Hasil Pencarian  ::  Simpan CSV :: Kembali

"Guna memperoleh profil reseptor estrogen dan progesteron sitosol baik di dalam jaringan endometriosis maupun endometrium pada pasien dengan atau tanpa endometriosis dilakukan suatu kajian iris-silang yang melibatkan 43 wanita infertil. Ini terdiri dari 31 (72,09%) kasus endometriosis dan 12 (27,91%) kasus nir-endometriosis; umur rerata masing-masing 32 ± 4 tahun dan 32 ± 3 tahun, dengan rerata panjang siklus haid masing-masing 31 ± 8 hari dan 29 ± 1 hari. Jaringan endometriosis diperoleh dengan eksisi selama tindakan laparoskopi operatif, sementara endometrium diperoleh dengan biopsi menyusul tindakan histeroskopi. Tindakan ini dilaksanakan dalam kurun periovulasi (Hari 13-18 siklus haid). Kandungan reseptor steroid seks dalam sitosol diukur secara kuantitatif menggunakan cara tera imunoenzimatik, dan dihitung sebagai reseptor steroid seks/protein sitosol (fmol/ml sitosol). Ditemukan bahwa konsentrasi rerata reseptor estrogen sitosol dalam jaringan terkait adalah: 512.99 fmol/ml di ovarium endometriotik dibandingkan dengan 2369.17 fmol/ml di ovarium normal, dan 601.02 fmol/ml di peritoneum endometriotik dibandingkan dengan 9607.61 fmol/ml di peritoneum normal, serta masing-masing 99.28 fmol/ml dan 608.33 fmol/ml di endometrium wanita dengan dan tanpa endometriosis. Konsentrasi rerata reseptor progesteron sitosol yang ditemukan di masing-masing jaringan adalah 50.64 fmol/ml di ovarium endometriotik dibandingkan 6496.42 fmol/ml di ovarium normal dan 1631.40 fmol/ml di peritoneum endometriotik dibandingkan 12466.99 fmol/ml di peritoneum normal, serta masing-masing 21.26 fmol/ml dan 599.61 fmol/ml di endometrium wanita dengan dan tanpa endometriosis. Tidak terdapat perbedaan bermakna pada konsentrasi reseptor antara masing-masing jaringan menurut asal to-pografiknya. Namun demikian, hasil ini dapat memperkirakan bahwa daya-tanggap terhadap penanganan hormonal pada kasus-kasus endometriosis akan bergantung pada kandungan reseptor steroid seks sitosol pada jaringan yang sakit, dan lesi-lesi peritoneal mungkin akan memberikan tanggapan yang lebih baik daripada yang di sisi lain. Diperlukan uji klinis lebih lanjut. (Med J Indones 2005; 14: 133-41)

---

In order to have a profile of cytosolic estrogen and progesterone receptors in either endometriotic tissue or endometrium in patients with and without endometriosis a cross-sectional study was performed involving 43 infertile women. They consisted of 31 (72.09%) en-dometriosis and 12 (27.91%) non-endometriosis cases; their average age was 32 ± 4 years and 32 ± 3 years respectively, with the ave-rage length of menstrual cycle 31 ± 8 days and 29 ± 1 days respectively. The endometriotic tissue was obtained by excision during ope-rative laparoscopy procedure, while the endometrium was obtained by biopsy following hysteroscopy procedure. These procedures were conducted within the periovulatory period (on Day 13-18 of the cycle). The sex steroid receptor content in the cytosol was measured quantitatively using enzyme-immunoassay method, and calculated as sex steroid receptor/cytosol protein (fmol/ml cytosol). It was found that the average cytosolic estrogen receptor concentration in the respective tissues were 512.99 fmol/ml in the endometriotic ovary compared with 2369.17 in normal ovary and 632.18 fmol/ml in the endometriotic peritoneum compared with 9607.61 fmol/ml in normal peritoneum; while 99.28 fmol/ml and 608.33 fmol/ml in the endometrium of women with endometriosis and those without endometriosis respectively. The average cytosolic progesterone receptor concentration found in the respective tissues were 50.64 fmol/ml in the endometriotic ovary compared with 6469.42 fmol/ml in normal ovary and 1631.40 fmol/ml in endometriotic peritoneum compared with 12466.99 in normal peritoneum, while 21.26 fmol/ml and 599.61fmol/ml in the endometrium of women with endometriosis and those without endometriosis respectively. There is no significant difference in the receptor concentration between each tissue according to its topographic origin. However, this result may assume that the responsivity on hormonal treatment in endometriosis cases will depend on the cytosolic sex steroid receptor content in the sick tissues, and the peritoneal lesions will possibly give better response than those in other sites. A further clinical trial is necessary. (Med J Indones 2005; 14: 133-41)"

