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Published in: World Journal of Urology 5/2003

01-11-2003 | Topic Paper

Androgen and estrogen receptors in the human corpus cavernosum penis: immunohistochemical and cell culture results

Authors: Dirk Schultheiss, Rafael Badalyan, Adrian Pilatz, Alexander I. Gabouev, Norbert Schlote, Jörg Wefer, Reinhard von Wasielewski, Heike Mertsching, Michael Sohn, Christian G. Stief, Udo Jonas

Published in: World Journal of Urology | Issue 5/2003

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Abstract

Despite the central and peripheral effects of androgens on the nervous system, the local effects of androgens in the corpus cavernosum penis and their importance for erectile function is still unclear. In this study corpus cavernosum biopsies of eight adult potent patients, aged 19–63 years, undergoing penile deviation surgery (group A) and 12 patients undergoing male-to-female transsexual surgery (group B) were immunostained for nuclear androgen and estrogen-alpha receptors. Additionally, primary corpus cavernosum endothelial cell cultures were obtained from six transsexual patients and exposed to testosterone, dihydrotestosterone, estradiol and progesterone likewise for 7 days. Total cell count was performed and cell metabolic activity was measured by a tetrazolium salt-based assay. Androgen and estrogen-alpha receptors were detected in stromal as well as in endothelial cells. Of all cell nuclei, 74.9% (SD 16.4) in group A and 63.5% (SD 17.1) in group B were positively stained for androgen receptors. The respective percentage of estrogen receptors was 11% (SD 9.5) and 21.2% (SD 12.6). An age-dependent difference in receptor distribution was not observed in either group. In the cell culture system only cultures exposed to testosterone and dihydrotestosterone showed a dose-dependent increase of cell metabolic activity compared to the cultures supplemented with estradiol and progesterone. The significant and age-independent high androgen and low estrogen-alpha receptor distribution found in both groups suggests a possible peripheral effect of androgens at the level of the corpus cavernosum penis in adult humans. This is supported by the observed effect of testosterone and dihydrotestosterone on cell count and endothelial cell metabolism in our cell culture system. The role of estrogens remains unclear.
Literature
1.
go back to reference Alcorn JF, Toepfer JR, Leipheimer RE (1999) The effects of castration on relaxation of rat corpus cavernosum smooth muscle in vitro. J Urol 161:686–689PubMed Alcorn JF, Toepfer JR, Leipheimer RE (1999) The effects of castration on relaxation of rat corpus cavernosum smooth muscle in vitro. J Urol 161:686–689PubMed
2.
go back to reference Andersson KE, Holmquist F, Bodker A (1992) Castration enhances NANC nerve-mediated relaxation in rabbit isolated corpus cavernosum. Acta Physiol Scand 146:405–406PubMed Andersson KE, Holmquist F, Bodker A (1992) Castration enhances NANC nerve-mediated relaxation in rabbit isolated corpus cavernosum. Acta Physiol Scand 146:405–406PubMed
3.
go back to reference Aversa A, Isidori AM, Spera G, Lenzi A, Fabbri A (2003) Androgens improve cavernous vasodilation and response to sildenafil in patients with erectile dysfunction. Clin Endocrinol (Oxf) 58:632–638 Aversa A, Isidori AM, Spera G, Lenzi A, Fabbri A (2003) Androgens improve cavernous vasodilation and response to sildenafil in patients with erectile dysfunction. Clin Endocrinol (Oxf) 58:632–638
4.
go back to reference Baba K, Yajima M, Carrier S, Akkus E, Reman J, Nunes L, Lue TF, Iwamoto T (2000) Effect of testosterone on the number of NADPH diaphorase-stained nerve fibers in the rat corpus cavernosum and dorsal nerve. Urology 56:533–538PubMed Baba K, Yajima M, Carrier S, Akkus E, Reman J, Nunes L, Lue TF, Iwamoto T (2000) Effect of testosterone on the number of NADPH diaphorase-stained nerve fibers in the rat corpus cavernosum and dorsal nerve. Urology 56:533–538PubMed
5.
go back to reference Baskin LS, Sutherland RS, DiSandro MJ, Hayward SW, Lipschutz J, Cunha GR (1997) The effect of testosterone on androgen receptors and human penile growth. J Urol 158:1113–1138PubMed Baskin LS, Sutherland RS, DiSandro MJ, Hayward SW, Lipschutz J, Cunha GR (1997) The effect of testosterone on androgen receptors and human penile growth. J Urol 158:1113–1138PubMed
