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Anatomy Department and the Center for Reproductive Endocrinology, University of California San Francisco, California 94143
Cancer Research Laboratory University of California, Berkeley California 94720
Department of Veterinary Biosciences, University of Illinois Urbana, Illinois 61801
Department of Urology University of California San Francisco, California 94143
Department of Biochemistry University of Leeds Leeds LS2 9JT, United Kingdom
Department of Urology Mie University, School of Medicine 2-174, Edobashi, Tsu City, Mie-Ken, 514, Japan
Correspondence: Address requests for reprints to: Dr. Gerald R. Cunha, Anatomy Department and the Center for Reproductive Endocrinology, UC San Francisco, Third and Parnassus, San Francisco, California 94143.
Abstract
I. Introduction: MALE accessory sex glands such as the prostate, seminal vesicle, and bulbourethral gland have served in various capacities as models for investigating the action of androgens in regulating epithelial growth, RNA and protein synthesis, and secretory activity. The most extensively studied gland of this group is the prostate. This gland is found exclusively in mammals and produces many components of semen such as fructose, zinc ions, and various proteins important for the formation of the copulatory plug in rodents. The impetus for investigating regulation of prostatic growth and function stems in part from the many pathological complications which affect this gland. The prostate is the site of various types of inflammatory and infectious conditions (1) as well as benign and malignant proliferative changes in aging males. Despite extensive research, little of the pathogenesis or natural history of these diseases has been elucidated (2). Benign prostatic hypertrophy (BPH), a disease in which the prostate resumes growth late in life, is the most common nonmalignant proliferative abnormality found in any internal organ (2). The incidence of BPH rises from 23% in men at 40 yr of age to 88% by the ninth decade (3). Adenocarcinoma of the prostate is the third leading cause of cancer deaths among men. Approximately 69 cases/100,000 men are diagnosed each year in the United States. It remains an intriguing paradox that malignant prostatic tumors are among the most prevalent neoplasms in men, while the seminal vesicles and bubulbourethral gland remain nearly immune to neoplastic change (<1 case of carcinoma of the seminal vesicle per year) (4).
Footnotes
* This work has been supported by March of Dimes Grant 1-837 and NIH Grants HD-17491, AM-32157, HD-21919, CA-05388, HD-06701, and HD-06580.
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C. Morrissey, A. Buser, J. Scolaro, J. O'Sullivan, A. Moquin, and M. Tenniswood Changes in Hormone Sensitivity in the Ventral Prostate of Aging Sprague-Dawley Rats J Androl, May 1, 2002; 23(3): 341 - 351. [Abstract] [Full Text] [PDF]
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 C. A. Lamartiniere, M. S. Cotroneo, W. A. Fritz, J. Wang, R. Mentor-Marcel, and A. Elgavish Genistein Chemoprevention: Timing and Mechanisms of Action in Murine Mammary and Prostate J. Nutr., March 1, 2002; 132(3): 552S - 558. [Abstract] [Full Text] [PDF]
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 T. Suwa, A. Nyska, J. K. Haseman, J. F. Mahler, and R. R. Maronpot Spontaneous Lesions in Control B6C3F1 Mice and Recommended Sectioning of Male Accessory Sex Organs Toxicol Pathol, February 1, 2002; 30(2): 228 - 234. [Abstract] [PDF]
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H. Qi, C. Fillion, Y. Labrie, J. Grenier, A. Fournier, L. Berger, M. El-Alfy, and C. Labrie AIbZIP, a Novel bZIP Gene Located on Chromosome 1q21.3 That Is Highly Expressed in Prostate Tumors and of Which the Expression Is Up-Regulated by Androgens in LNCaP Human Prostate Cancer Cells Cancer Res., February 1, 2002; 62(3): 721 - 733. [Abstract] [Full Text] [PDF]
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 D. C. Whitacre, S. Chauhan, T. Davis, D. Gordon, A. E. Cress, and R. L. Miesfeld Androgen Induction of in Vitro Prostate Cell Differentiation Cell Growth Differ., January 1, 2002; 13(1): 1 - 11. [Abstract] [Full Text] [PDF]
