I would like to introduce you to the spotlight articles for the July issue of Molecular Endocrinology. These articles are excellent examples of how molecular studies support and enhance clinical research.
“C-Type Natriuretic Peptide Stimulates Ovarian Follicle Development” by Sato et al. describes the action of C-type natriuretic peptide (CNP) as an autocrine/paracrine factor to stimulate ovarian follicle development. Because FSH treatment increases ovarian CNP expression, some of the actions of FSH in the ovary are mediated by CNP. Therefore, CNP may be an alternative treatment for infertile women who are not responsive to standard FSH treatment or are at risk for developing life-threatening complications of FSH therapy (i.e., ovarian hyperstimulation syndrome).
“Vitamin D Receptor Signaling Inhibits Atherosclerosis in Mice” by Szeto et al. demonstrates for the first time that macrophage vitamin D receptor signaling plays an inhibitory role in atherogenesis. Specifically, macrophage vitamin D receptor signaling attenuates atherosclerosis by blocking the activation of the local renin-angiotensin system in macrophages. This study reveals a new function of vitamin D in the cardiovascular system, broadens our understanding of the vitamin D endocrine system, and provides new insights into the therapeutic potential of vitamin D in cardiovascular disease.
The paper by Yang et al., “Increased DNA Methylation and Decreased Expression of PDX-1 in Pancreatic Islets from Patients with Type 2 Diabetes,” focuses on the gene for pancreatic duodenal homeobox 1 (PDX-1), a homeodomain-containing transcription factor that plays a key role in pancreas development and function. Mutations in PDX-1 can cause a monogenic form of diabetes (maturity-onset diabetes of the young 4) in humans, and silencing Pdx-1 in pancreatic β-cells of mice causes diabetes. Results from this study suggest that epigenetic modifications of the PDX-1 gene may play a role in the development of impaired insulin secretion seen in human diabetic islets as pancreatic islets from patients with type 2 diabetes exhibit decreased expression and increased DNA methylation of PDX-1 in parallel with impaired insulin secretion. Furthermore, experiments in clonal rat β-cells showed that hyperglycemia can enhance PDX-1 methylation and reduce its expression, providing a potential link between altered glucose metabolism and epigenetic modifications in β-cells that lead to reduced insulin expression and secretion.
The authors of these articles as well as all of this month's articles are commended on their fine research.
Donald B. DeFranco, Ph.D.
Editor-in-Chief, Molecular Endocrinology