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SERUM AND SEMEN PROSTATE SPECIFIC ANTIGEN CONCENTRATIONS ARE DIFFERENT IN YOUNG SPINAL CORD INJURED MEN COMPARED TO NORMAL CONTROLS
OO22-5347/99/1621-0089/0 THE JOURNAL OF UROLOGY Copyright 0 1999 by b R l C A
N UKOLOClCAL
Vol 162,89-91, July 19W Printed in U.S.A.
Assocv\T!oN, INC.
SERUM AND SEMEN PROSTATE SPECIFIC ANTIGEN CONCENTRATIONS ARE DIFFERENT IN YOUNG SPINAL CORD INJURED MEN COMPARED TO NORMAL CONTROLS CHARLES M. LYNNE, TEODORO C . ABALLA,TANG J. WANG,'" HARRY C . KITTENHOUSE," SEAN M. FERRELL ANI) NANCY L. BRACKETT From the D e p a r t m n t of urology and The Miami Project to Cure Pnra/ysis, UriiLwrsily O J M~ i a m i S(~hcm/of . ~ c d i c r r i c .h ' / ( i r r i i , h"oridu rrrid Hybritrcli Incorporated, Snri Diego, Cnliforrtici
ABSTRACT
Purpose: Recent investigations have indicated that factors within the seminal plasma m a y contribute to the condition of low sperm motility i n m e n with spinal cord injury. To determine w h e t h e r the prostate gland functions normally i n these m e n w e chose prostate specific antigen (PSA)as a m a r k e r of prostatic function, a n d compared s e r u m a n d semen concentrations i n spinal cord injured a n d healthy noninjured men. Materials a n d Methods: The s t u d y included 2 1 spinal cord injured m e n ( m e a n age 33.3 5 1.2 years) and 22 noninjured normal m e n (mean age 30.3 5 1.5 years). Blood w a s obtained from subjects following at least 24 h o u r s of abstinence from ejaculation and s e r u m PSA w a s determined b y modified enzyme immunoassay. Antegrade ejaculates from all subjects were frozen t o -8OC, exactly 15 minutes after collection. Seminal p l a s m a P S A w a s determined using Hybritech Tandem? MP assay. Results: Mean serum PSA concentration w a s 1.20 t 0.19 ng./ml. in spinal cord injured and 0.69 5 0.07 ng./ml. in noninjured m e n ( p <0.02). Mean seminal plasma PSA concentration w a s 0.59 2 0.11 mg./ml. in spinal cord injured a n d 1.29 5 0.15 mg./ml. in noninjured m e n ( p <0.001). Conclusions: O u r findings of elevated s e r u m and decreased seminal plasma PSA concentrations indicate that prostatic secretory dysfunction is present in m e n w i t h spinal cord injury. KEY WORDS:prostate-specific antigen, spinal cord injuries, spermatozoa, semen, fertility
microparticle enzyme immunoassay. To determine seminal plasma PSA normal men produced semen specimens by masturbation after a t least 3 days of abstinence from ejaculation. Antegrade ejaculates were obtained by vibratory stimulation in 15 spinal cord injured subjects, electroejaculation in 5 and masturbation in 1. For each subject an aliquot of 0.5 ml. raw semen stored in a 1.5 ml. tube was placed in a -8OC freezer exactly 15 minutes after collection and then stored 2 to 12 weeks until analyzed. PSA determination was performed using the Tandem MP PSA assay. A total of 4 multiple dilutions of each specimen were analyzed, and concentrations were calculated by multiplication of the diluted specimen assay results by the dilution factors. The coefficient of METHOD variance for the mean concentration of the 4 results was less A total of 21 spinal cord injured men and 22 healthy, than 10%for 39 of the 43 determinations and less than 20% normospermic men were studied. All were volunteers in the for all determinations. In 4 subjects only semen (no blood) Male Fertility Research Program of the Miami Project to was obtained for PSA determination. Cure Paralysis a t the University of Miami School of Medicine. Mean patient age was 33.3 f 1.2 years (range 24 to 42), RESULTS and the mean control age was 30.3 5 1.5 years (range 19 to 44). The level of spinal cord injury as determined by the Mean serum PSA concentration plus or minus standard University of Miami Neurospinal Index4 was cervical in 8 error of the mean was 1.20 f 0.19 ng./ml. (range 0.3 to 2.5, cases, TI-6 in 7, T7-12 in 4, L1 and below in 1, and unknown median 1.17) in spinal cord injured and 0.69 2 0.07 ng./mI. in 1. Mean interval since spinal cord injury was 10.1 2 0.96 (range 0.2 to 1.06, median 0.59) in normal men which was years (range 2 to 18). significant (fig. 1). Mean seminal plasma PSA concentration To determine seminal plasma PSA concentrations blood was 0.59 2 0.11 mg./ml. (range 0.009 to 1.71, median 0.48)in was obtained from subjects following at least 24 hours of spinal cord injured and 1.29 0.15 mg./ml. (range 0.39 to 3.0, abstinence from ejaculation. Serum PSA was determined by median 1.17) in normal men which was significant (fig. 2L5
The ejaculates of most men with spinal cord injury have normal sperm concentration but low sperm motility.1.2 Recent investigations have shown that factors within the seminal plasma contribute to this problem.3 The role of autonomic regulation of the prostate and its various secretory functions are not clearly understood. To determine if the prostate gland functions normally in spinal cord injured men we chose prostate specific antigen (PSA) as a marker of prostatic function, and compared serum and seminal plasma concentrations in spinal cord injured and healthy noninjured men.
Accepted for publication February 19, 1999. Supported by grants from the Miami Project to Cure Paralysis and the State of Florida Specific Appropriations. * Financial interest and/or other relationship with Beckman Coulter, Inc. t Hybritech, Inc., San Diego, California.
DISCUSSION
The ejaculates of most men with spinal cord injury have normal sperm concentration but poor sperm motility and viability.1.2 There are strong indications that the seminal 89
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ing urine or symptoms of autonomic dysreflexia. It is not known if our subjects had chronic or subclinical prostatitis but neither of these conditions has been shown to cause significant elevations in serum PSA.14-16 Denervation and disturbances in innervation, including spinal cord injury, have been reported to result in abnormalities of prostatic function and morphology. In experimental animals denervation of the prostate gland results in alterations of growth, cellular morphology and function.l7.1S Likewise, alterations in neural regulation have been shown to result in altered morphology and secretory activity.19-21 More specifically, spinal cord injury in rats has been shown to alter prostatic cellular morphology and function.22In a study of humans anatomy and innervation of the prostate gland were compared in men with and without spinal cord injury by
tion is present in men with spinal cord injury. Based on the available clinical and experimental studies reported, we believe that this dysfunction is secondary to a disturbance in innervation caused by the spinal cord injury. Ms. Maria Amador provided nursing care during sperm retrieval procedures in subjects with spinal cord injury, and Drs. Robert L. Wolfert and Roger Sokoloff provided helpful comments.
REFERENCES
1. Brackett, N. L., Santa-Cruz, C. and Lynne, C. M.: Sperm from spinal cord injured men lose motility faster than sperm from normal men: the effect is exacerbated at body compared to room temperature. J. Urol., 157: 2150,1997.
