Korean J Urol.  2007 Feb;48(2):152-157. 10.4111/kju.2007.48.2.152.

Gonadotropin Releasing Hormone (GnRH) and GnRH Receptor in Normal Bladder Epithelia and Their Role in Bladder Epithelial Proliferation

• Kim MO
• Lee JH
• Park MS
• Lee HL
• Bahk JY

• KMID: 2139753
• DOI: http://doi.org/10.4111/kju.2007.48.2.152

Abstract

PURPOSE: To confirm the production of extra-hypothalamic gonadotropin releasing hormone (GnRH) and GnRH receptor in bladder mucosal epithelia, and a potential role of GnRH on the bladder, normal human bladder tissues, and primary cultured dog bladder mucosal epithelia were studied.
MATERIALS AND METHODS
For this study, normal human bladder tissue from 4 patients and primary cultured normal bladder mucosal epithelial cells from 2 dogs were used. For localization of extra-hypothalamic GnRH and the extra-pituitary GnRH receptor, in situ hybridization and immunohistochemical staining were done. To evaluate the roles of exogenous GnRH in bladder mucosal cells, the culture media were supplemented with charcoal stripped serum and 4 different concentrations of GnRH (0, 10(-3), 10(-5) and 10(-7)M). The effect of exogenous GnRH was evaluated using a hemocytometer and fluorescence activated cell sorter (FACS).
RESULTS
GnRH and GnRH receptors, and their mRNA signals were localized in most of the both human bladder mucosal epithelia and dog bladder mucosal epithelia, but not in a few cells. There were no significant GnRH effects on cellular proliferation and cell cycle changes (p<0.05). CONCLISIONS: Bladder mucosal epithelium produces GnRH and GnRH receptors, but they do not effect either the proliferation or cell cycle changes. Although the exact function of extra-hypothalamic bladder GnRH is unknown, GnRH and GnRH receptors would be assumed to have unknown autocrine or paracrine relationships with each other.

Keyword

Gonadotropin-releasing hormone; Receptor; Mucosa

MeSH Terms

Animals
Cell Cycle
Cell Proliferation
Charcoal
Culture Media
Dogs
Epithelial Cells
Epithelium
Fluorescence
Gonadotropin-Releasing Hormone*
Gonadotropins*
Humans
In Situ Hybridization
Mucous Membrane
Receptors, LHRH*
RNA, Messenger
Urinary Bladder*
Charcoal
Culture Media
Gonadotropin-Releasing Hormone
Gonadotropins
RNA, Messenger
Receptors, LHRH

Figure

• 

  Fig. 1 Expressions of GnRH and GnRH receptor mRNA in the preoptic area of the rat brain and anterior pituitary. The white spots around the 3rd ventricle (A) in the dark field microscopic view indicate the expression of GnRH mRNA. GnRH receptor mRNA signals are detected in the anterior pituitary (B). The signals are in clusters in both views. Arrows: positive signals. OC: optic chiasma. GnRH: gonadotropin releasing hormone.

• 

  Fig. 2 Expressions of the GnRH (A) and GnRH receptors (B) mRNA signals from human bladder tissue. The signal numbers are different to each other, with some cells not expressing the signal. Arrow: mRNA signal. GnRH: gonadotropin releasing hormone.

• 

  Fig. 3 The expressions of the GnRH (A, C) and GnRH receptor (B, D) proteins in human normal bladder mucosa tissue (A, B) and primary cultured dog bladder mucosal epithelia (C, D). Brown color staining indicates positive staining for GnRHs and GnRH receptors. GnRH: gonadotropin releasing hormone.

Reference

1. Morisue K, Yamanaka N, Eto H, Kamidonu S, Nishimura R. Ectopic production of HCG beta by bladder carcinoma in vitro and in vivo. Nippon Hinyokika Gakkai Zasshi. 1996. 87:643–649.

2. Moreville M, Fritz RW, Mulholland SG. Enhancement of the bladder defense mechanism by an exogenous agent. J Urol. 1983. 130:607–609.

3. Vaidyanathan S, McCreavy DT, McDicken IW, Soni BM, Mansour P, Wlodarski B, et al. Immunohistochemical study of parathyroid hormone-related protein in vesical transitional epithelium of patients with spinal cord injury. Spinal Cord. 1999. 37:760–764.

4. Yamamoto M, Harm SC, Grasser WA, Thiede MA. Parathyroid hormone-related protein in the rat urinary bladder: a smooth muscle relaxant produced locally in response to mechanical stretch. Proc Nat Acad Sci USA. 1992. 89:5326–5330.

