title: Obesity alters gene expression for GH/IGF-I axis in mouse mammary fat pads: differential role of cortistatin and somatostatin.
abstract: Locally produced growth hormone (GH) and IGF-I are key factors in the regulation of mammary gland (MG) development and may be important in breast cancer development/progression. Somatostatin (SST) and cortistatin (CORT) regulate GH/IGF-I axis at various levels, but their role in regulating GH/IGF-I in MGs remains unknown. Since obesity alters the expression of these systems in different tissues and is associated to MG (patho) physiology, we sought to investigate the role of SST/CORT in regulating GH/IGF-I system in the MGs of lean and obese mice. Therefore, we analyzed GH/IGF-I as well as SST/CORT and ghrelin systems expression in the mammary fat pads (MFPs) of SST- or CORT-knockout (KO) mice and their respective littermate-controls fed a low-fat (LF) or a high-fat (HF) diet for 16 wks. Our results demonstrate that the majority of the components of GH/IGF-I, SST/CORT and ghrelin systems are locally expressed in mouse MFP. Expression of elements of the GH/IGF-I axis was significantly increased in MFPs of HF-fed control mice while lack of endogenous SST partially suppressed, and lack of CORT completely blunted, the up-regulation observed in obese WT-controls. Since SST/CORT are known to exert an inhibitory role on the GH/IGFI axis, the increase in SST/CORT-receptor sst2 expression in MFPs of HF-fed CORT- and SST-KOs together with an elevation on circulating SST in CORT-KOs could explain the differences observed. These results offer new information on the factors (GH/IGF-I axis) involved in the endocrine/metabolic dysregulation of MFPs in obesity, and suggest that CORT is not a mere SST sibling in regulating MG physiology.
authors: Department of Cell Biology, Physiology, and Immunology, University of Córdoba, Córdoba, Spain; Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Reina Sofía University Hospital, Córdoba, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Córdoba, Spain.
authors: Alicia
authors: A
authors: Villa-Osaba
authors: Department of Cell Biology, Physiology, and Immunology, University of Córdoba, Córdoba, Spain; Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Reina Sofía University Hospital, Córdoba, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Córdoba, Spain.
authors: Manuel D
authors: MD
authors: Gahete
authors: Department of Cell Biology, Physiology, and Immunology, University of Córdoba, Córdoba, Spain; Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Reina Sofía University Hospital, Córdoba, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Córdoba, Spain; Department of Medicine, University of Illinois at Chicago and Jesse Brown Veteran Affairs Medical Center, Research and Development Division, Chicago, Illinois, United States of America.
authors: José
authors: J
authors: Córdoba-Chacón
authors: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, United States of America.
authors: Luis
authors: L
authors: de Lecea
authors: Department of Cell Biology, Physiology, and Immunology, University of Córdoba, Córdoba, Spain; Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Reina Sofía University Hospital, Córdoba, Spain.
authors: Ana I
authors: AI
authors: Pozo-Salas
authors: Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Reina Sofía University Hospital, Córdoba, Spain; Lipids and Atherosclerosis Unit, Department of Medicine, Reina Sofía University Hospital, Córdoba, Spain.
authors: Francisco Javier
authors: FJ
authors: Delgado-Lista
authors: Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Reina Sofía University Hospital, Córdoba, Spain; Mammary Gland Unit, Reina Sofía University Hospital, Córdoba, Spain.
authors: Marina
authors: M
authors: Álvarez-Benito
authors: Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Reina Sofía University Hospital, Córdoba, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Córdoba, Spain; Lipids and Atherosclerosis Unit, Department of Medicine, Reina Sofía University Hospital, Córdoba, Spain.
authors: José
authors: J
authors: López-Miranda
authors: Department of Cell Biology, Physiology, and Immunology, University of Córdoba, Córdoba, Spain; Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Reina Sofía University Hospital, Córdoba, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Córdoba, Spain.
authors: Raúl M
authors: RM
authors: Luque
authors: Department of Cell Biology, Physiology, and Immunology, University of Córdoba, Córdoba, Spain; Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Reina Sofía University Hospital, Córdoba, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Córdoba, Spain.
authors: Justo P
authors: JP
authors: Castaño
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001835:Body Weight; D059305:Diet, High-Fat; D005260:Female; D054439:Ghrelin / Q000378:metabolism; D013006:Growth Hormone / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D020738:Leptin / Q000097:blood; D008321:Mammary Glands, Animal / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008820:Mice, Obese; D009479:Neuropeptides / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D017481:Receptors, Somatostatin / Q000235:genetics / Q000378:metabolism; D013004:Somatostatin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D054439:Ghrelin; D020738:Leptin; D009479:Neuropeptides; D017481:Receptors, Somatostatin; C099323:cortistatin; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone