SEARCH · PubMed Health

Results for “ESTRADIOL, THERAPEUTIC”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 577 records · Page 32Linked to original sources

PubMed1988

Hormonal regulation of bone growth and remodelling.

Many systemic and local hormones influence bone growth and remodelling. These include calcium regulating hormones, systemic growth regulators and local growth factors. Parathyroid hormone (PHT) is a potent stimulator of osteoclastic bone resorption and a direct inhibitor of osteoblastic collagen synthesis. However, intermittent low-dose PTH administration can increase bone formation in vivo. PTH may act indirectly via local factors. It has been shown to increase prostaglandin E2 (PGE2) and transforming growth factor beta (TGF-beta) release from bone. Both PGE2 and TGF-beta have complex effects on bone metabolism and are likely to be physiological regulators of bone remodelling. Oestradiol has been shown to inhibit bone resorption in vivo but not in vitro. While there is evidence for oestrogen receptors in cultured bone cells, the effect could still be indirect. Oestradiol can inhibit bone PGE2 release in an in vivo-in vitro model in the rat. Glucocorticoids are potent inhibitors of bone formation and inhibit PGE2 and interleukin 1 production both in vivo and in vitro. While many regulatory factors affect prostaglandin production in bone, the complex effects of PGE2 on bone metabolism make it difficult to predict the ultimate response. The major effects of PGE2 are stimulation of bone formation and resorption and an increase in bone turnover. However, opposite effects can occur at certain times and concentrations. Interactions among these factors could explain some physiological, pathological, and therapeutic responses in skeletal tissue.

Animals↗

PubMed2002

[Multiple miliary osteomas of the face].

Osteoma cutis is a single or multiple ectope calcification with development of bony structures in the skin. We distinguish between primary and secondary ossification. Multiple miliary osteoma in the face has mostly been described secondary to preexisting acne vulgaris. We present a 62-year-old woman who developed multiple miliary osteoma in the face together with repeated doses of estrogen and discuss pathogenesis and therapeutic possibilities.

Biopsy↗

PubMed2002

Oestrogens and puberty.

Oestrogens induce the development of female reproductive tissues. Endogenous human oestrogens include oestradiol, oestrone and oestriol. Oestrogen signalling in target tissues is dependent on the tissue concentration of oestrogen and the interaction of oestrogen receptors with an array of cell-specific co-regulator proteins. The diverse mechanisms of oestrogen signalling are complex and incompletely understood. In puberty, oestrogen is derived from both gonadal and peripheral sources. Originally, oestrogen was only thought to drive feminization in females; now, oestrogen is known to be important for pubertal development of males as well. Oestrogen is required for normal maturation of the neuroendocrine-gonadal axis and bone in both sexes, and a variety of other tissues are also responsive to oestrogen. Abnormal puberty can be associated with either excessive or inadequate oestrogen production. Girls deficient in oestrogen should receive replacement in physiological doses. Aromatase inhibitors and anti-oestrogens may prove to be useful therapeutic tools in some types of abnormal puberty.

Estradiol Congeners↗

PubMed1976

Effect of oral 17-beta-oestradiol on the liver in women with intrahepatic cholestasis (hepatosis) during previous pregnancy.

The effects of 17-beta-oestradiol in 14 women who had had intrahepatic cholestasis of pregnancy (hepatosis) were studied. This natural oestrogen was given orally in a daily dose of 5 mg for two 20-day periods with a 7-day interval between courses. The bromsulphthalein (BSP) retention rose during the treatment, but only occasionally to levels above the upper limit of normal. Other conventional liver function tests did not usually become abnormal. In a previous investigation in the same type of patients, we studied the effects of mestranol (a synthetic 17-alkylated oestrogen) in a daily dose of 0.1 mg with the same dose-schedule as the present investigation and 17-beta-oestradiol appeared to impair liver function less than mestranol. It might thus be safer to use 17-beta-oestradiol as a therapeutic agent.

Alanine Transaminase↗

PubMed2003

Tamoxifen, a selective estrogen receptor modulator, reduces ischemic damage caused by middle cerebral artery occlusion in the ovariectomized female rat.

