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PubMed1990

Influence of progestins on serum hormone levels in postmenopausal women with advanced breast cancer--II. A differential effect of megestrol acetate and medroxyprogesterone acetate on serum estrone sulfate and sex hormone binding globulin.

Serum estradiol, estrone, estrone sulfate and sex hormone binding globulin were measured in 10 postmenopausal patients with advanced breast cancer receiving sequential treatment with medroxyprogesterone acetate and megestrol acetate. Treatment with megestrol acetate caused a non-significant reduction in serum estradiol (mean reduction of 19%, 0.05 less than P less than 0.1) but significant reductions in serum estrone (mean reduction of 20%, P less than 0.02) and serum estrone sulfate (mean reduction of 54%, P less than 0.005) compared to treatment with medroxyprogesterone acetate. In contrast, treatment with medroxyprogesterone acetate reduced serum sex hormone binding globulin more compared to treatment with megestrol acetate (mean reduction of 69%, P less than 0.01). These findings suggest that the two progestins have differential effects on serum hormone levels. The finding that treatment with megestrol acetate causes a significant reduction in serum estrone sulfate level warrants further investigations of this potentially important mechanism of action of this drug in advanced breast cancer.

Aged↗
PubMed1985

17 beta-Hydroxysteroid oxidoreductase: a ubiquitous enzyme. Interconversion of estrone and estradiol-17 beta in BALB/c mouse tissues.

A survey was conducted to define the sites of 17 beta-hydroxysteroid oxidoreductase activity in organs and tissues of male and female BALB/c mice, as well as the favored direction of the oxidoreductase reaction in intact tissues. The enzyme activity was assayed by use of radiolabeled estrone and estradiol-17 beta as substrates. Estrone formation from estradiol-17 beta was demonstrated in all tissues. The formation of estradiol-17 beta from estrone was demonstrated in most tissues, however, it was barely detected or was undetectable in the glandular stomach, small intestine, cecum, and large intestine. Thus, 17 beta-hydroxysteroid oxidoreductase activity is expressed in all BALB/c mouse organs and tissues. Approximately two-thirds of the tissues and organs examined, including those of the reproductive tracts, favored the conversion of estrone to estradiol-17 beta rather than the reverse reaction. The results of this study, however, represent qualitative estimates of 17 beta-hydroxysteroid oxidoreductase activity in BALB/c mouse tissues that are uncorrected for conversion to hydroxylated metabolites. These in vitro findings suggest that the 17 beta-hydroxysteroid oxidoreductase catalyzed reduction of estrone may contribute to the maintenance of physiologic levels of estradiol-17 beta in estrogen responsive tissues.

17-Hydroxysteroid Dehydrogenases↗
PubMed1980

Plasma estrone sulfate levels in postmenopausal women.

Estrone sulfate levels were measured in the plasma of 63 postmenopausal women. The assay method involved prior extraction of the free estrogens, enzyme hydrolysis of the estrone sulfate with sulfatase and radioimmunoassay of the estrone liberated. The plasma levels ranged from 37 to 320 pg/ml (expressed as free estrone) with a mean value of 178 +/- 79 pg/ml. As observed in premenopause, estrone sulfate is quantitatively the most important circulating estrogen in postmenopausal women.

Aged↗
PubMed2005

Distribution of estrogens, 17beta-estradiol and estrone, in Canadian municipal wastewater treatment plants.

The distribution of female hormones, 17beta-estradiol and estrone, was determined in effluents of 18 selected municipal treatment plants across Canada. Replicate 24-h composite samples were collected from the influent and final effluent of each treatment plant, and the removal efficiency compared to the operational characteristics of the plants. In conventional activated sludge and lagoon treatment systems, the mean concentrations of 17beta-estradiol and estrone in influent were 15.6 ng/l (range 2.4-26 ng/l) and 49 ng/l (19-78 ng/l). In final effluents, the mean concentrations of both 17beta-estradiol and estrone were reduced to 1.8 ng/l (0.2-14.7 ng/l) and 17 ng/l (1-96 ng/l), respectively. 17beta-estradiol was removed effectively, >75% and as high as 98%, in most of the conventional mechanical treatment systems with secondary treatment. The removal of estrone was much more complex with removal varying from 98% to situations where the concentrations in the effluent were elevated above that detected in the influent. The estrogenicity, measured using a transfected estrogen receptor in yeast (YES) assay, was also variable, ranging from high removal to elevations of estrogenicity in final effluent. Although the apparent removals were not statistically correlated with either hydraulic (HRT) or solid (SRT) retention times, plants or lagoons with high SRT were very effective at reducing the levels of hormones. Well-operated plants that achieved nitrification also tended to have higher removal of hormones than those that did not nitrify. Laboratory aerobic reactor experiments confirmed the rapid removal of 17beta-estradiol, estrone, and estrogenicity when exposed to sewage slurries.