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T. J. Ahonen, P. L. Harkonen, H. Rui, and M. T. Nevalainen PRL Signal Transduction in the Epithelial Compartment of Rat Prostate Maintained as Long-Term Organ Cultures in Vitro Endocrinology, January 1, 2002; 143(1): 228 - 238. [Abstract] [Full Text] [PDF]
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O. Putz, C. B. Schwartz, S. Kim, G. A. LeBlanc, R. L. Cooper, and G. S. Prins Neonatal Low- and High-Dose Exposure to Estradiol Benzoate in the Male Rat: I. Effects on the Prostate Gland Biol Reprod, November 1, 2001; 65(5): 1496 - 1505. [Abstract] [Full Text] [PDF]
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O. Putz, C. B. Schwartz, G. A. LeBlanc, R. L. Cooper, and G. S. Prins Neonatal Low- and High-Dose Exposure to Estradiol Benzoate in the Male Rat: II. Effects on Male Puberty and the Reproductive Tract Biol Reprod, November 1, 2001; 65(5): 1506 - 1517. [Abstract] [Full Text] [PDF]
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J. G. Ramos, J. Varayoud, C. Sonnenschein, A. M. Soto, M. Munoz de Toro, and E. H. Luque Prenatal Exposure to Low Doses of Bisphenol A Alters the Periductal Stroma and Glandular Cell Function in the Rat Ventral Prostate Biol Reprod, October 1, 2001; 65(4): 1271 - 1277. [Abstract] [Full Text] [PDF]
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J. Gao, J. T. Arnold, and J. T. Isaacs Conversion from a Paracrine to an Autocrine Mechanism of Androgen-stimulated Growth during Malignant Transformation of Prostatic Epithelial Cells Cancer Res., July 1, 2001; 61(13): 5038 - 5044. [Abstract] [Full Text] [PDF]
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D. Waltregny, I. Leav, S. Signoretti, P. Soung, D. Lin, F. Merk, J. Y. Adams, N. Bhattacharya, N. Cirenei, and M. Loda Androgen-Driven Prostate Epithelial Cell Proliferation and Differentiation in Vivo Involve the Regulation of p27 Mol. Endocrinol., May 1, 2001; 15(5): 765 - 782. [Abstract] [Full Text]
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 S. C. Dixon, K. B. Knopf, and W. D. Figg The Control of Prostate-Specific Antigen Expression and Gene Regulation by Pharmacological Agents Pharmacol. Rev., March 1, 2001; 53(1): 73 - 92. [Abstract] [Full Text] [PDF]
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Z. M. Lei, S. Mishra, W. Zou, B. Xu, M. Foltz, X. Li, and Ch. V. Rao Targeted Disruption of Luteinizing Hormone/Human Chorionic Gonadotropin Receptor Gene Mol. Endocrinol., January 1, 2001; 15(1): 184 - 200. [Abstract] [Full Text]
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 S. Signoretti, D. Waltregny, J. Dilks, B. Isaac, D. Lin, L. Garraway, A. Yang, R. Montironi, F. McKeon, and M. Loda p63 Is a Prostate Basal Cell Marker and Is Required for Prostate Development Am. J. Pathol., December 1, 2000; 157(6): 1769 - 1775. [Abstract] [Full Text] [PDF]
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A. Colao, P. Marzullo, S. Spiezia, A. Giaccio, D. Ferone, G. Cerbone, A. Di Sarno, and G. Lombardi Effect of Two Years of Growth Hormone and Insulin-Like Growth Factor-I Suppression on Prostate Diseases in Acromegalic Patients J. Clin. Endocrinol. Metab., October 1, 2000; 85(10): 3754 - 3761. [Abstract] [Full Text]
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 C. Abate-Shen and M. M. Shen Molecular genetics of prostate cancer Genes & Dev., October 1, 2000; 14(19): 2410 - 2434. [Full Text]
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 G. T. G. Chang, M. Steenbeek, E. Schippers, L. J. Blok, W. M. van Weerden, D. C. J. G. van Alewijk, B. H. J. Eussen, G. J. van Steenbrugge, and A. O. Brinkmann Characterization of a Zinc-Finger Protein and Its Association With Apoptosis in Prostate Cancer Cells J Natl Cancer Inst, September 6, 2000; 92(17): 1414 - 1421. [Abstract] [Full Text] [PDF]
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R. A. Jarred, B. Cancilla, G. S. Prins, K. A. Thayer, G. R. Cunha, and G. P. Risbridger Evidence That Estrogens Directly Alter Androgen-Regulated Prostate Development Endocrinology, September 1, 2000; 141(9): 3471 - 3477. [Abstract] [Full Text] [PDF]
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A. F. Fribourg, K. E. Knudsen, M. W. Strobeck, C. M. Lindhorst, and E. S. Knudsen Differential Requirements for Ras and the Retinoblastoma Tumor Suppressor Protein in the Androgen Dependence of Prostatic Adenocarcinoma Cells Cell Growth Differ., July 1, 2000; 11(7): 361 - 372. [Abstract] [Full Text]
