors; and 2) the metabolic consequences of changing circulating GH levels, by using multiple mouse models with elevated or reduced circulating GH levels [i.e. transgenic animal models with extreme altered levels of GH (giants vs. dwarf), as well as models with alterations in GH levels within the physiologic range (Adult-onset, isolated, GH deficient/AOiGHD, somatostatin/cortistatin-deficient, somatotrope specific insulin-R/IFGI-R deficient mice, etc.]. Additionally, it is now also becoming apparent that different agents used to improve altered metabolic conditions (e.g. biguanides and statins in diabetes and obesity) might also target somatotropes to exert, at least part, some of their beneficial metabolic actions. Thus, overall, the data gathered over the last years reinforce the contention that a clear, bidirectional and (patho)physiologically relevant, interrelationship is in place between GH and metabolism under both normal and altered metabolic conditions, where somatotrope cells act as true homeostatic sensors of the organism, controlling whole body homeostasis and metabolism by integrating central and peripheral signals.
18 - 21 May 2019
European Society of Endocrinology