Effects of estrogen deprivation on human benign prostatic hyperplasia

Schweikert, Hans-Udo; Tunn, U.; Habenicht, U.‐F.; Arnold, Joshua D.; Senge, Th.; Schulze, Harald; Schröder, Fritz H.; Blom, J.; Ennemoser, O.; Horniger, W.; Bartsch, Georg

doi:10.1016/0960-0760(93)90261-t

Cited by 45 publications

(15 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Using direct measurements of estrogen production, Brodie et al (24) could find no evidence of aromatase activity in human prostate, even when testosterone metabolism was inhibited with 5␣-reductase inhibitors. In addition, aromatase inhibitors have no effect on canine benign prostatic hyperplasia (25) and have had little effect on human benign prostatic hyperplasia (26). Although it would be unlikely that estrogens could mimic the ability of androgens to prevent apoptosis in the rat prostate, we cannot rule out a role of local estrogen production in our testosterone dose response.…”

Section: Discussionmentioning

confidence: 71%

Relative potency of testosterone and dihydrotestosterone in preventing atrophy and apoptosis in the prostate of the castrated rat.

Wright¹,

Thomas²,

Douglas³

et al. 1996

J. Clin. Invest.

116

View full text Add to dashboard Cite

Although dihydrotestosterone (DHT) is the principal androgen in the prostate, testosterone can also act as an androgen in this tissue. To determine the relative potencies of testosterone and DHT in preventing prostate regression, castrated rats were implanted for 4 d with varying doses of testosterone in the presence or absence of the 5 ␣ -reductase inhibitor finasteride. In the absence of finasteride, testosterone in the prostate is converted to DHT, creating an intraprostatic DHT dose response. In the presence of finasteride, this conversion is blocked, and an intraprostatic testosterone dose response is achieved. DHT was 2.4 times more potent than testosterone at maintaining normal prostate weight and duct lumen mass, a measure of epithelial cell function. The two androgens were equipotent at preventing DNA fragementation and expression of testosterone-repressed prostate message, two measures of apoptosis (cell death). The intraprostatic testosterone concentration that results from finasteride treatment in rats is sufficient to inhibit apoptosis but will not maintain normal epithelial cell activity. In conclusion, whereas DHT is more potent than testosterone at stimulating prostate epithelial cell function as measured by ductal mass, the two androgens are equipotent at preventing prostate cell death after castration. These results explain why finasteride causes prostate involution in the rat with minimal evidence of prostate cell death.

show abstract

Section: Discussionmentioning

confidence: 71%

Relative potency of testosterone and dihydrotestosterone in preventing atrophy and apoptosis in the prostate of the castrated rat.

Wright¹,

Thomas²,

Douglas³

et al. 1996

J. Clin. Invest.

116

View full text Add to dashboard Cite

show abstract

“…Consequently, estrogen deprivation significantly reduces prostatic volume in BPH patients (Schweikert et al 1993). Since ERs had only been identified in the prostatic stroma, it was assumed that, at the beginning of BPH, estrogens caused proliferation of the prostatic stroma, and then the hyperplastic stroma induced epithelial cell growth, which in turn enhanced androgen action, because androgen receptors are predominantly localized in the prostatic epithelium (Bashirelahi et al 1979, Srinivasan et al 1995.…”

Section: Discussionmentioning

confidence: 99%

“…Estrogens are implicated in prostatic growth, and the hyperplastic changes seen in the prostate have been related to the exposure of prostatic tissue to increased intraprostatic and circulating estrogen levels (Zhao et al 1992, Schweikert et al 1993. Consequently, estrogen deprivation significantly reduces prostatic volume in BPH patients (Schweikert et al 1993).…”

Section: Discussionmentioning

confidence: 99%

Estrogen receptors alpha and beta in the normal, hyperplastic and carcinomatous human prostate

