• 한국발생생물학회지:발생과생식
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• 제10권3호
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• pp.197-202
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• 2006

어류의 체내에서 성분화를 유도하는 물질이 성스테로이드호르몬(sex steroid hormone)이라는 사실이 잘 밝혀져 있으며, 성스테로이드 생합성 효소의 하나인 aromatase도 성분화에 직접적인 역할을 하는 것으로 알려져 있다. 본 연구에서는 유전적으로 암컷인 틸라피아 자어(larvae) 집단을 aromatase 저해제(aromatase inhibitor, AI)인 Fadrozole로 침지 처리하여 초기 발생단계 중 어느 시기에 aromatase가 성분화 유도 작용을 하는 지를 조사하였다. Fadrozole 처리 유무 및 처리 농도의 차이는 부화 자어의 생존율에 유의한 차이를 유발하지 않았다. 하지만, 부화후 11일과 13일째에 고농도의 Fadrozole로 처리한 실험군의 자어는 유전적인 성이 암컷임에도 불구하고 유의하게 높은 비율의 자어가 수컷으로 분화하였다. 이 결과는 틸라피아 부화 자어가 스테로이드 생합성 효소의 저해에 아주 민감하게 반응하며, 이 종에서 aromatase의 주된 작용시기가 예상보다 훨씬 빠른 부화 후 11일 전후라는 사실을 보여준다. 또한 이상의 결과는 단 3시간의 AI 침지 처리가 유전적으로 설정되어 있는 성과 반대방향으로의 성분화를 유도하기에 충분할 정도로 강력함을 의미한다.

• Clinical and Experimental Reproductive Medicine
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• 제30권2호
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• pp.135-139
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• 2003

Objective: We investigated whether serum testosterone to estradiol ratio was decreased in infertile men and whether this condition can be corrected with oral aromatase inhibitor. Method: The serum testosterone to estradiol ratio of 26 men with testicular failure were compared with those of normal semen analysis parameter, 89 control reference group. All of 26 testicular failure group were diagnosed with the previous testicular biopsy. Then 46 men with oligospermia and/or asthenospermia were selected and treated with 1 mg of the aromatase inhibitor anastrozole ($Arimidex^{(R)}$) orally once daily for 3 months. Testosterone to estradiol ratio and semen analyses were evaluated during anastrozole therapy. Results: The testosterone level of testicular failure group was significantly lower and the testosterone to estradiol ratio was more decreased than normal semen parameter group. Forty six on-anastrozole group had significantly lower testosterone (4.6 versus 5.7 ng/ml, p<0.01) and higher estradiol (15.9 versus 23.4 pg/ml, p<0.01) than pre-anastrozole group, resulting in a decreased testosterone to estradiol ratio ($0.21{\pm}0.07$ versus $0.39{\pm}0.15$, p<0.01). Semen analyses before and during anastrozole treatment revealed significant increases in sperm count (35.5 versus 52.2 million sperm per ml, p<0.01) and motility (22.9% versus 29.3%, p<0.01). Conclusions: We identified infertile men with testicular failure had hormonal changes characterized by a decreased serum testosterone to estradiol ratio. The ratio can be corrected with aromatase inhibitor, resulting in a significant improvement in semen parameters.

• 대한생식의학회:학술대회논문집
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• 대한불임학회 2005년도 제48차 춘계 학술대회
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• pp.97-104
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• 2005

• Journal of Breast Disease
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• 제6권2호
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• pp.46-51
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• 2018

Purpose: Endocrine therapy is the preferred treatment for hormone receptor (HR)-positive metastatic breast cancer (MBC). We investigated the efficacy of combined aromatase inhibitor (AI) and luteinizing hormone-releasing hormone (LHRH) agonist in premenopausal patients with HR-positive MBC. Methods: We retrospectively analyzed the medical records of 21 HR-positive premenopausal MBC patients treated with combined AI and LHRH agonist therapy. Results: The median follow-up period was 32.9 months. The overall response rate was 47.6%, with three complete responses (14.3%) and seven partial responses (33.3%). Nine patients (42.9%) achieved stable disease lasting more than 6 months; thus, the clinical benefit rate was 90.4%. The median time to progression was 45.4 months. No patients experienced grade 3 or 4 toxicity. Conclusion: Combined AI and LHRH agonist treatment safely and effectively induced remission or prolonged disease stabilization, suggesting that this could be a promising treatment option for HR-positive premenopausal patients with MBC.

