Abstract
Prostate carcinoma and benign prostate hyperplasia (BPH) with associated lower urinary tract symptoms (LUTS) are among the most prevalent and clinically relevant diseases in men. BPH is characterized by an enlargement of prostate tissue associated with increased tone of smooth muscle cells (SMCs) which surround the single glands composing the prostate. Secretions of the glands leave the prostate through local excretory ducts during the emission phase of ejaculation. Pharmacological treatment of BPH suggests different local drug targets based on reduction of prostate smooth muscle tone as the main effect and disturbed ejaculation as a common side effect. This highlights the need for detailed investigation of single prostate glands and ducts. We combined structural and functional imaging techniques—notably, clear lipid-exchanged, acrylamide-hybridized rigid imaging/immunostaining/in situ hybridization–compatible tissue-hydrogel (CLARITY) and time-lapse imaging—and defined glands and ducts as distinct SMC compartments in human and rat prostate tissue. The single glands of the prostate (comprising the secretory part) are characterized by spontaneous contractions mediated by the surrounding SMCs, whereas the ducts (excretory part) are quiescent. In both SMC compartments, phosphodiesterase (PDE)-5 is expressed. PDE5 inhibitors have recently emerged as alternative treatment options for BPH. We directly visualized that the PDE5 inhibitors sildenafil and tadalafil act by reducing spontaneous contractility of the glands, thereby reducing the muscle tone of the organ. In contrast, the ductal (excretory) system and thus the prostate’s contribution to ejaculation is unaffected by PDE5 inhibitors. Our differentiated imaging approach reveals new details about prostate function and local drug actions and thus may support clinical management of BPH.—Kügler, R., Mietens, A., Seidensticker, M., Tasch, S., Wagenlehner, F. M., Kaschtanow, A., Tjahjono, Y., Tomczyk, C. U., Beyer, D., Risbridger, G. P., Exintaris, B., Ellem, S. J., Middendorff, R. Novel imaging of the prostate reveals spontaneous gland contraction and excretory duct quiescence together with different drug effects.
| Original language | English |
|---|---|
| Pages (from-to) | 1130-1138 |
| Number of pages | 9 |
| Journal | FASEB Journal |
| Volume | 32 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 1 Mar 2018 |
Keywords
- 3D imaging
- Contractility
- PDE5 inhibitors
- Time-lapse imaging
Cite this
}
Novel imaging of the prostate reveals spontaneous gland contraction and excretory duct quiescence together with different drug effects. / Kügler, Robert; Mietens, Andrea; Seidensticker, Mathias; Tasch, Sabine; Wagenlehner, Florian M.; Kaschtanow, Andre; Tjahjono, Yudy; Tomczyk, Claudia U.; Beyer, Daniela; Risbridger, Gail P.; Exintaris, Betty; Ellem, Stuart J.; Middendorff, Ralf.
In: FASEB Journal, Vol. 32, No. 3, 01.03.2018, p. 1130-1138.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Novel imaging of the prostate reveals spontaneous gland contraction and excretory duct quiescence together with different drug effects
AU - Kügler, Robert
AU - Mietens, Andrea
AU - Seidensticker, Mathias
AU - Tasch, Sabine
AU - Wagenlehner, Florian M.
AU - Kaschtanow, Andre
AU - Tjahjono, Yudy
AU - Tomczyk, Claudia U.
AU - Beyer, Daniela
AU - Risbridger, Gail P.
AU - Exintaris, Betty
AU - Ellem, Stuart J.
