Biomedical subjects

Tetsu Yano

Publications and source records attributed to Tetsu Yano.

At least 19 recordsLinked to original sources

PubMed2004

Evidence for the presence of toll-like receptor 4 system in the human endometrium.

We investigated whether Toll-like receptor (TLR) 4 is at work in the human endometrium. The expression of TLR4 mRNA in endometrial epithelial cells (EECs) and stromal cells (ESCs) was detected by RT-PCR and in situ hybridization. Western blotting analysis revealed the TLR4 protein expression in both cell populations. Treatment of lipopolysaccharide (LPS), the actions of which are mediated through TLR4, significantly increased IL-8 secretion from cultured ESCs in a dose-dependent fashion. The stimulatory effect of LPS was inhibited by the addition of neutralizing antibodies for TLR4 and CD14. LPS also stimulated nuclear translocation of nuclear factor-kappaB in ESCs, which was also inhibited by these antibodies. On the other hand, LPS did not stimulate IL-8 secretion in cultured EECs. However, LPS stimulated IL-8 secretion from EECs in the presence of soluble CD14. Flow cytometric analysis revealed that CD14 was expressed on the cell surface of ESCs but not EECs. In addition, immunohistochemical analysis showed that CD14 was stained in ESCs but not EECs. Pretreatment of interferon-gamma (IFN-gamma) enhanced LPS-induced IL-8 secretion from ESCs. IFN-gamma increased the expression of TLR4 mRNA. It also increased the amounts of mRNA for CD14, MD2, and MyD88, which are needed for LPS recognition in concert with TLR4. In summary, we demonstrated that both ESCs and EECs express TLR4 and respond to LPS through TLR4. We further showed that EECs, not ESCs, required soluble CD14 for TLR4 activation. Interestingly, IFN-gamma, an antiinfectious cytokine, was found to activate the TLR4 system in ESCs. Altogether, the results imply that the TLR4 system might represent local immunity in the human endometrium with differential modes of TLR4 actions between ESCs and EECs.

Adaptor Proteins, Signal Transducing↗

PubMed2004

BRCA1 function mediates a TRAP/DRIP complex through direct interaction with TRAP220.

Breast cancer susceptibility gene 1 (BRCA1) is a tumor suppressor gene mutated in a high percentage of hereditary breast and ovarian cancers. The multifunctional BRCA1 protein acts on cell cycle control, exerting several highly specialized DNA repair processes through diverse domains. Gene regulation through its C-terminal domain (BRCT) is indispensable for BRCA1-mediated tumor suppression, suggesting the possibility that the BRCT domain interacts with co-regulator complexes. Using a biochemical approach with HeLa S3 nuclear extracts, we isolated BRCT-associated complexes and identified one of the purified components as TRAP220. We then performed interaction studies in vivo (co-immunoprecipitation) and in vitro (glutathione S-transferase pull-down assays) and showed that BRCT directly interacted with TRAP220. This in vitro interaction was completely abolished by BRCT point mutations typical of those found in patients with BRCA1 that lack transactivation function. BRCA1 transactivation function was dependent on TRAP220 expression level in a transient expression assay. Moreover, a cell survival assay showed that antisense TRAP220 expression to disrupt endogenous TRAP220 expression significantly reduced the survival rate potentiated by BRCA1 after DNA damage. These results suggested that a TRAP220 complex play an important role as putative co-activator complexes in BRCA1-mediated tumor suppression.

BRCA1 Protein↗

PubMed2004

Association of PTEN mutation with HPV-negative adenocarcinoma of the uterine cervix.