Biological Assay↗
PubMed2006

Inhibition of estrone sulfatase by aromatase inhibitor-based estrogen 3-sulfamates.

Our rationale is based on the finding that estrone 3-sulfamate (EMATE, 2d), a typical estrone sulfatase (ES) inhibitor, can be hydrolyzed and the pharmacological effect of the free estrogen contributes to the bioactivity of the sulfamate. A number of 3-sulfamoylated derivatives of the good aromatase inhibitors, 2- and 4-halogeno (F, Cl, and Br) estrones and their estradiol analogs as well as 6beta-methyl and phenyl estrones, were synthesized and evaluated as inhibitors of ES in human placental microsomes in comparison with the lead compound EMATE. Among them, 2-chloro- and 2-bromoestrone 3-sulfamates (2b and 2c), along with their estradiol analogs 3b and 3c, were powerful competitive inhibitors with K(i)'s ranging between 4.0 and 11.3 nM (K(i) for EMATE, 73 nM). These four sulfamates as well as the 2-fluoro analogs 2a and 3a inactivated ES in a time-dependent manner more efficiently than EMATE, and 2-halogeno estrone sulfamates 2 also caused a concentration-dependent loss of ES activity. The results may be useful for developing a new class of drugs having a dual function, ES inhibition and aromatase inhibition, for the treatment of breast cancer.

Aromatase Inhibitors↗
PubMed2001

Effects of estrone sulfate alone or with medroxyprogesterone acetate on serum lipoprotein levels in postmenopausal women.

OBJECTIVE: To determine the effects of estrone sulfate alone or with different doses of medroxyprogesterone acetate on serum lipid and lipoprotein levels. METHODS: A multicenter, double-masked, randomized trial for 1 year involved 682 postmenopausal women, aged 53.8 +/- 0.2 years (mean +/- standard deviation) with intact uteri. Subjects received fixed daily doses of 0.625 mg of estrone sulfate and one of the following regimens: placebo; 2.5 mg daily of medroxyprogesterone acetate; 5 mg daily of medroxyprogesterone acetate; or 10 mg of medroxyprogesterone acetate for the first 12 days of each 28-day cycle. Fasting lipid and lipoprotein levels were measured at baseline and weeks 12, 16, 24, 30, 36, and 52 of treatment. Absolute mean changes from baseline were determined by paired t test, and treatment effects were determined by analysis of variance. RESULTS: Total cholesterol levels decreased significantly (P <.05) from baseline in all study groups; however, reduction was significantly greater (P <.001) in the 2.5-, 5-, and 10-mg groups (-13.3%, -15.2%, and -14.1%) than in the placebo group (-4.9%). Low-density lipoprotein cholesterol levels decreased significantly and equally in all groups (-10.1% to -12.3%). High-density lipoprotein cholesterol levels increased by 3.2% with unopposed estrogen (P <.05) and did not change from baseline with combined therapy. Triglyceride and very low-density lipoprotein cholesterol levels increased by 13.4% and 2.7%, respectively, in the placebo group, did not change in the 2.5-mg group, decreased by 10.2% and 2.0% and by 11.4% and 2.2% in the 5- and 10-mg groups, respectively (P <.05). CONCLUSION: Estrone sulfate at the daily dose of 0.625 mg alone or with medroxyprogesterone acetate significantly improved lipoprotein levels. Combined therapy with medroxyprogesterone acetate and estrone sulfate was associated with statistically significantly greater reduction in total cholesterol and statistically significantly less increase in triglyceride levels than unopposed estrone sulfate therapy.

Cholesterol, HDL↗
PubMed1996

Sulfation by guinea pig chorion and uterus: differential action towards estrone and estradiol.