Previous work has demonstrated that physiological concentrations of 17beta-estradiol can protect the female rat brain against middle cerebral artery occlusion (MCAO)-induced ischemic damage. The present study examined whether therapeutic doses of the clinically relevant selective estrogen receptor modulator (SERM), tamoxifen, can similarly protect the female rat brain against ischemic stroke damage. Adult female rats were bilaterally ovariectomized and implanted subcutaneously with either a placebo or tamoxifen time-release pellet (0.1, 0.8 or 2.4 mg/kg/day). One week later, the animals underwent permanent MCAO to assess the protective ability of the different tamoxifen doses on brain infarct size. As expected, MCAO produced a large infarct ( approximately 53%) of the affected cerebral hemisphere in placebo (control) animals. The 0.1 mg/kg/day dose of tamoxifen did not exhibit any significant protective effects, however; the 0.8 and 2.4 mg/kg/day doses of tamoxifen, which are in the therapeutic range, dramatically reduced infarct of the affected cerebral hemisphere ( approximately 70% reduction) as compared to the controls. The reduction of infarct size was primarily due to protection of two major structures, the cerebral cortex and striatum. Laser Doppler analysis further revealed that tamoxifen had no significant effect on cerebral blood flow either before or after MCAO, suggesting that tamoxifen protection is independent of cerebral blood flow changes. Further studies showed that tamoxifen pellets implanted at the time of MCAO did not reduce infarct size, suggesting that pretreatment with tamoxifen is necessary to observe a protective effect. These studies suggest that clinically important SERMs may have an additional unrecognized beneficial effect of protection of the female brain.

Animals↗

PubMed2004

Tamoxifen--what next?

Most patients with advanced breast cancer (ABC) ultimately die due to disease progression. Consequently, treatments for ABC are predominantly palliative in nature and, therefore, the tolerability profile of a given treatment is particularly relevant in these patients. While cytotoxic chemotherapy and endocrine therapy exhibit efficacy in hormone-sensitive, advanced disease, it is endocrine therapy that combines efficacy with minimal acute toxicity. Tamoxifen has been the chosen endocrine therapy for postmenopausal, hormone-sensitive, ABC for over 20 years. More recently, new endocrine agents with different mechanisms of action from tamoxifen have been introduced. Evidence indicates that the aromatase inhibitors anastrozole (Arimidex; AstraZeneca; Wilmington, DE), letrozole (Femara; Novartis Pharmaceuticals Corp.; East Hanover, NJ) and exemestane (Aromasin; Pharmacia Corp.; Peapack, NJ) offer superior efficacy and tolerability to tamoxifen in the first-line treatment of postmenopausal, hormone-sensitive ABC. Similarly, after tamoxifen failure, fulvestrant (Faslodex; AstraZeneca), a new estrogen receptor (ER) antagonist that downregulates the ER, is at least as effective as anastrozole, is well tolerated, and is not cross-resistant with tamoxifen. Unlike tamoxifen, fulvestrant has no known agonist effects. The sequential use of such agents may prolong the time during which endocrine therapies can be used, thereby avoiding the more acute toxicities associated with cytotoxic chemotherapy. Indeed, a series of studies has shown that this sequential use is a relevant, active, and well-tolerated option. Establishing the comparative efficacies and optimal sequences that incorporate the newer endocrine agents will be central in determining the future role of hormonal therapy in ABC; the results of this work will determine the relative place of tamoxifen in what is a rapidly changing therapeutic environment.

Antineoplastic Agents, Hormonal↗

PubMed2006

Estrogen dependent growth inhibitory effects of tamoxifen but not genistein in solid tumors derived from estrogen receptor positive (ER+) primary breast carcinoma MCF7: single agent and novel combined treatment approaches.

While many studies have documented tamoxifen's benefits as an adjuvant therapy in the treatment and prevention of recurrent breast cancer in estrogen receptor positive (ER+) breast carcinoma, this beneficial effect may decrease with long-term tamoxifen use. This experimental study was designed to compare the cytotoxic responses of ER+ primary breast cancer solid tumors derived from the MCF7 cell line to experimental therapeutics, including genistein, tamoxifen, all-trans retinoic acid (ATRA) and parthenolide in the presence and absence of exogenous beta-estradiol. The results of this study suggest that the growth inhibitory effects of tamoxifen, were dependent on beta-estradiol levels. In contrast, the cytotoxic effects of the isoflavone soy derivative, genistein, were observed to be independent of exogenous estrogen. Moreover, combined therapy using tamoxifen and genistein produced enhanced cytotoxic effects also independent of beta-estradiol levels. Additional studies involving the use of the novel agents all trans retinoic acid (ATRA) and parthenolide produced notable tumor responses and combined effects that were also estrogen-independent. Overall, these preclinical research findings suggest possible clinical applications suggesting that genistein might be a useful clinical adjuvant, particularly in post-menopausal women in whom breast cancer occurs more frequently. Moreover, this research suggests that combined treatment approaches involving the use of tamoxifen in conjunction with agents that inhibit NFkappaB pathway signaling, such as parthenolide and genistein, warrant further study.