Serous, mucinous, endometrioid, and clear cell adenocarcinomas arise from reproductive organs of mullerian origin. Although the mutation of PTEN, a tumor suppressor, is known to be involved in tumorigenesis of endometrioid adenocarcinomas of the endometrium and ovary, the role of PTEN alteration in endometrioid adenocarcinoma of the cervix remains to be investigated. To elucidate the molecular pathogenesis of cervical adenocarcinoma and adenosquamous carcinoma, and in particular to examine the potential role of PTEN mutation in endometrioid-type cancer of the cervix, we analyzed 32 cervical adeno- or adenosquamous carcinomas (8 endometrioid adenocarcinomas, 14 mucinous adenocarcinomas and 10 adenosquamous carcinomas) for PTEN mutations and HPV infections. PTEN mutation was detected in 2 of 8 (25.0%) endometrioid cases, 2 of 14 (14.3%) mucinous cases, and none of 10 (0%) adenosquamous cases. HPV DNA was detected in 11 out of 18 (61.1%) PTEN wild-type adenocarcinomas and 8 out of 10 (80.0%) adenosquamous carcinomas. Among 11 HPV-negative adenocarcinomas, 40.0% (2/5) endometrioid cases and 33.3% (2/6) mucinous cases were shown to be PTEN mutated, while no cases (0/21) were PTEN-mutant in the remainder (i.e. adenosquamous carcinomas and HPV-positive adenocarcinomas). The current observations suggest that PTEN mutation is frequently detected in HPV-negative adenocarcinomas of the cervix and the most prevalent occurrence of PTEN mutation in endometrioid subtype is keeping with endometrial and ovarian carcinomas.

Adenocarcinoma, Mucinous↗

PubMed2004

Concentration of osteoprotegerin (OPG) in peritoneal fluid is increased in women with endometriosis.

BACKGROUND: Failure of apoptosis of refluxed endometrial cells within the peritoneal cavity is a possible etiologic factor for development of endometriosis. Osteoprotegerin (OPG) is a survival factor that exerts its effect by binding to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), thus preventing TRAIL from binding to the apoptosis receptors DR4 and DR5. In the present study, we addressed the possibility that the TRAIL/OPG system is involved in the pathogenesis of endometriosis. METHODS: Concentrations of OPG and TRAIL in the peritoneal fluid (PF) of women with or without endometriosis were measured using specific enzyme-linked immunoabsorbent assay. The expression of DR4 and DR5 in the endometriotic tissue was examined by reverse transcription-polymerase chain reaction. RESULTS: OPG concentrations in PF of women with endometriosis were significantly higher than those of women without endometriosis (P=0.006). With respect to the stages of the disease, the concentrations of OPG in women with stage III/IV endometriosis were significantly higher than in those without endometriosis and those with stage I/II endometriosis. On the other hand, the ratios of TRAIL/OPG concentrations were significantly lower in stage III/IV endometriosis compared to those in non-endometriosis and stage I/II endometriosis. DR5 mRNA expression was clearly detected in all the endometriotic tissues studied. CONCLUSIONS: These findings suggest that the TRAIL/OPG system is involved in the pathophysiology of endometriosis, possibly affecting the apoptosis of endometriotic cells.

Adult↗

PubMed2003

Full activation of estrogen receptor alpha activation function-1 induces proliferation of breast cancer cells.

The effects of estrogen and anti-estrogen are mediated through the estrogen receptors (ER) alpha and beta, which function as ligand-induced transcriptional factors. Recently, one of the phthalate esters, n-butylbenzyl phthalate (BBP), has been shown to induce estrogen receptor-mediated responses. By using the truncated types of ER mutants, we revealed that activation function-1 (AF-1) activity was necessary for the BBP-dependent transactivation function of ERalpha. AF-1 is also known to be responsible for the partial agonistic activity of tamoxifen. Whereas tamoxifen exhibits an anti-estrogenic effect on proliferation of the MCF-7 breast cancer cell line, BBP showed an estrogenic effect on MCF-7 to stimulate proliferation. In vivo and in vitro binding assays revealed that whereas 4-hydroxytamoxifen (OHT) induced binding of ERalpha to both an AF-1 coactivator complex (p68/p72 and p300) and corepressor complexes (N-CoR/SMRT), BBP selectively enhanced the binding to the AF-1 coactivators. We also showed that the transcriptional activity of OHT-bound ERalpha was modulated by the ratio between the AF-1 coactivator and corepressor complexes. Expression of a dominant-negative type of N-CoR inhibited the interaction between OHT-bound ERalpha and N-CoR/SMRT and enhanced the transcriptional activity of OHT-bound ERalpha. Furthermore, the cell growth of MCF-7 stably expressing the dominant-negative type of N-CoR was enhanced by the addition of OHT. These results indicated that fully activated AF-1 induces the stimulation of breast cancer growth and that the ratio between AF-1 coactivators and corepressors plays a key role to prevent proliferation of tumor by tamoxifen.

3T3 Cells↗

PubMed2003

Concentrations of interferon-gamma-induced protein-10 (IP-10), an antiangiogenic substance, are decreased in peritoneal fluid of women with advanced endometriosis.

