Editorial: molecular endocrinology articles in the spotlight for June 2012.

Welcome to the June issue of Molecular Endocrinology. The following papers are recommended for your reading. In “The Glucocorticoid-Induced Leucine Zipper (Gilz/ Tsc22d3-2) Gene Locus Plays a Crucial Role in Male Fertility” by Suarez et al., the authors analyzed mice deficient for GILZ and unveiled a novel role of this protein for male fertility. Specifically, the authors showed that GILZ-deficient male mice were infertile due to an agedependent dysplasia of testes tissue that led to the eventual complete disruption of spermatogenesis. Associated with this loss of germ cells and spermatozoa was an increased number of interstitial Leydig cells. Surprisingly, in this knockout model, GILZ was not crucial for thymus development, inflammatory responses, and cytokine secretion as would have been predicted from various results obtained in vitro. Future studies will certainly be directed at establishing the mechanisms for the GILZ protein’s role in spermatogenesis, perhaps providing novel targets or pathways for the development of new male fertility drugs. “The Steroid and Xenobiotic Receptor Negatively Regulates B-1 Cell Development in the Fetal Liver” by Casey and Blumberg examines the important role SXR plays as a developmental regulator of the B-1 B cell compartment in the fetal liver. Previous work by this group showed that mice lacking SXR develop lymphoproliferations of B-1 cells that develop into multifocal lymphomas with advancing age. In their latest work, they show that activation of SXR in utero inhibits the development of a B-1 B lymphocyte progenitor population in fetal liver, which subsequently leads to a significantly decreased population of B-1 cells at adulthood. Given the role of B-1 cell production of IgM in the innate immune response to an influenza virus infection, prenatal exposure to SXR agonists could limit the ability of offspring to mount an effective immune response against this potentially deadly virus. Hu et al.’s “Peroxisome Proliferator-Activated Receptor Decouples Fatty Acid Uptake from Lipid Inhibition of Insulin Signaling in Skeletal Muscle” examines the effects of direct peroxisome proliferator-activated receptor (PPAR ) action in skeletal muscle. This nuclear receptor has been known to act directly in skeletal muscle to decrease adiposity and enhance insulin sensitivity, but the mechanisms responsible for these effects have not been determined. In the study by Hu et al., PPAR was found to increase fatty acid uptake through up-regulation of fatty acid translocases (e.g., CD36), restore palmitateinhibited insulin signaling to AKT despite increasing palmitate uptake, and coordinately reverse lipotoxic inhibition at the phosphoinositide dependent kinase 1 PDK1-AKT signaling nexus. These findings provide some explanation for the potential direct insulin-sensitizing action of thiazolidinediones (TZD) in skeletal muscle, although indirect effects of TZD may also operate to enhance insulin-induced glucose uptake in this tissue. These studies and others in this issue highlight the impact of endocrinology research in a variety of physiological and pathophysiological conditions ranging from diabetes to male infertility and innate immunity. Congratulations to these researchers, as well as those who produced all of the excellent science in this issue, on broadening our knowledge in such diverse areas. Donald B. DeFranco, Ph.D. Editor-in-Chief, Molecular Endocrinology