Anticarcinogenic Agents↗

PubMed1991

[Current treatments of cancer of the prostate].

Cancer of the prostate mainly occurs in elderly men and is becoming more frequent as the general European population gets older. Only through continuing progress in the already well developed therapeutic methods will mortality due to this cancer be curtailed. Prognosis of cancer limited to the prostate gland has been improved by radical surgery which reduces morbidity and mortality and advanced radiotherapy techniques. The potentially curable forms, still mainly detected by systematic rectal examination, can be defined better with magnetic resonance imagery and biological markers. Hormonal treatment for more extended or metastatic cancers is now based on several effective, well tolerated products. Chemotherapy has not been able to solve the problem of hormonal escape for which other therapeutic techniques are now under study.

Androgen Antagonists↗

PubMed1989

Transdermal therapeutic systems and rate controlled drug delivery.

One of the key design features of transdermal therapeutic systems, namely the system rate-control, and its impact on systemic therapy, are reviewed. Specifically, TTS(scopolamine) and TTS(estradiol) are evaluated as examples of the rate-controlled transdermal products. The use of these TTS products has resulted in controlled plasma concentration of drug and reduced side effects by the use of TTS(scopolamine) and more physiologic estradiol to estrone ratio with the transdermal dosage form of estradiol.

Administration, Cutaneous↗

PubMed1985

[The menopause. Therapeutic regimens].

The author considers successively the hormonal and non-hormonal treatments of menopausal disorders in isolating the different therapeutic schemes adapted to different types of anomaly.

Climacteric↗

PubMed1996

[Which stimulation for poor responders? Critical study of results and methods of research].

No therapeutic approach is regularly effective to correct poor ovarian responses. High gonadotropin doses from the beginning of stimulation can increase plasma estradiol level and number of preovulatory follicles, but generally fail to improve ongoing pregnancy rate, in ovulation induction and in vitro fertilization as well. LHRH agonists in long protocol gave in our experience the best results. In short protocol their "flare-up" effect is useful, but plasma LH and progesterone are also increased in follicular phase. The clomiphen citrate--hMG association is more effective on oocyte and embryo quality than quantity. Results of spontaneous cycle and growth hormone or GRF co-treatment are disappointing. Using GnRH agonist micro-doses needs for more precise assessment. Oocyte donation can be the last solution for some of these patients.

Adult↗

PubMed1999

Efficacy on climacteric symptoms of a new estradiol transdermal patch with active matrix in comparison with a reference reservoir patch. Two long-term randomized multicenter parallel-group studies.

METHODS: Two randomized prospective multicentre parallel group studies were performed (one in Germany and the other in Italy) in symptomatic postmenopausal women. The goal was to assess the efficacy on climacteric symptoms and the safety of a new estradiol (CAS 50-28-2) transdermal patch with solid active matrix (SAM) in comparison to a conventional liquid reservoir (LR) type estradiol transdermal patch. Both patches released 50 micrograms/day estradiol. One group of patients received the SAM patch and the other the LR patch in 4-week cycles, with a twice-weekly application of the patches for 3 weeks, followed by one week without patches. Progestin opposition was achieved with medroxyprogesterone acetate 5 mg/day orally in the last 11 days of patch application in the German study and with 10 mg/day in the last 12 days of patch application in the Italian study. Both studies were divided into two Parts: Part 1 with three 4-week cycles for a total of 12 weeks and Part 2 for other ten 4-weeks cycles in which the patches could be applied also continuously. The total duration of the study was therefore 52 weeks. RESULTS: Germany study. 133 patients resulted randomized to the SAM group and 129 to the LR group. Both estradiol patches quickly relieved climacteric symptoms already during the first 3 weeks of patch application, as shown by the rapid decrease of the Kupperman Index. At the end of Part 1, in the SAM group 91% and in the LR group 96% of patients reported relief from climacteric symptoms. At the end of Part 2 the percentages were 98% and 95%, respectively. The two patches were therapeutically equivalent with a power greater than 99.7%. Both patches were systemically fairly well tolerated. Only 4.5% of patients in the SAM group and 3.9% in the LR group discontinued prematurely for possible adverse reactions related to estradiol. There was no significant difference between the two patches with regard to systemic tolerability. Conversely, with regard to local skin reactions, the SAM patch was significantly (p < 0.01) better tolerated than the LR patch. The adhesion to the skin of the SAM patches was better than that of the LR patches. RESULTS. Italian study. 139 patients resulted randomized to the SAM patch and 128 to the LR patch. Also in this study both types of patches relieved the climacteric symptoms already during the first 3 weeks of patch application, as shown by the rapid decrease of the visual analogue scale (VAS) recordings of severity of hot flushes and of sweats. At the end of Part 1 both patches relieved 95% of patients from climacteric symptoms. At the end of Part 2, i.e. after 52 weeks, 100% of patients were relieved from climacteric symptoms. Of these, 72% in the SAM group and 78% in the LR group reported complete disappearance of symptoms. Also in the Italian study, therefore, the two patches were found therapeutically equivalent. Both patches stopped or even reversed bone mineral loss in L2-L4 and had some favorable effects on lipid metabolism. Both patches were systemically equally fairly well tolerated with premature discontinuations for systemic adverse drug reactions in only 5.0% of patients in the SAM group and 3.9% in the LR group. Conversely, as in the German study, the SAM patches were significantly better tolerated by the skin (p < 0.0001). CONCLUSIONS: The two types of estradiol transdermal patches were equivalent in providing an effective and rapid relief from climacteric symptoms. Systemically both patches were fairly well tolerated. The SAM patches were significantly better tolerated by the skin. The better local tolerability combined with better adhesion and cosmetic properties render the SAM patches very patient friendly and improve the compliance in the long term estrogen replacement therapy required to reduce osteoporosis and cardiovascular risks.