The activities of estrogen sulfotransferase, estrogen sulfatase and estradiol 17beta-dehydrogenase change considerably in the guinea pig uterine compartment during gestation. This study was undertaken to inquire if the chorion membrane could influence the pattern of estrogen resulting when substrates were applied to the fetal surface of the chorion while it was attached, late in gestation, to the uterine wall. This tissue system resulted in a differential handling of estrone and estradiol. Estrone was largely excluded from the tissue, remaining mainly in free steroidal form. Estradiol was considerably converted to its 3-sulfate which was mainly retained by the chorion. Parallel experiments with chorion and uterus separately failed to discriminate between the two substrates. Hydrolysis of estrone sulfate and estradiol 3-sulfate was similar in all three tissue systems. It appears that the interaction of chorion with uterus late in gestation causes a difference in tissue action towards the two steroid substrates of closely related structure. The results suggest a limitation in tissue uptake of estrone compared with estradiol, or a much greater sulfotransferase activity towards estradiol. Whole cytosols of late gestational chorion catalyzed sulfation of estradiol at about double the velocity of estrone. This may only partly account for the difference in the intact chorion-uterine tissue system.

Animals↗
PubMed2003

Removal of the natural hormone estrone from aqueous solutions using nanofiltration and reverse osmosis.

The ability of a variety of nanofiltration and reverse osmosis membranes to retain the natural hormone estrone are examined here as a function of solution conditions. While size exclusion dominates retention with the tighter membranes, both size exclusion and adsorptive effects appear to be instrumental in maintaining high retention on nanofiltration membranes that otherwise exhibit relatively low ion retentions. These adsorptive effects may be driven by hydrogen bonding between estrone and the membrane. Electrostatic attraction appears to aid retention with an apparent slight decrease in retention at high NaCl concentrations. Deprotonation of estrone leads to a significant decrease in retention, most likely as a result of the effect of strong electrostatic repulsive forces decreasing the proximity of the negatively charged estrone to the negatively charged membrane surface and thus lowering the potential for adsorptive retention. This deprotonation effect is absent for tight RO membranes. The results reported here indicate that while open nanofiltration membranes may be effective in retaining estrone under some conditions, the extent of retention may be very susceptible to maintenance of adsorptive capacity at the membrane surface and depend on solution chemistry.

Adsorption↗
PubMed1998

Roles of cytochromes P450 1A2 and 3A4 in the oxidation of estradiol and estrone in human liver microsomes.

Of seven cDNA-expressed human cytochrome P450 (P450) enzymes (P450s 1A2, 2B6, 2C9, 2C19, 2D6, 2E1, and 3A4) examined, P450 1A2 was the most active in catalyzing 2- and 4-hydroxylations of estradiol and estrone. P450 3A4 and P450 2C9 also catalyzed these reactions although to lesser extents than P450 1A2. P450 1A2 also efficiently oxidized estradiol at the 16alpha-position but was less active in estrone 16alpha-hydroxylation; the latter reaction and also estradiol 16alpha-hydroxylation were catalyzed by P450 3A4 at significant levels. Anti-P450 1A2 antibodies inhibited 2- and 4-hydroxylations of these two estrogens catalyzed by liver microsomes of some of the human samples examined. Estradiol 16alpha-hydroxylation was inhibited by both anti-P450 1A2 and anti-P450 3A4, while estrone 16alpha-hydroxylation was significantly suppressed by anti-P450 3A4 in human liver microsomes. Fluvoxamine efficiently inhibited the estrogen hydroxylations in human liver samples that contained high levels of P450 1A2, while ketoconazole affected these activities in human samples in which P450 3A4 levels were high. alpha-Naphthoflavone either stimulated or had no effect on estradiol hydroxylation catalyzed by liver microsomes; the intensity of this effect depended on the human samples and their P450s. Interestingly, in the presence of anti-P450 3A4 antibodies, alpha-naphthoflavone was found to be able to inhibit estradiol and estrone 2-hydroxylations catalyzed by human liver microsomes. The results suggest that both P450s 1A2 and 3A4 have major roles in oxidations of estradiol and estrone in human liver and that the contents of these two P450 forms in liver microsomes determine which P450 enzymes are most important in hepatic estrogen hydroxylation by individual humans. P450 3A4 may be expected to play a more important role for some of the estrogen hydroxylation reactions than P450 1A2. Knowledge of roles of individual P450s in these estrogen hydroxylations has relevance to current controversies in hormonal carcinogenesis [Service, R. F. (1998) Science 279, 1631-1633].

Aryl Hydrocarbon Hydroxylases↗
PubMed2001

Effect of oleoyl-estrone treatment on the expression of beta1- beta2- and beta3-adrenoreceptors in rat adipose tissues.

