Hormonal Control of Prostatic Differentiation and Morphogenesis: The Impact of Apoptosis and Steroid Hormone Receptor Expression

  • G. Aumüller
  • P. M. Holterhus
  • W. Eicheler
  • H. Renneberg
  • M. Bacher
  • L. Konrad
  • H. Bonkhoff
  • F. Rauch
  • H. G. Mannherz
Part of the Ernst Schering Research Foundation Workshop book series (SCHERING FOUND, volume 14)


Apoptosis or active cell death (Bursch et al. 1992) is a process whereby cells die in response to specific physiological signals. The morphological sequence of events, as described by Kerr et al. (1972; for review, see Wyllie et al. 1980; Fesus et al. 1991; Fesus 1993) appears to be common to most epithelial cells. They require an expenditure of metabolic energy, active gene expression, and protein biosynthesis. Histologically, the process is characterized by cell shrinking to the extent that they pull away from neighboring cells and the basement membrane, undergoing both nuclear and cytoplasmic condensation. The latter results in the formation of the so-called apoptotic bodies, thought to require increased expression of tissue transglutaminase (Piacentini et al. 1991; Fukuda et al. 1993). Apoptotic bodies are sequestered either by neighboring cells or macrophages, thereby escaping access to the immune system. Chromatin condensation is thought to result from activation of an endogenous Ca2+, Mg2+-dependent endonuclease. Internucleosomal DNA is preferentially digested, resulting in a visual “ladder” of DNA fragments in multimers of 180 base pair units upon electrophoresis, which can be visualized in situ by means of the so-called terminal transferase reaction (Gavrieli et al. 1992).