"Latar belakang: Resistensi progesteron akibat gangguan ekspresi reseptor progesteron pada jaringan endometriosis telah diketahui menjadi faktor yang memperberat kondisi klinis pasien endometriosis. Tujuan penelitian ini adalah untuk menganalisis tingkat metilasi DNA pada promoter gen PR-B pada berbagai jaringan endometriosis seperti eutopik endometrium, lesi ektopik peritoneum, endometrioma dan darah menstruasi serta pengaruhnya terhadap ekspresi mRNAnya dibandingkan dengan kontrol endometrium normal; untuk mengetahui patomekanisme endometriosis pada berbagai lokasi terkait dengan resistensi progesteron.Metode: Penelitian ini menggunakan desain potong lintang yang melibatkan 20 sampel untuk masing-masing kelompok kasus dan kontrol. Tingkat metilasi DNA dari gen PR-B diukur menggunakan metode Methylated Specific PCR MSP lalu intensitas pita di dalam gel agarose dihitung dengan software ImageJ. Presentase intensitas pita pada sampel dibandingkan dengan kontrol positif disebut dengan tingkat metilasi DNA. Pengukuran ekspresi relatif mRNA PR-B menggunakan qRT-PCR dua tahap dan analisis dilakukan dengan metode Livak.Hasil: Dari penelitian ini didapatkan perbedaan bermakna antara tingkat metilasi DNA gen PR-B pada jaringan endometriosis ektopik peritoneum 72,4 termetilasi , endometrioma 85 termetilasi dan eutopik endometrium 72,21 termetilasi dibandingan dengan kontrol p

---

Background: Progesterone resistance, due to alteration of progesterone receptor PR expression in endometriosis, was known as a disrupt factor in response to progesterone. The aim of this study is to analyze DNA methylation level on PR B promoter in various tissues include eutopic endometrium, ectopic peritoneal, endometrioma and menstrual blood from endometriosis patient as well as the implication on it's mRNA relatif expression compare with normal endometrium control to know the patomechanisms of endometriosis in various lession in term of progesterone resistance.

Methods: It was a cross sectional study, involved 20 sample for both patient and control. DNA isolate from each sample were converted by bisulfite conversion. DNA methylation level of PR B gene was analysis by Methylated Specific PCR MSP method, then band intensity in gel agarose was measured by ImageJ software. Percentage of band intensity in sample compared with positive control was determined as DNA methylaton level. Quantitative real time PCR was conducted to assess expression of mRNA PR B for each sample and Livak method was used to analysis it's relatif expression compare with control.

Result: There were significant different of methylation level of PR B gene in ectopic peritoneal endometriosis 72,40 methylated , endometrioma 85 methylated and eutopic endometrium 72,21 methylated compared with control p"

"Latar belakang. Endometriosis adalah suatu penyakit radang kronik yang dicirikan dengan adanya pertumbuhan jaringan mirip endometrium yang dapat ditemukan pada peritoneum, ovarium, dan septum retrovagina. Penyakit ini merupakan penyakit multifaktorial yang dapat disebabkan oleh faktor genetik dan lingkungan. Selain itu, faktor hormonal diketahui mempengaruhi perkembangan dan klinis endometriosis. Resistensi hormon progesteron merupakah salah satu penyebab terjadinya endometriosis karena sering dihubungkan dengan rendahnya kadar dan aktivitas kerja reseptor hormon progesteron pada endometriosis. Polimorfisme gen reseptor progesteron (PROGINS=progesterone receptor gene polymorphism) diketahui berkaitan dengan risiko endometriosis. Penelitian ini bertujuan untuk mengetahui hubungan polimorfisme gen reseptor progesteron (PR) rs139646398 dengan endometriosis di Indonesia. Metode penelitian. Penelitian cross sectional ini menggunakan 30 sampel jaringan endometriosis ovarium dari wanita penderita endometriosis dan 17 jaringan endometrium dari wanita tanpa endometriosis. Sampel DNA dari subjek diisolasi, dilakukan PCR, diikuti dengan proses elektroforesis, dan dilanjutkan dengan DNA sequencing. Hasil. Hasilnya dianalisis secara statistik dengan uji Fisher. Tidak ditemukan perbedaan yang signifikan frekuensi genotip rs139646398 dari gen PR pada endometriosis ovarium dan kontrol (p=0,638). Penelitian ini menunjukkan tidak adanya hubungan antara polimorfisme gen reseptor progesteron rs139646398 dengan endometriosis di Indonesia. Kesimpulan. Penelitian ini menunjukkan tidak adanya hubungan antara polimorfisme gen reseptor progesteron rs139646398 dengan endometriosis di Indonesia.

