Elevated Estrogen Receptor Expression in Human Prostatic Stromal Cells by Androgen Ablation Therapy

Kruithof-Dekker, Inge G.; Têtu, Bernard; Janssen, P. J. A.; Kwast, Theodorus H. van der

doi:10.1016/s0022-5347(01)65749-5

Cited by 53 publications

(27 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This close relationship between the two classes of receptor has been demonstrated in cultured human prostatic stromal cells in which exposure to estradiol also raised the level of AR. 6 A similar phenomenon has also been reported in cultured prostatic carcinoma cell lines, 28 in stromal cells of prostatic carcinoma from patients treated with androgen ablation therapy 10 and in castrated dogs treated with oestrogen. 5 Culture of stromal cells with different concentrations of estradiol and testosterone, produced no consistent pattern of ERa and AR expression between the various treatments.…”

Section: Discussionsupporting

confidence: 74%

Upregulation of estrogen and androgen receptors modulate expression of FGF-2 and FGF-7 in human, cultured, prostatic stromal cells exposed to high concentrations of estradiol

Smith

Rhodes

et al. 2002

Prostate Cancer Prostatic Dis

View full text Add to dashboard Cite

This study was performed to develop an experimental model in which expression of estrogen receptors (ER) by human prostatic stromal cells could be reproducibly enhanced relative to similar cells with low ER expression. The second aim was to characterise changes in expression of ER, androgen receptor (AR), FGF-2 and FGF-7 in stromal cells exposed to high and low concentrations of estradiol and testosterone mimicking the different sex hormone levels between young and elderly men. Five strains of human prostatic stromal cells, isolated from BPH resections, were grown in steroid-free medium plus 1 mmol 17b-estradiol. After 10 days, cells were passaged and grown in the same medium without estradiol until confluent. In a second study four cell strains were exposed to high and low concentrations of 17b-estradiol and testosterone for 10 days. Cells were labelled with fluorescent antibodies to ERa, AR, FGF-2 and FGF-7 and the fluorescence intensity measured by flow cytometry. Following exposure to 1 mmol estradiol, stromal cells showed reduced expression of AR and ERa but after passage without estradiol they showed a 25% increase in both receptors over controls. Different combinations of sex hormones induced inconsistent changes with respect to expression of ER, AR and FGFs in the various cell-strains. However, there was a highly significant correlation between AR, ER and FGF-2 and FGF-7, which was cell strain-specific. Thus, changes in sex hormone balance per se may not be solely responsible for the observed increases in prostatic ER levels in BPH. Since expression of ER is correlated with synthesis of FGF-2 and FGF-7, it is likely that increases in stromal ER may mediate the synthesis of stromallyderived growth factors which contribute to the aetiopathogenesis of benign prostatic hyperplasia.

show abstract

Section: Discussionsupporting

confidence: 74%

Upregulation of estrogen and androgen receptors modulate expression of FGF-2 and FGF-7 in human, cultured, prostatic stromal cells exposed to high concentrations of estradiol

Smith

Rhodes

et al. 2002

Prostate Cancer Prostatic Dis

View full text Add to dashboard Cite

show abstract

“…Recent studies have demonstrated high levels of oestrogen receptors (ER) in human hyperplastic prostates which are located predominantly within cells of the stroma. [3][4][5] These stromal ER are of the alpha subtype, 3,4,6 the beta subtype being not detected immunohistochemically or flow cytometrically (as confirmed by preliminary studies for this investigation). In addition to their complement of androgen receptors (AR) and ERa, stromal cells also synthesise growth factors 7,8 by a process controlled by binding of androgens to AR.…”

Section: Introductionsupporting

confidence: 63%

Relationship between upregulated oestrogen receptors and expression of growth factors in cultured, human, prostatic stromal cells exposed to estradiol or dihydrotestosterone

