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F Labrie

Publications and source records attributed to F Labrie.

At least 91 records · Page 5Linked to original sources
PubMed1995

Localisation of 15-hydroxy prostaglandin dehydrogenase (PGDH) and steroidogenic enzymes in the equine placenta.

15-hydroxy prostaglandin dehydrogenase (PGDH) is the critical enzyme that determines metabolism of primary prostaglandins. Its expression is determined in part by steroid hormones, particularly progesterone, formed from delta(5) steroids through 3beta-hydroxysteroid dehydrogenase (3beta-HSD) activity. To assess whether the regulation of PGDH might occur in a paracrine, autocrine or intracrine fashion, we used immunohistochemistry (IHC) to determine the localisation of key steroidogenic enzymes in the equine placenta and compared these patterns to the distribution of immunoreactive (IR-) PGDH. Placental tissue was obtained from pony or Thoroughbred mares at about Days 150, 250-280 and >300 of pregnancy (term 320 to 360 days; n=5-8 each group). IR-PGDH, 3beta-HSD, cholesterol side chain cleavage enzyme (P450(scc)) and 17-hydroxylase/lyase (P450(C17)) were localised using specific antibodies and the avidin-biotin peroxidase technique and visualised using diaminobenzidine as substrate. IR-P450(scc) was present in trophoblast cells, but not in maternal tissues of the microcotyledons. In contrast, at Days 150 and 280, IR-PGDH was present in maternal epithelial and interstitial cells in the microcotyledons, but was not detected in trophoblast epithelium, chorioallantois or endometrial glands. After Day 300, IR-PGDH was present in the maternal epithelium and interstitial cells of the placenta and it was also present in trophoblast cells in some specimens.

3-Hydroxysteroid Dehydrogenases↗
PubMed1995

Genetic linkage mapping of HSD3B1 and HSD3B2 encoding human types I and II 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase close to D1S514 and the centromeric D1Z5 locus.

The enzyme 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase (3 beta-HSD) catalyses an essential step in the biosynthesis of all steroid hormones. Consequently, classical 3 beta-HSD deficiency is responsible for a severe form of congenital adrenal hyperplasia. The HSD3B1 and HSD3B2 genes encoding the types I and II 3 beta-HSD isoenzymes, respectively, have been previously assigned by in situ hybridization to the chromosome 1p13.1 region. To determine the physical distance between these two genes, NotI and SacII digests of genomic DNA were resolved by pulse-field gel electrophoresis and hybridized with type I and type II 3 beta-HSD cDNAs used as probes. The detection of a single band under low stringency conditions indicates that HSD3B1 and HSD3B2 are located within an approximately 0.29 megabase SacII DNA fragment. We constructed a high resolution genetic map of the region flanking the polymorphic HSD3B1 and HSD3B2 genes including ten Généthon markers and the two NIH/CEPH markers AMY2B and D1Z5. The HSD3B1A and HSD3B2A markers were mapped relative to other reference markers through eight CEPH reference families. The order of polymorphic genes and markers is: pter-[AMY2B-D1S239]-D1S457-D1S502-D1S250-+ ++D1S252-[HSD3B1A -HSD3B2A-D1S514]-[D1Z5-D1S442]-D1S305-D 1S303-D1S484-qter. The D1S514 marker was thus closely linked to HSD3B1A (theta < 0.001; lod = 14.13) and HSD3B2 (theta = 0.008; lod = 35.36). The HSD3B loci are located 1-2 cM of the centromeric marker D1Z5.

Animals↗
PubMed1995

Differential expression and regulation of connexin-43 and cell-cell coupling in myocytes from the circular and longitudinal layers of bovine myometrium.