Adult female rats received a constant i.v. infusion of oleoyl-estrone (3.5 pmol/kg day) in a lipidic suspension for 14 days. On days 0 (no treatment), 3, 6, 10 and 14, as well as on day 14 for controls (receiving only the lipid); the rats were killed and the expression of the beta1-, beta2- and beta3-adrenoceptor genes, in brown adipose tissue and in subcutaneous and periovaric white adipose tissue, were measured by RNA protection assay, and compared with that of cyclophyllin. The beta3-adrenoceptor was the most expressed in all adipose tissues, whereas beta2 was the less expressed in brown adipose tissue. Oleoyl-estrone significantly, but moderately, increased the expression of beta-adrenoceptors in the three adipose tissues: beta1 increased in subcutaneous, beta2 and beta3 in periovaric and beta3 in brown adipose tissue. Oleoyl-estrone also decreased beta3 expression in subcutaneous white adipose tissue. On day 10, adipocytes isolated from periovaric white adipose tissue of oleoyl-estrone-treated rats showed higher cAMP response to an isoproterenol challenge than the controls. The mechanism by which oleoyl-estrone elicits the wasting of fat reserves could be mediated by adrenergic pathways, at least in part.

Adipose Tissue↗
PubMed2003

Effect of oral oleoyl-estrone on the energy balance of diabetic rats.

We studied the effects of a 10-day oral 10 micromol/kg oleoyl-estrone (OE) treatment on streptozotocin-diabetic Wistar, Goto-Kakizaki and control Wistar rats. Streptozotocin rats lost more than half the energy ingested as urine glucose. Oleoyl-estrone induced the loss of body weight (mainly body fat) in all groups. Energy expenditure was similar in the three groups of rats studied. Water turnover was deranged in streptozotocin rats, which spent 14% of energy available heating the water drunk. Body lipids were highest in Goto-Kakizaki; lipid levels in streptozotocin rats were very low. Oleoyl-estrone decreased body lipid content in Wistar and Goto-Kakizaki; oleoyl-estrone decreased triacylglycerols (44% in Wistar and Goto-Kakizaki and 22% in streptozotocin rats) and phospholipids but did not affect body cholesterol. Oleoyl-estrone decreased insulin and leptin, did not affect blood glucose but decreased plasma glucose in all groups. There were no changes in plasma triacylglycerols or fatty acids, but HDL, LDL and cholesterol decreased in all groups. The same effects of OE on insulin, plasma (but not blood) glucose and leptin were observed in both models, but the presence of insulin seems to be needed for OE to normalise glycaemia and to facilitate the uptake and utilisation of glucose by tissues. This different handling of glucose and triacylglycerol energy accounts for the disparate effects of OE on energy balance. The main conclusion of this study is that OE function as a lipid-mobilising hormone is dependent on the mass of reserves available, which in turn is closely related to insulin status. Lack of insulin thus results in limited OE effects, and insulin resistance does not prevent or limit the effects of OE on energy homeostasis or the mobilisation of fat.

Administration, Oral↗
PubMed1996

Activation of 17beta-estradiol and estrone by dimethyldioxirane and inhibition of rat liver nuclear and nucleolar RNA synthesis in vitro.

17beta-estradiol (E2), estrone and diethylstilbestrol (DES) had no effect on nuclear and nucleolar RNA synthesis in vitro. However, after reacting with dimethyldioxirane (DMDO), a versatile epoxide-forming oxidant, these estrogens were able to inhibit and in a dose-dependent manner nuclear and nucleolar RNA synthesis in vitro. It was also found that the time required for the maximal activation of these chemicals by DMDO varied: estrone, 10 min; E2, 30 min; DES, 60 min. Tamoxifen (TAM) was also able to inhibit nuclear and nucleolar RNA synthesis in a dose-dependent manner, but the mechanism of this inhibition was more complex. Control experiments clearly indicated, unlike E2, estrone and DES, TAM per se was able to directly inhibit RNA synthesis in vitro. TAM after activation by DMDO was able to further inhibit RNA synthesis contributing part of the total observed inhibition. These data show for the first time that E2, estrone, DES and TAM can be activated by DMDO and possibly to epoxides. We propose that epoxidation of E2 and estrone may be the underlying mechanism of carcinogenesis for these estrogens in vivo.

Animals↗
PubMed1980

Estrone beta-glucosidase activity in human placenta.

