Not So Giants: Mice Lacking Both Somatostatin and Cortistatin Have High GH Levels but Show No Changes in Growth Rate or IGF-1 Levels

• DOI: 10.1210/en.2015-1132
• Publication Date: 2015-04-01T16:04:52Z
• Authors: S. Pedraza-Arévalo; J. Córdoba-Chacón; A. I. Pozo-Salas; F. L.-López; L. de Lecea; M. D. Gahete; J. P. Castaño; R. M. Luque
• Keywords: Male; Mice, Knockout; 0303 health sciences; Neuropeptides; Hypothalamus; Growth Hormone-Releasing Hormone; Real-Time Polymerase Chain Reaction; Mice; 03 medical and health sciences; Liver; Animals; Female; Insulin-Like Growth Factor I; Somatostatin

Abstract Somatostatin (SST) and cortistatin (CORT) are two highly related neuropeptides involved in the regulation of various endocrine secretions. In particular, SST CORT primary negative regulators GH secretion. Consequently, single or knockout mice exhibit elevated levels; however, this does not lead to increased IGF-1 levels somatic growth. This apparent lack correspondence has been suggested result from compensatory mechanisms between both peptides. To test hypothesis, study we explored, for first time, consequences simultaneously deleting endogenous by generating a double SST/CORT mouse model exploring its metabolic phenotype. Our results demonstrate that simultaneous deletion induced drastic elevation levels, which, surprisingly, did changes growth rate suggesting existence additional factors/systems that, absence CORT, could counteract actions. Notably, circulating were accompanied pituitary expression alterations main (GHRH ghrelin) their receptors receptor, GHS receptors) at hypothalamic level. However, although double-SST/CORT male exhibited normal glucose insulin they had improved sensitivity compared with control mice. Therefore, these suggest an intricate interplay among known (SST/CORT), likely unknown, inhibitory components GH/IGF-1 axis regulate glucose/insulin homeostasis.