Androgen Receptor Benign Prostatic Hyperplasia Ventral Prostate Prostatic Epithelium Active Cell Death 
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  1. Aurntiller G (1979) Prostate gland and seminal vesicles. In: Oksche A, Vollrath L (eds) Handbuch der mikroskopischen Anatomie des Menschen, vol VII16. Springer, Berlin Heidelberg New YorkGoogle Scholar
  2. Aumiiller G (1991) Postnatal development of the prostate. Bull Assoc Anat 75 (229): 39–42Google Scholar
  3. Aumiiller G, Stofft E, Tunn U (1980) Fine structure of the canine prostatic complex. Anat Embryol 160: 327–340CrossRefGoogle Scholar
  4. Aumiiller G, Seitz J, Bischof W (1983) Immunohistochemical study on the initiation of acid phosphatase secretion in the human prostate. J Androl 4: 183–191Google Scholar
  5. Bacher M, Rausch U, Goebel HW, Polzar B, Mannherz HG, Aumiiller G (1993) II. Stromal and epithelial cells from rat ventral prostate during androgen deprivation and estrogen treatment. Regulation of transcription. Exp Clin Endocrinol 101: 78–86Google Scholar
  6. Bettuzzi S, Hiipakka RA, Gilna P, Liao S (1989) Identification of an androgen-repressed mRNA in rat ventral prostate as coding for sulphated glycoprotein 2 by cDNA cloning and sequence analysis. Biochem J 257: 293–296PubMedGoogle Scholar
  7. Bonkhoff H, Stein U, Remberger K (1993) Androgen receptor status in endocrine-paracrine cell types of the normal, hyperplastic, and neoplastic human prostate. Virchows Arch [A] 423: 291–294CrossRefGoogle Scholar
  8. Bonkhoff H, Stein U, Remberger K (1994a) The proliferative function of basal cells in the normal and hyperplastic human prostate. Prostate 24: 114–118PubMedCrossRefGoogle Scholar
  9. Bonkhoff H, Stein U, Remberger K (1994b) Multidirectional differentiation in the normal, hyperplastic, and neoplastic human prostate: simultaneous demonstration of cell-specific epithelial markers. Hum Pathol 25: 42–46PubMedCrossRefGoogle Scholar
  10. Bursch W, Oberhammer F, Schulte-Hermann R (1992) Cell death by apoptosis and its protective role against disease. Trends Pharmacol Sci 13: 245–251PubMedCrossRefGoogle Scholar
  11. Buttyan R, Olsson CA, Pintar J, Chang CS, Bandyk M, Ng P-Y, Sawczuk IS (1989) Induction of the TRPM-2 gene in cells undergoing programmed death. Mol Cell Biol 9: 3473–3481PubMedGoogle Scholar
  12. Colombel M, Olsson CA, Ng P-Y, Buttyan R (1992) Hormone-regulated apoptosis results from reentry of differentiated prostate cells onto a defective cell cycle. Cancer Res 52: 4313–4319PubMedGoogle Scholar
  13. Colombel M, Symmans F, Gil S, O’Toole KM, Chopin D, Benson M, Olsson CA, Korsmeyer S, Buttyan R (1993) Detection of the apoptosis-suppressing oncoprotein bd-2 in hormone-refractory human prostate cancers. Am J Pathol 143: 390–400PubMedGoogle Scholar
  14. di Sant’Agnese PA (1992) Neuroendocrine differentiation in carcinoma of the prostate. Cancer [Suppl] 70: 254–268CrossRefGoogle Scholar
  15. English HF, Kyprianou N, Isaacs JT (1989) Relationship between DNA fragmentation and apoptosis in the programmed cell death in the rat prostate following castration. Prostate 15: 233–250PubMedCrossRefGoogle Scholar
  16. Fesus L (1993) Biochemical events in naturally occurring forms of cell death. FEBS Lett 328: 1–5PubMedCrossRefGoogle Scholar
  17. Fesus L, Thomazy V, Falus A (1987) Induction and activation of tissue transglutaminase during programmed cell death. FEBS Lett 224: 104–108PubMedCrossRefGoogle Scholar
  18. Fesus L, Davies PJA, Piacentini M (1991) Apoptosis: molecular mechanisms in programmed cell death. Eur J Cell Biol 56: 170–177PubMedGoogle Scholar
  19. Flickinger CJ (1971) Ultrastructural observations on the postnatal development of the rat prostate. Z Zellforsch 113: 157–173PubMedCrossRefGoogle Scholar
  20. Friedrichs B, Riedmiller H, Goebel HVV, Rausch U, Aumtiller G (1994) Immunological characterization and activity of transglutaminases in human normal and malignant prostate and prostate cancer cell lines. Urol Res (submitted)Google Scholar
  21. Fukuda K, Kojiro M, Chiu J-F (1993) Induction of apoptosis by transforming growth factor-[31 in the rat hepatoma cell line McA-RH7777: a possible association with tissue transglutaminase expression. Hepatology 18: 945–953PubMedCrossRefGoogle Scholar
  22. Gavrieli Y, Sherman Y, Ben Sasson SA (1992) Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol 119: 493–501PubMedCrossRefGoogle Scholar