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M. K. Dienhart, R. J. Sommer, R. E. Peterson, A. N. Hirshfield, and E. K. Silbergeld Gestational Exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin Induces Developmental Defects in the Rat Vagina Toxicol. Sci., July 1, 2000; 56(1): 141 - 149. [Abstract] [Full Text] [PDF]
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H. Ka, T. E. Spencer, G. A. Johnson, and F. W. Bazer Keratinocyte Growth Factor: Expression by Endometrial Epithelia of the Porcine Uterus Biol Reprod, June 1, 2000; 62(6): 1772 - 1778. [Abstract] [Full Text]
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S. Lu, G. Jenster, and D. E. Epner Androgen Induction of Cyclin-Dependent Kinase Inhibitor p21 Gene: Role of Androgen Receptor and Transcription Factor Sp1 Complex Mol. Endocrinol., May 1, 2000; 14(5): 753 - 760. [Abstract] [Full Text]
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F. Gori, L. C. Hofbauer, C. A. Conover, and S. Khosla Effects of Androgens on the Insulin-Like Growth Factor System in an Androgen-Responsive Human Osteoblastic Cell Line Endocrinology, December 1, 1999; 140(12): 5579 - 5586. [Abstract] [Full Text]
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R. M. Adam, J. G. Borer, B. J. Williams, J. A. Eastham, K. R. Loughlin, and M. R. Freeman Amphiregulin Is Coordinately Expressed with Heparin-Binding Epidermal Growth Factor-Like Growth Factor in the Interstitial Smooth Muscle of the Human Prostate Endocrinology, December 1, 1999; 140(12): 5866 - 5875. [Abstract] [Full Text]
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T. J. Ahonen, P. L. Härkönen, J. Laine, H. Rui, P. M. Martikainen, and M. T. Nevalainen Prolactin Is a Survival Factor for Androgen-Deprived Rat Dorsal and Lateral Prostate Epithelium in Organ Culture Endocrinology, November 1, 1999; 140(11): 5412 - 5421. [Abstract] [Full Text]
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D. M. Sutkowski, R. L. Goode, J. Baniel, C. Teater, P. Cohen, A. M. McNulty, H. M. Hsiung, G. W. Becker, and B. L. Neubauer Growth Regulation of Prostatic Stromal Cells by Prostate-Specific Antigen J Natl Cancer Inst, October 6, 1999; 91(19): 1663 - 1669. [Abstract] [Full Text] [PDF]
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M. Dimitrijevic-Bussod, V. S. Balzaretti-Maggi, and D. M. Gadbois Extracellular Matrix and Radiation G1 Cell Cycle Arrest in Human Fibroblasts Cancer Res., October 1, 1999; 59(19): 4843 - 4847. [Abstract] [Full Text] [PDF]
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J. Singh and D. J. Handelsman Imprinting by Neonatal Sex Steroids on the Structure and Function of the Mature Mouse Prostate Biol Reprod, July 1, 1999; 61(1): 200 - 208. [Abstract] [Full Text]
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A. Colao, P. Marzullo, S. Spiezia, D. Ferone, A. Giaccio, G. Cerbone, R. Pivonello, C. Di Somma, and G. Lombardi Effect of Growth Hormone (GH) and Insulin-Like Growth Factor I on Prostate Diseases: An Ultrasonographic and Endocrine Study in Acromegaly, GH Deficiency, and Healthy Subjects J. Clin. Endocrinol. Metab., June 1, 1999; 84(6): 1986 - 1991. [Abstract] [Full Text]
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R. Bhatia-Gaur, A. A. Donjacour, P. J. Sciavolino, M. Kim, N. Desai, P. Young, C. R. Norton, T. Gridley, R. D. Cardiff, G. R. Cunha, et al. Roles for Nkx3.1 in prostate development and cancer Genes & Dev., April 15, 1999; 13(8): 966 - 977. [Abstract] [Full Text]
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S. Lu, M. Liu, D. E. Epner, S. Y. Tsai, and M.-J. Tsai Androgen Regulation of the Cyclin-Dependent Kinase Inhibitor p21 Gene through an Androgen Response Element in the Proximal Promoter Mol. Endocrinol., March 1, 1999; 13(3): 376 - 384. [Abstract] [Full Text]
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A. Thomson and G. Cunha Prostatic growth and development are regulated by FGF10 Development, January 8, 1999; 126(16): 3693 - 3701. [Abstract] [PDF]
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W. Y. Chang, M. J. Wilson, L. Birch, and G. S. Prins Neonatal Estrogen Stimulates Proliferation of Periductal Fibroblasts and Alters the Extracellular Matrix Composition in the Rat Prostate Endocrinology, January 1, 1999; 140(1): 405 - 415. [Abstract] [Full Text]
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