motility of normal men. J. Urol., 155: 1632,1996. 4. Hose, K. J., Green, B. A., Smith, R. S., Adkins, R. H. and
plasma is the main contributor to this phenomenon.3 We assessed whether prostatic dysfunction is present in men with spinal cord injury. We chose PSA as a marker of prostatic secretory activity because alterations in seminal and serum PSA concentrations have been previously described in other pathological states6 and assays for its measurement are well developed. PSA is a serine protease secreted by prostatic epithelial cells and its main biological function is t o digest seminogelin I and 11, and fibronectin, and to facilitate sperm motility. In vitro PSA has been shown to cleave insulin-like growth factor binding protein I11 to release insulin-like growth factor I.7-9 PSA is normally secreted into the prostatic acini. Semen concentrations of PSA are approximately lo6 times higher than that found in serum.10 PSA may reach the blood either by diffusing through the epithelial cell membrane into the surrounding prostatic stroma and, hence, nearby capillaries or by some disruption of the cytoarchitecture causing leakage into the capillary bed," which may result from a local process, such as prostatitis, or from disturbances in innervation or some other cause. Symptomatic bacterial prostatitis has been shown to cause elevations of serum PSA concentrations experimentally and clinically. These elevated PSA concentrations normalize after antibiotic treatment."-13 None of the subjects in our study had symptomatic prostatitis or other active urinary tract infections as judged clinically by the absence of fever, change
MacDonald, A. M.: University of Miami Neuro-Spinal Index (UMNI): a quantitative method for determining spinal cord function. Paraplegia, 1 8 331,1980. 5. Wang, T. J.,Rittenhouse, H. G., Wolfert, R. L., Lynne, C. M. and Brackett, N. L.: PSA Concentrations in seminal plasma (Letter to the Editor). Clin. Chem., 44:895, 1998. 6. Shortliffe, L. M. D., Sellers, R. G. and Schachter, J.: The characterization of nonbacterial prostatitis: search for an etiology. J. Urol., 148: 1461,1992. 7. Iwamura, I., Hellman, J., Cockett, A. T., Lilja, H. and Gershagen, S.: Alteration of the hormonal bioactivity of parathyroid hormone-related protein (PTHrP) as a result of limited proteolysis by prostate-specific antigen. Urology, 4 8 317, 1996. 8. Cohen, P., Graves, H. C., Peehl, D. M., Kamarei, M., Giudice, L. C. and Rosenfeld, R. G.: Prostate-specific antigen (PSA) is a n insulin-like growth factor binding protein-3 protease found in seminal plasma. J. Clin. Endow. Metab., 7 5 1046,1992. 9. Cramer, S. D., Chen, Z. and Peehl, D. M.: Prostate specific antigen cleaves parathyroid hormone-related protein in the PTH-like domain: inactivation of PTHrP-stimulated CAMPaccumulation in mouse osteoblasts. J. Urol., 156 526, 1996. 10. McCormack, R. T.,Rittenhouse, H. G., Finlay, J. A., Sokoloff, R. L., Wang, T. J., Wolfert, R. L., Lilja, H. and Oesterling, J. E.: Molecular forms of prostate-specific antigen and the human kallikrein gene family: a new era. Urology, 45: 729, 1995. 11. Hasui, Y., Marutsuka, K., Asada, Y., Ide, H., Nishi, S. and Osada, Y.: Relationship between serum prostate specific antigen and histological prostatitis in patients with benign prostatic hyperplasia. Prostate, 25 91, 1994.