  23. Hoshikawa Y, Satoh Y, Ichii S (1991) Isolation and characterization of cDNA clones for castration-induced mRNAs in the rat ventral prostate. Endocrinol Jpn 38: 619–626PubMedCrossRefGoogle Scholar
  24. Jiang H, Kochhar DM (1992) Induction of tissue transglutaminase and apoptosis by retinoic acid in the limb bud. Teratology 46: 333–340PubMedCrossRefGoogle Scholar
  25. Kellokumpu-Lehtinen P (1983) Localization of acid phosphatase activity in testosterone treated prostatic urethra of human fetuses. Prostate 4: 265–270PubMedCrossRefGoogle Scholar
  26. Kellokumpu-Lehtinen P, Santti R, Pelliniemi IJ (1980) Correlation of early cytodifferentiation on the human fetal prostate and Leydig cells. Anat Rec 196: 263–273PubMedCrossRefGoogle Scholar
  27. Kerr JFR, Searle J (1973) Deletion of cells by apoptosis during castration-induced involution of the prostate. Virchows Arch [B] 13: 87–102Google Scholar
  28. Kerr JFR, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide range implications in tissue kinetics. Br J Cancer 26: 239–257PubMedCrossRefGoogle Scholar
  29. Krijnen JLM, Janssen PJA, Ruizeveld de Winter JA, van Krimpen H, Schröder FH, van der Kwast TH (1993) Do neuroendocrine cells in human prostate cancer express androgen receptor? Histochemistry 100: 393–39830PubMedCrossRefGoogle Scholar
  30. Kyprianou N, Isaacs JT (1988) Activation of programmed cell death in rat ventral prostate after castration. Endocrinology 122: 552–562PubMedCrossRefGoogle Scholar
  31. Kyprianou N, Isaacs JT (1989) Expression of transforming growth factor-13 in the rat ventral prostate during castration-induced programmed cell death. Mol Cell Endocrinol 3: 1515–1522CrossRefGoogle Scholar
  32. Kyprianou N, English HF, Isaacs JT (1989) Activation of Ca2+-Mg2+-dependent endonuclease as an early event in castration induced prostatic cell death. Prostate 13: 103–117CrossRefGoogle Scholar
  33. Martikainen P, Isaacs JT (1990) Role of calcium in the programmed death of rat prostatic glandular cells. Prostate 17: 175–187PubMedCrossRefGoogle Scholar
  34. Montironi R, Magi Galluzzi C, Scarpelli M, Giannulis I, Diamanti L (1993) Occurrence of cell death (apoptosis) in prostatic intra-epithelial neoplasia. Virchows Arch [A] 423: 351–357CrossRefGoogle Scholar
  35. Montpetit ML, Lawless KR, Tenniswood M (1986) Androgen repressed messages in the rat ventral prostate. Prostate 8: 25–36PubMedCrossRefGoogle Scholar
  36. Peitsch MC, Mannherz HG, Tschopp J (1994) The apoptosis endonucleases: cleaning up after cell death? Trends Cell Biol 4: 37–41PubMedCrossRefGoogle Scholar
  37. Piacentini M, Fesus L, Farrace MG, Ghibelli L, Piredda L, Melino G (1991) The expression of “tissue” transglutaminase in two human cancer cell lines is related with the programmed cell death (apoptosis). Eur J Cell Biol 54: 246–254PubMedGoogle Scholar
  38. Rouleau M, Léger J, Tenniswood M (1990) Ductal heterogeneity of cytokeratins, gene expression, and cell death in the rat ventral prostate. Mol Endocrinol 4: 2003–2013PubMedCrossRefGoogle Scholar
  39. Sandford NL, Searle JW, Kerr JFR (1984) Successive waves of apoptosis in the rat prostate after repeated withdrawal of testosterone stimulation. Pathology 16: 406–410PubMedCrossRefGoogle Scholar
  40. Sen S, d’Incalci M (1992) Apoptosis: biochemical events and relevance to cancer chemotherapy. FEBS Lett 307: 122–127PubMedCrossRefGoogle Scholar
  41. Thomazy V, Fesus L (1989) Differential expression of tissue transglutaminase in human cells. Cell Tissue Res 255: 215–224PubMedCrossRefGoogle Scholar
  42. Wyllie AH, Kerr JFR, Currie AR (1980) Cell death: the significance of apoptosis. Int Rev Cytol 68: 251–306PubMedCrossRefGoogle Scholar
  43. Zhao GQ, Bacher M, Friedrichs B, Schmidt W, Rausch U, Goebel HW, Tuohimaa P, Aumilller G (1993) Functional properties of isolated stroma and epithelium from rat ventral prostate during androgen deprivation and estrogen treatment. Exp Clin Endocrinol 101: 69–77PubMedCrossRefGoogle Scholar
  44. Zondek T, Mansfield MD, Attree SL, Zondek LH (1986) Hormonal levels in the fetal and neonatal prostate. Acta Endocrinol (Copenh) 112: 447–456Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1995

Authors and Affiliations

  • G. Aumüller
  • P. M. Holterhus
  • W. Eicheler
  • H. Renneberg
  • M. Bacher
  • L. Konrad
  • H. Bonkhoff
  • F. Rauch
  • H. G. Mannherz

There are no affiliations available

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