PROBLEM: To assess whether interferon-gamma-induced protein-10 (IP-10), a chemokine that has antiangiogenic activities, may be involved in the pathogenesis of endometriosis. METHOD OF STUDY: A total of 120 patients undergoing laparoscopy for pain and/or infertility were recruited, and peritoneal fluid (PF) and bone marrow derived cells in PF were collected. Concentrations of IP-10 in PF were measured with a specific enzyme-linked immunosorbent assay. Expression of IP-10 and IP-10 receptor, CXCR3, in bone marrow derived cells in PF, peritoneum and endometriotic cells was analyzed by reverse transcription-polymerase chain reaction. RESULTS: All of the PF samples examined contained detectable concentrations of IP-10. In women with advanced stages of endometriosis, IP-10 concentrations in PF were significantly lower than those of women in early stages (P = 0.02). The IP-10 concentrations in women with advanced endometriosis also appeared to be lower than those without endometriosis although the difference was statistically marginal (P = 0.06). The expression of both IP-10 and CXCR3 was clearly detected in the bone marrow derived cells in PF, peritoneum and endometriotic stromal cells. CONCLUSIONS: Decreased concentrations of IP-10 in PF from women with advanced stages of endometriosis may imply that the peritoneal environment of these women is permissive to the development of the disease by enhancing angiogenesis and/or modulating inflammatory/immunological responses.

Adult↗

PubMed2003

Upregulation of interleukin-8 by hypoxia in human ovaries.

PROBLEM: To evaluate the effect of hypoxia on interleukin (IL)-8 expression in human ovarian follicles. METHOD OF STUDY: Follicular fluid (FF) from each follicle was separately collected from women undergoing in vitro fertilization and embryo transfer. Concentrations of oxygen, progesterone, estradiol, IL-1alpha/beta, IL-8, and tumor necrosis factor (TNF)-alpha in FF were measured. Isolated granulosa-lutein cells (GLC) from obtained FF were cultured under normoxic or hypoxic conditions, and concentrations of IL-8 in culture media were measured. RESULTS: Simple regression analysis demonstrated a significant negative correlation between the concentrations of IL-8 and oxygen in FF (r = 0.50, P < 0.0001). However, none of the concentrations of progesterone, estradiol, IL-1beta, and TNF-alpha in FF showed a significant correlation with IL-8 concentrations. Hypoxia stimulated the secretion of IL-8 by cultured GLC over twofolds compared with a normoxic control (P < 0.05). CONCLUSIONS: These findings suggest that IL-8, like other angiogenic factors, is upregulated under hypoxic condition, which argues that hypoxia in the ovarian follicles comes into play in ovarian functions by inducing a range of proangiogenic and chemoattractive substances.

Adult↗

PubMed2003

Characteristic images of deeply infiltrating rectosigmoid endometriosis on transvaginal and transrectal ultrasonography.

BACKGROUND: To evaluate the usefulness of transvaginal and transrectal ultrasonography for diagnosis and management of deeply infiltrating rectosigmoid endometriosis. METHODS: A series of six patients (aged 32-39 years) with rectosigmoid endometriosis underwent transvaginal and transrectal ultrasonography. In three patients undergoing surgical resection of the intestine, the ultrasonographic findings were compared with macroscopic and microscopic findings. In one patient, sequential observations of the lesion using ultrasonography were conducted before and after medical treatment and following childbirth. RESULTS: In all cases, the lesion was detected as a hypoechoic irregular-shaped area surrounded by a hyperechoic rim located posterior to the uterus, with size ranging from 18 x 17 to 29 x 28 mm in diameter. The comparison of the ultrasonographical findings with histology revealed that the hypoechoic irregular-shaped area corresponded to a layer of hypertrophic muscularis propria of the lesion, while the hyperechoic rim represented the layer including the mucosa, submucosa and serosa. In one patient, the lesion decreased in size and lost its central hypoechoic area after childbirth in association with pain relief. CONCLUSIONS: Transvaginal and transrectal ultrasonography provides characteristic appearances for rectosigmoid endometriosis that correlate well with its histological findings. The procedures would be useful in the management of rectosigmoid endometriosis.

Adult↗

PubMed2003

Akt as a possible intracellular mediator for decidualization in human endometrial stromal cells.

