Stroma of human benign prostatic hyperplasia: preferential tissue for androgen metabolism and oestrogen binding

Krieg, Michael; Klötzl, G.; Kaufmann, J.; Voigt, Kai‐Ingo

doi:10.1530/acta.0.0960422

Cited by 126 publications

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“…Since the involvement of estrogen in stromal hypertrophy is well known, it has been used previously for induction of prostatic hyperplasia in dogs [7]. There is evidence from animal as well as human studies suggesting an important role of the stroma and estrogens in the pathogenesis of benign prostatic hyperplasia (BPH) in man [3, 5 , [2,9,11,12,21,271. Our earlier studies have demonstrated a tenfold higher PIP concentration in benign prostatic tissue and urine (unpublished data) levels of this PIP in BPH patients have also been observed.…”

Section: Discussionmentioning

confidence: 99%

Modulation of Rat Prostatic Inhibinlike Peptide (PIP) by Steroids and Protein Hormones

Teni

Sheth

1988

Archives of Andrology

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Prostatic inhibinlike peptide (PIP) was detected in the ventral but not in the dorsal lobe of rat prostate.On orchiectomy, PIP concentration in the ventral prostate increased significantly, whereas it decreased on testosterone administration and attained value comparable with that in intact control. Estradiol-170-treated animals exhibited high levels of PIP in absence of significant alterations in the protein content. The effect of prolactin and human chorionic gonadotropin on PIP concentration was not so prominent at the dose levels studied. The present study thus demonstrates negative regulation of PIP by testosterone and stimulatory effect of estradiol-170 on PIP in rat ventral prostrate. INTRODUCTIONThere is a high concentration of prostatic inhibinlike peptide (PIP) in the normal and hyperplastic human prostate [4, 23, 301. Biologically active rat PIP has been shown by in vivo [lo] as well as in vitro studies [20]. High levels of PIP observed in the prostate-rich secretions of human seminal plasma (HSP) have further substantiated its prostatic origin [ 11. The importance of PIP as a prostatic tissue marker [4] and in confirming the prostatic origin of difficult-to-diagnose invasive tumors in metastic lesions [25] has been demonstrated by immunocytochemical localization studies. These data led us to study the status of immunoreactive PIP in the rat ventral and dorsal prostate and its modulation by steroid and protein hormones. MATERIALS AND METHODSSteroid and protein hormones used for the study were procured from Sigma Chemicals. Ninety-dayold male rats of Sprague Dawley strain were divided into the following groups: group I, intact controls; group 11, effect of castration; group 111, in vivo effect of steroid hormones: (a) testosterone (T) (500 pg), subgroup contained a minimum of five rats. All the animals except the intact controls were bilaterally castrated. Twenty-four hours after castration, the animals in groups I11 and IV were treated daily with the above-mentioned doses of respective hormones, administered subcutaneously for six days. Three hours after the last injection, animals of all the groups were killed and prostates excised. The dorsal and ventral lobes were weighed separately and homogenized individually in 0.01 M PBS, pH 7.0, and centrifuged at 800 g for 30 min at 4 "C. The supernatants were stored at -20 "C until analyzed for protein by Lowry's Method [14] and PIP by radioimmunoassay (RIA) [29]. A homologous preparation of PIP isolated from HSP [26] was used as a reference standard and as an antigen for radioiodination using Iz5I, obtained from Radiochemical Centre, Amersham, U. K. Iodination was carried out according to the method of Greenwood et al.[6] with appropriate modifications [29]. The specific activity of the labeled hormone ranged from 100 to 150 pCiIpg PIP. Specific antibodies to PIP were raised in rabbit by active immunization. Details regarding the high specificity of this antiserum and RIA methodology have been described [22]. The sensitivity of the assay was 0.7 to 40 ng o...