• 대한생식의학회:학술대회논문집
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• 대한불임학회 2004년도 제47차 추계학술대회
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• pp.85.2-86
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• 2004

• Asian Pacific Journal of Cancer Prevention
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• 제13권3호
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• pp.979-983
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• 2012

Background : Previous studies have suggested a lack of complete cross-resistance between steroidal (exemestane) and non-steroidal aromatase inhibitors (nSAI). Methods : Eighty-eight metastatic breast cancer (MBC) patients who received 25 mg of exemestane orally once a day at the National Cancer Center, Korea, between 2003 and 2009, were reviewed retrospectively. All patients had received nSAI for metastatic disease prior to exemestane therapy. Results : The median age was 52 years (range, 33-79), and 13 (14.8%) patients were premenopausal who concomitantly received GnRH agonist. Exemestane was given as a second- (80.7%) or third-line (19.3%) hormone therapy. The clinical benefit (CB) rate (complete response + partial response + stable disease ${\geq}$ 24 weeks) was 30.7%, with a median CB duration of 10.0 months (range, 6.3-78.7). The median progression-free survival (PFS) was 3.0 months (95% confidence interval [CI], 1.99-4.01) and the overall survival (OS) 21.5 months (95% CI, 17.96-25.04), with a median followup of 50.3 months. Patients who achieved CB had longer OS than those patients who did not (29.6 vs 17.9 months; P=0.002). On univariate analysis of predictive factors, patients who had achieved CB from previous nSAI tended to show lower CB rate (24.6% vs 44.4%, respectively; P=0.063) and shorter PFS (2.8 vs 4.8 months, respectively; p=0.233) than patients who had not. Achieving CB from previous nSAI became independent predictive factor for CBR to exemestane on multivariable analysis (Odds ratio = 2.852, P = 0.040). Conclusions : Exemestane after nSAI failure was effective in prolonging CB duration. The drug's efficacy seemed to be inferior in patients who had benefit from previous nSAI use.

• 여성건강간호학회지
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• 제27권1호
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• pp.49-57
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• 2021

Purpose: Aromatase inhibitors (AIs) are widely prescribed for postmenopausal women with breast cancer and are known to cause musculoskeletal pain. This study aimed to identify factors associated with AI continuation intention among breast cancer survivors (BCS). Methods: A cross-sectional survey was conducted on 123 BCS (stages I-III), who had been taking AIs for at least 6 weeks. Participants were recruited from a cancer center in Goyang, Korea, from September to November 2019. Descriptive statistics, Welch analysis of variance, Pearson correlation coefficients, and simple linear regression were used for the analysis. Results: Beliefs about endocrine therapy was a significant predictor of AI continuation intention (β=.66, p<.001). The majority of participants (87.0%) reported experiencing musculoskeletal pain since taking AIs and the score for the worst pain severity within 24 hours was 5.08±2.80 out of 10. Musculoskeletal pain, however, was not associated with AI continuation intention. Fear of cancer recurrence (FCR) was clinically significant (≥13) for 74.0% of the respondents (mean, 17.62±7.14). Musculoskeletal pain severity and pain interference were significantly associated with FCR (r=.21, p<.05; r=.35, p<.01, respectively). Pain interference was significantly associated with beliefs about endocrine therapy (r=-.18, p<.05). Conclusion: AI continuation intention can be modified by reinforcing patients' beliefs about endocrine therapy. Musculoskeletal pain may have a negative effect on beliefs about endocrine therapy and increase FCR among BCS. Thus, awareness of musculoskeletal pain during AI therapy should be raised and further research is required to develop multidisciplinary pain management strategies and clinical guidelines to reinforce beliefs about endocrine therapy.