---

Endometriosis is a chronic inflammatory disease characterized by the growth of endometrial-like tissues that can be found in peritoneum, ovary, and retrovaginal septum. This disease is a multifactorial disease caused by genetic and environmental factors. In addition, hormonal factors are known to influence the development and clinical symptom of endometriosis. Progesterone resistance is one of the causes of endometriosis. It is often associated with low levels or activity of hormone progesterone receptor in endometriosis patients. Progesterone receptor gene polymorphism (PROGINS) is known to be associated with the risk of endometriosis. This study aims to determine the relationship between progesterone receptor (PR) gene polymorphism rs139646398 with endometriosis.

Methods. This cross sectional study used 30 endometriosis ovary samples from women suffered endometriosis and 17 endometrium tissues from women without endometriosis. DNA samples from subjects were isolated, PCR was carried out, then followed by electrophoresis, and continued with DNA sequencing.

Results. The results were statistically analysed by Fisher’s test. There was no statistically significant difference in genotype frequency of rs139646398 of the PR gene in ovarian endometriosis and controls (p=0.638).

Conclusion. This study shows no relationship between progesterone receptor gene polymorphism rs139646398 and endometriosis in Indonesia."

"Latar Belakang: Endometriosis menjadi penyakit dengan teka-teki yang memerlukan penyelesaian. Prevalensinya bervariasi dengan rentang yang luas. 0,7-44% pada populasi umum. 26,5% pada kelompok 40-44 tahun, namun 52,7% pada usia 18-29 tahun. Ilmu, tehnologi dan penelitian yang ada belum menghasilkan terapi terkini menurunkan prevalensinya. Anti inflamasi non-steroid terapi non-hormonal penghilang nyeri mempunyai efek samping pada pemakaian jangka panjang, terapi hormonal mempengaruhi siklus menstruasi dan fertilitas. Modalitas terapi perlu dikembangkan mengatasi endometriosis. Peroxisome Proliferator Activated Receptor gamma merupakan faktor transkripsi terikat pada membran nukleus sebagai anti inflamasi potensial. Aktivasi PPAR gamma oleh ligan menghambat faktor transkripsi nuclear factor-κB menurunkan ekspresi gen sitokin inflamasi, menurunkan TNF α, menginduksi sekresi IL-8 menghambat proliferasi sel. Agonis selektif PPARγ diharapkan menjadi pilihan terapi non-hormonal jangka panjang endometriosis masa mendatang. Belum ada penelitian mengevaluasi ekpresi PPARγ pada jaringan endometrium endometriosis dan tidak endometriosis. Tujuan: Penelitian ini membandingkan ekpresi mRNA PPARγ endometrium subjek endometriosis dan tidak endometriosis.Metode: Penelitian potong lintang pada Desember 2016-Oktober 2017 di Kamar Operasi RS Ciptomangunkusumo. Dua puluh lima pasien endometriosis yang menjalani laparoskopi atau laparotomi yang memenuhi syarat penelitian direkrut consecutive sampling diperiksa tampilan PPAR Gamma pada dinding endometrium endometriosis dan tidak endometriosis; jaringan endometriosis dari dinding kista endometriosis. Ekspresi PPAR Gamma diperiksa menggunakan two step real time PCR. Penelitian ini disetujui oleh Komite Etik dan Penelitian tahun 2016. Hasil: Ekspresi PPARγ endometrium subjek endometriosis dan tidak endometriosis tidak berbeda bermakna (p 0,58). Ekspresi mRNA PPARγ jaringan endometrium dan endometriosis subjek endometriosis tidak berbeda bermakna (p 0,89). Ekspresi PPARγ jaringan endometriosis dan endometrium subjek tidak endometriosis tidak berbeda bermakna (p 0,68). Kesimpulan: Penilaian ekspresi mRNA PPARγ belum dapat digunakan sebagai dasar target terapi endometriosis. Penelitian lanjutan memisahkan jaringan epitel dan stromanya dapat dilakukan untuk membuktikan peran PPARγ pada patogenesis endometriosis.

