Role of Cortistatin in the Endocrine System

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1 ISSN CN / Q http / / cjbmb bjmu edu cn Chinese Journal of Biochemistry and Molecular Biology ~ 143 * cortistatin CST somatostatin CST Mas 2 CST CST Q57 Q956 Role of Cortistatin in the Endocrine System WANG Jing-Lan XI Qian-Yun ZHANG Yong-Liang * College of Animal Sciences Southern China Agriculture University Guangzhou China Abstract Cortistatin CST is a novel neuropeptide of the somatostatin homologous family which is mainly expressed in cortex and able to suppress the cortical activities CST binds to somatostatin receptor ghrelin receptor or Mas-related gene X2 receptor thus to mediate various biological effects such as the induction of slow-wave sleep participation of inflammation and the regulation of neuroendocrine functions Studies suggested that CST might be considered a natural alternative of somatostatin with endocrine properties In this review we summarized the findings that demonstrated CST functions in endocrine system at cellular or whole body levels Key words cortistatin endocrine function 1996 de Lecea C SST cdna mrna KR RK KK RR 2 cortistatin CST CST somatostatin SST CST 14 CST-14 somatostatin receptors SSTRs 29 CST CST CST CST-14 CST-17 SST SSTR FWKT Table CST SST CST CST CST 4 No * Tel zhangyl@ scau edu cn Received September Accepted November Supported by National Natural Science Foundation of China No * Corresponding author Tel N 27 zhangyl@ scau edu cn

2 CST SST growth hormone secretagogue receptor 1a GHSR1a receptor MrgX2 SSTRs 7 2 CST G GHSR-1a 1996 Northern CST 7 G 4 CST 5 PCR RT-PCR CST CST 9 CST CST Table 1 Mas X 2 Mas-related gene X2 ghrelin 8 MrgX2 Mas CST SSTRs 1a SST Similarities and differences between CST and SST Similarities Differences References Similar chemical structure Encoded by different genes 2 High affinity to SSTRs CST but not SST binds to MrgX2 and GHSR-1a 10 Co-expressed in GABAergic interneurons Inhibitory peptide Enhance M-current Similar impairment of memory processing CST but not SST expressed in tissues and cells of the immune system Regulated by different signals CST antagonizesacetylcholine in cortices SST potentiates acetylcholine responses Some similar endocrine activities Have different mechanisms 13 Anti-inflammatory and anti-nociceptive The inhibitory effect of CST on inflammatory cytokine production is greater than SST 14 3 CST Rubinfeld CST CST growth hormone CST SSTR G nmol / L Ca 2 + GH mitogen-activated protein SST CST nmol / L kinases MAPK protein PRL SSTR5 tyrosine phosphatase PTP 15 Ca 2 + / K Luque 17 Na + / H + CST GH C A2 CST 10-9 mol / L 3 2 GH prolactin PRL CST growth hormone releasing hormone GHRH GH CST mol / CST L GH GHRH

3 2 141 GH SST 2009 Baranowska 22 SST CST SST GH CST CST-14 CST SST PRL GH 1 h luteinizing hormone LH follicle- 18 CST 100 stimulating hormone FSH nmol / L CST adrenocorticotropic hormone ACTH CST SST GH PRL CST ACTH CST PRL PRL SST 23 CST GH ACTH SST Broglio 24 CST 100 CST ghrelin nmol / L GH ACTH CST GH SST PRL GHSR ghrelin 13 PRL ACTH CST ~ mol / L CST SST GH GHRH ghrelin GH CST ~ 10-7 mol / L GH 19 SST CST 2006 Grottoli 27 corticotropin releasing hormone CRH CST GH SST KCL CRH CST Cushing's disease 28 CST Deghenghi 21 CST-14 ACTH GH SST-14 SST CST CST GH ghrelin GH GHRH GH SST CST SST Table 2 The regulatory actions of CST on endocrine secretions Species In vitro In vivo Normal Rat Stimulates GH release in a dose dependent manner Inhibits GH and PRL release Mouse Inhibits ACTH and GH release Stimulates PRL release Pig Dose-dependent inhibitory and stimulatory effects on GH secretion Baboon Dose-dependent inhibitory and stimulatory effects on GH secretion Human Inhibits GH insulin and ghrelin secretion Adenma Human Inhibits GH and PRL secretion Inhibits GH insulin ACTH PRL secretion Suppresses GH response to GHRH and ghrelin

