Editorial: Molecular Endocrinology Articles in the Spotlight for October 2012

Abstract

The October issue of Molecular Endocrinology is packed with excellent science. I would like to highlight a few articles especially recommended for your reading. In the article, “Cell-Autonomous Regulation of Brown Fat Identity Gene UCP1 by Unliganded Vitamin D Receptor,” Malloy et al demonstrate that regulation of the critical brown fat gene UCP1 by vitamin D receptor (VDR), which regulates brown fat identity genes in human cells is direct, resulting in cell autonomous control of this mediator of energy metabolism. The regulation of UCP1 by VDR is ligand independent, suggesting that hormonal intake or stores of vitamin D are unlikely to impact the beiging phenotype of adipocyte tissue. The ligand independence of the regulation will stimulate development of selective VDR antagonists (SVDRMs) that promote cellular beiging but do not impair other VDR activities like the regulation of calcium homeostasis. This study also suggests that mutations or polymorphisms in the VDR gene could impact the amount of beige or brown fat in humans and may therefore be worthy of investigation. “Targeting Stromal Androgen Receptor Suppresses Prolactin-Driven Benign Prostatic Hyperplasia (BPH)” by Lai et al describes the first stromal fibromuscular androgen receptor (AR) knockout, which used a probasin promoter driven prolactin transgenic (Pb-PRL tg) mouse, to study stromal AR function in BPH development. Specifically, elimination of stromal fibromuscular AR led to reduced prostate size, diminished epithelial/stromal cell proliferation, and alleviated microenvironmental changes including extracellular matrix remodeling and immune cells infiltration. Furthermore, stromal fibromuscular AR was able to modulate an epithelial-stromal interaction through the epithelial prolactin/prolactin receptor-granulocyte macrophage-colony stimulating factor-stromal signal transducer and activator of transcription 3 axes to facilitate the stromal cell growth. The report by Laryea et al, “Disrupting Hypothalamic Glucocorticoid Receptors Causes HPA Axis Hyperactivity and Excess Adiposity” (freely available at http://mend. endojournals.org/) demonstrates the essential role of glucocorticoid receptor-mediated negative feedback regulation in the paraventricular nucleus of the hypothalamus. Although chronic exposure to elevated glucocorticoids is often associated with anxiety and despair-related behavioral changes, the elevation resulting from disrupted paraventricular nucleus (PVN) glucocorticoid receptor (GR) does not. This may reflect adaptive mechanisms in other brain regions that attenuate glucocorticoid receptor activation. Alternatively, the normal circadian rhythm that is maintained in these animals may allow compensation to occur. Importantly, the loss of GR in the PVN is somehow protective against high circulating glucocorticoid levels. This study highlights the substantial differences in phenotypes that can emerge with conditional deletion of different versions of the same gene. Congratulations to all the authors in this issue for their fine work and research. Donald B. DeFranco, PhD Editor-in-Chief, Molecular Endocrinology E D I T O R I A L