6.
go back to reference Becker AJ, Uckert S, Stief CG, Truss MC, Machtens S, Scheller F, Knapp WH, Hartmann U, Jonas U (2000) Cavernous and systemic testosterone levels in different phases of human penile erection. Urology 56:125–129CrossRefPubMed Becker AJ, Uckert S, Stief CG, Truss MC, Machtens S, Scheller F, Knapp WH, Hartmann U, Jonas U (2000) Cavernous and systemic testosterone levels in different phases of human penile erection. Urology 56:125–129CrossRefPubMed
7.
go back to reference Becker AJ, Uckert S, Stief CG, Scheller F, Knapp WH, Hartmann U, Jonas U (2001) Cavernous and systemic testosterone plasma levels during different penile conditions in healthy males and patients with erectile dysfunction. Urology 58:435–440PubMed Becker AJ, Uckert S, Stief CG, Scheller F, Knapp WH, Hartmann U, Jonas U (2001) Cavernous and systemic testosterone plasma levels during different penile conditions in healthy males and patients with erectile dysfunction. Urology 58:435–440PubMed
8.
go back to reference Costarella CE, Stallone JN, Rutecki GW, Whittier FC (1996) Testosterone causes direct relaxation of rat thoracic aorta. J Pharmacol Exp Ther 277:34–39PubMed Costarella CE, Stallone JN, Rutecki GW, Whittier FC (1996) Testosterone causes direct relaxation of rat thoracic aorta. J Pharmacol Exp Ther 277:34–39PubMed
9.
go back to reference Crescioli C, Maggi M, Vannelli GB, Ferruzzi P, Granchi S, Mancina R, Muratori M, Forti G, Serio M, Luconi M (2003) Expression of functional estrogen receptors in human fetal male external genitalia. J Clin Endocrinol Metab 88:1815–1824PubMed Crescioli C, Maggi M, Vannelli GB, Ferruzzi P, Granchi S, Mancina R, Muratori M, Forti G, Serio M, Luconi M (2003) Expression of functional estrogen receptors in human fetal male external genitalia. J Clin Endocrinol Metab 88:1815–1824PubMed
10.
go back to reference Ding AQ, Stallone JN (2001) Testosterone-induced relaxation of rat aorta is androgen structure specific and involves K+ channel activation. J Appl Physiol 91:2742–2750 Ding AQ, Stallone JN (2001) Testosterone-induced relaxation of rat aorta is androgen structure specific and involves K+ channel activation. J Appl Physiol 91:2742–2750
11.
go back to reference Godec CJ, Bates H, Labrosse K (1985) Testosterone receptors in corpora cavernosa of penis. Urology 26:237–239PubMed Godec CJ, Bates H, Labrosse K (1985) Testosterone receptors in corpora cavernosa of penis. Urology 26:237–239PubMed
12.
go back to reference Goldstein I (2003) The association of ED (erectile dysfunction) with ED (endothelial dysfunction) in the International Journal of Impotence Research: The Journal of Sexual Medicine. Int J Impot Res 15:229–230CrossRefPubMed Goldstein I (2003) The association of ED (erectile dysfunction) with ED (endothelial dysfunction) in the International Journal of Impotence Research: The Journal of Sexual Medicine. Int J Impot Res 15:229–230CrossRefPubMed
13.
go back to reference Gonzalez-Cadavid N, Vernet D, Fuentes Navarro A, Rodriguez JA, Swerdloff RS, Rajfer J (1993) Up-regulation of the levels of androgen receptor and its mRNA by androgens in smooth-muscle cells from rat penis. Mol Cell Endocrinol 90:219–229CrossRefPubMed Gonzalez-Cadavid N, Vernet D, Fuentes Navarro A, Rodriguez JA, Swerdloff RS, Rajfer J (1993) Up-regulation of the levels of androgen receptor and its mRNA by androgens in smooth-muscle cells from rat penis. Mol Cell Endocrinol 90:219–229CrossRefPubMed
14.
go back to reference Heaton JP, Morales A (2003) Endocrine causes of impotence (nondiabetes). Urol Clin North Am 30:73–81PubMed Heaton JP, Morales A (2003) Endocrine causes of impotence (nondiabetes). Urol Clin North Am 30:73–81PubMed
15.
go back to reference Jain P, Rademaker AW, McVary KT (2000) Testosterone supplementation for erectile dysfunction: results of a meta-analysis. J Urol 164:371–375PubMed Jain P, Rademaker AW, McVary KT (2000) Testosterone supplementation for erectile dysfunction: results of a meta-analysis. J Urol 164:371–375PubMed
16.
go back to reference Jesmin S, Mowa CN, Matsuda N, Salah-Eldin AE, Togashi H, Sakuma I, Hattori Y, Kitabatake A (2002) Evidence for a potential role of estrogen in the penis: detection of estrogen receptor-alpha and -beta messenger ribonucleic acid and protein. Endocrinology 143:4764–4774CrossRefPubMed Jesmin S, Mowa CN, Matsuda N, Salah-Eldin AE, Togashi H, Sakuma I, Hattori Y, Kitabatake A (2002) Evidence for a potential role of estrogen in the penis: detection of estrogen receptor-alpha and -beta messenger ribonucleic acid and protein. Endocrinology 143:4764–4774CrossRefPubMed