Adhesiveness↗

PubMedDate not supplied

Expression and regulation of estrogen receptor beta in human breast tumors and cell lines.

Expression of estrogen receptor beta (ER-beta) and its regulation by estradiol and anti-estrogens was analyzed in breast cancer cells. We determined that ER-beta is expressed in normal and tumor human breast tissue as well as in breast cancer cell lines. We observed moderate levels of ER-beta expression in both T47D and T47D-V22 (a T47D variant cell line) cells, in contrast with T47DCo (a T47D variant cell line) cells when compared to ER-alpha expression. While T47DCo (a T47D variant cell line), BT474, MDA-MB-231, MDA-MB-453, MDA-MB-468 and MCF-7 express low levels of ER-beta, other cell lines including the T47D-Y (a T47D variant cell line), MDA-MB-435, BT-549, and SKBr-3 cells express undetectable levels of ER-beta. Interestingly, ER-beta and ER-alpha are apparently not co-expressed in the breast tissue analyzed. Estradiol induced 30-40-fold increased ER-beta mRNA expression in T47D cells over control untreated cells. Moreover, the anti-estrogen, 4-hydroxy-tamoxifen (4OH-Tam) strongly inhibited estradiol induction of ER-beta expression, but had little or no effect on estradiol induction of ER-alpha. A pure anti-estrogen, ICI-182,780, completely abolished the ability of estradiol to up-regulate the expression of ER. In addition, both actinomycin D and cyclohexymide inhibited estradiol induction of ER-beta mRNA, indicating that de novo mRNA and protein synthesis are probably required for this induction. In summary, this study demonstrates that ER-beta is expressed in breast cancer, and it is regulated by estradiol. Moreover, the studies demonstrate that estradiol up-regulation of ER-beta mRNA in T47D cells can be abolished by anti-estrogens. Thus, ER-beta expression may serve as a prognostic, diagnostic and/or therapeutic marker for breast cancer. To the best of our knowledge, this is the first report regarding hormonal regulation of ER-beta in human mammary cells.

Breast Neoplasms↗

PubMed2000

New calmodulin antagonists inhibit in vitro growth of human breast cancer cell lines independent of their estrogen receptor status.

Calmodulin plays a key role in the regulation of cell proliferation and calmodulin antagonists may offer a new therapeutic approach in the treatment of breast cancer. Three new specific calmodulin antagonists with improved potency were synthesized and screened on human breast cancer cell lines known to be estrogen receptor (ER)-positive or -negative. These calmodulin antagonists significantly inhibited cell growth as measured by the MTT proliferation assay (p<0.001). Their IC50 values were in the low micromolar range against both ER-positive and -negative variants of the MCF-7 cell line. Two other breast cancer cell lines (ER-positive T-47D and ER-negative MDA-MB-231) were also inhibited by these calmodulin antagonists with IC50 values in a similar range. The level of inhibition was independent of any stimulation of cell growth by estradiol. Calmodulin antagonists effectively reduced cell growth of both ER-positive and -negative human breast cancer cell lines in vitro. Calmodulin antagonists represent a novel therapeutic approach requiring further investigation.