The 105 000g supernatant from human placental homogenates, prepared in the presence of sodium taurocholate and Cutscum, contained beta-glucosidase activity towards estrone glucoside as well as towards 4-methylumbelliferyl glucoside (4-MU-glucoside) and glucocerebroside. After partial purification, the estrone glucosidase was found to be active only after the addition of negatively charged phospholipid, whereas the other beta-glucosidases did not exhibit this requirement. The estrone glucosidase was separated from the 4-MU-glucosidase by chromatography on Sephadex G-200 with 0.1% sodium taurocholate in the eluting buffer. The estrone glucosidase was mainly contained in material with a pI of 4.7, while the 4-MU-glucosidase was distributed in fractions with pI values of 4.7 and 6.2 to 6.4. The partially purified estrone glucosidase had a pH optimum of 5.8, as distinct from that of 6.4 found for the 4-MU-glucosidase, and differed markedly from the 4-MU-glucosidase in its response to treatment with heat, sulfhydryl reagents, and detergents. Its sensitivity to changes in pH differed from those reported for glucocerebrosidase.

Detergents↗
PubMed2006

Role of polymorphic human cytochrome P450 enzymes in estrone oxidation.

Estrogen and its metabolites are believed to play important roles in breast cancer. The influence of genetic polymorphisms in the enzymes responsible for formation and disposition of estrogen on breast cancer risk may shed light on the importance of estrogen metabolites in this disease. However, for such studies to be valid, it is important to correctly identify the enzymes involved in estrogen bioactivation. Therefore, we assessed the human cytochrome P450-dependent oxidation of estrone using substrate concentrations that more closely approximate the maximum expected concentrations in breast tissue. The in vitro metabolism of estrone by recombinant human cytochrome P450 enzymes and human liver microsomes was studied. The formation of estrone metabolites (2-hydroxyestrone, 4-hydroxyestrone, and 16alpha-hydroxyestrone) was monitored by high-performance liquid chromatography. 2-Hydroxyestrone formation was catalyzed predominantly by CYP1A2, CYP1A1, and CYP1B1 enzymes; 4-hydroxyestrone formation was catalyzed predominantly by CYP1B1, CYP1A2, and CYP1A1 enzymes; and 16alpha-hydroxyestrone formation was catalyzed predominantly by CYP2C19, CYP1A1, and CYP3A5. This study confirms the important role of members of the CYP1 family in the 2-hydroxylation and 4-hydroxylation of estrone, but the enzymes identified as responsible for the 16alpha-hydroxylation of estrone are different from those previously identified. The relative importance of these enzymes in vivo would depend on the specific tissue expression of the enzymes. These enzymes are all known to be genetically variant in the human population, and additional studies to assess the role CYP1A2, CYP2C19, and CYP3A5 in breast cancer risk are indicated.

Biomarkers, Tumor↗
PubMed1981

Enhanced responsiveness of lactotrophs in ectopic pituitaries to bromocryptine and estrone acetate.

Intrasellar and transplanted pituitaries removed from the same rats were studied using light microscopy, immunocytology, electron microscopy and ultrastructural morphometry following treatment with bromocryptine and/or estrone acetate. Ectopic lactotrophs of rats treated with bromocryptine showed an increase in storage granule size and number, which was not observed in the lactotrophs of corresponding intrasellar pituitaries. In lactotrophs of intrasellar and ectopic pituitaries, treatment with estrone acetate caused a decrease of storage granule size, while rough endoplasmic reticulum (RER) and Golgi region volume density increased. When rats were treated with a combination of bromocryptine and estrone acetate, intrasellar lactotrophs exhibited increased volume density and diameter size in forming granules as well as increased RER volume density. In ectopic lactotrophs, combined treatment led to a decrease in RER, volume densities of Golgi region and forming granules, as well as increased storage granule size. It can be concluded that ectopic lactotrophs were more sensitive to the inhibiting effects of bromocryptine treatment than intrasellar lactotrophs. Intrasellar lactotrophs were more susceptible to estrone acetate than bromocryptine treatment. As a result, the increased responsiveness of ectopic lactotrophs to estrone acetate was less conspicuous.

Animals↗
PubMed1983

Uptake, receptor and biological response of estrone in the fetal uterus of guinea pig.