The expression and localization of the gap junction protein connexin-43 (Cx-43) as well as functional coupling were studied in myocytes from the two layers of the bovine myometrium: the circular and the longitudinal layers. Intercellular communication (measured by Lucifer yellow dye transfer through gap junctions) was more intense in the circular than in the longitudinal layer of the bovine myometrium. The circular layer also exhibited a greater degree of punctuate immunofluorescence to Cx-43. Myocytes from the circular layer expressed more Cx-43 messenger RNA (mRNA; 2.38 +/- 0.46, Cx-43 over 18S RNA) than the longitudinal layer (1.46 +/- 0.48, Cx-43 over 18S RNA; P < 0.05). The modulation of Cx-43 expression by sex steroids in the two myometrial layers was tested using a pure steroidal antiestrogen, EM-139. In myocytes from the circular layer, the level of Cx-43 mRNA was decreased after treatment with 0.1 microM EM-139 (1.37 +/- 0.25, Cx-43 over 18S RNA) compared to that in untreated cells (2.38 +/- 0.46, Cx-43 over 18S RNA), representing a 40% inhibition. In parallel, cell-cell coupling and the amount of Cx-43 protein were also reduced after antiestrogen treatment. In contrast, treatment of cells from the longitudinal layer with the antiestrogen did not significantly affect the level of Cx-43 mRNA, protein, or cell-cell coupling. These data demonstrate that Cx-43 protein and mRNA are expressed and regulated differentially in myocytes from the circular and longitudinal layers of bovine myometrium. Furthermore, the circular myometrial layer may represent a preferential target for estrogen regulation of the biochemical and mechanical processes controlling contractility.

Animals↗
PubMed1995

Combination of screening and preoperative endocrine therapy: the potential for an important decrease in prostate cancer mortality.

Prostate cancer is the second cause of cancer death in men in the Western world; its medical and social impact is comparable to that of breast cancer in women. Although it is well recognized that early treatment is the only possibility for reducing the high rate of death from prostate cancer, screening and even early treatment are controversial issues due mainly to arguments based upon old literature and lack of awareness of the significant advances recently made in this field. As it is well known that surgical removal of organ-confined prostate cancer cures the disease, and it has been demonstrated that annual screening with prostate-specific antigen coupled with digital rectal examination followed, when indicated, by transrectal ultrasonography of the prostate more than doubles the proportion of organ-confined disease, screening alone offers the possibility of at least doubling the number of patients curable from prostate cancer or the potential for a cure to an estimated 45% of prostate cancer patients compared to a maximum of 20% in the absence of screening. It is important to mention that screening does not detect small and insignificant cancers, especially when random biopsies are not performed routinely. The critical volume of prostate cancer is estimated at 0.3 cm or a tumor 7.5 mm in diameter, if spherical. Such a tumor should increase serum prostate-specific antigen by 0.5 ng/mL. Contrary to the belief that screening detects cancers that are too small, the fact is that screening detects prostate cancer too late or nonorgan- or nonspecimen-confined cancer in 35-50% of cases. There is, thus, a narrow window when prostate cancer can be detected at a curable stage, and even the best available screening techniques cannot succeed in all cases. It should be mentioned that the recent improvements of the technique of radical prostatectomy have markedly improved the acceptability of surgery. Concerning the recent publicity related to watchful waiting, it is essential to indicate that all such reports support the notion that prostate cancer grows slowly, but steadily and irremediably, with increasing malignancy and risk of distant metastases and death if sufficient time is allowed. Another serious limitation of watchful waiting is that the available prognostic factors have a large margin of error and cannot predict with certainty the rate of progression of the tumor.(ABSTRACT TRUNCATED AT 400 WORDS)

Androgen Antagonists↗
PubMed1995

Nonsalt-losing male pseudohermaphroditism due to the novel homozygous N100S mutation in the type II 3 beta-hydroxysteroid dehydrogenase gene.