To gain an insight into intracellular mechanisms involved in differentiation of human endometrial cells into decidual cells, we examined the presence of Akt, an emerging intracellular mediator in human endometrial stromal cells (ESC). We explored the mechanisms regulating Akt phosphorylation during the process of progesterone-induced decidualization using a primary cell culture system of ESC. Both Akt and phosphorylated Akt (phospho-Akt) were present in ESC. The total Akt level in ESC cultured for 12 days in the absence of ovarian hormones was similar to ESC treated with estradiol (E(2)) at 10 ng/ml, progesterone at 100 ng/ml or E(2) plus progesterone (E(2)progesterone), whereas the levels of phospho-Akt were markedly decreased with progesterone or E(2) progesterone, compared to control cells. Notably, phospho-Akt levels increased during 12 days of culture in parallel with an increase in total Akt in untreated cells. An increase of phospho-Akt in the E(2) progesterone-treated cells was marginal. The level of phospho-Akt in E(2) progesterone-treated cells was markedly reduced compared to control cells at all time points examined. Treatment of the cells with 8-bromo-cAMP decreased the amount of phospho-Akt in ESC in as short a period as 15 min, while no discernible change was observed in the untreated cells. Conversely, H89, an inhibitor of protein kinase A (PKA), significantly increased the amount of phospho-Akt. The addition of H-89 reversed the decrease in the level of phospho-Akt seen in the cells treated with E(2) progesterone. Thus, we demonstrated the presence of Akt and its phosphorylated form in human ESC. We further suggest that Akt phosphorylation through the cAMP/PKA signal transduction pathway may regulate cellular functions coupled with decidualization.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed2003

Possible roles of thrombin-induced activation of protease-activated receptor 1 in human luteinized granulosa cells.

The presence of thrombin and its receptor, protease-activated receptor 1 (PAR 1), in the ovary suggests that thrombin may regulate ovarian function. In particular, to address the possible role of thrombin in ovulation, a phenomenon displaying mimicry of inflammation, we investigated the effects of thrombin and PAR 1 on the production of inflammation-related substances in human luteinized granulosa cells (LGC). Thrombin stimulated the production of IL-8 and monocyte chemoattractant protein-1 by cultured LGC. The stimulatory effects of thrombin were inhibited by both inhibitors of thrombin (hirudin and PPACK) and a protein kinase C inhibitor (calphostin C). The PAR 1 agonist, SFLLRN, also stimulated the production of IL-8 and monocyte chemoattractant protein-1. Thrombin and SFLLRN stimulated the geletinase activities of LGC, the effect of both being inhibited by hirudin and PPACK. Immunocytochemical study showed that thrombin and SFLLRN induced translocation of nuclear factor kappaB to the nucleus from the cytoplasm in LGC. Expression of PAR 1 mRNA was detected in LGC by RT-PCR analysis. These findings suggest that thrombin plays physiological roles in ovulation by enhancing the production of chemoattractive and gelatinolytic substances by granulosa cells by a mechanism involving PAR 1.

Adult↗

PubMed2003

Endometrial stromal cells undergoing decidualization down-regulate their properties to produce proinflammatory cytokines in response to interleukin-1 beta via reduced p38 mitogen-activated protein kinase phosphorylation.

The decidualized endometrium plays a role in regulating trophoblast invasion for successful implantation and maintenance of pregnancy. IL-1 beta, a proinflammatory cytokine, has been suggested to play a role in this process. Recently, several lines of evidence indicate the importance of p38 MAPK in various inflammatory responses. We investigated whether endometrial stromal cells (ESC) change their inflammatory responses to IL-1 beta as related to p38 MAPK phosphorylation during the process of decidualization. ESC were decidualized by the treatment with progesterone for 9 d, as determined as such by an increase in the production of prolactin and cAMP by the cells. Whereas IL-1 beta increased the production of IL-6, IL-8, and monocyte chemotactic protein-1, and expression of cyclooxygenase-2 mRNA in ESC cultured without treatment, the stimulatory effects of IL-1 beta were reduced in the decidualized cells. Treatment with SB202190, a p38 MAPK inhibitor, also reduced the stimulatory effects of IL-1 beta in nondecidualized ESC. P38 MAPK phosphorylation was increased by IL-1 beta in nondecidualized ESC, whereas the IL-1 beta-induced increase was suppressed in the decidualized cells. Treatment with 8-bromo-cAMP reduced IL-1 beta-induced phosphorylation of p38 MAPK in nondecidualized ESC. In contrast, treatment with H89, a protein kinase A inhibitor, reversed a reduction in IL-1 beta-induced p38 MAPK phosphorylation in the decidualized cells. In summary, decidualization seems to be a process during which endometrial cells diminish their response to IL-1 beta, a known key factor for implantation, leading to the down-regulation of inflammation-like events, which may be relevant to controlled trophoblast invasion. The altered property of decidualized cells is thought to be caused by attenuation of IL-1 beta-induced p38 MAPK phosphorylation in a way that involves the activation of the cAMP/protein kinase A pathway.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed2003

