Immunhistochemische und stereologische Untersuchungen zur Differenzierung und Verteilung neuroendokriner Zellen in der menschlichen Prostata

Ziel der vorliegenden Arbeit war die nähere Charakterisierung der neuroendokrinen Zellen in der menschlichen Prostata bezüglich ihrer Herkunft, der Verteilung sowie ihres Altersganges. Das Untersuchungsmaterial umfasste männliche Embryonen von 57 mm bis 65 mm SSL, entsprechend der...

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1. Verfasser: Leonhard, Marcus Christof
Beteiligte: Aumüller, Gerhard (Prof. Dr. med.) (BetreuerIn (Doktorarbeit))
Format: Dissertation
Sprache:Deutsch
Veröffentlicht: Philipps-Universität Marburg 2003
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Object of the examination was a further characterization of prostatic neuroendocrine cells (ne-cells) in relation to their origin, distribution and development. The specimens comprised male embryos from 57 mm ? 65 mm crown-rump length (CRL), according to the 9th ? 13th week of gestation (wog), one foetus from the 36th wog, infantile, adolescent (around puberty) and adult prostates. The sections were labeled immunohistochemically, partly using a new established double-labeling technique, by different antibodies against neuroendocrine cells (anti-Chromogranin A (CgA), anti-Serotonin, anti-Calcitonin) and steroidhormonreceptors (anti-Androgenreceptor (AR), anti-Estrogenreceptors (ER)). The reactions were analyzed semiquantitatively, using a computer assisted morphometry system. The total amount of CgA-positive cells in the prostatic epithelium is about 2 %, the amount of Serotonin- and Calcitonin-positive cells is even lower, about 1 %. For the first time we demonstrated that in an embryo of 57 mm CRL, according to the 9th wog, there are no ne-cells in the epithelium of the urogenital sinus, but in the epithelium of the rectum. At this point of time, numerous ne-cells could be found in paraganglia, lying dorsolateral of the urogenital sinus. First in an embryo of 60 mm CRL, CgA-positive cells are detectable in the stroma, the epithelium, and a bit later in the the budding glands of the developing prostate. Partly, the stromal immunoreactive cells are located between the paraganglia and the epithelium of the urogenital sinus. Furthermore we proved a gradient for the ne-cells with a decreasing density from the central to the peripheral portions of the prostate. Comprising, the findings argue for a migration of the ne-cells from the paraganglia - and from the neural crest indirectly - to the epithelium of the urogenital sinus and therefor for a neurogenic origin of the prostatic ne-cells, even though we did never demonstrate a ne-cell penetrating the basal menbrane. Taking together the existing mono-stem-cell concept of prostatic cells should be replaced by a dual stem-cell concept with own progenitor cells for both the basal / secretory cells and the ne-cells, although an autochthonous genesis of the ne-cells could not be excluded definetly. Further examinations are needed to answer this question. Using double-labeling techniques we demonstrated, that ne-cells in ?healthy? specimens do not express AR or ER, therefor androgens and estrogens could only act indirectly, possibly. As far as benign prostatic hyperplasia and prostatic carcinoma are concerned, ne-cells attract interest as they seem to play a central role in the formation of these diseases. So much the better the establishment of adequate models is necessary to answer these questions.Object of the examination was a further characterization of prostatic neuroendocrine cells (ne-cells) in relation to their origin, distribution and development. The specimens comprised male embryos from 57 mm ? 65 mm crown-rump length (CRL), according to the 9th ? 13th week of gestation (wog), one foetus from the 36th wog, infantile, adolescent (around puberty) and adult prostates. The sections were labeled immunohistochemically, partly using a new established double-labeling technique, by different antibodies against neuroendocrine cells (anti-Chromogranin A (CgA), anti-Serotonin, anti-Calcitonin) and steroidhormonreceptors (anti-Androgenreceptor (AR), anti-Estrogenreceptors (ER)). The reactions were analyzed semiquantitatively, using a computer assisted morphometry system. The total amount of CgA-positive cells in the prostatic epithelium is about 2 %, the amount of Serotonin- and Calcitonin-positive cells is even lower, about 1 %. For the first time we demonstrated that in an embryo of 57 mm CRL, according to the 9th wog, there are no ne-cells in the epithelium of the urogenital sinus, but in the epithelium of the rectum. At this point of time, numerous ne-cells could be found in paraganglia, lying dorsolateral of the urogenital sinus. First in an embryo of 60 mm CRL, CgA-positive cells are detectable in the stroma, the epithelium, and a bit later in the the budding glands of the developing prostate. Partly, the stromal immunoreactive cells are located between the paraganglia and the epithelium of the urogenital sinus. Furthermore we proved a gradient for the ne-cells with a decreasing density from the central to the peripheral portions of the prostate. Comprising, the findings argue for a migration of the ne-cells from the paraganglia - and from the neural crest indirectly - to the epithelium of the urogenital sinus and therefor for a neurogenic origin of the prostatic ne-cells, even though we did never demonstrate a ne-cell penetrating the basal menbrane. Taking together the existing mono-stem-cell concept of prostatic cells should be replaced by a dual stem-cell concept with own progenitor cells for both the basal / secretory cells and the ne-cells, although an autochthonous genesis of the ne-cells could not be excluded definetly. Further examinations are needed to answer this question. Using double-labeling techniques we demonstrated, that ne-cells in ?healthy? specimens do not express AR or ER, therefor androgens and estrogens could only act indirectly, possibly. As far as benign prostatic hyperplasia and prostatic carcinoma are concerned, ne-cells attract interest as they seem to play a central role in the formation of these diseases. So much the better the establishment of adequate models is necessary to answer these questions.