title: Phosphodiesterase-3B is expressed in proopiomelanocortin and neuropeptide Y neurons in the mouse hypothalamus.
abstract: Leptin signaling in the hypothalamus is obligatory for normal food intake and body weight homeostasis. It is now well established that besides the signal transducer and activator of transcription-3 (STAT3) pathway, several non-STAT3 pathways mediate leptin signaling in the hypothalamus. We have previously demonstrated that leptin stimulates phosphodiesterase-3B (PDE3B) activity in the hypothalamus, and PDE3 inhibitor cilostamide reverses anorectic and bodyweight reducing effects of leptin. Recently, we have demonstrated that cilostamide reversed the leptin-induced increase in proopiomelanocortin (POMC) gene expression in the hypothalamus. Because POMC and neuropeptide Y (NPY) neurons are thought to be the major targets of leptin signaling in the hypothalamus, to establish the physiological role of the PDE3B pathway it is important to demonstrate if PDE3B is expressed in these neurons. To this end we examined co-localization of PDE3B with POMC and NPY neurons using immunocytochemistry in POMC-GFP and NPY-GFP mice, respectively. Results showed that PDE3B was highly localized throughout the various hypothalamic sites including the arcuate nucleus (ARC), ventromedial nucleus, dorsomedial nucleus, ventral premammillary nucleus, paraventricular nucleus, and lateral hypothalamus. Importantly, almost all NPY (91.7%) and POMC (97.7%) neurons co-expressed PDE3B. These results suggest a direct role of the PDE3B pathway in mediating leptin signaling in the POMC and NPY neurons-a potential mechanism of leptin signaling in the hypothalamus.
authors: Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Magee-Womens Research Institute, Pittsburgh, PA 15213, USA.
authors: Maitrayee
authors: M
authors: Sahu
authors: David G
authors: DG
authors: Litvin
authors: Abhiram
authors: A
authors: Sahu
mesh_terms: D000818:Animals; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3 / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D005786:Gene Expression Regulation / Q000235:genetics; D007031:Hypothalamus / Q000201:enzymology* / Q000378:metabolism; D020738:Leptin / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009434:Neural Pathways / Q000201:enzymology; D009474:Neurons / Q000201:enzymology* / Q000378:metabolism; D009478:Neuropeptide Y / Q000096:biosynthesis* / Q000235:genetics; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
chemical_list: D020738:Leptin; D009478:Neuropeptide Y; D011333:Pro-Opiomelanocortin; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; C517293:Pde3b protein, mouse