AU - Middendorff, Ralf
PY - 2018/3/1
Y1 - 2018/3/1
N2 - Prostate carcinoma and benign prostate hyperplasia (BPH) with associated lower urinary tract symptoms (LUTS) are among the most prevalent and clinically relevant diseases in men. BPH is characterized by an enlargement of prostate tissue associated with increased tone of smooth muscle cells (SMCs) which surround the single glands composing the prostate. Secretions of the glands leave the prostate through local excretory ducts during the emission phase of ejaculation. Pharmacological treatment of BPH suggests different local drug targets based on reduction of prostate smooth muscle tone as the main effect and disturbed ejaculation as a common side effect. This highlights the need for detailed investigation of single prostate glands and ducts. We combined structural and functional imaging techniques—notably, clear lipid-exchanged, acrylamide-hybridized rigid imaging/immunostaining/in situ hybridization–compatible tissue-hydrogel (CLARITY) and time-lapse imaging—and defined glands and ducts as distinct SMC compartments in human and rat prostate tissue. The single glands of the prostate (comprising the secretory part) are characterized by spontaneous contractions mediated by the surrounding SMCs, whereas the ducts (excretory part) are quiescent. In both SMC compartments, phosphodiesterase (PDE)-5 is expressed. PDE5 inhibitors have recently emerged as alternative treatment options for BPH. We directly visualized that the PDE5 inhibitors sildenafil and tadalafil act by reducing spontaneous contractility of the glands, thereby reducing the muscle tone of the organ. In contrast, the ductal (excretory) system and thus the prostate’s contribution to ejaculation is unaffected by PDE5 inhibitors. Our differentiated imaging approach reveals new details about prostate function and local drug actions and thus may support clinical management of BPH.—Kügler, R., Mietens, A., Seidensticker, M., Tasch, S., Wagenlehner, F. M., Kaschtanow, A., Tjahjono, Y., Tomczyk, C. U., Beyer, D., Risbridger, G. P., Exintaris, B., Ellem, S. J., Middendorff, R. Novel imaging of the prostate reveals spontaneous gland contraction and excretory duct quiescence together with different drug effects.
AB - Prostate carcinoma and benign prostate hyperplasia (BPH) with associated lower urinary tract symptoms (LUTS) are among the most prevalent and clinically relevant diseases in men. BPH is characterized by an enlargement of prostate tissue associated with increased tone of smooth muscle cells (SMCs) which surround the single glands composing the prostate. Secretions of the glands leave the prostate through local excretory ducts during the emission phase of ejaculation. Pharmacological treatment of BPH suggests different local drug targets based on reduction of prostate smooth muscle tone as the main effect and disturbed ejaculation as a common side effect. This highlights the need for detailed investigation of single prostate glands and ducts. We combined structural and functional imaging techniques—notably, clear lipid-exchanged, acrylamide-hybridized rigid imaging/immunostaining/in situ hybridization–compatible tissue-hydrogel (CLARITY) and time-lapse imaging—and defined glands and ducts as distinct SMC compartments in human and rat prostate tissue. The single glands of the prostate (comprising the secretory part) are characterized by spontaneous contractions mediated by the surrounding SMCs, whereas the ducts (excretory part) are quiescent. In both SMC compartments, phosphodiesterase (PDE)-5 is expressed. PDE5 inhibitors have recently emerged as alternative treatment options for BPH. We directly visualized that the PDE5 inhibitors sildenafil and tadalafil act by reducing spontaneous contractility of the glands, thereby reducing the muscle tone of the organ. In contrast, the ductal (excretory) system and thus the prostate’s contribution to ejaculation is unaffected by PDE5 inhibitors. Our differentiated imaging approach reveals new details about prostate function and local drug actions and thus may support clinical management of BPH.—Kügler, R., Mietens, A., Seidensticker, M., Tasch, S., Wagenlehner, F. M., Kaschtanow, A., Tjahjono, Y., Tomczyk, C. U., Beyer, D., Risbridger, G. P., Exintaris, B., Ellem, S. J., Middendorff, R. Novel imaging of the prostate reveals spontaneous gland contraction and excretory duct quiescence together with different drug effects.
KW - 3D imaging
KW - Contractility
KW - PDE5 inhibitors
KW - Time-lapse imaging
UR - http://www.scopus.com/inward/record.url?scp=85043521867&partnerID=8YFLogxK
U2 - 10.1096/fj.201700430R
DO - 10.1096/fj.201700430R
M3 - Article
AN - SCOPUS:85043521867
VL - 32
SP - 1130
EP - 1138
JO - FASEB Journal
JF - FASEB Journal
SN - 0892-6638
IS - 3
ER -