Recently, the structure of two genes encoding isoenzymes responsible for 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase (3 beta HSD) activity in the human was elucidated. This activity is an essential step in the biosynthesis of all classes of steroid hormones. In the classic severe form of 3 beta HSD deficiency, patients present with adrenal insufficiency, various degrees of salt loss, and incomplete masculinization in males. Here we report the characterization of the molecular basis of congenital adrenal hyperplasia due to 3 beta HSD deficiency in a male pseudohermaphrodite born from consanguineous parents and having no clinical salt loss. To analyze the structure of the type I and II 3 beta HSD genes of the patient, DNA fragments, generated by polymerase chain reaction amplification of the four exons and the exon-intron boundaries of these genes, were directly sequenced. The patients carried a homozygous missense mutation converting Asn100 to Ser in exon 3 of his type II 3 beta HSD gene. His parents were heterozygous for the same point mutation. The absence of clinical salt loss associated with a male pseudohermaphroditism suggested that 3 beta HSD activity was impaired to different levels in the testes and adrenal. To elucidate whether this N100S missense mutation affected preferentially a steroidogenic pathway, enzymatic activity was analyzed by in vitro analysis of mutant recombinant enzyme generated by site-directed mutagenesis after its transient expression in COS-1 cells. Using homogenates from transfected cells, the N100S 3 beta HSD enzyme showed a Km value for pregnenolone of 25 +/- 3 mumol/L compared with 3.5 +/- 0.2 mumol/L for the normal human type II 3 beta HSD enzyme. Similar results were obtained using dehydroepiandrosterone as substrate. In addition to decreasing apparent affinity, the N100S mutation decreased the relative specific activity (Vmax), leading to a relative specificity (relative Vmax/Km) 2.7% and 11% that of normal type II 3 beta HSD using pregnenolone or dehydroepiandrosterone as substrate, respectively. Moreover, the mutant N100S protein had an apparent decreased affinity for NAD+, with a Km value of 650 +/- 66 mumol/L compared with 20 +/- 2 mumol/L for normal type II 3 beta HSD. Except for the hypothetical effect of local factors, these findings suggest that a very weak residual activity of the normal type II 3 beta HSD enzyme could prevent salt loss, but it was insufficient for normal male sex differentiation.(ABSTRACT TRUNCATED AT 400 WORDS)

3-Hydroxysteroid Dehydrogenases↗
PubMed1995

Overlapping cis-acting elements located in the first intron of the gene for type I 3 beta-hydroxysteroid dehydrogenase modulate its transcriptional activity.

High levels of expression for the gene encoding human type I 3 beta-hydroxysteroid dehydrogenase (3 beta-HSDI) have been detected in placenta and skin but not in adrenals, which, however, express high levels of type II 3 beta-HSD. In this study, we addressed the issue of whether the differential pattern of cell-specific expression for type I 3 beta-HSD can be explained by the differential utilization of cis-acting regulatory elements present in the 3 beta-HSDI gene regulatory sequences. Deletion analyses indicated that removal of intron 1 strongly impaired the transcriptional activity directed by the 3 beta-HSDI basal promoter. Consequently, we focused our attention to the characterization of the 128 base pair first intronic sequence from the 3 beta-HSDI gene. A single protected region, designated the 3 beta I-A element, was identified by DNase I footprinting. Gel mobility shift assays indicated that at least four nuclear proteins with distinct biochemical and binding properties possess the ability to bind the 3 beta I-A element to produce four DNA-protein complexes (R1 to R4). However, the one producing R1, a 37-kilodalton protein that has been found in both human choriocarcinoma JEG-3 and adrenal cortex adenocarcinoma SW13 cells, as well as in all tested tissue culture cells, clearly accounts for the major 3 beta I-A-binding species. Site-directed mutagenesis provided the evidence that the 3 beta I-A element acts positively on the 3 beta-HSD-I gene promoter-mediated transcriptional activity upon transient transfection of both JEG-3 and SW13 cells. No homology has been found between the 3 beta I-A element and target sequences for other known transcription factors. In addition, of the four proteins binding the 3 beta I-A element, that producing R2 was identified as the positive transcription factor Sp1, whereas the identity of the remaining factors is still unknown. This is consistent with the presence of an Sp1 motif overlapping the 3 beta I-A element in intron 1, therefore pointing toward an important function played by this particular region in 3 beta-HSDI basal, but not cell-specific, gene expression.

3-Hydroxysteroid Dehydrogenases↗
PubMed1995

Relation of steroid hormones to glucose tolerance and plasma insulin levels in men. Importance of visceral adipose tissue.

