Phenotypic modulation of the canine prostate after long‐term treatment with androgens and estrogens

Aumüller, Gerhard; Funke, P.-J.; Hahn, Alfred W.A.; Hoffbauer, Gudrun; Tunn, U.; Neumann, F.

doi:10.1002/pros.2990030406

Cited by 42 publications

(11 citation statements)

References 30 publications

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“…Levine et al (1992) suggested that the absence of smooth muscle cells in their cultures might have accounted for the lack of oestrogen responsiveness; it has been reported that prostatic stroma reverts to more generalized mesenchymal cell type after several passages in culture (Ricciardelli et al 1989). Several authors have pointed to the possible aetiological role of activated smooth muscle cells in BPH (Bartsch & Rohr 1981, Aumiiller et al 1982, Rohr & Bartsch 1983, Zhao et al 1992). However, Zhao et al (1992) found that smooth muscle cells from the rat prostate responded less markedly to oestrogen than fibroblasts, although the most dramatic effects of oestrogen on the activation of smooth muscle cells have been seen in the canine prostate (Aumiiller et al 1982) but a glandular, not stromal, hyperplasia develops under oestrogen/androgen activation.…”

Section: Discussionmentioning

confidence: 99%

Androgen and oestrogen responsiveness of stromal cells derived from the human hyperplastic prostate: oestrogen regulation of the androgen receptor

Collins

Zhiming²,

Gilmore³

et al. 1994

Journal of Endocrinology

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Stromal cells derived from collagenase-digested benign hyperplastic adult prostates were isolated and grown in culture. Androgen and oestrogen receptor status were determined and growth in response to mibolerone (a synthetic androgen) and oestradiol-17 beta was measured. In addition, the ability of oestrogens to regulate the androgen receptor in stromal cells was investigated. [3H]Thymidine incorporation into DNA was stimulated by mibolerone in primary and secondary cultures, but sensitivity was lost with subsequent passages. Androgen stimulation of [3H]thymidine incorporation was consistently inhibited by the anti-androgen cyproterone acetate. Oestradiol-17 beta also stimulated [3H]thymidine incorporation into DNA, and this effect was inhibited by the anti-oestrogen tamoxifen. Sensitivity to oestradiol was lost with subsequent passages. A combination of mibolerone and oestradiol was not synergistic in increasing [3H]thymidine incorporation into DNA, but maximal stimulation occurred at 100-fold lower concentrations of mibolerone and oestradiol when the two hormones were applied in combination. Specific high-affinity [3H]mibolerone- and [3H]oestradiol-binding sites were demonstrated by radioligand binding in intact cells. The affinity for oestradiol binding to its receptor exceeded that quantified for mibolerone binding to the androgen receptor, whilst the number of oestradiol-binding sites was approximately tenfold less than that quantified for mibolerone. Treatment with oestradiol down-regulated the number of [3H]mibolerone binding sites 1.7-fold (P < 0.005) as early as day 2 after oestradiol treatment. In conclusion, we successfully cultured stromal cells derived from hyperplastic prostates which retained sensitivity to androgen and oestrogen.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionmentioning

confidence: 99%

Androgen and oestrogen responsiveness of stromal cells derived from the human hyperplastic prostate: oestrogen regulation of the androgen receptor

Collins

Zhiming²,

Gilmore³

et al. 1994

Journal of Endocrinology

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“…Like man, dogs and rodents have hormone responsive prostates making them particularly important in BPH research. The administration of androgens and estrogens to recreate a hormonal environment similar to men as they age, reliably produces prostatic growth in dogs [24, 36, 40–46] and rats [47, 48]. Key research utilizing these models have significantly moved the field of BPH research forward although prostate anatomy in dogs and rats differs significantly from the human prostate.…”

Section: Models Of Bphmentioning

confidence: 99%

Androgens and estrogens in benign prostatic hyperplasia: Past, present and future