Breast Neoplasms↗

PubMed1983

Inhibition of human placental progesterone and estrogen synthesis in early human gestation by aminoglutethimide in vivo.

The inhibitory effect of d,l-aminoglutethimide (AG) on the synthesis of progesterone and estradiol in early human pregnancy (8th-12th week of gestation) was investigated in volunteers; control group (n = 11), AG group [1000 mg AG orally at test begin (n = 6)]. Venous blood samples were taken at the beginning of the test and 0.5, 1, 2, 4, 8 and 24 h thereafter. In controls, no significant changes in serum progesterone and estradiol could be observed during 24 h. In the AG group, a decrease in progesterone and estradiol could be observed within 1 h after the test began; lowest serum steroid concentrations were reached after 4 h. Relative to the initial values taken as 100%, the greatest decrease in progesterone ranged between 37 and 83%, 62 +/- 15% (means +/- SD)(n = 6); the greatest decrease in estradiol ranged between 32 and 78%, 51 +/- 17% (means +/- SD)(n = 6). Twenty four hours after AG treatment, both steroids reached similar concentrations to those found at test begin. No clinical signs (e.g. uterine bleeding, contractions) for the abortifacient action of AG were observed. In conclusion, a single dose of AG (1000 mg given orally) cannot induce a therapeutic abortion in early pregnancy. In accordance with in vitro studies, the inhibitory effect of AG on placental progesterone formation is due to an inhibition of mitochondrial cholesterol side chain cleavage. The decrease in estradiol is thought to be related to an inhibition of placental aromatase.

Aminoglutethimide↗

PubMed2001

Endothelial protective and antishock effects of a selective estrogen receptor modulator in rats.

This study investigated whether idoxifene, a selective estrogen receptor modulator (SERM), exerted protective effects against ischemia-reperfusion-induced shock. Ovariectomized rats were treated with vehicle, idoxifene, or 17beta-estradiol for 4 days. Rats were subjected to splanchnic artery occlusion (SAO) followed by reperfusion (SOA/R). In vehicle-treated rats, SAO/R resulted in hypotension, hemoconcentration, increased plasma tumor necrosis factor (TNF)-alpha levels, intestinal neutrophil accumulation, and endothelial dysfunction. 17beta-Estradiol treatment increased plasma estradiol concentration and reduced SAO/R-induced tissue injury. Idoxifene treatment had no effect on plasma estradiol concentration but reduced SAO/R-induced hemoconcentration (+8.8 +/- 1.3 vs. +14 +/- 1.3% in the vehicle group, P < 0.01), TNF-alpha production (98 +/- 3.2 vs. 214 +/- 13 pg/ml, P < 0.01), and neutrophil accumulation (0.025 +/- 0.005 vs. 0.047 +/- 0.005 U/g protein, P < 0.01). It also improved endothelial function, prolonged survival time (172 +/- 3.5 vs. 147 +/- 8 min, P < 0.01), and increased survival rate (69 vs. 23%, P < 0.01). Moreover, treatment with 17beta-estradiol or idoxifene in vivo reduced TNF-alpha-induced endothelial dysfunction in vitro. Taken together, these results demonstrated that idoxifene exerted estrogen-like, endothelial-protective, and antishock effects in ovariectomized rats, suggesting that SERMs have therapeutic potential in tissue injury resulting from ischemia-reperfusion.

Animals↗

PubMed1988

Inhibition of peripheral aromatization in baboons by an enzyme-activated aromatase inhibitor (MDL 18,962).