Elevated serum soluble vascular endothelial growth factor receptor 1 (sVEGFR-1) levels in women with preeclampsia.

Hoping to get more insight into a role of vascular endothelial growth factor (VEGF), a putative substance involved in the development of preeclampsia, we measured concentrations of soluble VEGF receptor-1 (sVEGFR-1), a natural antagonist of VEGF, in serum from women with (n = 31) and without (n = 52) preeclampsia. The concentrations of sVEGFR-1 in serum from women with preeclampsia (median 7791 pg/mL) were > 6-fold higher than those from control (1132 pg/mL, p < 0.0001). The levels of sVEGFR-1 decreased markedly after delivery in both groups. Serum sVEGFR-1 levels of non-preeclamptic women were positively correlated with gestational age (r = 0.570, p < 0.0001), whereas those of preeclamptic women exhibited no correlation with gestational age (r = -0.130, p = 0.476). These findings may point to an involvement of sVEGFR-1 in the pathophysiology of preeclampsia possibly by antagonizing of VEGF effects on the formation of placental vasculature and maternal endothelial cell function.

Adult↗

PubMed2003

Genome-wide cDNA microarray analysis of gene-expression profiles involved in ovarian endometriosis.

Using a cDNA microarray consisting of 23,040 genes, we analyzed gene-expression profiles of ovarian endometrial cysts from 23 patients in order to identify genes involved in endometriosis. By comparing expression patterns between endometriotic tissues and corresponding eutopic endometria, we identified 15 genes that were commonly up-regulated in the endometrial cysts during both proliferative and secretory phases of the menstrual cycle, 42 that were up-regulated only in the proliferative phase, and 40 that were up-regulated only in the secretory phase. The up-regulated elements included genes encoding some HLA antigens, complement factors, ribosomal proteins, and TGFBI. On the other hand, 337 genes were commonly down-regulated throughout the menstrual cycle, 144 only in the proliferative phase, and 835 only in the secretory phase. The down-regulated elements included the tumor suppressor TP53, genes related to apoptosis such as GADD34, GADD45A, GADD45B and PIG11, and the gene encoding OVGP1, a protein involved in maintenance of early pregnancy. Semi-quantitative RT-PCR experiments supported the results of our microarray analysis. These data should provide useful information for finding candidate genes whose products might serve as molecular targets for diagnosis or treatment of endometriosis.

Adult↗

PubMed2002

Bisphenol A induces apoptosis and G2-to-M arrest of ovarian granulosa cells.

We investigated the impact of bisphenol A (BPA) on murine ovarian granulosa cells. Ovarian granulosa cells were cultured with 100 fM to 100 microM BPA for 24 h to 72 h. BPA decreased granulosa cell viability in a dose- and time-dependent manner. The lowest concentration that induced a significant decrease was 100 pM (89.2 +/- 4.0% of the control). TUNEL analysis demonstrated that treatment with BPA increased apoptosis of granulosa cells in a dose- and time-dependent manner. In addition, flow cytometry analyses revealed that treatment with BPA resulted in G2-to-M arrest, which was most prominent at 48 h. BPA increased the expression of Bax and concomitantly decreased the expression of Bcl2 at both protein and mRNA levels of granulosa cells. These findings suggest that low, presumably environmentally relevant doses of BPA, decrease the viability of granulosa cells by inducing apoptosis and G2-to-M arrest. Up-regulation of Bax and down-regulation of Bcl2 were suggested to be involved in this apoptotic effect.