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Section: Discussionmentioning

confidence: 99%

Modulation of Rat Prostatic Inhibinlike Peptide (PIP) by Steroids and Protein Hormones

Teni

Sheth

1988

Archives of Andrology

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“…In addition to epithelial effects, estrogens induce a preferential stimulation of prostate stromal cell proliferation, consequently, combined administration of estrogens with androgens has been used to experimentally induce BPH in dogs [26,27]. In humans, the estradiol:DHT ratio increases moderately within normal prostate epithelial and stromal cells upon aging, however, the increased ratio is massive within BPH tissue which directly implicates estradiol in the disease process [28].…”

Section: Estrogens In the Male And Effects On The Prostate Glandmentioning

confidence: 99%

The role of estrogens and estrogen receptors in normal prostate growth and disease

2008

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Keywordsprostate; prostate cancer; estrogens; estradiol; estrogen receptor Estrogens have significant direct and indirect effects on prostate gland development and homeostasis and have been long suspected in playing a role in the etiology of prostatic diseases. Direct effects are mediated through prostatic estrogen receptors alpha (ERα) and beta (ERβ) with expression levels changing over time and with disease progression. The present review examines the evidence for a role of estrogens and specific estrogen receptors in prostate growth, differentiation and disease states including prostatitis, benign prostatic hyperplasia (BPH) and cancer and discusses potential therapeutic strategies for growth regulation via these pathways. Estrogens in the Male and Effects on the Prostate GlandWhile low levels of circulating estrogens are present throughout life in males, there are two time periods, during in utero development and aging, when males are exposed to relatively higher levels of circulating estradiol which have been shown to impact the prostate gland. In addition, estrogens may be produced locally within the prostate via conversion of testosterone to 17β-estradiol by aromatase expressed within the prostate stroma [1,2], thus estrogen action in the prostate may occur independent of serum levels of this steroid.During the third trimester of in utero development in humans, rising maternal estradiol and declining fetal androgen production result in an elevated estrogen/testosterone (E/T) ratio. This relative increase in estradiol has been shown to directly stimulate extensive squamous metaplasia within the developing prostatic epithelium which regresses immediately after birth when estrogen levels rapidly decline [3,4]. Although the natural role for estrogens during prostatic development is unclear, it has been proposed that excessive estrogenization during prostatic development may contribute to the high incidence of BPH and prostatic carcinoma currently observed in the aging male population [5]. African-American men have a two-fold increased risk of prostatic carcinoma as compared to their Caucasian counterparts and it has been suggested that this is related, in part, to elevated levels of maternal estrogens during early gestation in this population [6,7]. Indicators of pregnancy estrogen levels such as length of Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers

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“…The prostatic epithelium and stroma were separated from each other exactly as described earlier [16], The relative purity of the epi thelial and the stromal fraction was more than 80%, estimated by measuring in both tissue fractions acid phosphatase as a marker for epithelial cells and hydroxyproline as a marker for stromal elements [12,16]. For enzyme measurement, aliquots of the frozen homoge nates were pulverized in a porcelain mortar chilled with liquid nitro gen.…”

Section: Tissue Preparationmentioning

confidence: 99%

Enzyme Activities in Tissue of Human Benign Prostatic Hyperplasia after Three Months' Treatment with the Sabalserrulata Extract IDS 89 (Strogen®) or Placebo

Weisser¹,

Behnke²,

Helpap³

et al. 1997

Eur Urol

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Stroma of human benign prostatic hyperplasia: preferential tissue for androgen metabolism and oestrogen binding

Cited by 126 publications

References 0 publications

Modulation of Rat Prostatic Inhibinlike Peptide (PIP) by Steroids and Protein Hormones

Modulation of Rat Prostatic Inhibinlike Peptide (PIP) by Steroids and Protein Hormones

The role of estrogens and estrogen receptors in normal prostate growth and disease

Enzyme Activities in Tissue of Human Benign Prostatic Hyperplasia after Three Months' Treatment with the Sabalserrulata Extract IDS 89 (Strogen®) or Placebo

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