---

Background: Endometriosis becomes a disease with a puzzle that requires completion. Prevalence varies with wide ranges. 0.7-44% in the general population. 26.5% in the 40 to 44 years group, but 52.7% at the age of 18-29 years. Existing science and research have not resulted in current therapy reducing its prevalence. Non-steroidal antiinflammatory non-hormonal pain relief therapy has side effects on long-term use, hormonal therapy affects the menstrual cycle and fertility. Therapeutic modalities need to be developed to overcome endometriosis. Peroxisome Proliferator Activated Receptor gamma is a transcription factor bound to the nuclear membrane as a potential anti-inflammatory. Activation of gamma PPAR by ligand inhibits nuclear factor-κB transcription factor decreases expression of inflammatory cytokine gene, decreases TNF α, inducing IL-8 secretion inhibiting cell proliferation. PPAR sel-selective agonists are expected to be the preferred long-term non-hormonal therapy of future endometriosis. Objective: This study compared PPAR expression in endometriosis and endometrial subjects of endometriosis and not endometriosis.Method: Cross-sectional study in December 2016-October 2017 at Operation Room of RS Ciptomangunkusumo. Twenty-five endometriosis patients undergoing laparoscopy or laparotomy who qualified for the study were recruited consecutive sampling examined PPAR Gamma display on the endometrial wall of endometriosis and not endometriosis; endometriosis of the cervical wall of endometriosis. The PPARγ expression was examined using two step real time PCR. The study was approved by the Ethics and Research Committee of 2016. Result: The PPAR expression of the endometrium of endometriosis and nonendometriosis did not differ significantly (p 0.58). Expression of PPAR gamma endometrial and endometriosis tissue subject of endometriosis was not significantly different (p 0.89). PPAR expression of endometriosis and endometrial tissue of the subjects not endometriosis was not significantly different (p 0.68). Conclusion: PPAR expressivity assessment has not been used as a target for endometriosis therapy. Further studies separating epithelial tissue and stroma can be performed to prove the role of PPARγ in the pathogenesis of endometriosis."

"Endometriosis adalah kelainan ginekologis yang ditandai dengan adanya jaringan endometrium yang tumbuh di luar uterus. Penyakit ini bersifat multifaktorial, salah satunya dipengaruhi genetik. Polimorfisme genetik gen reseptor progesteron (PR) diketahui berhubungan dengan penyakit endometriosis. Penelitian ini bertujuan untuk mengetahui hubungan antara polimorfisme gen PR rs544843047 di bagian promoter dengan endometriosis di Indonesia. Penelitian ini menggunakan desain cross sectional, dengan membandingkan 25 jaringan endometriosis dari wanita penderita endometriosis dan 21 jaringan endometrium dari wanita tanpa endometriosis. Molekul DNA dari kedua jenis jaringan diisolasi, diamplifikasi dengan menggunakan metode PCR. Analisis perubahan nukleotida pada gen PR dilakukan dengan metode sequencing. Hasil penelitian menunjukkan frekuensi genotip dan alel pada SNP gen PR rs544843047 adalah genotip TT 100% dan alel T 100%. Penelitian ini menyimpulkan bahwa tidak ada hubungan antara SNP gen PR pada rs544843047 dengan penyakit endometriosis di Indonesia.

---

Endometriosis is a gynecological disorder characterized by the presence of endometrial tissues that grow outside the uterus. This disease is multifactorial cause, one of which is influenced by genetics factor, and genetic polymorphism of the Progesterone Receptor (PR) gene is known to be associated with endometriosis. The aim of this study was to determine the relationship between PR gene polymorphism rs544843047 in the promoter and endometriosis in Indonesia. A cross sectional design was used in this study, comparing 25 endometriosis tissues of women with endometriosis and 21 endometrial tissues of women without endometriosis. DNA molecules from both types of tissues were isolated, then amplified using the PCR method. While analysis of nucleotide changes in the PR gene was conducted by sequencing. The results showed that the genotypic and allelle frequencies of the PR rs544843047 SNP were 100% TT genotype and 100% T allele. This research concludes that there are no association between SNP PR gene in rs544843047 and endometriosis in Indonesia."