OBJECTIVE: Low plasma testosterone levels are associated with hyperinsulinemia and glucose intolerance in men. However, it is unclear whether these abnormalities are related to the concomitant alteration in regional adipose tissue (AT) accumulation associated with reduced androgen levels. RESEARCH DESIGN AND METHODS: We measured plasma steroid levels in a sample of 79 men, ranging from lean to obese (aged 29-42 years), for whom an oral glucose tolerance test (OGTT), anthropometric and computed tomography (CT) measurements of body fatness, and AT distribution were performed. Sex hormone binding globulin (SHBG) and the following steroids were measured after extraction from plasma and chromatography: dehydroepiandrosterone, androstenedione, androst-5-ene-3 beta,17 beta-diol, testosterone, estrone, and estradiol (E2). RESULTS: Several significant negative correlations were found between adrenal C19 steroid precursors, testosterone, SHBG, and fasting insulin levels, as well as between plasma glucose and insulin concentrations measured during the OGTT (-0.25 < or = r < or = -0.35, 0.05 > or = P > or = 0.001). The best steroid correlate of plasma glucose and insulin homeostasis indexes was the E2: testosterone ratio (0.34 < or = r < or = 0.42, 0.005 > or = P > or = 0.001). However, after correction of steroid levels for either fat mass, body mass index (BMI), or visceral AT area, as measured by CT, no significant residual associations were noted between testosterone, adrenal C19 steroid, SHBG, and estrogen levels and indexes of plasma glucose-insulin homeostasis, although the positive association between the E2: testosterone ratio and glucose area remained significant after adjustment for total body fat mass and BMI. Furthermore, 15 pairs of obese subjects, matched for visceral AT area, showing either low or high levels of the steroids studied, did not differ in fasting insulin and postglucose plasma insulin levels or in glucose tolerance. CONCLUSIONS: These results suggest that the previously reported relationships between androgen levels and indexes of plasma glucose-insulin homeostasis are mediated, to a large extent, by concomitant alterations in levels of total body fat and visceral AT in men.

Adipose Tissue↗
PubMed1995

Downstaging by combination therapy with flutamide and an LHRH agonist before radical prostatectomy.

A total of 161 patients diagnosed as having stage B (134 patients) or C (27 patients) prostate cancer were randomly assigned to radical prostatectomy alone or to 3 months of neoadjuvant combination therapy with the anti-androgen flutamide and an LHRH agonist before radical prostatectomy. Neoadjuvant combination therapy before radical prostatectomy decreased cancer positive surgical margins from 33.8% in the control group to only 7.8%, thus leaving 92.2% of patients with negative margins at surgery for a 39.2% increase in specimen confined disease. Although on average the final stage determined at histopathological examination of the surgical specimen was more advanced than predicted at initial diagnosis in 33.8% of control patients, an opposite observation was made in the group of men who received the 3 month neoadjuvant combination therapy where the final stage, instead of being more advanced, was less advanced than at diagnosis in an average of 21.1% of men for a net 54.9% improvement of staging in favour of combination therapy. On the other hand, organ confined disease increased from 49.3% to 77.8% of patients after 3 months of combination therapy, for a 57.9% increase in the incidence of organ confined disease. Although long term follow up of these patients is required to determine the impact on survival, the marked influence of neoadjuvant combination therapy on the stage of the disease suggests the possibility of a major improvement in the morbidity and mortality from prostate cancer.

Aged↗
PubMed1995

["Intracrinology". Autonomy and freedom of peripheral tissues].

Hormone-sensitive cancers, namely those of the prostate, breast and uterus, constitute one third of all cancers. In addition to the classical steroidogenic tissues, namely the ovaries, testes, adrenals and placenta, a large series of peripheral tissues possess all the enzymatic systems required for the formation of active androgens and estrogens from a relatively large supply of precursor steroids namely, dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S) provided by the adrenals. This report describes the structure, function and tissue-specific expression and regulation of the 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase, 17 beta-hydroxysteroid dehydrogenase, 5 alpha-reductase gene families as well as some information about the aromatase gene. While, so far, most therapeutical approaches have been aimed and limited at controlling steroid formation by the classical steroidogenic tissues, it is clear that major efforts should now be turned towards intracrinology in order to better understand the physiological mechanisms controlling local steroid formation in peripheral target tissues and to develop improved therapy for hormono-sensitive diseases, especially breast, prostate, and uterine cancers.

17-Hydroxysteroid Dehydrogenases↗
PubMed1994

Structure of human estrogen and aryl sulfotransferase gene. Two mRNA species issued from a single gene.