In vivo and in situ subcutaneous injection of 30 muCi of 3H-estrone (3H-E1) to guinea pig fetuses was carried out to study the dynamics of the selective uptake and retention of this estrogen in the uterus and other fetal organs. In the fetal uterus an increase in the uptake of radioactivity with time was found which was maximal 1 h after injection of 3H-E1. The analysis of radioactive material showed that in the fetal uterus unmetabolized 3H-E1 accounts for 65-75% of the total radioactivity between 10 and 60 min after the injection and its maximal concentration is 2.5-15 times and 10 times higher than the maximal concentrations found in other fetal organs and fetal plasma, respectively. Significant amounts of 3H-E1 were also present in lung (33-60% of the total radioactivity in this tissue), brain (37-52%) and ovary (18-47%), while an important conversion of 3H-E1 into 3H-estradiol was observed in the kidney (20-26%). Estrogen sulfates, essentially estrone sulfate, represented the greater part of the fetal plasma radioactivity (30-49%). 3H-E1-specific binding sites in the cytosol of the fetal uterus were found with physicochemical characteristics (specifically limited to natural and synthetic estrogens, Kd = 8.1 +/- 1.2 x 10(-10) M (SD), sedimentation coefficient 8S) similar to those of the typical estrogen receptor. The cytosol receptor-3H-E1 complex has a dissociation rate constant (K-1) of 16 +/- 0.7 x 10(-4) s-1 at 25 degrees C. The responsiveness of the fetal uterus to estrone treatment was studied after subcutaneous administration of estrone to pregnant guinea pigs (1 mg/kg/day for 3 consecutive days). Two biological responses were observed: an increase in fetal uterine weight (50-100% in relation to the nontreated animals) and a significant stimulation of progesterone receptor protein (10-16 times higher than in control animals). At the same time, there was a 50-70% decrease in the total estrogen receptor concentration. It is concluded that estrone could be involved in the biological responses to estrogen in the fetal uterus of guinea pig.

Animals↗
PubMed1975

Identification and measurement of urinary estrone, estradiol-17 beta, estriol, pregnanediol and androsterone during the menstrual cycle of the orangutan.

Urinary estrone, estradiol-17beta, estriol, pregnanediol and androsterone were identified and measured during 3 menstrual cycles in 2 female orangutans. In 2 of the cycles, the animals excreted 1-8 mug/day estrone, 0.5-6 mug/day estradiol-17beta, 1-8 mug/day estriol, 20-206 mug/day pregnanediol and 120-522 mug/day androsterone during the first half of the menstrual cycle. In the second half of the cycle, corresponding values were 3-21 mug/day estrone, 2-10 mug/day estradiol-17beta, 1-9 mug/day estriol, 54-800 mug/day pregnanediol and 90-1158 mug/day androsterone. In 1 cycle, the estrogen values for the second half were considerably higher, possibly due to the animal becoming pregnant just before this study commenced. The values for estrone and estradiol-17beta are similar to those found in the human and chimpanzee menstrual cycle. The values for estriol were lower than in the human but higher than in the chimpanzee. Levels for urinary pregnanediol and androsterone were significantly lower than in the human. Variations during the menstrual cycle for estrone were characterized by a midcycle peak followed by a second peak in the luteal phase. No definite pattern was apparent for estradiol-17beta or estriol. Both urinary pregnanediol and androsterone levels were low during the first half of the cycle, started to rise just after midcycle, and showed a peak during the second half of the menstrual cycle.

Androsterone↗
PubMed1993

Effect of aging on endogenous level of 5 alpha-dihydrotestosterone, testosterone, estradiol, and estrone in epithelium and stroma of normal and hyperplastic human prostate.

It is widely believed that benign prostatic hyperplasia (BPH) is associated with aging. Thus, the question arises whether or not a correlation exists between the well known prostatic androgen and estrogen accumulation and aging. To address this question, we measured 5 alpha-dihydrotestosterone (DHT), testosterone, estradiol, and estrone in epithelium and stroma of six normal (NPR) and 19 BPH and correlated the values with the age of the donors (26-87 yr). The mean DHT level in NPR epithelium was significantly higher than in NPR stroma, and also significantly higher than in epithelium and stroma of BPH. The epithelial DHT level of NPR and BPH decreased with age, the correlation being statistically significant. The stromal DHT level of NPR and BPH showed no correlation with age. Concerning testosterone, generally rather low values were found which showed no correlation with age. The mean levels of estradiol and estrone were significantly higher in BPH stroma as compared to BPH epithelium as well as to NPR epithelium and stroma. In NPR, the mean levels of estradiol and estrone were significantly higher in epithelium than stroma. In NPR and BPH, the stromal estradiol and estrone levels increased significantly with age. In epithelium such a correlation between the estrogen levels and age was not found. Our results indicate that the prostatic accumulation of DHT, estradiol, and estrone is in part intimately correlated with aging, leading with increasing age to a dramatic increase of the estrogen/androgen ratio particularly in stroma of BPH.

Adult↗