"Tujuan: Menilai keberadaan reseptor PPARγ serta membandingkan tampilan reseptor PPARγ pada endometrium eutopik dan ektopik pada penderita endometriosis Metode: Penelitian ini merupakan penelitian potong lintang (cross sectional). Sepuluh subjek penderita endometriosis yang menjalani laparoskopi atau laparotomi, yang masuk dalam kriteria penerimaan (consecutive sampling) diambil dua percontoh, yakni endometrium eutopik dan endometrium ektopik yang berasal dari dinding kista endometriosis saat dilakukan pembedahan kemudian dilihat tampilan reseptor PPARγ dengan two-step RT-qPCR. Tampilan masing-masing percontoh diuji statistik dengan uji tes-t berpasangan dan tes korelasi Pearson. Hasil: Didapatkan tampilan reseptor PPARγ pada endometrium eutopik dan endometrium ektopik penderita endometriosis dengan metode RT-qPCR. Tampilan resptor PPARγ endometrium eutopik dan ektopik didapatkan secara statistik tidak berbeda bermakna (1.16 lipatan relatif vs 1.25 lipatan relatif; p=0.26). Pada uji korelasi Pesrson didapatkakan korelasi positif lemah antara tampilan PPARγ endometrium eutopik dan ektopik (r=0.16). Kesimpulan: Tampilan reseptor PPARγ pada endometrium eutopik dan ektopik penderita endometriosis didapatkan dengan metode two-step RT-qPCR. Dengan semikuantifikasi tampilan reseptor PPARγ tidak didapatkan perbedaan antara tampilan reseptor PPARγ pada endometrium eutopik dan ektopik pada penderita endometriosis. Terdapat korelasi positif lemah antara tampilan reseptor PPARγ pada endometrium eutopik dan ektopik pada penderita endometriosis.

---

Objective: To evaluate the expression of the PPARγ receptor and to compare its expression in the eutopic and ectopic endometrium in women with endometriosis Method: This is a cross sectional study. Ten female subjects with endometriosis that underwent laparoscopy or laparotomy that fulfilled the inclusion criteria were recruited by consecutive sampling. Two samples were taken, eutopic endometrium and ectopic endometrium from endometriosis cyst wall during surgery of each subject, PPARγ expression was examined by two-step RT-qPCR. Each sample was statistically examined using the paired t-test and Pearson’s corelation test.

Result: PPARγ was found to be expressed in the eutopic and ectopic endometrium of women with endometriosis using the RT-qPCR method. The expression of PPARγ was not statistically different in eutopic and ectopic endometrium (1.16 relative fold vs 1.25 relative fold:p=0.26). By Pearson’s corelation there was a weak positive corelation between PPARγ expression of the eutopic and ectopic endometrium (r=0.16).

Conclusion: PPARγ was detected by two-step RT-qPCR in eutopic and ectopic endometrium of women with endometriosis. Semiquantification of PPARγ expression showed that there was no significant difference betweenits expression in the eutopic and ectopic endometrium of women with endometriosis. There was a weak postive corelation of PPARγ expression between the eutopic and ectopic endometrium of women with endometriosis."