17.
go back to reference Kaufman JM, T’Sjoen G (2002) The effects of testosterone deficiency on male sexual function. Aging Male 5:242–247PubMed Kaufman JM, T’Sjoen G (2002) The effects of testosterone deficiency on male sexual function. Aging Male 5:242–247PubMed
18.
go back to reference Keast JR (1999) The autonomic nerve supply of male sex organs—an important target of circulating androgens. Behav Brain Res 105:81–92PubMed Keast JR (1999) The autonomic nerve supply of male sex organs—an important target of circulating androgens. Behav Brain Res 105:81–92PubMed
19.
go back to reference Ling S, Dai A, Williams MR, Myles K, Dilley RJ, Komesaroff PA, Sudhir K (2002) Testosterone (T) enhances apoptosis-related damage in human vascular endothelial cells. Endocrinology 143:1119–1125PubMed Ling S, Dai A, Williams MR, Myles K, Dilley RJ, Komesaroff PA, Sudhir K (2002) Testosterone (T) enhances apoptosis-related damage in human vascular endothelial cells. Endocrinology 143:1119–1125PubMed
20.
go back to reference Matsumoto A, Prins GS (1998) Age-dependent changes in androgen receptor immunoreactivity in motoneurons of the spinal nucleus of the bulbocavernosus of male rats. Neurosci Lett 243:29–32PubMed Matsumoto A, Prins GS (1998) Age-dependent changes in androgen receptor immunoreactivity in motoneurons of the spinal nucleus of the bulbocavernosus of male rats. Neurosci Lett 243:29–32PubMed
21.
go back to reference Mills TM, Dai Y, Stopper VS, Lewis RW (1999) Androgenic maintenance of the erectile response in the rat. Steroids 64:605–609PubMed Mills TM, Dai Y, Stopper VS, Lewis RW (1999) Androgenic maintenance of the erectile response in the rat. Steroids 64:605–609PubMed
22.
go back to reference Mills TM, Lewis RW (1999) The role of andorgens in the erectile response: a 1999 perspective. Mol Urol 3:75–86PubMed Mills TM, Lewis RW (1999) The role of andorgens in the erectile response: a 1999 perspective. Mol Urol 3:75–86PubMed
23.
go back to reference Nonomura K, Sakakibara N, Demura T, Mori T, Koyanagi T (1990) Androgen binding activity in the spongy tissue of mammalian penis. J Urol 144:152–155PubMed Nonomura K, Sakakibara N, Demura T, Mori T, Koyanagi T (1990) Androgen binding activity in the spongy tissue of mammalian penis. J Urol 144:152–155PubMed
24.
go back to reference Park KH, Kim SW, Kim KD, Paick JS (1999) Effects of androgens on the expression of nitric oxide synthase mRNAs in rat corpus cavernosum. BJU Int 83:327–333PubMed Park KH, Kim SW, Kim KD, Paick JS (1999) Effects of androgens on the expression of nitric oxide synthase mRNAs in rat corpus cavernosum. BJU Int 83:327–333PubMed
25.
go back to reference Penson DF, Ng C, Cai L, Rajfer J, Gonzalez-Cadavid NF (1996) Androgen and pituitary control of penile nitric oxide synthase and erectile function in the rat. Biol Reprod 55:567–574PubMed Penson DF, Ng C, Cai L, Rajfer J, Gonzalez-Cadavid NF (1996) Androgen and pituitary control of penile nitric oxide synthase and erectile function in the rat. Biol Reprod 55:567–574PubMed
26.
go back to reference Rajfer J, Namkung PC, Petra PH (1980) Identification, partial characterization and age-related changes of a cytoplasmic androgen receptor in the rat penis. J Steroid Biochem 13:1489–1492PubMed Rajfer J, Namkung PC, Petra PH (1980) Identification, partial characterization and age-related changes of a cytoplasmic androgen receptor in the rat penis. J Steroid Biochem 13:1489–1492PubMed
27.
go back to reference Rossi P, Menchini Fabris F, Fiorini I, Palego P, Simi S, Rossi B, Sarteschi LM, Carpi A (1998) Comparison between plasma concentrations of testosterone, nitric oxide and endothelin 1–2 in penile and brachial venous blood: preliminary results in men with psychogenic impotence. Biomed Pharmacother 52:308–310PubMed Rossi P, Menchini Fabris F, Fiorini I, Palego P, Simi S, Rossi B, Sarteschi LM, Carpi A (1998) Comparison between plasma concentrations of testosterone, nitric oxide and endothelin 1–2 in penile and brachial venous blood: preliminary results in men with psychogenic impotence. Biomed Pharmacother 52:308–310PubMed
