Expression of Messenger Ribonucleic Acid Encoding for Phosphodiesterase Isoenzymes in Human Female Genital Tissues

Abstract

Objectives 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. Aim 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. Main Outcome Measures 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. Conclusion 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.

Diabetes and sexual dysfunction: current perspectives

“…Acting on NO-mediated smooth muscle relaxation to increase vasodilatation, PDE5 inhibitors might theoretically improve vaginal lubrication and vulvar engorgement. In contrast, few successes have been reported for the use of these agents in the treatment of sexual arousal problems in women; this is likely due to the inconsistencies observed between the physiological and psychological factors on sexual response,133 or the low PDE5 levels noted in the female reproductive system 134…”

Immunohistochemical distribution of cyclic nucleotide phosphodiesterase (PDE) isoenzymes in the human vagina: A potential forensic value?

“…Interestingly, the authors presented evidence for a predominant expression of PDE1A and 4A in vaginal the epithelial layer. 20 In conclusion, the non-homogenous distribution of PDE isoenzymes, especially the cAMP-PDE4, in thin sections of the human vaginal wall, which we observed in our study, provides rationale to explore further as to whether there is a value of PDE4 as an immunohistochemical vaginal epithelial marker protein in forensic science. Such studies should also include specimens from the male penile epidermis and glans penis, as well as from the oral and rectal mucosa of male and female individuals.…”

Sexual dysfunction in women: What can urologists contribute?

“…Uckert et al [28,29] evaluated messenger ribonucleic acid expression encoding for cyclic adenosine monophosphate, cyclic guanosine monophosphate, and PDE isoenzymes in female genital tissues. On the messenger ribonucleic acid expression level, various PDE isoforms, including PDE5, are expressed in the clitoris, labia, and vagina.…”

“…Replacement of genital tissues with sex steroids improves genital structure and function. Phosphodiesterase type 5 (PDE5) inhibitors [28][29][30] act on PDE5 enzymes present in female genital tissues and facilitate arousal responses.…”