"Endometriosis adalah kelainan ginekologis yang dimanifestasikan dengan adanya kelenjar dan sel endometrium yang berkembang di luar uterus. Endometriosis merupakan penyakit multifaktorial dimana faktor genetik dan lingkungan berinteraksi menyebabkan timbulnya penyakit ini. Beberapa penelitian telah melaporkan bahwa endometriosis merupakan penyakit yang terkait dengan hormon estrogen. Mekanisme kerja estrogen ditentukan oleh kuantitas dan aktivitas reseptor estrogen. Namun demikian analisa variasi genetik, ekspresi dan aktivitas estrogen reseptor sampai saat ini belum banyak diketahui. Tujuan Penelitian ini adalah untuk menganalisa variasi genetik, ekspresi mRNA dan aktivasi ER pada jaringan endometriosis. Alel gen reseptor estrogen REα dan REβ dari 83 sampel penderita endometriosis dibandingkan dengan 76 kontrol menggunakan metoda PCR RFLP. Pengukuran ekspresi mRNA dari 18 jaringan penderita endometriosis dan 18 kontrol dilakukan dengan menggunakan metoda kuantitatif Real Time PCR (qRT-PCR). Pengukuran kadar estrogen serum (E2) dilakukan dengan metoda ELISA. Deteksi aktivasi ER dilakukan dengan uji fosforilasi reseptor estrogen β (serin 105) dengan metoda Western Blot. Hasil uji Chi-square ditemukan bahwa frekuensi alel A (normal) dan alel G (mutan) pada gen REα SNP rs9340799 dalam populasi berbeda bermakna (p=0,012) dan OR 1,772 dan kedua frekuensi alel dari hasil uji keseimbangan menurut Hardy-Weinberg berbeda bermakna (p = 0,003). Frekuensi alel (normal dan mutan) dalam populasi REα SNP rs2234693 tidak menunjukkan perbedaan bermakna dan seimbang dalam populasi. Frekuensi genotip pada SNP REβ rs4986938 pada endometriosis dibandingkan kontrol berbeda bermakna (p=0,015) dan OR 0,311 dengan populasi seimbang. Menurut keseimbangan Hardy-Weinberg dan frekuensi alel normal G dan alel mutan A juga berbeda bermakna (p=0,034) dan OR =0,438. Hasil pengukuran ekspresi mRNA menunjukkan terjadi peningkatan ekspresi ERβ 49,52 kali disbanding kontrol sedangkan REα tidak menunjukkan perbedaan dibandingkan kontrol. Kadar estradiol serum (E2) fase proliferasi tidak menunjukkan perbedaan bermakna dibanding kontrol. Hasil uji Spearman menunjukkan tidak ada korelasi kadar estradiol dengan ekspresi REα dan REβ (p>0,05). Fosforilasi ERβ pada Serin 105 menunjukkan penurunan pada kelompok endometriosis dibandingkan jaringan normal dengan perbandingan nilai intensitas pita yakni 0,1 pada endometriosis dan 4,2 pada kontrol. Sebagai kesimpulan, frekuensi alel A dan G gen REα berbeda bermakna pada SNP rs9340799 dan frekuensi alel di dalam populasi tidak seimbang. Distribusi genotip normal GG dan mutan AA serta frekuensi alel G dan alel A gen REβ berbeda bermakna pada SNP rs4986938. Ekspresi (mRNA) REβ lebih tinggi secara signifikans pada kelompok endometriosis dibandingkan kontrol. Ekspresi protein Fosforilasi ERβ pada Serin 105 menunjukkan penurunan pada endometriosis dibandingkan jaringan normal.

---

Endometriosis is a gynecological disorder that is manifested by the presence of endometrium glands and cells that grow and develop outside the uterus. Endometriosis is a multifactorial with genetic and environmental factors interacting to cause this disease. Several studies have reported that endometriosis is a disease associated with the hormone estrogen. The mechanism of action of estrogen depends on the quantity and activity of estrogen receptors. However, genetic variation, expression and estrogen receptor activation in endometriois patients have not been fully characterized.

The aim of this study was to analyze genetic variation, ER expression and determine ER activation in endometriosis patients. This study determined the alleles of the estrogen receptor gene REα and REβ from 83 blood samples from endometriosis patients compared with 76 controls using the RFLP PCR method. Quatitative Real time PCR was used to analyze mRNA expression of REβ genes from 18 tissues with endometriosis and 18 controls. Measurement of serum estrogen (E2) levels was carried out using the ELISA method. Furthermore, the phosphorylation test of estrogen receptor (serin 105) was carried out using the Western Immunobloting method.

The results of the Chi-square test found that the frequencies of the A (normal) allele and G (mutant) allele in the REα SNP gene rs9340799 in the population were significantly different (p=0.012) and OR 1.772 and the two allele frequencies from the results of the balance test according to Hardy-Weinberg were significantly different. (p = 0.003). Allele frequencies (normal and mutant) in the REα SNP population of rs2234693 did not show significant and balanced differences in the population. The genotype frequency of SNP REβ rs4986938 in endometriosis compared to control was significantly different (p=0.015) and OR 0.311 with a balanced population. According to the Hardy-Weinberg balance, the frequencies of the normal G allele and the mutant A allele were also significantly different (p=0.034) and OR=0.438. Erβ expression showed 49,52 folds increase compared to control (p=0.00), whereas ERα did not show a significat different compared to control. There was no different in serum estradiol (E2) levels compared to controls.

The results of the Spearman test showed that there was no correlation between serum estradiol levels and the expression of REβ and REβ (p>0.05). Phosphorylation Ser105 of ERβ showed a decrease in the endometriosis group compared to control with a comparison of values ​​of 0.1 and 4 2. As a conclusion, The A and G allele frequencies of the RE gen gene were significantly different in SNP rs9340799 and the allele frequencies in the population were not balanced. The distribution of normal genotypes of GG and AA mutants and the frequency of G allele and A allele of REβ gene were significantly different at SNP rs4986938. REβ (mRNA) expression was significantly higher in the endometriosis group than the control group. Phosphorylated ERβ protein expression in Serin 105 showed a decrease in endometriosis compared to normal tissue."

