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

PLoS One. 2015 Mar 25;10(3):e0120955. doi: 10.1371/journal.pone.0120955. eCollection 2015.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism*
  • Animals
  • Body Weight
  • Diet, High-Fat
  • Female
  • Ghrelin / metabolism
  • Growth Hormone / metabolism*
  • Insulin-Like Growth Factor I / metabolism*
  • Leptin / blood
  • Mammary Glands, Animal / metabolism*
  • Mice
  • Mice, Knockout
  • Mice, Obese
  • Neuropeptides / deficiency
  • Neuropeptides / genetics
  • Neuropeptides / metabolism*
  • Obesity / metabolism
  • Obesity / pathology
  • Real-Time Polymerase Chain Reaction
  • Receptors, Somatostatin / genetics
  • Receptors, Somatostatin / metabolism
  • Somatostatin / deficiency
  • Somatostatin / genetics
  • Somatostatin / metabolism*
  • Up-Regulation

Substances

  • Ghrelin
  • Leptin
  • Neuropeptides
  • Receptors, Somatostatin
  • cortistatin
  • Somatostatin
  • Insulin-Like Growth Factor I
  • Growth Hormone

Grants and funding

This work has been funded by the following grants: BFU2010-19300, PI-0369-2012, BIO-0139, PI13/00651, CIBERobn (to RML and JPC), and “Sara Borrell” program CD11/00276 (to MDG). Ciber is an initiative of Instituto de Salud Carlos III, Ministerio de Sanidad, Servicios Sociales e Igualdad, Spain. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.