The peripheral aromatization ([rho]BM) of androstenedione (A) and testosterone (T) was measured before and after administration of the aromatase inhibitor 10-(2 propynyl)estr-4-ene-3,17-dione (MDL-18,962) to five mature female baboons, Papio annubis. The measurements were made by infusing [3H]androstenedione/[14C]estrone or [3H]testosterone/[14C]estradiol for 3.5 h and collecting blood samples during the infusions and all urine for 96 h from the start of the infusion. Blood samples were analyzed for radioactivity as infused and product steroids, and the data were used to calculate MCRs. An aliquot of the pooled urine was analyzed for the glucuronides of estrone and estradiol and used to calculate the [rho]BM. MDL-18,962 was administered as a pulse in polyethylene glycol-400 (1-5 ml) either iv or via gastric tube 30 min before administration of the radiolabeled steroids. Control studies were done with and without polyethylene glycol-400 administration. When MDL-18,962 was given iv at 4 mg/kg, the aromatization of A was decreased 91.8 +/- 0.9% from the control value of 1.23 +/- 0.13% to 0.11 +/- 0.01%. At the same dose, aromatization of T was decreased 82.0 +/- 7.1%, from a control value of 0.20 +/- 0.03% to 0.037 +/- 0.018%. When MDL-18,962 was given iv at doses of 0.4, 0.1, 0.04, and 0.01 mg/kg, the values for aromatization of A were 0.16 +/- 0.03%, 0.18 +/- 0.06%, 0.37 +/- 11%, and 0.65 +/- 0.09%, respectively. The administration of MDL-18,962 via gastric tube at 4 mg/kg as a pulse decreased the aromatization of A from 1.35 +/- 0.06% to 0.43 +/- 0.12%, an inhibition of 67.2 +/- 10.7%. When administered via gastric tube daily for 5 days at 4 mg/kg, the aromatization of A fell from 1.35 +/- 0.06% to 0.063 +/- 0.003%, an inhibition of 84.4 +/- 0.5%. The MCRs of A and estrone were not altered by any dose of MDL-18,962 regardless of the mode of administration, but there was an increase in the MCRs of T and estradiol at the only dose (4 mg/kg, iv) at which these steroids were infused. The interconversions between the androgens and between the estrogens were not altered by the administration of MDL-18,962 at 4 mg/kg, iv. The enzyme-activated inhibitor MDL-18,962 is an effective inhibitor of [rho BM] in female baboons and could prove to be a useful therapeutic agent in treating estrogen-dependent breast cancer.

Androstenedione↗

PubMed2006

Estradiol as an anti-aromatase agent in human breast cancer cells.

Estradiol (E(2)) is an important risk factor in the development and progression of breast cancer. However, a "direct effect" of E(2) in breast cancerization has not yet been demonstrated. The estrogen receptor complex can mediate the activation of oncogens, proto-oncogens, nuclear proteins and other target genes that can be involved in the transformation of normal to cancerous cells. Breast cancer cells possess all the enzymes (sulfatase, aromatase, 17beta-hydroxysteroid dehydrogenase (17beta-HSD)) necessary for the local bioformation of E(2). In the last years, many studies have shown that treatment of breast cancer patients using anti-aromatase agents has beneficial therapeutic effects. The aromatase activity is very low in most breast cancer cells but was significantly increased in a hormone-dependent breast cancer cell line: the MCF-7aro, using the aromatase cDNA transfection and G-418 (neomycin) selection. In the present study, we explore the effect of E(2) on the aromatase activity of this cell line. The MCF-7aro cell line was a gift from Dr. S. Chen (Beckman Research Institute, Duarte, U.S.A.). For experiments the cells were stripped of endogenous steroids and incubated with physiological concentrations of [(3)H]-testosterone (5 x 10(-9)mol/l) alone or in the presence of E(2) (5 x 10(-5), 5 x 10(-7) and 5 x 10(-9)mol/l) for 24h at 37 degrees C. The cellular radioactivity uptake was determined in the ethanolic supernatant and the DNA content in the remaining pellet. [(3)H]-E(2), [(3)H]-estrone ([(3)H]-E(1)) and [(3)H]-testosterone were characterized by thin layer chromatography and quantified using the corresponding standard. It was observed that [(3)H]-testosterone is converted mainly into [(3)H]-E(2) and not to E(1), which suggests very low or absence of oxidative 17beta-HSD (type 2) activity in these experimental conditions. The aromatase activity, corresponding to the conversion of [(3)H]-testosterone to [(3)H]-E(2) after 24h, is relatively high, since the concentration of E(2) was 2.74+/-0.11pmol/mg DNA in the non-treated cells. E(2) inhibits this conversion by 77, 57 and 21%, respectively, at the concentrations of 5 x 10(-5), 5 x 10(-7) and 5 x 10(-9)mol. In previous studies, it was demonstrated that E(2) exerts a potent anti-sulfatase activity in the MCF-7 and T-47D breast cancer cells. The present data show that E(2) can also block the aromatase activity. The dual inhibition of the aromatase and sulfatase activities, two crucial enzymes for the biosynthesis of E(2) by E(2) itself in breast cancer add interesting and attractive information for the use of estrogen therapeutic treatments.

Aromatase↗