title: Amplification of FSH signalling by CFTR and nuclear soluble adenylyl cyclase in the ovary.
abstract: The cAMP/PKA pathway is one of the most important signalling pathways widely distributed in most eukaryotic cells. The activation of the canonical cAMP/PKA pathway depends on transmembrane adenylyl cyclase (tmAC). Recently, soluble adenylyl cyclase (sAC), which is activated by HCO3-or Ca2+, emerges to provide an alternative way to activate cAMP/PKA pathway with the cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated Cl-/HCO3--conducting anion channel, as a key player. This review summarizes new progress in the investigation of the CFTR/HCO3--dependent sAC signalling and its essential role in various reproductive processes, particularly in ovarian functions. We present the evidence for a CFTR/HCO3--dependent nuclear sAC signalling cascade that amplifies the FSH-stimulated cAMP/PKA pathway, traditionally thought to involve tmAC, in granulosa for the regulation of oestrogen production and granulosa cell proliferation. The implication of the CFTR/HCO3-/sAC pathway in amplifying other receptor-activated cAMP/PKA signalling in a wide variety of cell types and pathophysiological processes, including aging, is also discussed.
authors.affiliation: Epithelial Cell Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, NT, Hong Kong SAR, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: Epithelial Cell Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, NT, Hong Kong SAR, China.
authors.forename: Hsiao Chang
authors.initials: HC
authors.lastname: Chan
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D002467:Cell Nucleus / Q000201:enzymology*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism*; D005260:Female; D043373:Follicle Stimulating Hormone, Human / Q000378:metabolism*; D006801:Humans; D010053:Ovary / Q000201:enzymology* / Q000503:physiopathology; D011085:Polycystic Ovary Syndrome / Q000201:enzymology / Q000503:physiopathology; D015290:Second Messenger Systems
chemical_list: D001639:Bicarbonates; C505032:CFTR protein, human; D043373:Follicle Stimulating Hormone, Human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; C579271:ADCY10 protein, human; D000262:Adenylyl Cyclases
keywords: 
  CFTR
  ; 
  FSH
  ; 
  HCO
  3
  −
  ; 
  sAC
  ; ovarian function