Animals↗

PubMed2002

Human chorionic gonadotropin combined with progesterone for luteal support improves pregnancy rate in patients with low late-midluteal estradiol levels in IVF cycles.

PURPOSE: To investigate how late-midluteal estradiol levels relate to the pregnancy outcome in IVF cycles, and to assess whether human chorionic gonadotropin (hCG) for luteal support benefits the pregnancy outcome of patients with low late-midluteal estradiol levels. METHODS: The pregnancy rate of 436 women undergoing first IVF cycles with long protocol and luteal support with progesterone alone were analyzed. Unsuccessful women with low late-midluteal estradiol levels (< 100 pg/mL) proceeded with the exploratory second IVF cycles where they were randomly given with either progesterone alone (P protocol) or hCG +progesterone (P+hCG protocol) for luteal support. RESULTS: Pregnancy rate in women with low late-midluteal estradiol levels was significantly lower compared to that with medium (100-500 pg/mL) and high (> 500 pg/mL) levels (13.3, 26.8, and 36.3%, respectively). P+hCG protocol increased late-midluteal estradiol levels and produced a significantly higher pregnancy rate (31.7%) than P protocol (13.7%). CONCLUSIONS: hCG in combination with progesterone for luteal support was suggested to benefit women undergoing IVF with low late-midluteal estradiol levels.

Adult↗

PubMed2002

Ovarian hyperstimulation syndrome complicated by peritonitis due to perforated appendicitis.

We describe a case of ovarian hyperstimulation syndrome (OHSS) complicated by peritonitis due to perforated appendicitis. A 29-year-old woman presented with abdominal distension after ovarian stimulation with HMG followed by ovulation induction with HCG. Massive ascites with swollen ovaries was observed on ultrasound, and she was admitted on the diagnosis of OHSS. Daily infusion of serum albumin and low dose dopamine failed to increase her urine output and her abdominal symptoms became increasingly deteriorated after her urine pregnancy test turned out to be positive. Paracentesis performed for alleviation of her abdominal distension revealed infected, foul-smelling fluid. An emergency laparotomy was performed, and the definite diagnosis was made as panperitonitis due to perforated appendicitis with right tubal pregnancy. Appendectomy, right tubectomy and vigorous irrigation with drainage were performed. The case implies that OHSS might not only mask typical manifestations of appendicitis, but could also compromise concurrent intraperitoneal infection.

Adult↗

PubMed2002

Role of laparoscopy in the treatment of endometriosis-associated infertility.

Endometriosis is assumed to be one of the causative factors of infertility, although the mechanism remains to be elucidated. Mechanical factors distorting the pelvic anatomy and/or changes in the biochemical and cellular environment in the peritoneal cavity are possible contributing factors impairing fertility. Laparoscopy is a widely used diagnostic and therapeutic means of treating endometriosis-associated infertility. However, pregnancy outcome after laparoscopy varies depending on preexisting tubal adhesions and endometriosis. Without tubal adhesions, the pregnancy rate is essentially the same irrespective of the presence or stages of endoemetriosis. Minimal/mild endometriosis benefited the most from laparoscopic manipulation when tubal adhesions were present. On the other hand, IVF-ET outcome of patients who previously underwent laparoscopy was not influenced by preexisiting tubal adhesions and endometriosis.

Adult↗

PubMed2002

A case of estrogen-producing Brenner tumor with a stromal component as a potential source for estrogen.

BACKGROUND: Although Brenner tumors with endocrine activities have been reported, the source or mechanisms for hormone production is poorly known at present. CASE REPORT: A 66-year-old Japanese woman presented with atypical vaginal bleeding. A left ovarian tumor was detected on ultrasonography and CT scanning. Her serum estradiol level was elevated (73.5 pg/ml). We performed total hysterectomy, bilateral salpingo-oophorectomy and partial omentectomy. The ovarian tumor was diagnosed as a benign Brenner tumor associated with simple hyperplasia of the endometrium. Postoperatively, the serum estradiol level decreased. Immunoreactivity of cytochrome P-450 aromatase was detected in stromal cells. CONCLUSION: Stromal contribution to the secretion of estrogen was shown in this case. Considering the known source of estrogen production being tumor cells in certain cases of Brenner tumor, there seem to be two types of estrogen-producing Brenner tumors depending on the source of estrogen, i.e. tumor cells or stromal cells.

Aged↗