H-K-ATPase (Hydrogen-Potassium transport) mediates hormonal effects on morphological changes in benign prostatic hypertrophy
List all Project Mentors & Advisor(s)
Dr. Suguru Nakamura
Second Project Mentor & Advisor(s)
Dr. Jeffrey Osborne
Presentation Format
Poster Presentation
Abstract/Description
Background: The prostate, the key secondary male reproductive organ, serves an important function of alkalizing seminal fluid and protecting genetic information in the acidity of the vaginal tract. As males age, the most common urologic condition manifests as an enlargement of the prostate known as benign prostatic hypertrophy (BPH). The purpose of this study is to examine the relationship between hormonal regulation and the morphological changes in BPH. Furthermore, we examine whether such hormonal regulation is mediated by HKA.
Methods: The experiments were designed to test the effects of the primary male androgen, testosterone propionate (TP), as well as the female hormone, estradiol (E2). Sprague-Dawley outbred rats were divided into three groups; control group, TP group, and TP-E2 group. Both the TP and the E2 were diluted in vegetable oil and covered to eliminate light exposure. Subcutaneous injections of TP at 3 mg/mL were administered to induce BPH in rats. After 6 weeks of TP-induced BPH, we divided these rats into two groups. In one group of BPH rats, we injected 60 µg of E2, and in another group of BPH rats, we injected 120 µg of E2 subcutaneously. The rats were sacrificed under anesthesia, and the prostate specimens were dissected. The rat’s body weight and the prostate tissue weight were measured as the organ quotient. The total prostate specimens were divided into two groups, one tissue group was fixed and embedded in paraffin using histopathological methods to examine the effects on morphological changes in BPH. The other tissue group was examined by Western blot for analysis of HKA by using anti-HKA alpha antibody.
Results: The data indicate significant hypertrophy of the luminal cells in rats with 3 mg TP (11/15/14) compared to the control (524.542 ± 4.637 vs. 350.583 ± 1.996, P-value < 0.005). Furthermore, the experimental group with 3 mg TP (11/13/14) and 60 µg E2 (1/13/15) showed inhibitory effects compared to TP-induced BPH (385.571 ± 7.265 vs. 524.542 ± 4.637, P-value < 0.005). Lastly, the experimental group with 3 mg TP (11/13/14) and 120 µg E2 (1/13/15) showed significant inhibitory effect compared to TP-induced BPH (465.857 ± 8.259 vs. 524.542 ± 4.637, P-value < 0.005). However, the inhibitory effects of the 60 µg E2 group were more significant than the inhibitory effects of the 120 µg E2 group (385.571 ± 7.265 vs. 465.857 ± 8.259, P-value < 0.005), suggesting the importance of maintaining a proper E2:TP ratio. Western blot analysis shows up-regulation of specific bands for HKA alpha subunit at ~97 kDa for TP-induced BPH and down-regulation of HKA in the TP+E2 treatment groups.
Conclusions: Our results show that TP induced benign prostate hypertrophy. Furthermore, E2 is shown to inhibit BPH; however, the effect of E2 inhibition on BPH requires the optimal ratio between E2 and TP. If such a ratio is not reached, then BPH inhibition will not occur by E2. Both the induction and inhibition of hypertrophic cells suggests that the prostate is under hormonal regulation. The proper E2:TP ratio plays a crucial role in the pathogenesis of BPH. Such knowledge of E2:TP ratio in humans may help to prevent or cure BPH in the future.
Location
Barkley Room, Curris Center
Start Date
April 2016
End Date
April 2016
Affiliations
Honors Thesis
H-K-ATPase (Hydrogen-Potassium transport) mediates hormonal effects on morphological changes in benign prostatic hypertrophy
Barkley Room, Curris Center
Background: The prostate, the key secondary male reproductive organ, serves an important function of alkalizing seminal fluid and protecting genetic information in the acidity of the vaginal tract. As males age, the most common urologic condition manifests as an enlargement of the prostate known as benign prostatic hypertrophy (BPH). The purpose of this study is to examine the relationship between hormonal regulation and the morphological changes in BPH. Furthermore, we examine whether such hormonal regulation is mediated by HKA.
Methods: The experiments were designed to test the effects of the primary male androgen, testosterone propionate (TP), as well as the female hormone, estradiol (E2). Sprague-Dawley outbred rats were divided into three groups; control group, TP group, and TP-E2 group. Both the TP and the E2 were diluted in vegetable oil and covered to eliminate light exposure. Subcutaneous injections of TP at 3 mg/mL were administered to induce BPH in rats. After 6 weeks of TP-induced BPH, we divided these rats into two groups. In one group of BPH rats, we injected 60 µg of E2, and in another group of BPH rats, we injected 120 µg of E2 subcutaneously. The rats were sacrificed under anesthesia, and the prostate specimens were dissected. The rat’s body weight and the prostate tissue weight were measured as the organ quotient. The total prostate specimens were divided into two groups, one tissue group was fixed and embedded in paraffin using histopathological methods to examine the effects on morphological changes in BPH. The other tissue group was examined by Western blot for analysis of HKA by using anti-HKA alpha antibody.
Results: The data indicate significant hypertrophy of the luminal cells in rats with 3 mg TP (11/15/14) compared to the control (524.542 ± 4.637 vs. 350.583 ± 1.996, P-value < 0.005). Furthermore, the experimental group with 3 mg TP (11/13/14) and 60 µg E2 (1/13/15) showed inhibitory effects compared to TP-induced BPH (385.571 ± 7.265 vs. 524.542 ± 4.637, P-value < 0.005). Lastly, the experimental group with 3 mg TP (11/13/14) and 120 µg E2 (1/13/15) showed significant inhibitory effect compared to TP-induced BPH (465.857 ± 8.259 vs. 524.542 ± 4.637, P-value < 0.005). However, the inhibitory effects of the 60 µg E2 group were more significant than the inhibitory effects of the 120 µg E2 group (385.571 ± 7.265 vs. 465.857 ± 8.259, P-value < 0.005), suggesting the importance of maintaining a proper E2:TP ratio. Western blot analysis shows up-regulation of specific bands for HKA alpha subunit at ~97 kDa for TP-induced BPH and down-regulation of HKA in the TP+E2 treatment groups.
Conclusions: Our results show that TP induced benign prostate hypertrophy. Furthermore, E2 is shown to inhibit BPH; however, the effect of E2 inhibition on BPH requires the optimal ratio between E2 and TP. If such a ratio is not reached, then BPH inhibition will not occur by E2. Both the induction and inhibition of hypertrophic cells suggests that the prostate is under hormonal regulation. The proper E2:TP ratio plays a crucial role in the pathogenesis of BPH. Such knowledge of E2:TP ratio in humans may help to prevent or cure BPH in the future.