title: Distribution and function of 3',5'-Cyclic-AMP phosphodiesterases in the human ovary.
abstract: The concentration of the important second messenger cAMP is regulated by phosphodiesterases (PDEs) and hence an attractive drug target. However, limited human data are available about the PDEs in the ovary. The aim of the present study was to describe and characterise the PDEs in the human ovary. Results were obtained by analysis of mRNA microarray data from follicles and granulosa cells (GCs), combined RT-PCR and enzymatic activity analysis in GCs, immunohistochemical analysis of ovarian sections and by studying the effect of PDE inhibitors on progesterone production from cultured GCs. We found that PDE3, PDE4, PDE7 and PDE8 are the major families present while PDE11A was not detected. PDE8B was differentially expressed during folliculogenesis. In cultured GCs, inhibition of PDE7 and PDE8 increased basal progesterone secretion while PDE4 inhibition increased forskolin-stimulated progesterone secretion. In conclusion, we identified PDE3, PDE4, PDE7 and PDE8 as the major PDEs in the human ovary.
authors.affiliation: Laboratory of Reproductive Biology, The Juliane Marie Centre for Women, Children, and Reproduction - Copenhagen University Hospital, Copenhagen University, Copenhagen 2100, Denmark; Medical Department, LEO Pharma, Ballerup 2750, Denmark. Electronic address: tonnyspetersen@gmail.com.
authors.forename: T S
authors.initials: TS
authors.lastname: Petersen
authors.affiliation: Laboratory of Reproductive Biology, The Juliane Marie Centre for Women, Children, and Reproduction - Copenhagen University Hospital, Copenhagen University, Copenhagen 2100, Denmark.
authors.forename: S G
authors.initials: SG
authors.lastname: Kristensen
authors.affiliation: Laboratory of Reproductive Biology, The Juliane Marie Centre for Women, Children, and Reproduction - Copenhagen University Hospital, Copenhagen University, Copenhagen 2100, Denmark.
authors.forename: J V
authors.initials: JV
authors.lastname: Jeppesen
authors.affiliation: The Fertility Clinic, Herlev Hospital, Copenhagen University Hospital, Copenhagen University, Herlev 2730, Denmark.
authors.forename: M L
authors.initials: ML
authors.lastname: Grøndahl
authors.affiliation: The Fertility Clinic, Holbæk Sygehus, Holbæk 4300, Denmark.
authors.forename: M L
authors.initials: ML
authors.lastname: Wissing
authors.affiliation: The Fertility Clinic, The Juliane Marie Centre for Women, Children, and Reproduction - Copenhagen University Hospital, Copenhagen University, Copenhagen 2100, Denmark.
authors.forename: K T
authors.initials: KT
authors.lastname: Macklon
authors.affiliation: Laboratory of Reproductive Biology, The Juliane Marie Centre for Women, Children, and Reproduction - Copenhagen University Hospital, Copenhagen University, Copenhagen 2100, Denmark.
authors.forename: C Y
authors.initials: CY
authors.lastname: Andersen
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D005576:Colforsin / Q000494:pharmacology; D015925:Cryopreservation; D005260:Female; D015870:Gene Expression; D006107:Granulosa Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000145:classification / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010053:Ovary; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D061251:Primary Cell Culture; D011374:Progesterone / Q000096:biosynthesis / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D007527:Isoenzymes; D010726:Phosphodiesterase Inhibitors; D012333:RNA, Messenger; D005576:Colforsin; D011374:Progesterone; D015105:3',5'-Cyclic-AMP Phosphodiesterases
keywords: 3′,5′-Cyclic-AMP phosphodiesterases; Ovary; Phosphodiesterase inhibitors; cAMP signalling