The clinical implications of the difference between castration, gonadotrophin releasing‐hormone (GnRH) antagonists and agonist treatment on the morphology and expression of GnRH receptors in the rat ventral prostate

• Published in: BJU international 2003-02, Vol.91 (3), p.227-233
• Main Authors: Tieva, Å., Bergh, A., Damber, J.‐E.
• Format: Article
• Language: English
• Subjects: agonist; Animals; antagonist; Biological and medical sciences; competitive RT‐PCR; GnRH receptors; Gonadotropin-Releasing Hormone - pharmacology; Hormones. Endocrine system; Immunohistochemistry; Male; Medical sciences; Orchiectomy; Pharmacology. Drug treatments; pituitary; Pituitary Gland - drug effects; prostate; Prostate - chemistry; Prostate - drug effects; rat; Rats; Rats, Sprague-Dawley; Receptors, LHRH - analysis; Receptors, LHRH - drug effects; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - analysis
• ISSN: 1464-4096; 1464-410X
• DOI: 10.1046/j.1464-410X.2003.03054.x

OBJECTIVE To examine the effects of castration and continuous gonadotrophin releasing‐hormone (GnRH) agonist and antagonist therapy on the expression of GnRH‐receptors type I (GnRH‐RI) in rat ventral prostate (VP) and pituitary tissue, and to compare the effects on prostate morphology. MATERIAL AND METHODS Mature Sprague‐Dawley rats were assigned to four treatment groups: group 1, vehicle only; group 2, GnRH agonist goserelin (100 µg/rat/day); group 3, GnRH antagonist cetrorelix (100 µg/rat/day); and group 4, orchidectomy. After 4 weeks the body weights were recorded and VP and pituitary tissue analysed for GnRH‐RI expression using a competitive reverse transcriptase–polymerase chain reaction and immunohistochemistry. RESULTS GnRH antagonist and orchidectomy decreased testosterone secretion and VP volume similarly, but the effects were not identical. The involution of the glandular lumina was more pronounced after orchidectomy while the antagonist therapy was more effective in suppressing epithelial cell proliferation. In the VP, GnRH‐RI mRNA levels were increased after GnRH analogue therapy, but were unaffected by orchidectomy. In the pituitary, GnRH‐RI mRNA expression was higher in response to orchidectomy and decreased after GnRH analogue treatment. CONCLUSION Treatment with a GnRH antagonist for 4 weeks is more effective than an agonist in suppressing testosterone and inducing VP involution. The GnRH antagonist was more effective in suppressing VP epithelial cell proliferation than was castration, suggesting that it induces reduced proliferation by interfering with effects of locally produced GnRH. These results suggest that different regulatory mechanisms may operate in the rat VP than in the pituitary to control GnRH‐RI mRNA expression.