"Endometriosis adalah kelainan ginekologis yang dimanifestasikan dengan adanya kelenjar dan sel endometrium yang berkembang di luar uterus. Endometriosis merupakan penyakit multifaktorial dimana faktor genetik dan lingkungan berinteraksi menyebabkan timbulnya penyakit ini. Beberapa penelitian telah melaporkan bahwa endometriosis merupakan penyakit yang terkait dengan hormon estrogen. Mekanisme kerja estrogen ditentukan oleh kuantitas dan aktivitas reseptor estrogen. Namun demikian analisa variasi genetik, ekspresi dan aktivitas estrogen reseptor sampai saat ini belum banyak diketahui. Tujuan Penelitian ini adalah untuk menganalisa variasi genetik, ekspresi mRNA dan aktivasi ER pada jaringan endometriosis. Alel gen reseptor estrogen REα dan REβ dari 83 sampel penderita endometriosis dibandingkan dengan 76 kontrol menggunakan metoda PCR RFLP. Pengukuran ekspresi mRNA dari 18 jaringan penderita endometriosis dan 18 kontrol dilakukan dengan menggunakan metoda kuantitatif Real Time PCR (qRT-PCR). Pengukuran kadar estrogen serum (E2) dilakukan dengan metoda ELISA. Deteksi aktivasi ER dilakukan dengan uji fosforilasi reseptor estrogen β (serin 105) dengan metoda Western Blot. Hasil uji Chi-square ditemukan bahwa frekuensi alel A (normal) dan alel G (mutan) pada gen REα SNP rs9340799 dalam populasi berbeda bermakna (p=0,012) dan OR 1,772 dan kedua frekuensi alel dari hasil uji keseimbangan menurut Hardy-Weinberg berbeda bermakna (p = 0,003). Frekuensi alel (normal dan mutan) dalam populasi REα SNP rs2234693 tidak menunjukkan perbedaan bermakna dan seimbang dalam populasi. Frekuensi genotip pada SNP REβ rs4986938 pada endometriosis dibandingkan kontrol berbeda bermakna (p=0,015) dan OR 0,311 dengan populasi seimbang. Menurut keseimbangan Hardy-Weinberg dan frekuensi alel normal G dan alel mutan A juga berbeda bermakna (p=0,034) dan OR =0,438. Hasil pengukuran ekspresi mRNA menunjukkan terjadi peningkatan ekspresi ERβ 49,52 kali dibanding kontrol sedangkan REα tidak menunjukkan perbedaan dibandingkan kontrol. Kadar estradiol serum (E2) fase proliferasi tidak menunjukkan perbedaan bermakna dibanding kontrol. Hasil uji Spearman menunjukkan tidak ada korelasi kadar estradiol dengan ekspresi REα dan REβ (p>0,05). Fosforilasi ERβ pada Serin 105 menunjukkan penurunan pada kelompok endometriosis dibandingkan jaringan normal dengan perbandingan nilai intensitas pita yakni 0,1 pada endometriosis dan 4,2 pada kontrol. Sebagai kesimpulan, frekuensi alel A dan G gen REα berbeda bermakna pada SNP rs9340799 dan frekuensi alel di dalam populasi tidak seimbang. Distribusi genotip normal GG dan mutan AA serta frekuensi alel G dan alel A gen REβ berbeda bermakna pada SNP rs4986938. Ekspresi (mRNA) REβ lebih tinggi secara signifikans pada kelompok endometriosis dibandingkan kontrol. Ekspresi protein Fosforilasi ERβ pada Serin 105 menunjukkan penurunan pada endometriosis dibandingkan jaringan normal.

