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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Format: | Doctoral Thesis |
Language: | German |
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Philipps-Universität Marburg
2003
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Table of Contents:
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.