5. Grammatico D, Grignon DJ, Eberwein P, Shepherd RR, Hearn SA, Walton JC. Transitional cell carcinoma of the renal pelvis with choriocarcinomatous differentiation. Immunohistochemical and immunoelectron microscopic assessment of human chorionic gonadotropin production by transitional cell carcinoma of the urinary bladder. Cancer. 1993. 71:1835–1841.

6. Yoshimoto Y, Wolfsen AF, Odell WD. Human chorionic gonadotrophin-like substance in nonendocrine tissues of normal subjects. Science. 1977. 197:575–577.

7. Heyderman E, Chapman DV, Richardson TC, Calvert I, Rosen SW. Human chorionic gonadotropin and human placental lactogen in extragonadal tumors. An immununoperoxidase study of ten non-germ cell neoplasms. Cancer. 1985. 56:2674–2682.

8. Saez S, Martin PM. Evidence of estrogen receptors in the trigone area of the human urinary bladder. J Steroid Biochem. 1981. 15:317–320.

9. Bodker A, Bruun J, Balslev E, Iversen HG, Meyhoff HH, Andersson KE. Estrogen receptors in the human male prostatic urethra and prostate in prostatic cancer and benign prostatic hyperplasia. Scand J Urol Nephrol. 1999. 33:237–242.

10. Silverman AJ, Krey LC. The luteinizing hormone releasing hormone (LHRH) neuronal networks of the guinea pig brain. I. Intra-and extra hypothalamic projections. Brain Res. 1978. 157:233–246.

11. Naor Z, Clayton RN, Catt KJ. Characterization of gonadotropin-releasing hormone receptors in cultured rat pituitary cells. Endocrinology. 1980. 107:1144–1152.

12. Gibbons JM, Mitnick M, Chieffo V. In vitro biosynthesis of TSH- and LH-releasing factors by the human placenta. Am J Obstet Gynecol. 1975. 121:127–131.

13. Bahk JY, Hyun JS, Chung SH, Lee H, Kim MO, Lee BH, et al. Stage specific identification of the expression of GnRH mRNA and localization of the GnRH receptor in mature rat and adult human testis. J Urol. 1995. 154:1958–1961.

14. Bahk JY, Hyun JS, Kim MO, Kown IK, Park KD, Kim YH. Study for the ureteral reconstruction with tissue engineering using poly (glycolide/e-caprolactone scaffold-1. Korean J Urol. 2001. 42:371–378.

15. Duello TM, Tsai SJ, Van Ess PJ. In situ demonstration and characterization of progonadotropin-releasing hormone messenger ribonucleic acid in first trimester human placentas. Endocrinology. 1993. 133:2617–2623.

16. Shibata MA, Shirai T, Asakawa E, Hirose M, Fukushima S. Inhibition by dehydroepiandrosterone of butylated hydroxyanisole (BHA) promotion of rat-bladder carcinogenesis and enhancement of BHA-induced forestomach hyperplasia. Int J Cancer. 1993. 53:819–823.

17. Shirai T, Yamamoto A, Iwasaki S, Tamano S, Masui T. Induction of invasive carcinomas of the seminal vesicles and coagulating glands of F344 rats by administration of N-methylnitrosourea or N-nitrosobis (2-oxopropyl)amine and followed by testosterone propionate with or without high-fat diet. Carcinogenesis. 1991. 12:2169–2173.

18. Gunha GR, Lung B. The importance of stroma in morphogenesis and functional activity of urogenital epithelium. In Vitro. 1979. 15:50–71.

19. Huggins CB. The formation of bone under the influence of epithelium of the urinary tract. Clin Orthop Relat Res. 1968. 59:7–19.

20. Johnson FR, McMinn MR. Transitional epithelium and osteogenesis. J Anat. 1956. 90:106–116.

21. Shen SS, Smith CL, Hsieh JT, Yu J, Kim IY, Jian W, et al. Expression of estrogen receptors-α and -β in bladder cancer cell line and human bladder cancer tissues. Cancer. 2006. 106:2610–2616.

22. Bahk JY, Hyun JS, Lee H, Kim MO, Cho GJ, Lee BH, et al. Expression of Gonadotropin releasing hormone (GnRH) and GnRH receptor mRNA in prostate cancer cells and effect of GnRH on the proliferation of prostate cancer cells. Urol Res. 1998. 26:259–264.