Expression of messenger ribonucleic acid encoding for phosphodiesterase isoenzymes in human female genital tissues.
OBJECTIVE
The use of inhibitors of phosphodiesterase 5 (PDE5) has been suggested to treat symptoms of female sexual dysfunction (FSD). Nonetheless, there has been a relatively low success rate of PDE5 inhibitors in FSD in comparison with male erectile dysfunction. The elevated expression of PDE5 in the human penile erectile tissue is considered the reason for the high clinical efficacy of PDE5 inhibitors in the pharmacotherapy of male erectile dysfunction.


OBJECTIVE
To evaluate by means of molecular biology the expression of messenger ribonucleic acid expression (mRNA) encoding for cyclic AMP and cyclic GMP PDE isoenzymes in female genital tissues.


METHODS
The amount of mRNA transcripts specifically encoding for cyclic AMP- and/or cyclic GMP-degrading PDE isoenzymes was determined.


METHODS
Human clitoral, labial, and vaginal tissue was obtained from four female cadavers (age at death: 18-42 years). The expression of mRNA specifically encoding for PDE1A, 1B, 1C, 2A, 4A, 5A, 10A, and 11A was elucidated by means of real-time polymerase chain reaction (PCR) analysis (TaqMan). Human penile erectile tissue (corpus cavernosum [HCC]) was used as a reference tissue.


RESULTS
mRNA encoding for all PDE isoforms mentioned above is expressed in the female genital tissues. Different magnitudes of mRNA expression were observed: a predominant expression of mRNA encoding for PDE1A but only insignificant amounts of PDE1B, 1C, 4A, 10, and 11A mRNA were registered. With PDE1A being the only exception, the mRNA expression was always higher in the HCC than in the female genital tissues. Especially, the expression of mRNA encoding for PDE5 was several-fold higher in the HCC.


CONCLUSIONS
On the mRNA level, various PDE isoforms are expressed in the clitoris, labia, and vagina. It remains to be established as to whether the low expression of PDE5 in female genital tissue might be a negative predictor for the success of PDE5 inhibitors in the treatment of FSD.
Uckert
Stefan
S
Hannover Medical School--Department of Urology, Hannover, Germany, and IPF Pharmaceuticals GmbH - Urological Research Unit, Hannover, Germany. streetgang@gmx.de
Ellinghaus
Peter
P
Albrecht
Knut
K
Jonas
Udo
U
Oelke
Matthias
M
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism* / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D002987:Clitoris / Q000378:metabolism* / Q000502:physiology; D000242:Cyclic AMP; D006152:Cyclic GMP; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis; D008297:Male; D010413:Penis / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012735:Sexual Dysfunction, Physiological / Q000188:drug therapy; D014844:Vulva / Q000378:metabolism* / Q000502:physiology
D007527:Isoenzymes; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D006152:Cyclic GMP