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Cortistatin Is Not a Somatostatin Analogue but Stimulates Prolactin Release and Inhibits GH and ACTH in a Gender-Dependent Fashion: Potential Role of Ghrelin

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posted on 22.11.2013 by Jose Cordoba-Chacon, Manuel D. Gahete, Ana I. Pozo-Salas, Antonio J. Martínez-Fuentes, Luis de Lecea, Francisco Gracia-Navarro, Rhonda D. Kineman, Justo P. Castano, Raul M. Luque
Cortistatin (CST) and somatostatin (SST) evolve from a common ancestral gene and share remarkable structural, pharmacological, and functional homologies. Although CST has been considered as a natural SST-analogue acting through their shared receptors (SST receptors 1–5), emerging evidence indicates that these peptides might in fact exert unique roles via selective receptors [e.g. CST, not SST, binds ghrelin receptor growth hormone secretagogue receptor type 1a (GHS-R1a)]. To determine whether theroleofendogenousCSTisdifferentfromSST,wecharacterizedtheendocrine-metabolicphenotype of male/female CST null mice (cort / ) at hypothalamic-pituitary-systemic (pancreas-stomach-adrenal- liver) levels. Also, CST effects on hormone expression/secretion were evaluated in primary pituitary cell cultures from male/female mice and female primates (baboons). Specifically, CST exerted an unexpected stimulatory role on prolactin (PRL) secretion, because both male/female cort / mice had reduced PRL levels, and CST treatment (in vivo and in vitro) increased PRL secretion, which could be blocked by a GHS-R1a antagonist in vitro and likely relates to the decreased success of female cort / in first-litterpupcare at weaning. In contrast,CSTinhibitedGHandadrenocorticotropin-hormone axes in a gender-dependent fashion. In addition, a rise in acylated ghrelin levels was observed in female cort / mice, which were associated with an increase in stomach ghrelin/ghrelin O-acyl transferase expression. Finally, CST deficit uncovered a gender-dependent role of this peptide in the regulation of glucose-insulin homeostasis, because male, but not female, cort / mice developed insulin resistance. The fact that these actions are not mimicked by SST and are strongly gender dependent offers new grounds to investigate the hitherto underestimated physiological relevance of CST in the regulation of physiological/metabolic processes.

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Funding

This work was supported by Ayudas Predoctorales de Formacion en Investigacion en Salud del Fondo de Investigacion Sanitaria Grants ISCIII:FI06/00804 (to J.C.-C.) and FPU-AP20052473 (TO M.D.G.); BFU2010-19300 and CTS-5051 (to J.P.C.); and Programa Ramon y Cajal del Ministerio de Educacion y Ciencia Grants RYC-2007-00186 and JC2008-00220, BFU2008-01136/BFI (to R.M.L.).

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Publisher Statement

This is a copy of an article published in the Endocrinology © 2011, Endocrine Society. The final published version is available at endojournals.org doi: 10.1210/en.2011-1542

Publisher

Endocrine Society

Language

en_US

issn

1945-7170

Issue date

01/12/2011

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