PROSTATE SPECIFIC ANTIGEN IN SPINAL CORD INJURED MEN VERSUS CONTROLS
91
12. Neal, D.E., Jr., Clejan, S., Sarma, D. and Moon, T. D.: Prostate functional integrity in the rat prostate. Biol. Reprod., 44.1171, specific antigen and prostatitis. I. Effect of prostatitis on se1991. rum PSA in the human and nonhuman primate. Prostate, 20: 19. Golomb, E.,KrugLilcova, A., Dvir, D., Parnes, N.and Abramovici, 105,1992. A.: Induction of atypical prostatic hyperplasia in rats by sym13. Dalton, D. L.: Elevated serum prostate-specific antigen due to pathomimetic stimulation. Prostate, 94:214,1998. acute bacterial prostatitis. Urology, 33:465,1989. 20. Carvalho, T. L.,Petenusci, S. O., Favaretto, A. L. and Kempinas. 14. Tchetgen, M. B. and Oesterling, J. E.: The effect of prostatitis, W. G.: Morphometric and biochemical evaluation of rat prosurinary retention, ejaculation, and ambulation on the serum tate and seminal vesicle following chemical sympathectomy with guanethidine. Arch. Int. Physiol. Biochim., 98: 225,1990. prostate-specific antigen concentration. Urol. Clin. N. Amer., 2 4 283, 1997. 21. Kempinas, W.G.,Petenusci, S. O., Rosa, E. S.A. A., Favaretto, A. L. and Carvalho, T. L.: The hypophyseal-testicular axis and 15. Campo, R., Tchetgen, M.-B., Oesterling, J. E. and Schellhammer, sex accessory glands following chemical sympathectomy with P.: The effect of a short course of antibiotics on the serum PSA guanethidine of pre-pubertal to mature rats. Andrologia. 28: concentration. J . Urol., part 2, 165 4254 abstract 459,1996. 16. Nadler, R.B., Humphrey, P. A., Smith, D. S., Catalona, W. J. and 117,1996. Ratliff, T. L.: Effect of inflammation and benign prostatic 22. Huang, H. F.,Li, M. T., Linsenmeyer, T. A., Ottenweller, J. E., Pogach, L. M. and Irwin, R. J.: The effects of spinal cord injury hyperplasia on elevated serum prostate specific antigen levels. J. Urol., 154: 407,1995. on the status of messenger ribonucleic acid for TRPM 2 and androgen receptor in the prostate of the rat. J. Androl., IS: 17. McVary, K.T., Razzaq, A., Lee, C., Venegas, M. F., Rademaker, 250, 1997. A. and McKenna, K. E.: Growth of the rat prostate gland is facilitated by the autonomic nervous system. Biol. Reprod., 61: 23. Benaim, E. A.,Soboorian, H., Roebrborn,C. G. and McConnell, J. D.: The structure and intrinsic innervation of the prostate in 99,1994. patients with spinal cord injuries. J. Urol., part 2, 169: 106, 18. Wang, J. M., McKenna, K. E., McVary, K. T. and Lee, C.: Reabstract 407,1998. quirement of innervation for maintenance of structural and
N UKOLOClCAL
Vol 162,89-91, July 19W Printed in U.S.A.
Assocv\T!oN, INC.
SERUM AND SEMEN PROSTATE SPECIFIC ANTIGEN CONCENTRATIONS ARE DIFFERENT IN YOUNG SPINAL CORD INJURED MEN COMPARED TO NORMAL CONTROLS CHARLES M. LYNNE, TEODORO C . ABALLA,TANG J. WANG,'" HARRY C . KITTENHOUSE," SEAN M. FERRELL ANI) NANCY L. BRACKETT From the D e p a r t m n t of urology and The Miami Project to Cure Pnra/ysis, UriiLwrsily O J M~ i a m i S(~hcm/of . ~ c d i c r r i c .h ' / ( i r r i i , h"oridu rrrid Hybritrcli Incorporated, Snri Diego, Cnliforrtici
ABSTRACT
Purpose: Recent investigations have indicated that factors within the seminal plasma m a y contribute to the condition of low sperm motility i n m e n with spinal cord injury. To determine w h e t h e r the prostate gland functions normally i n these m e n w e chose prostate specific antigen (PSA)as a m a r k e r of prostatic function, a n d compared s e r u m a n d semen concentrations i n spinal cord injured a n d healthy noninjured men. Materials a n d Methods: The s t u d y included 2 1 spinal cord injured m e n ( m e a n age 33.3 5 1.2 years) and 22 noninjured normal m e n (mean age 30.3 5 1.5 years). Blood w a s obtained from subjects following at least 24 h o u r s of abstinence from ejaculation and s e r u m PSA w a s determined b y