4 GH CST SST Table 2 CST SST GH SSTR CST GHSR1a GH CST GH role of ghrelin J SST CST SST 14 Markovics A Szoke E CST J Mol Neurosci 2012 CST CST References 1 Broglio F Grottoli S Arvat E et al Endocrine actions of cortistatin in vivo studies J Mol Cell Endocrinol Spier A D de Lecea L Cortistatin a member of the somatostatin neuropeptide family with distinct physiological functions J Brain Res Brain Res Rev J somatotropes J J Mol Endocrinol Liu Yue Yin Xin-Hua Qi Yong-Fen Progress in biological effects of cortistatin J Prog Physiol Sci de Lecea L Criado J R Prospero-Garcia O et al A cortical neuropeptide with neuronal depressant and sleep-modulating properties J Nature de Lecea L Cortistatin functions in the central nervous system J Mol Cell Endocrinol Annunziata M Luque R M Duran-Prado M et al Somatostatin and somatostatin analogues reduce PDGF-induced endometrial cell proliferation and motility J Hum Reprod Volante M Rosas R Allia E et al Somatostatin cortistatin and their receptors in tumours J Mol Cell Endocrinol van Hagen P M Dalm V A Staal F et al The role of cortistatin in the human immune system J Mol Cell Endocrinol Cordoba-Chacon J Gahete M D Duran-Prado M et al Truncated somatostatin receptors as new players in somatostatin-cortistatin pathophysiology J Ann N Y Acad Sci Capuano A Curro D Navarra P et al Cortistatin modulates calcitonin gene-related peptide release from neuronal tissues of rat Comparison with somatostatin J Peptides Broglio F Papotti M Muccioli G et al Brain-gut communication cortistatin somatostatin and ghrelin J Trends Endocrinol Metab Fabre V Spier A Winsky-Sommerer R et al Cortistatin-A Novel Member of the Somatostatin Gene Family J Somatostatin Cordoba-Chacon J Gahete M D Pozo-Salas A I et al Cortistatin is not a somatostatin analogue but stimulates prolactin release and inhibits GH and ACTH in a gender-dependent fashion potential Endocrinology Sandor K et al Comparison of the antiinflammatory and anti-nociceptive effects of cortistatin-14 and somatostatin-14 in distinct in vitro and in vivo model systems J J Zhao Zeng-Yang Xi Qian-Yun Zhang Yong-Liang Physiological function and kinetic characteristics of somatostatin receptors J Chin J Biochem Mol Biol Rubinfeld H Hadani M Barkai G et al Cortistatin inhibits growth hormone release from human fetal and adenoma pituitary cells and prolactin secretion from cultured prolactinomas J J Clin Endocrinol Metab Luque R M Peinado J R Gracia-Navarro F et al Cortistatin mimics somatostatin by inducing a dual dose-dependent stimulatory and inhibitory effect on growth hormone secretion in 18 Baranowska B Chmielowska M Wolinska-Witort E et al Direct effect of cortistatin on GH release from cultured pituitary cells in the rat J Neuroendocrinol Lett Cordoba-Chacon J Gahete M D Culler M D et al Somatostatin dramatically stimulates growth hormone release from primate somatotrophs acting at low doses via somatostatin receptor 5 and cyclic AMP J J Neuroendocrinol Tringali G Greco M C Lisi L et al Cortistatin modulates the expression and release of corticotrophin releasing hormone in rat braincomparison with somatostatin and octreotide J Peptides Deghenghi R Avallone R Torsello A et al Growth hormoneinhibiting activity of cortistatin in the rat J J Endocrinol Invest RC31-RC33 22 Baranowska B Bik W Baranowska-Bik A et al Cortistatin and pituitary hormone secretion in rat J J Physiol Pharmacol Córdoba-Chacón J Gahete M D Pozo-Salas A I et al Cortistatin Is Not a Somatostatin Analogue but Stimulates Prolactin Release and Inhibits GH and ACTH in a Gender-Dependent Fashion Potential Role of Ghrelin J Endocrinology Broglio F Koetsveld Pv P Benso A et al Ghrelin secretion is inhibited by either somatostatin or cortistatin in humans J J Clin Endocrinol Metab Broglio F Arvat E Benso A et al Endocrine activities of

5 2 143 cortistatin-14 and its interaction with GHRH and ghrelin in humans J J Clin Endocrinol Metab Gottero C Prodam F Destefanis S et al Cortistatin-17 and -14 exert the same endocrine activities as somatostatin in humans J Growth Horm IGF Res Grottoli S Gasco V Broglio F et al Cortistatin-17 and somatostatin-14 display the same effects on growth hormone prolactin and insulin secretion in patients with acromegaly or prolactinoma J J Clin Endocrinol Metab Giordano R Picu A Bonelli L et al The activation of somatostatinergic receptors by either somatostatin- 14 or cortistatin-17 often inhibits ACTH hypersecretion in patients with Cushing's disease J Eur J Endocrinol Yang Nature Yang Yang Yang 1 2 ME1 ME2 Mdm2 Yang ME1 ME2 Yang Science Daily Jan