28.
go back to reference Schiavi RC, White D, Mandeli J, Levine AC (1997) Effect of testosterone administration on sexual behavior and mood in men with erectile dysfunction. Arch Sex Behav 26:231–241PubMed Schiavi RC, White D, Mandeli J, Levine AC (1997) Effect of testosterone administration on sexual behavior and mood in men with erectile dysfunction. Arch Sex Behav 26:231–241PubMed
29.
go back to reference Schirar A, Chang C, Rousseau JP (1997) Localization of androgen receptor in nitric oxide synthase- and vasoactive intestinal peptide-containing neurons of the major pelvic ganglion innervating the rat penis. J Neuroendocrinol 9:141–150PubMed Schirar A, Chang C, Rousseau JP (1997) Localization of androgen receptor in nitric oxide synthase- and vasoactive intestinal peptide-containing neurons of the major pelvic ganglion innervating the rat penis. J Neuroendocrinol 9:141–150PubMed
30.
go back to reference Shabsigh R (1997) The effects of testosterone on the cavernous tissue and erectile function. World J Urol 15:21–26PubMed Shabsigh R (1997) The effects of testosterone on the cavernous tissue and erectile function. World J Urol 15:21–26PubMed
31.
go back to reference Shabsigh R, Raymond JF, Olsson CA, O’Toole K, Buttyan R (1998) Androgen induction of DNA synthesis in the rat penis. Urology 52:723–728PubMed Shabsigh R, Raymond JF, Olsson CA, O’Toole K, Buttyan R (1998) Androgen induction of DNA synthesis in the rat penis. Urology 52:723–728PubMed
32.
go back to reference Takane KK, Husmann DA, McPhaul MJ, Wilson JD (1991) Androgen receptor levels in the rat penis are controlled differently in distinctive cell types. Endocrinology 128:2234–2238PubMed Takane KK, Husmann DA, McPhaul MJ, Wilson JD (1991) Androgen receptor levels in the rat penis are controlled differently in distinctive cell types. Endocrinology 128:2234–2238PubMed
33.
go back to reference Tietjen DN, Uramoto GY, Tindall DJ, Husmann DA (1998) Micropenis in hypogonadotropic hypogonadism: response of the penile androgen receptor to testosterone treatment (Discussion 79). J Urol 160:1054–7PubMed Tietjen DN, Uramoto GY, Tindall DJ, Husmann DA (1998) Micropenis in hypogonadotropic hypogonadism: response of the penile androgen receptor to testosterone treatment (Discussion 79). J Urol 160:1054–7PubMed
34.
go back to reference Traish AM, Park K, Dhir V, Kim NN, Moreland RB, Goldstein I (1999) Effects of castration and androgen replacement on erectile function in a rabbit model. Endocrinology 140:1861–1868PubMed Traish AM, Park K, Dhir V, Kim NN, Moreland RB, Goldstein I (1999) Effects of castration and androgen replacement on erectile function in a rabbit model. Endocrinology 140:1861–1868PubMed
35.
go back to reference Watkins TW, Keast JR (1999) Androgen-sensitive preganglionic neurons innervate the male rat pelvic ganglion. Neuroscience 93:1147–1157PubMed Watkins TW, Keast JR (1999) Androgen-sensitive preganglionic neurons innervate the male rat pelvic ganglion. Neuroscience 93:1147–1157PubMed
36.
go back to reference Webb CM, McNeill JG, Hayward CS, de Zeigler D, Collins P (1999) Effects of testosterone on coronary vasomotor regulation in men with coronary heart disease. Circulation 100:1690–1696PubMed Webb CM, McNeill JG, Hayward CS, de Zeigler D, Collins P (1999) Effects of testosterone on coronary vasomotor regulation in men with coronary heart disease. Circulation 100:1690–1696PubMed
37.
go back to reference Wilson CM, McPhaul MJ (1996) A and B forms of the androgen receptor are expressed in a variety of human tissues. Mol Cell Endocrinol 120:51–57CrossRefPubMed Wilson CM, McPhaul MJ (1996) A and B forms of the androgen receptor are expressed in a variety of human tissues. Mol Cell Endocrinol 120:51–57CrossRefPubMed
Metadata
Title
Androgen and estrogen receptors in the human corpus cavernosum penis: immunohistochemical and cell culture results
Authors
Dirk Schultheiss
Rafael Badalyan
Adrian Pilatz
Alexander I. Gabouev
Norbert Schlote
Jörg Wefer
Reinhard von Wasielewski
Heike Mertsching
Michael Sohn
Christian G. Stief
Udo Jonas
Publication date
01-11-2003
Publisher
Springer-Verlag
Published in
World Journal of Urology / Issue 5/2003
Print ISSN: 0724-4983
Electronic ISSN: 1433-8726
DOI
https://doi.org/10.1007/s00345-003-0371-y

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