modified enzyme immunoassay. Antegrade ejaculates from all subjects were frozen t o -8OC, exactly 15 minutes after collection. Seminal p l a s m a P S A w a s determined using Hybritech Tandem? MP assay. Results: Mean serum PSA concentration w a s 1.20 t 0.19 ng./ml. in spinal cord injured and 0.69 5 0.07 ng./ml. in noninjured m e n ( p <0.02). Mean seminal plasma PSA concentration w a s 0.59 2 0.11 mg./ml. in spinal cord injured a n d 1.29 5 0.15 mg./ml. in noninjured m e n ( p <0.001). Conclusions: O u r findings of elevated s e r u m and decreased seminal plasma PSA concentrations indicate that prostatic secretory dysfunction is present in m e n w i t h spinal cord injury. KEY WORDS:prostate-specific antigen, spinal cord injuries, spermatozoa, semen, fertility
microparticle enzyme immunoassay. To determine seminal plasma PSA normal men produced semen specimens by masturbation after a t least 3 days of abstinence from ejaculation. Antegrade ejaculates were obtained by vibratory stimulation in 15 spinal cord injured subjects, electroejaculation in 5 and masturbation in 1. For each subject an aliquot of 0.5 ml. raw semen stored in a 1.5 ml. tube was placed in a -8OC freezer exactly 15 minutes after collection and then stored 2 to 12 weeks until analyzed. PSA determination was performed using the Tandem MP PSA assay. A total of 4 multiple dilutions of each specimen were analyzed, and concentrations were calculated by multiplication of the diluted specimen assay results by the dilution factors. The coefficient of METHOD variance for the mean concentration of the 4 results was less A total of 21 spinal cord injured men and 22 healthy, than 10%for 39 of the 43 determinations and less than 20% normospermic men were studied. All were volunteers in the for all determinations. In 4 subjects only semen (no blood) Male Fertility Research Program of the Miami Project to was obtained for PSA determination. Cure Paralysis a t the University of Miami School of Medicine. Mean patient age was 33.3 f 1.2 years (range 24 to 42), RESULTS and the mean control age was 30.3 5 1.5 years (range 19 to 44). The level of spinal cord injury as determined by the Mean serum PSA concentration plus or minus standard University of Miami Neurospinal Index4 was cervical in 8 error of the mean was 1.20 f 0.19 ng./ml. (range 0.3 to 2.5, cases, TI-6 in 7, T7-12 in 4, L1 and below in 1, and unknown median 1.17) in spinal cord injured and 0.69 2 0.07 ng./mI. in 1. Mean interval since spinal cord injury was 10.1 2 0.96 (range 0.2 to 1.06, median 0.59) in normal men which was years (range 2 to 18). significant (fig. 1). Mean seminal plasma PSA concentration To determine seminal plasma PSA concentrations blood was 0.59 2 0.11 mg./ml. (range 0.009 to 1.71, median 0.48)in was obtained from subjects following at least 24 hours of spinal cord injured and 1.29 0.15 mg./ml. (range 0.39 to 3.0, abstinence from ejaculation. Serum PSA was determined by median 1.17) in normal men which was significant (fig. 2L5
The ejaculates of most men with spinal cord injury have normal sperm concentration but low sperm motility.1.2 Recent investigations have shown that factors within the seminal plasma contribute to this problem.3 The role of autonomic regulation of the prostate and its various secretory functions are not clearly understood. To determine if the prostate gland functions normally in spinal cord injured men we chose prostate specific antigen (PSA) as a marker of prostatic function, and compared serum and seminal plasma concentrations in spinal cord injured and healthy noninjured men.
Accepted for publication February 19, 1999. Supported by grants from the Miami Project to Cure Paralysis and the State of Florida Specific Appropriations. * Financial interest and/or other relationship with Beckman Coulter, Inc. t Hybritech, Inc., San Diego, California.