Royuela¹,

Miguel²,

Fr³

et al. 2001

Journal of Endocrinology

138

View full text Add to dashboard Cite

Two different estrogen receptors (ER-and ER-) have been described, which are differentially involved in regulating the normal function of reproductive tissues. ERwas considered for a long time to be the only estrogen receptor, and it has been detected in the stromal cells of the human prostate but not in the epithelium. To obtain new information about the differential effects of both receptor types, we have investigated their localization in normal prostates, benign prostatic hyperplasia (BPH), and prostatic cancer (PC) by immunohistochemistry, ELISA and Western blot. Epithelial immunostaining was absent in normal prostates and was present in BPH (10% of cells) and PC (80% of cells), whereas about 15% of stromal cells were positively immunostained for ER-in the three types of prostatic specimens studied. Epithelial immunostaining for ER-was detected in normal prostates (13% of cells), BPH (30% of cells) and PC (79% of cells), whereas stromal immunostaining for ER-was absent in normal and hyperplastic prostates and was present in PC (12% of cells). The complementary presence of both receptor types in the normal prostate (ER-in the epithelium and ER-in the stroma) might explain the mechanism of estrogen action in the development of BPH. The increased epithelial immunostaining for both ERand ER-in BPH and PC suggests that the involvement of estrogen receptors in hyperplasia and cancer concerns mainly the epithelium.

show abstract

“…Although there is an immense literature that deals with the endocrinology of the normal and abnormal prostate (2), there are great gaps in our understanding. For instance, although there is a general beliefthat estrogens are important in the pathogenesis ofBPH (3,4), there has never been a clear demonstration of a direct estrogenic effect on the prostate. Further, there is an apparent paradox involving two widely accepted endocrinologic facts.…”

mentioning

confidence: 99%

Estradiol causes the rapid accumulation of cAMP in human prostate.

Nakhla

Khan

Romas

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

123

View full text Add to dashboard Cite

Androgens are widely acknowledged to be central to the pathogensis of benign prostatic hypertrophy (BPH). However (GIBCO) with 5% fetal bovine serum containing penicillin (100 units/ml), streptomycin sulfate (100 ,ug/ml), and amphotericin (0.25 gg/ml) and was incubated for 2-3 days. It was then minced into 1-mm3 portions and transferred to 16-mm wells in serum-free medium (0.5 ml of RPMI 1640) for about 18 hr before the start of an experiment. All additions (SHBG, steroids, controls) were made in serum free RPMI 1640.Cell culture. Fibroblast-enriched cultures (17) were prepared from surgical specimens obtained as above. Fragments (1-3 mm3) were placed in 25 ml of digestion buffer (10 mM Hepes/142 mM NaCl/6.7 mM KC1, pH 7.4) and stirred for 30 min at 370C in an atmosphere of 95% air/5% CO2. After discarding the supernatant, fresh digestion buffer supplemented with 1% collagenase, 0.67 mM CaCl2, 20 mM dextrose, and 0.05% DNase was added to the tissue for 30 min at 370C. The supernatant was discarded again and the digestion was repeated twice. The cells released after the second and third digestion were collected, washed twice, and plated in fresh attachment medium (Ham's F12 supplemented with 5% fetal bovine serum). The medium was changed after 7 days and every 3-4 days thereafter. Three to four weeks after the original isolation, >95% of the cells had the typical morphology of fibroblasts. About 18 hr before the beginning of an experiment, cells were placed in serum-free medium (Ham's F12), and detached with a nonenzymatic cell dissociation solution (Sigma). They then were washed once and suspended (0.2-0.5 mg of protein per ml) in serum-free medium containing 50 nM SHBG. Prostatic epithelial cells were provided by D. M. Peehl (Stanford University) and were isolated as described by her (18). They underwent the same experimental protocol as the fibroblasts.Abbreviations: BPH, benign prostatic hypertrophy; SHBG, sex hormone-binding globulin. 5402The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

show abstract

Effects of estrogen deprivation on human benign prostatic hyperplasia

Cited by 45 publications

References 10 publications

Relative potency of testosterone and dihydrotestosterone in preventing atrophy and apoptosis in the prostate of the castrated rat.

Relative potency of testosterone and dihydrotestosterone in preventing atrophy and apoptosis in the prostate of the castrated rat.

Estrogen receptors alpha and beta in the normal, hyperplastic and carcinomatous human prostate

Estradiol causes the rapid accumulation of cAMP in human prostate.

Contact Info

Product

Resources

About