Obesity alters gene expression for GH/IGF-I axis in mouse mammary fat pads: differential role of cortistatin and somatostatin

• Published in: PloS one 2015-03, Vol.10 (3), p.e0120955-e0120955
• Main Authors: Villa-Osaba, Alicia, Gahete, Manuel D, Córdoba-Chacón, José, de Lecea, Luis, Pozo-Salas, Ana I, Delgado-Lista, Francisco Javier, Álvarez-Benito, Marina, López-Miranda, José, Luque, Raúl M, Castaño, Justo P
• Format: Article
• Language: English
• Subjects: Adipose Tissue - metabolism; Analysis; Animals; Atherosclerosis; Biology; Body Weight; Breast cancer; Control; Diet, High-Fat; Endocrinology; Female; Gene expression; Ghrelin; Ghrelin - metabolism; Growth hormone; Growth Hormone - metabolism; Growth hormones; High fat diet; House mouse; Immunology; Insulin; Insulin-like growth factor I; Insulin-Like Growth Factor I - metabolism; Insulin-like growth factors; Leptin - blood; Low fat diet; Mammary gland; Mammary Glands, Animal - metabolism; Medicine; Metabolism; Mice; Mice, Knockout; Mice, Obese; Morphogenesis; Neuropeptides - deficiency; Neuropeptides - genetics; Neuropeptides - metabolism; Obesity; Obesity - metabolism; Obesity - pathology; Physiological aspects; Physiology; Real-Time Polymerase Chain Reaction; Receptors, Somatostatin - genetics; Receptors, Somatostatin - metabolism; Somatostatin; Somatostatin - deficiency; Somatostatin - genetics; Somatostatin - metabolism; Somatotropin; Up-Regulation
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0120955

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.