Smith

Rhodes

et al. 2004

Prostate Cancer Prostatic Dis

View full text Add to dashboard Cite

This study investigated the hypothesis that, in benign prostatic hyperplasia (BPH), upregulated oestrogen receptors (ER) and the action of androgens differentially regulate expression of stromal growth factors. Eight human prostatic stromal cell strains were subjected to a procedure to upregulate their ER by exposing them to 1 lmol 17b-estradiol for 10 days followed by passage and growth in the absence of steroids. Four of the cell strains instead received 100 nmol dihydrotestosterone for 48 h. Immunoexpression of ERa, AR and six growth factors was quantified by flow cytometry in each case. Expression of ERa was significantly increased in six of eight cell strains. Expressions of six growth factors (FGF-2, FGF-7, IGF-1, TGF-b 1 NGF and e NOS) were elevated but only for FGF-7 was it significant. There was a significant positive correlation between the change in ERa and the change in FGF-2 and FGF-7, but not the other growth factors. Exposure to dihydrotestosterone reduced expression of ERa and all six growth factors, compared with oestrogentreated cells but not significantly. It is concluded that upregulated ERa in prostatic stroma may have a greater modulating influence on synthesis of certain growth factors than the direct action of androgens and, by enhancing synthesis of FGF-2 and FGF-7, could play a significant role in the development of BPH.

show abstract

“…Taken together, these findings suggest that flutamide may have testosteroneindependent affects on splenocytes. In fact, androgen depletion by castration or flutamide treatment has been shown to increase estrogen receptor expression in a variety of cells, including T cells (West et al 1990, Bodker et al 1994, Kruithof-Dekker et al 1996, Samy et al 2000. Furthermore, preliminary studies suggest that, not only are estrogen concentrations increased after burn as previously reported (Woolf et al 1985, Lephart et al 1987, but flutamide treatment further augments this increase (K A N Messingham, M A Emanuele and E J Kovacs, unpublished observation).…”

Section: Discussionmentioning

confidence: 65%

Testosterone receptor blockade restores cellular immunity in male mice after burn injury

Messingham¹,

Shirazi²,

Duffner³

et al. 2001

Journal of Endocrinology

View full text Add to dashboard Cite

Males are known to have increased risk for septic complications after traumatic injury, which appears to be mediated by the inhibitory effects of testosterone on immune function. The role of testosterone in immunity after burn injury, however, remains unclear. Herein, we examined the effects of a testosterone receptor antagonist, flutamide, on delayed type hypersensitivity response (DTH), splenocyte proliferation, interleukin (IL)-2 secretion, and IL-2 receptor (IL-2R) expression in male BALB/c mice subjected to a 15% total body surface area burn or sham injury. Burn-or sham-injured mice were given flutamide s.c. at 30 min and 24 h after injury. At 48 h, burn injury caused a 48% (P<0·001) decrease in DTH response; however, mice that received flutamide treatment did not demonstrate significant suppression of DTH. Likewise, splenocyte proliferation and IL-2 production were depressed in burned animals in comparison with sham-injured controls, and flutamide treatment resulted in a partial restoration of these responses. In vitro studies indicated that splenocytes from sham-and burninjured mice were equally sensitive to the suppressive effects of 5 -dihydrotestosterone in regard to proliferation and IL-2 production. Further evaluation revealed a decrease in IL-2R expression on splenocytes from burned mice and a partial restoration of this expression with flutamide treatment. Thus blocking testosterone receptor activation improves the cellular immunity in thermally injured mice, possibly through restoration of IL-2 production and IL-2R expression. It remains to be determined whether the effects of testosterone in this injury model are direct or indirect.

show abstract

Elevated Estrogen Receptor Expression in Human Prostatic Stromal Cells by Androgen Ablation Therapy

Abstract: Androgen deprivation leads to an upregulation of stromal ER expression in human prostate. Estrogen-induced morphological epithelial changes could be explained by a paracrine interaction between stromal and epithelial cells.

Cited by 53 publications

References 24 publications

Upregulation of estrogen and androgen receptors modulate expression of FGF-2 and FGF-7 in human, cultured, prostatic stromal cells exposed to high concentrations of estradiol

Upregulation of estrogen and androgen receptors modulate expression of FGF-2 and FGF-7 in human, cultured, prostatic stromal cells exposed to high concentrations of estradiol

Relationship between upregulated oestrogen receptors and expression of growth factors in cultured, human, prostatic stromal cells exposed to estradiol or dihydrotestosterone

Testosterone receptor blockade restores cellular immunity in male mice after burn injury

Contact Info

Product

Resources

About