DISCUSSION
The ejaculates of most men with spinal cord injury have normal sperm concentration but poor sperm motility and viability.1.2 There are strong indications that the seminal 89
I
3-
E
0
\
m E I
a cn
e E a
Is
-
2-
0 0.69 kO.07
1-
*
cno
-
7
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3-
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a cn
S
la!
cn
i
p < 0.001
4-
A
m
1-20f 0.19
a0 *
I0
0 1.29f0.15
*
0.59 f 0.11
* w
ing urine or symptoms of autonomic dysreflexia. It is not known if our subjects had chronic or subclinical prostatitis but neither of these conditions has been shown to cause significant elevations in serum PSA.14-16 Denervation and disturbances in innervation, including spinal cord injury, have been reported to result in abnormalities of prostatic function and morphology. In experimental animals denervation of the prostate gland results in alterations of growth, cellular morphology and function.l7.1S Likewise, alterations in neural regulation have been shown to result in altered morphology and secretory activity.19-21 More specifically, spinal cord injury in rats has been shown to alter prostatic cellular morphology and function.22In a study of humans anatomy and innervation of the prostate gland were compared in men with and without spinal cord injury by
tion is present in men with spinal cord injury. Based on the available clinical and experimental studies reported, we believe that this dysfunction is secondary to a disturbance in innervation caused by the spinal cord injury. Ms. Maria Amador provided nursing care during sperm retrieval procedures in subjects with spinal cord injury, and Drs. Robert L. Wolfert and Roger Sokoloff provided helpful comments.
REFERENCES
1. Brackett, N. L., Santa-Cruz, C. and Lynne, C. M.: Sperm from spinal cord injured men lose motility faster than sperm from normal men: the effect is exacerbated at body compared to room temperature. J. Urol., 157: 2150,1997.
motility of normal men. J. Urol., 155: 1632,1996. 4. Hose, K. J., Green, B. A., Smith, R. S., Adkins, R. H. and
plasma is the main contributor to this phenomenon.3 We assessed whether prostatic dysfunction is present in men with spinal cord injury. We chose PSA as a marker of prostatic secretory activity because alterations in seminal and serum PSA concentrations have been previously described in other pathological states6 and assays for its measurement are well developed. PSA is a serine protease secreted by prostatic epithelial cells and its main biological function is t o digest seminogelin I and 11, and fibronectin, and to facilitate sperm motility. In vitro PSA has been shown to cleave insulin-like growth factor binding protein I11 to release insulin-like growth factor I.7-9 PSA is normally secreted into the prostatic acini. Semen concentrations of PSA are approximately lo6 times higher than that found in serum.10 PSA may reach the blood either by diffusing through the epithelial cell membrane into the surrounding prostatic stroma and, hence, nearby capillaries or by some disruption of the cytoarchitecture causing leakage into the capillary bed," which may result from a local process, such as prostatitis, or from disturbances in innervation or some other cause. Symptomatic bacterial prostatitis has been shown to cause elevations of serum PSA concentrations experimentally and clinically. These elevated PSA concentrations normalize after antibiotic treatment."-13 None of the subjects in our study had symptomatic prostatitis or other active urinary tract infections as judged clinically by the absence of fever, change
MacDonald, A. M.: University of Miami Neuro-Spinal Index (UMNI): a quantitative method for determining spinal cord function. Paraplegia, 1 8 331,1980. 5. Wang, T. J.,Rittenhouse, H. G., Wolfert, R. L., Lynne, C. M. and Brackett, N. L.: PSA Concentrations in seminal plasma (Letter to the Editor). Clin. Chem., 44:895, 1998. 6. Shortliffe, L. M. D., Sellers, R. G. and Schachter, J.: The characterization of nonbacterial prostatitis: search for an etiology. J. Urol., 148: 1461,1992. 7. Iwamura, I., Hellman, J., Cockett, A. T., Lilja, H. and Gershagen, S.: Alteration of the hormonal bioactivity of parathyroid hormone-related protein (PTHrP) as a result of limited proteolysis by prostate-specific antigen. Urology, 4 8 317, 1996. 8. Cohen, P., Graves, H. C., Peehl, D. M., Kamarei, M., Giudice, L. C. and Rosenfeld, R. G.: Prostate-specific antigen (PSA) is a n insulin-like growth factor binding protein-3 protease found in seminal plasma. J. Clin. Endow. Metab., 7 5 1046,1992. 9. Cramer, S. D., Chen, Z. and Peehl, D. M.: Prostate specific antigen cleaves parathyroid hormone-related protein in the PTH-like domain: inactivation of PTHrP-stimulated CAMPaccumulation in mouse osteoblasts. J. Urol., 156 526, 1996. 10. McCormack, R. T.,Rittenhouse, H. G., Finlay, J. A., Sokoloff, R. L., Wang, T. J., Wolfert, R. L., Lilja, H. and Oesterling, J. E.: Molecular forms of prostate-specific antigen and the human kallikrein gene family: a new era. Urology, 45: 729, 1995. 11. Hasui, Y., Marutsuka, K., Asada, Y., Ide, H., Nishi, S. and Osada, Y.: Relationship between serum prostate specific antigen and histological prostatitis in patients with benign prostatic hyperplasia. Prostate, 25 91, 1994.
