Mal-Soon Shin1, Kyung Jin Chung2, Il-Gyu Ko1, Sang-Hoon Kim1, Jun-Jang Jin1, Sung-Eun Kim1, Jae-Min Lee1, Eun-Sang Ji1, Tae-Woon Kim1, Han-Sam Cho1, Chang Hee Kim2, Young-Sam Cho3, Chang-Ju Kim1, Khae-Hawn Kim4. 1. Department of Physiology, College of Medicine, Kyung Hee University, Dongdaemun-gu, Seoul, 130-701, Republic of Korea. 2. Department of Urology, Gachon University Gil Medical Center, Gachon University School of Medicine, Incheon, 405-760, Republic of Korea. 3. Department of Urology, School of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University, Jongro-gu, Seoul, 110-746, Republic of Korea. 4. Department of Urology, Gachon University Gil Medical Center, Gachon University School of Medicine, Incheon, 405-760, Republic of Korea. kimcho99@gilhospital.com.
Abstract
PURPOSE: Chemical castration using luteinizing hormone-releasing hormone agonists and/or anti-androgens is an alternative to surgical castration. Goserelin and bicalutamide are representative drugs used for chemical castration. The effects of chemical castration on sexual functions are well documented; however, the possibility that chemical castration might induce undesirable effects on brain functions has been raised. We investigated the effects of chemical castration and surgical castration on spatial learning ability in relation to cell proliferation and apoptosis in hippocampus. METHODS: Bilateral orchiectomy was performed for surgical castration, and chemical castration was induced by treatment with goserelin or bicalutamide for 28 days. To find out the effects of goserelin and bicalutamide with those of orchiectomy on the spatial learning ability, radial eight-arm maze test was performed. To find out the effects of goserelin and bicalutamide with those of orchiectomy in relation to cell proliferation and apoptosis in the hippocampus, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining, and immunohistochemistry for 5-bromo-2'-deoxyuridine, doublecortin, and caspase-3 were performed. Western blot for brain-derived neurotrophic factor, tyrosine kinase receptor B, Bax, and Bcl-2 in the hippocampus was also performed. RESULTS: Orchiectomy caused deterioration of spatial learning ability with suppression of cell proliferation and enhancement of apoptosis in the hippocampus. However, treatment with goserelin and bicalutamide had no effect on spatial learning ability. Cell proliferation and apoptosis were not altered by treatment with goserelin and bicalutamide either. CONCLUSIONS: Surgical castration causes deterioration of spatial learning ability, while chemical castration does not impair spatial learning ability. We should find out further mechanisms affect to the relationship between androgen level and neurogenesis and neuronal apoptosis.
PURPOSE: Chemical castration using luteinizing hormone-releasing hormone agonists and/or anti-androgens is an alternative to surgical castration. Goserelin and bicalutamide are representative drugs used for chemical castration. The effects of chemical castration on sexual functions are well documented; however, the possibility that chemical castration might induce undesirable effects on brain functions has been raised. We investigated the effects of chemical castration and surgical castration on spatial learning ability in relation to cell proliferation and apoptosis in hippocampus. METHODS: Bilateral orchiectomy was performed for surgical castration, and chemical castration was induced by treatment with goserelin or bicalutamide for 28 days. To find out the effects of goserelin and bicalutamide with those of orchiectomy on the spatial learning ability, radial eight-arm maze test was performed. To find out the effects of goserelin and bicalutamide with those of orchiectomy in relation to cell proliferation and apoptosis in the hippocampus, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining, and immunohistochemistry for 5-bromo-2'-deoxyuridine, doublecortin, and caspase-3 were performed. Western blot for brain-derived neurotrophic factor, tyrosine kinase receptor B, Bax, and Bcl-2 in the hippocampus was also performed. RESULTS: Orchiectomy caused deterioration of spatial learning ability with suppression of cell proliferation and enhancement of apoptosis in the hippocampus. However, treatment with goserelin and bicalutamide had no effect on spatial learning ability. Cell proliferation and apoptosis were not altered by treatment with goserelin and bicalutamide either. CONCLUSIONS: Surgical castration causes deterioration of spatial learning ability, while chemical castration does not impair spatial learning ability. We should find out further mechanisms affect to the relationship between androgen level and neurogenesis and neuronal apoptosis.
Authors: C J Tyrrell; A V Kaisary; P Iversen; J B Anderson; L Baert; T Tammela; M Chamberlain; A Webster; G Blackledge Journal: Eur Urol Date: 1998 Impact factor: 20.096