• Animal Bioscience
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• 제35권11호
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• pp.1666-1674
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• 2022

Objective: Letrozole, a potent aromatase inhibitor, is known to have the potential to modify male reproductive function by altering sex hormone levels. This study aimed to evaluate the semen and testicular characteristics and hormonal profile of aged Mrakhoz bucks (Capra hircus) treated with letrozole. Methods: Twelve Markhoz male goats, aged between 4.5 to 5.5 years with an average body weight (BW) of 61.05±4.97 kg were used for the study. Animals were randomly divided into two equal groups and subcutaneously received either 0.25 mg/kg BW of letrozole or a control every week for 2 months. The semen collections were performed every 10 days, and blood samples and testicular biometric records were collected at 20 days intervals. Results: Letrozole causes increased testosterone and follicle-stimulating hormone levels, testosterone to estradiol ratio, semen index and reaction time during the period from 20th to 60th days (p<0.05). Furthermore, letrozole-treated bucks had higher semen volume, sperm concentration, and total sperm per ejaculate from 30th to 60th days (p<0.05). However, no differences occurred between the groups in scrotal circumference, relative testicular volume, semen pH, abnormality, acrosome integrity, and membrane integrity of sperm during the study (p>0.05). The serum luteinizing hormone levels, sperm viability, motility, and progressive motility increased, and estradiol levels decreased after 40th to 60th days of letrozole treatment (p<0.05). Conclusion: Letrozole application to aged Markhoz bucks provokes reproductive hormonal axis which, in turn, induces enhancement of semen production and quality.

• Environmental Analysis Health and Toxicology
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• 제31권
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• pp.10.1-10.8
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• 2016

Objectives Aromatase inhibitors that block estrogen synthesis are a proven first-line hormonal therapy for postmenopausal breast cancer. Although it is known that standardized extract of Ginkgo biloba (EGb761) induces anti-carcinogenic effects like the aromatase inhibitors, the effects of EGb761 on steroidogenesis have not been studied yet. Therefore, the effects of EGb761 on steroidogenesis and aromatase activity was studied using a H295R cell model, which was a good in vitro model to predict effects on human adrenal steroidogenesis. Methods Cortisol, aldosterone, testosterone, and $17{\beta}$-estradiol were evaluated in the H295R cells by competitive enzyme-linked immunospecific assay after exposure to EGb761. Real-time polymerase chain reaction were performed to evaluate effects on critical genes in steroid hormone production, specifically cytochrome P450 (CYP11/ 17/19/21) and the hydroxysteroid dehydrogenases ($3{\beta}$-HSD2 and $17{\beta}$-HSD1/4). Finally, aromatase activities were measured with a tritiated water-release assay and by western blotting analysis. Results H295R cells exposed to EGb761 (10 and $100{\mu}g/mL$) showed a significant decrease in $17{\beta}$-estradiol and testosterone, but no change in aldosterone or cortisol. Genes (CYP19 and $17{\beta}$-HSD1) related to the estrogen steroidogenesis were significantly decreased by EGb761. EGb761 treatment of H295R cells resulted in a significant decrease of aromatase activity as measured by the direct and indirect assays. The coding sequence/Exon PII of CYP19 gene transcript and protein level of CYP19 were significantly decreased by EGb761. Conclusions These results suggest that EGb761 could regulate steroidogenesis-related genes such as CYP19 and $17{\beta}$-HSD1, and lead to a decrease in $17{\beta}$-estradiol and testosterone. The present study provides good information on potential therapeutic effects of EGb761 on estrogen dependent breast cancer.

• Journal of Microbiology and Biotechnology
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• 제16권9호
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• pp.1405-1409
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• 2006

Polysaccharides from the starfish Asterina pectinifera were assessed in vitro for their chemopreventive potential in human breast cancer. The polysaccharides from A. pectinifera inhibited cell proliferation in the estrogen receptor-positive (MCF-7) and estrogen receptor-negative (MDA-MB-231) human breast carcinoma cell lines. In addition, the polysaccharides were found to be an inhibitor of cytochrome P450 1A1-mediated ethoxyresorufin O-deethylase activity, and caused a dose-dependent inhibition of aromatase activity in microsomes isolated from a human placenta. There was a significant reduction in the ornithine decarboxylase activity to 30.7% of the control in the polysaccharide-treated MCF-7 breast cancer cells. Therefore, the polysaccharides from A. pectinifera merit further investigation with respect to breast cancer chemoprevention.