PROSTATE SPECIFIC ANTIGEN IN SPINAL CORD INJURED MEN VERSUS CONTROLS
91
12. Neal, D.E., Jr., Clejan, S., Sarma, D. and Moon, T. D.: Prostate functional integrity in the rat prostate. Biol. Reprod., 44.1171, specific antigen and prostatitis. I. Effect of prostatitis on se1991. rum PSA in the human and nonhuman primate. Prostate, 20: 19. Golomb, E.,KrugLilcova, A., Dvir, D., Parnes, N.and Abramovici, 105,1992. A.: Induction of atypical prostatic hyperplasia in rats by sym13. Dalton, D. L.: Elevated serum prostate-specific antigen due to pathomimetic stimulation. Prostate, 94:214,1998. acute bacterial prostatitis. Urology, 33:465,1989. 20. Carvalho, T. L.,Petenusci, S. O., Favaretto, A. L. and Kempinas. 14. Tchetgen, M. B. and Oesterling, J. E.: The effect of prostatitis, W. G.: Morphometric and biochemical evaluation of rat prosurinary retention, ejaculation, and ambulation on the serum tate and seminal vesicle following chemical sympathectomy with guanethidine. Arch. Int. Physiol. Biochim., 98: 225,1990. prostate-specific antigen concentration. Urol. Clin. N. Amer., 2 4 283, 1997. 21. Kempinas, W.G.,Petenusci, S. O., Rosa, E. S.A. A., Favaretto, A. L. and Carvalho, T. L.: The hypophyseal-testicular axis and 15. Campo, R., Tchetgen, M.-B., Oesterling, J. E. and Schellhammer, sex accessory glands following chemical sympathectomy with P.: The effect of a short course of antibiotics on the serum PSA guanethidine of pre-pubertal to mature rats. Andrologia. 28: concentration. J . Urol., part 2, 165 4254 abstract 459,1996. 16. Nadler, R.B., Humphrey, P. A., Smith, D. S., Catalona, W. J. and 117,1996. Ratliff, T. L.: Effect of inflammation and benign prostatic 22. Huang, H. F.,Li, M. T., Linsenmeyer, T. A., Ottenweller, J. E., Pogach, L. M. and Irwin, R. J.: The effects of spinal cord injury hyperplasia on elevated serum prostate specific antigen levels. J. Urol., 154: 407,1995. on the status of messenger ribonucleic acid for TRPM 2 and androgen receptor in the prostate of the rat. J. Androl., IS: 17. McVary, K.T., Razzaq, A., Lee, C., Venegas, M. F., Rademaker, 250, 1997. A. and McKenna, K. E.: Growth of the rat prostate gland is facilitated by the autonomic nervous system. Biol. Reprod., 61: 23. Benaim, E. A.,Soboorian, H., Roebrborn,C. G. and McConnell, J. D.: The structure and intrinsic innervation of the prostate in 99,1994. patients with spinal cord injuries. J. Urol., part 2, 169: 106, 18. Wang, J. M., McKenna, K. E., McVary, K. T. and Lee, C.: Reabstract 407,1998. quirement of innervation for maintenance of structural and