2011

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Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms (LUTS) are common clinical problems in urology. While the precise molecular etiology remains unclear, sex steroids have been implicated in the development and maintenance of BPH. Sufficient data exists linking androgens and androgen receptor pathways to BPH and use of androgen reducing compounds, such as 5α-reductase inhibitors which block the conversion of testosterone into dihydrotestosterone, are a component of the standard of care for men with LUTS attributed to an enlarged prostate. However, BPH is a multifactorial disease and not all men respond well to currently available treatments, suggesting factors other than androgens are involved. Testosterone, the primary circulating androgen in men, can also be metabolized via CYP19/aromatase into the potent estrogen, estradiol-17β. The prostate is an estrogen target tissue and estrogens directly and indirectly affect growth and differentiation of prostate. The precise role of endogenous and exogenous estrogens in directly affecting prostate growth and differentiation in the context of BPH is an understudied area. Estrogens and selective estrogen receptor modulators (SERMs) have been shown to promote or inhibit prostate proliferation signifying potential roles in BPH. Recent research has demonstrated that estrogen receptor signaling pathways may be important in the development and maintenance of BPH and LUTS; however, new models are needed to genetically dissect estrogen regulated molecular mechanisms involved in BPH. More work is needed to identify estrogens and associated signaling pathways in BPH in order to target BPH with dietary and therapeutic SERMs.

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“…Smooth muscle cells in "synthetic" or "metabolic" state have been described as "activated" smooth muscle cells in experimental canine or age-dependent human BPH [6,7]. Rohr and Bartsch [8], Bartsch and Rohr [9], and Ghanadian and Puah [ 101 pointed to the possible etiological significance of "activated' ' smooth muscle cells in BPH stroma.…”

Section: Introductionmentioning

confidence: 99%

“…[7,33,34], where prostatic smooth muscle cells appear Stereological analysis of relative volume percentage of nucleus(Fig. 26), cytoplasm (Fig.…”

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confidence: 99%

Estrogen‐induced morphological and immunohistochemical changes in stroma and epithelium of rat ventral prostate

et al. 1992

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Prostatic smooth muscle cells have been regarded to play a major pathogenetic role during the development of benign prostatic hyperplasia (BPH) in elderly men. Altered hormonal signals (increased estrogen) have been made responsible for the "metabolic" transformation of prostatic smooth muscle cells, which were thought to produce increased amounts of connective tissue fibers observed in BPH. In order to find out the role of metabolically "activated" smooth muscle cells, hormone stimulation experiments were performed in male rats. The effects of androgen deprivation and estrogen stimulation were recorded by semiquantitative analysis of intermediate and myofilament proteins in stromal smooth muscle cells. In castrated or estrogen-treated or estrogen-treated and castrated animals, the reduction of the glandular lumen is the most obvious morphological alteration, accompanied by an increase in connective tissue. Regressive changes occurred most rapidly in castrated animals (already within the first week), slower in castrated estrogen-treated animals and still slower in normal estrogen-treated animals. Regression of the epithelium was accompanied by a marked decrease in immunoreactivity for prostatic binding protein (PBP) in castrated animals, while PBP immunoreactivity in estrogenized animals was retained for up to 6 weeks. Smooth muscle cells became atrophic in castrated animals. This effect was attenuated in estrogen-treated animals. There was no indication for enhanced collagen synthesis by smooth muscle cells. Actin and desmin-immunoreactivity were only slightly altered in experimental animals and showed a changed distribution pattern. Prostatic smooth muscle cells respond less markedly to hormonal alterations than do the fibroblasts.

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Phenotypic modulation of the canine prostate after long‐term treatment with androgens and estrogens

Cited by 42 publications

References 30 publications

Androgen and oestrogen responsiveness of stromal cells derived from the human hyperplastic prostate: oestrogen regulation of the androgen receptor

Androgen and oestrogen responsiveness of stromal cells derived from the human hyperplastic prostate: oestrogen regulation of the androgen receptor

Androgens and estrogens in benign prostatic hyperplasia: Past, present and future

Estrogen‐induced morphological and immunohistochemical changes in stroma and epithelium of rat ventral prostate

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