Atresia and luteolysis are well-documented processes in which most of the growing ovarian follicles and all corpora lutea, respectively, are eliminated by apoptosis. We have previously reported that LH and FSH enhance caspase-3 and -7 activity and apoptosis in the theca-interstitial cells of rat preovulatory follicles in culture. Here we have used cultured follicles to examine whether LH-induced caspase activation is related to the ability of LH to stimulate steroid production. In these studies, we used three inhibitors of enzymes involved in steroid production: aminoglutethimide and ketoconazole, acting on cytochrome P450 side-chain cleavage (P450scc) located at the mitochondria, and epostane, acting on 3beta-hydroxysteroid dehydrogenase located at the endoplasmic reticulum. We found that treatment with either aminoglutethimide or ketoconazole, but not with epostane, significantly reduced LH-induced caspase-3 and -7 activation and apoptosis, suggesting the mediation of LH-induced caspase activation by P450scc. Supplementing pregnenolone, the product of P450scc catalysis, to follicles treated with aminoglutethimide did not restore LH-induced caspase activation. On the other hand, treatment with antioxidants inhibited LH-induced caspase activation. Moreover, LH treatment was associated with an increase in reactive oxygen species which was inhibited by aminoglutethimide. Thus, P450scc catalysis results in an increase in reactive oxygen species, which in turn may trigger/facilitate caspase-3 activation. Finally, we found that in rat corpora lutea in vivo, an increase in steroidogenesis was accompanied by an increase in caspase activity. Thus, this study reveals a linkage between two seemingly distinct processes in which LH-induced caspase activation in cultured rat preovulatory follicles is coupled to mitochondrial steroidogenesis via P450scc.
(Cell Reports 14, 1602–1610; February 23, 2016) In the originally published version of this article, there was a mistake in Figure S1B: the two fields originally presented were adjacent views of the same gastrocnemius muscle sample. At the time of image acquisition, the images presented in the paper were mislabeled. To correct for this mistake, the authors returned to the original slides (prepared at the original time of collection; prior to publication) and chose two different experiments containing three mice from each genotype (a total of six mice/slides) and acquired images of each. The authors have used these pictures to prepare a corrected version of Figure S1, which has now been corrected online and appears below. The authors regret this error.Figure S1Characteristics of Mice Deficient for Muscle MTCH2 (original)View Large Image Figure ViewerDownload Hi-res image Download (PPT) Loss of Muscle MTCH2 Increases Whole-Body Energy Utilization and Protects from Diet-Induced ObesityBuzaglo-Azriel et al.Cell ReportsFebruary 11, 2016In BriefThe MTCH2 locus is associated with increased obesity in humans. Buzaglo-Azriel et al. show that muscle MTCH2 deficiency in mice provides protection from a high-fat diet and that this protection is most likely due to increased muscle metabolism, leading to elevated whole-body energy demand and heat production. Full-Text PDF Open Access