Estrone sulfate is the predominant form of estrogens found in the circulation in women and could thus serve as precursor for active estrogens in target tissues by removal of the sulfate group through the action of endogenous steroid sulfatase. Recently, we isolated a cDNA encoding human placental estrogen sulfotransferase that differs from brain aryl sulfotransferase only in the 5'-noncoding sequence. To increase our knowledge of the regulation and tissue-specific expression of sulfotransferase gene, we screened a lambda EMBL3 library of human leucocyte genomic DNA using the estrogen sulfotransferase cDNA as probe and isolated a clone containing almost the whole gene sequence. Sequencing of the gene indicates that it is included in approximately 7.7 kilobases and contains nine short exons separated by eight introns. The two first exons, named exon 1a and exon 1b, are noncoding and correspond to the 5'-untranslated sequences of human brain and human placental estrogen sulfotransferase cDNAs, respectively. Transfection of chloramphenicol acetyltransferase reporter gene vectors containing the 5'-flanking sequence upstream from exon 1a and exon 1b in human adrenal adenocarcinoma cells indicates that both sequences possess promoter activity. The present results thus indicate that brain aryl sulfotransferase and placental human placental estrogen sulfotransferase mRNA species are transcribed from a single gene by alternate exon 1a and exon 1b promoters, respectively. Using DNA from panels of human/rodent somatic cell hybrids and amplification of the gene by polymerase chain reaction, the human placental estrogen sulfotransferase gene was assigned to chromosome 16.

Adenocarcinoma↗
PubMed1994

Potent stimulatory effect of interleukin-1 alpha on apolipoprotein D and gross cystic disease fluid protein-15 expression in human breast-cancer cells.

To better understand the multiple hormonal control of the expression of apolipoprotein D (apo-D) and gross cystic disease fluid protein-15 (GCDFP-15, also designated prolactin-inducible protein), which are 2 major proteins found in benign breast-disease fluid, we investigated their regulation by interleukin-1 alpha (IL-1 alpha) in the presence or absence of steroid hormones in ZR-75-1 human breast cancer cells. Exposure of these cells to IL-1 alpha decreased basal cell proliferation by half and markedly reduced the mitogenic action of 17 beta-estradiol (E2), the half-maximal inhibitory effect being exerted at 1.5 pM. In parallel, IL-1 alpha stimulated apo-D and GCDFP-15 secretion with a similar potency. The antiproliferative effect of IL-1 alpha was additive to the inhibition of cell proliferation caused by dihydrotestosterone (DHT) or the glucocorticoid dexamethasone (DEX). In parallel, IL-1 alpha-induced stimulation of apo-D and GCDFP-15 secretion was additive to that exerted by DHT or DEX. The sensitivity of the apo-D and GCDFP-15 responses to the stimulatory action of DHT or DEX was not changed by the presence of IL-1 alpha. IL-1 alpha also increased apo-D and GCDFP-15 mRNA levels. The present findings demonstrate the potent stimulatory effect of IL-1 alpha on basal as well as androgen- and glucocorticoid-induced apo-D and GCDFP-15 expression. The present data strongly suggest that IL-1 alpha and steroids may modulate the secretion of these 2 proteins through different transduction pathways.

Apolipoproteins↗
PubMed1994

Synthesis and antiestrogenic activity of diaryl thioether derivatives.

The reaction of 1,2-diarylethanol and mercapto side chain catalyzed by ZnI2 was used as a key step in the short (three to five steps) and efficient synthesis of 17 diaryl thioether derivatives. Several of these compounds contain a methyl butyl amide chain and an hydroxyaryl moiety, respectively, for antiestrogenic activity and binding affinity on estrogen receptor. No binding affinity for crude cytosolic preparation of the estrogen receptor was observed for compounds without phenolic group, while a low affinity (0.01-0.05%) was measured for mono- or diphenol derivatives. Like the pure steroidal antiestrogen EM-139, these novel nonsteroidal compounds did not exert any stimulatory effect on cell proliferation of (ER+) ZR-75-1 human breast cancer cells and partially reversed the amplitude of the stimulatory effect induced by estradiol on this (ER+) cell line. No proliferative or antiproliferative effect on (ER-) MDA-MB-231 human breast cancer cells was also observed for three of these compounds (39-41). Among the newly synthesized nonsteroidal compounds, the thioether derivative 41 (N-butyl-N-methyl-13,14-bis(4'-hydroxyphenyl)-12-thiatetradecanamide+ ++), with a long methylbutylalkanamide side chain and a diphenolic nucleus, was selected as the best antiestrogenic compound. However, this compound was 100-fold less antiestrogenic in (ER+) ZR-75-1 cells than the steroidal antiestrogen EM-139.

