Evaluation of the mouse prostate as a suitable model for the study of human prostate function.
BACKGROUND
Research into prostate development and function is mainly carried out in rats and guinea pigs. While these animals have proven to be good models of human prostate function, their use is limited when compared with what could be achieved using the various currently available gene knockout mice. This study aimed to ascertain whether the mouse prostate was a viable model for studying human prostate function.


METHODS
Sections from mouse prostate glands were histochemically processed to visualise the neurotransmitters and receptors present. Isolated organ bath studies were conducted in Krebs-Henseleit solution at 37 degrees C to delineate the physiological mechanisms involved in contractility.


RESULTS
Positive histochemical staining for noradrenaline and acetylcholinesterase (AChE) was observed in the fibromuscular stroma. AChE-positive staining was also observed in epithelial cells lining prostatic acini. Immunoreactivity to P2X(1) and P2X(7) purinoceptors was observed in the fibromuscular stroma and immunoreactivity to P2X(4) purinoceptors in the glandular epithelium. Positive immunostaining for neuropeptide Y, big endothelin, calcitonin gene-related peptide (CGRP), substance P, and neurokinin A was observed in the fibromuscular stroma. Frequency-response curves (1.0 ms pulse duration, 60 V, 0.1-20 Hz) to electrical field stimulation yielded frequency-dependent contractions that were attenuated by tetrodotoxin (P < .001), guanethidine (P < .001), and prazosin (P = .01). Suramin (P = .21), alpha,beta-methylene ATP (P = .84), and atropine (P = .76) caused no significant effects. Concentration-response curves to endogenously administered phenylephrine yielded concentration-dependent contractions (pEC(50) = 6.1 +/- 0.3, maximum response 0.20 +/- 0.03 g), which were attenuated by prazosin (P < .001).


CONCLUSIONS
Histochemistry suggests that mouse prostates have a similar innervation to that of humans and other laboratory animals. Furthermore, responses to nerve stimulation are noradrenergic and mediated by alpha(1)-adrenoceptors. Therefore, the mouse prostate is a suitable model for human prostate function and a viable isolated preparation for contractility studies.
Gray
Katherine T
KT
Department of Pharmaceutical Biology and Pharmacology, Faculty of Pharmacy, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia.
Ventura
Sabatino
S
D000110:Acetylcholinesterase / Q000378:metabolism; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005240:Feasibility Studies; D006145:Guanethidine / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation / Q000378:metabolism / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D010477:Perfusion; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011467:Prostate / Q000294:innervation / Q000378:metabolism / Q000502:physiology*; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D018377:Neurotransmitter Agents; D017981:Receptors, Neurotransmitter; D018048:Receptors, Purinergic P2; D010656:Phenylephrine; D013779:Tetrodotoxin; D000110:Acetylcholinesterase; D009638:Norepinephrine; D011224:Prazosin; D006145:Guanethidine