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Updated: Jun 2, 2026
Ultrasonography of the Adult Male Urinary Tract for Urinary Functional Testing
Published on: August 14, 2019
Cyclic GMP signaling in rat urinary bladder, prostate, and epididymis: tissue-specific changes with aging and in
Dieter Müller1, Amal K Mukhopadhyay, Michail S Davidoff
1Institute of Anatomy and Cell Biology, Justus-Liebig-University, Aulweg 123, 35385 Giessen, Germany. hans-dieter.mueller@anatomie.med.uni-giessen.de
Abstract:
Aging of the male reproductive system leads to changes in endocrine signaling and is frequently associated with the emergence of prostate hyperplasia and bladder dysfunctions. Recent reports highlight prostate and bladder as promising targets for therapeutic interventions with inhibitors of the cyclic GMP (cGMP)-degrading phosphodiesterase 5 (PDE5). However, the cGMP signaling system in these organs is as yet poorly characterized, and the possibility of age-related alterations has not been addressed. This study investigates key proteins of cGMP pathways in bladder, prostate, and epididymis of young (3 months) and old (23-24 months) Wistar rats. Local differences in the abundance of PDE5, soluble guanylyl cyclase (sGC) and particulate guanylyl cyclases (GC-A, GC-B), endothelial nitric oxide synthase, and cGMP-dependent protein kinase I (PRKG1 (cGKI)) revealed pronounced tissue-specific peculiarities. Although cGMP-generating enzymes were not affected by age in all organs, we recognized age-related decreases of PDE5 expression in bladder and a selective diminishment of membrane-associated PRKG1 in epididymis. In disagreement with published data, all cGMP pathway proteins including PDE5 are poorly expressed in prostate. However, prostatic PRKG1 expression increases with aging. Androgen withdrawal during temporary Leydig cell elimination induced a massive (>12-fold) upregulation of PRKG1 in prostate but not in other (penis and epididymis) androgen-dependent organs. These findings identify PRKG1 as a key androgen-sensitive signaling protein in prostate of possible importance for growth regulation. The elucidated effects may have significance for age-associated pathologies in the male lower-urinary tract.
Insights
Aging affects male reproductive organs, with decreased PDE5 in the bladder and increased PRKG1 in the prostate. This study explores cGMP pathway proteins in aging rats, revealing tissue-specific changes relevant to lower urinary tract health.
Area of Science:
- Reproductive biology
- Urology
- Molecular signaling
Background:
- Male reproductive system aging is linked to endocrine changes, prostate hyperplasia, and bladder dysfunction.
- Cyclic GMP (cGMP) signaling, targeted by PDE5 inhibitors, is crucial but poorly understood in these organs.
- Age-related alterations in cGMP pathways remain largely uninvestigated.
Purpose of the Study:
- To investigate age-related changes in key cGMP pathway proteins in the bladder, prostate, and epididymis of Wistar rats.
- To characterize tissue-specific expression patterns and age-dependent modifications of these proteins.
Main Methods:
- Comparative analysis of cGMP pathway proteins (PDE5, sGC, GC-A, GC-B, eNOS, PRKG1) in young and old Wistar rats.
- Tissue sampling from bladder, prostate, and epididymis.
- Assessment of protein expression and localization.
Main Results:
- Pronounced tissue-specific expression of cGMP pathway proteins was observed.
- Age-related decrease in PDE5 expression in the bladder and membrane-associated PRKG1 in the epididymis.
- Prostate showed low expression of most cGMP proteins but increased PRKG1 with aging, significantly upregulated by androgen withdrawal.
Conclusions:
- PRKG1 is identified as a key androgen-sensitive protein in the prostate, potentially involved in growth regulation.
- Age-associated changes in cGMP pathway proteins, particularly PRKG1, may contribute to male lower urinary tract pathologies.
- Findings highlight tissue-specific regulation and age-dependent modulation of cGMP signaling in the male reproductive system.