Breast Neoplasms↗
PubMed1994

Prostate cancer.

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Adult↗
PubMed1994

Metastatic prostate cancer pulmonary nodules: beneficial effects of combination therapy and subsequent withdrawal of flutamide.

A case is presented of a middle-aged man suffering from stage D2 prostate cancer with pulmonary metastases who responded favorably, first, to endocrine combination therapy with the antiandrogen flutamide and an LHRH agonist for 5.5 years, and, second, to the subsequent withdrawal of Flutamide at the time of the progression of the disease. This case has several exceptional features: absence of bone metastases, pulmonary metastatic nodules characterized as focal neuroendocrine differentiation, and a positive response to antiandrogen withdrawal upon relapse of metastases after initial positive response. The concept of escape to androgen blockade and development of androgenic hypersensitivity is discussed.

Acid Phosphatase↗
PubMed1994

Localization of 3 beta-hydroxysteroid dehydrogenase in rat brain as studied by in situ hybridization.

Recent evidence suggests that brain cells can synthesize steroids de novo. The steroidogenic enzyme 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) gene family of enzymes is involved in the biosynthesis of all classes of active steroids. In the present study, we have used in situ hybridization performed with a 35S-labeled cDNA-encoding rat type I 3 beta-HSD to localize the expression of member(s) of this gene family in the adult rat brain. A specific hybridization signal could only be detected in a restricted area of the medulla ventrally and laterally bordering the fourth ventricle. This area contains the nucleus propositus hypoglossi as well as some vestibular nuclei: the nucleus vestibularis medialis, the nucleus vestibularis lateralis, and the nucleus vestibularis spinalis. At high resolution, the silver grains representing a hybridization signal were detected exclusively in neurons. The present data strongly suggest that a restricted population of neurons might be involved in steroid biosynthesis in the adult rat brain. The role of the member(s) of the rat 3 beta-HSD family in the nuclei of two cranial nerves remains to be investigated.

3-Hydroxysteroid Dehydrogenases↗
PubMed1994

Immunocytochemical localization of 5 alpha-reductase in rat brain.

The presence of steroid 5 alpha-reductase in brain tissue is well-documented. In order to determine with precision the brain areas and nerve cell types containing this enzyme in adult rat, we have studied its immunocytochemical localization using antibodies to the sequence peptide comprising amino acids 227 to 240 of the enzyme. At the light microscopic level, 5 alpha-reductase immunoreactive material appeared to be present only in glial and ependymal cells, including tanycytes. Immunolabeled cells were found in high concentration in the hypothalamus, thalamus, hippocampus, cerebral cortex, cerebral cortex, and circumventricular organs. Immunoelectron microscopic studies demonstrated that immunoreactive material was diffusely distributed throughout the cytoplasm of glial and ependymal cells, thus confirming the association of 5 alpha-reductase immunoreactivity with nonneuronal cells. These data suggest that glial cells play an important role in the conversion of testosterone to dihydrotestosterone or progesterone to dihydroprogesterone under in vivo conditions in adult rat.

Animals↗
PubMed1994

Prevention by dehydroepiandrosterone of the development of mammary carcinoma induced by 7,12-dimethylbenz(a)anthracene (DMBA) in the rat.

The concentration of serum dehydroepiandrosterone sulfate (DHEA-S) and DHEA decreases markedly during aging, and low circulating levels of DHEA have been associated with a higher incidence of breast cancer in women. Using 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma in the rat as model, we have studied the effect of increasing serum levels of DHEA released from Silastic implants on the incidence of these tumors in the rat. Treatment with increasing doses of DHEA leading to serum DHEA levels comparable to those observed in normal adult women (7.1 +/- 0.6 nM and 17.5 +/- 1.1 nM) caused a progressive inhibition of tumor development from 68% bearing tumors in control animals to 22% and 11%, respectively. The average tumor area per rat decreased from 2.81 cm2 in intact control animals to 0.96 and 0.09 cm2 in the groups treated with the same doses of DHEA, respectively. The present data indicate that circulating levels of DHEA similar to those found in normal adult premenopausal women exert a potent inhibitory effect on the development of DMBA-induced mammary tumors in the rat, thus suggesting the possibility of a new and more physiological approach for the prevention of breast cancer in women.

9,10-Dimethyl-1,2-benzanthracene↗