Expression of cAMP and cGMP-phosphodiesterase isoenzymes 3, 4, and 5 in the human clitoris: immunohistochemical and molecular biology study.
OBJECTIVE
Only a little research has focused on the evaluation of female sexual function. With sexual stimulation, the clitoris becomes engorged with blood and tumescent. Nevertheless, only little is known about the significance of the cyclic nucleotide-mediated signal transduction in the control of this process. We sought to elucidate the presence of the phosphodiesterase (PDE) isoenzymes 3, 4, and 5 in the human clitoris using immunohistochemical and molecular biology methods.


METHODS
Thin sections of clitoral specimens were incubated with primary antibodies directed against PDE isoenzymes 3, 4, and 5. Next, the sections were incubated with either Texas red or fluorescein isothiocyanate-labeled secondary antibodies, and visualization was done using laser microscopy. The expression of mRNA encoding for various PDE isoenzymes was evaluated using reverse transcriptase polymerase chain reaction.


RESULTS
Immunofluorescence indicating the presence of PDE4 (cyclic adenosine monophosphate-PDE) was observed in the nonvascular smooth musculature of the corpus cavernosum clitoris, sinusoidal endothelial and subendothelial layers, and nerve fibers innervating the tissue. Immunoreactivity specific for PDE5 (cyclic guanosine monophosphate-PDE) was limited to the smooth muscle of the clitoral erectile tissue. The fluorescein isothiocyanate reaction indicating the expression of PDE3 (cyclic adenosine monophosphate-PDE) was registered to a certain degree only in the clitoral epidermis. In the reverse transcriptase polymerase chain reaction studies, a predominant expression of mRNA encoding for PDE1A was registered, but only small amounts of mRNA encoding for PDE4 and PDE5 were detected.


CONCLUSIONS
Our results have demonstrated the presence of cyclic adenosine monophosphate-PDE and cyclic guanosine monophosphate-PDE in the human clitoris and may indicate a regulatory function of these enzymes in the cyclic nucleotide-mediated control of smooth muscle tone.
Oelke
Matthias
M
Department of Urology, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands. sue_de_99@yahoo.de
Hedlund
Petter
P
Albrecht
Knut
K
Ellinghaus
Peter
P
Stief
Christian G
CG
Jonas
Udo
U
Andersson
Karl-Erik
KE
Uckert
Stefan
S
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000096:biosynthesis*; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D000293:Adolescent; D000328:Adult; D002987:Clitoris / Q000378:metabolism* / Q000502:physiology; D000242:Cyclic AMP; D006152:Cyclic GMP; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis; D008297:Male; D010413:Penis / Q000378:metabolism*; D010727:Phosphoric Diester Hydrolases / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019529:Sexuality / Q000502:physiology; D015398:Signal Transduction
D007527:Isoenzymes; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517381:PDE5A protein, human; D006152:Cyclic GMP