Distribution and function of 3',5'-Cyclic-AMP phosphodiesterases in the human ovary

T S Petersen; S G Kristensen; J V Jeppesen; M L Grøndahl; M L Wissing; K T Macklon; C Y Andersen

doi:10.1016/j.mce.2015.01.004

Distribution and function of 3',5'-Cyclic-AMP phosphodiesterases in the human ovary

Mol Cell Endocrinol. 2015 Mar 5:403:10-20. doi: 10.1016/j.mce.2015.01.004. Epub 2015 Jan 8.

Authors

T S Petersen¹, S G Kristensen², J V Jeppesen², M L Grøndahl³, M L Wissing⁴, K T Macklon⁵, C Y Andersen²

Affiliations

¹ 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.
² Laboratory of Reproductive Biology, The Juliane Marie Centre for Women, Children, and Reproduction - Copenhagen University Hospital, Copenhagen University, Copenhagen 2100, Denmark.
³ The Fertility Clinic, Herlev Hospital, Copenhagen University Hospital, Copenhagen University, Herlev 2730, Denmark.
⁴ The Fertility Clinic, Holbæk Sygehus, Holbæk 4300, Denmark.
⁵ The Fertility Clinic, The Juliane Marie Centre for Women, Children, and Reproduction - Copenhagen University Hospital, Copenhagen University, Copenhagen 2100, Denmark.

PMID: 25578602
DOI: 10.1016/j.mce.2015.01.004

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.

Keywords: 3′,5′-Cyclic-AMP phosphodiesterases; Ovary; Phosphodiesterase inhibitors; cAMP signalling.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors
3',5'-Cyclic-AMP Phosphodiesterases / classification
3',5'-Cyclic-AMP Phosphodiesterases / genetics*
3',5'-Cyclic-AMP Phosphodiesterases / metabolism
Adult
Colforsin / pharmacology
Cryopreservation*
Female
Gene Expression
Granulosa Cells / cytology
Granulosa Cells / drug effects
Granulosa Cells / enzymology*
Humans
Immunohistochemistry
Isoenzymes / antagonists & inhibitors
Isoenzymes / classification
Isoenzymes / genetics
Isoenzymes / metabolism
Oligonucleotide Array Sequence Analysis
Ovary*
Phosphodiesterase Inhibitors / pharmacology
Primary Cell Culture
Progesterone / biosynthesis
Progesterone / metabolism
RNA, Messenger / genetics*
RNA, Messenger / metabolism
Reverse Transcriptase Polymerase Chain Reaction

Substances

Isoenzymes
Phosphodiesterase Inhibitors
RNA, Messenger
Colforsin
Progesterone
3',5'-Cyclic-AMP Phosphodiesterases