---

Endometriosis is a gynecological disorder that is manifested by the presence of endometrium glands and cells that grow and develop outside the uterus. Endometriosis is a multifactorial with genetic and environmental factors interacting to cause this disease. Several studies have reported that endometriosis is a disease associated with the hormone estrogen. The mechanism of action of estrogen depends on the quantity and activity of estrogen receptors. However, genetic variation, expression and estrogen receptor activation in endometriois patients have not been fully characterized. The aim of this study was to analyze genetic variation, ER expression and determine ER activation in endometriosis patients. This study determined the alleles of the estrogen receptor gene REα and REβ from 83 blood samples from endometriosis patients compared with 76 controls using the RFLP PCR method. Quatitative Real time PCR was used to analyze mRNA expression of REβ genes from 18 tissues with endometriosis and 18 controls. Measurement of serum estrogen (E2) levels was carried out using the ELISA method. Furthermore, the phosphorylation test of estrogen receptor (serin 105) was carried out using the Western Immunobloting method. The results of the Chi-square test found that the frequencies of the A (normal) allele and G (mutant) allele in the REα SNP gene rs9340799 in the population were significantly different (p=0.012) and OR 1.772 and the two allele frequencies from the results of the balance test according to Hardy-Weinberg were significantly different. (p = 0.003). Allele frequencies (normal and mutant) in the REα SNP population of rs2234693 did not show significant and balanced differences in the population. The genotype frequency of SNP REβ rs4986938 in endometriosis compared to control was significantly different (p=0.015) and OR 0.311 with a balanced population. According to the Hardy-Weinberg balance, the frequencies of the normal G allele and the mutant A allele were also significantly different (p=0.034) and OR=0.438. Erβ expression showed 49,52 folds increase compared to control (p=0.00), whereas ERα did not show a significat different compared to control. There was no different in serum estradiol (E2) levels compared to controls. The results of the Spearman test showed that there was no correlation between serum estradiol levels and the expression of REβ and REβ (p>0.05). Phosphorylation Ser105 of ERβ showed a decrease in the endometriosis group compared to control with a comparison of values of 0.1 and 4 2. As a conclusion, The A and G allele frequencies of the RE gen gene were significantly different in SNP rs9340799 and the allele frequencies in the population were not balanced. The distribution of normal genotypes of GG and AA mutants and the frequency of G allele and A allele of REβ gene were significantly different at SNP rs4986938. REβ (mRNA) expression was significantly higher in the endometriosis group than the control group. Phosphorylated ERβ protein expression in Serin 105 showed a decrease in endometriosis compared to normal tissue."

"Kondisi infertilitas yang dialami oleh Wanita memiliki prevalensi yang tinggi. Kegagalan implantasi salah satu penyebab rendahnya keberhasilan IVF sebagai teknologi reproduksi berbantuan. Defek pada reseptivitas endometrium menyebabkan perkembangan kurang adekuat untuk proses implantasi. Progesteron berperan dalam peningkatan reseptivitas endometrium sehingga perlu dilakukan eksplorasi potensi senyawa bahan alam sebagai dasar pengembangan alternatif terapi alternatif infertilitas. Tujuan dari penelitian ini yaitu melakukan penapisan dan evaluasi senyawa bahan alam yang berpotensi sebagai kandidat modulator reseptor progesteron. Metode yang digunakan adalah penapisan virtual berbasis literatur secara sistematis, simulasi penambatan molekuler; analisis prediksi absorbsi, distribusi, metabolism, ekskresi dan toksisitas (ADMET), simulasi dinamika molekuler dan uji ikatan kompetitif reseptor progesteron secara in vitro. Berdasarkan hasil skrinig literatur informasi terkait 12 senyawa yang memiliki kemampuan modulasi reseptor progesteron. Hasil simulasi penambatan molekuler, analisis ADMET dan simulasi dinamika molekuler diperoleh kandidat 6 senyawa potensial dalam hal pengikatan dengan reseptor progesteron pada situs aktif dan stabil dengan reseptor progesteron serta memiliki profil farmakokinetika yang baik. Senyawa tersebut yaitu apigenin, kaempferol, naringenin, baicalein, paeoniflorin dan e-Guggulsterone. Uji konfirmasi ikatan dengan reseptor progesteron manusia secara in vitro menunjukkan senyawa yang memiliki nilai IC50 paling mendekati dengan kontrol progesteron yaitu apigenin (1,10 μM) dan e-guggulsterone (1,35 μM). Selanjutnya yaitu senyawa Baicalein (13,85 μM), Kaempferol (16 μM) dan Naringenin (47,97 μM). Paeoniflorin (0,98 μM) memiliki nilai IC 50 paling rendah dibandingkan dengan senyawa lainnya akan tetapi grafik menunjukkan tidak adanya perubahan nilai polarisasi terhadap perubahan konsentrasi senyawa sehingga data dianggap tidak valid (R= 0,18). Dapat ditarik kesimpulan kandidat senyawa yang berpotensi untuk dikembangkan sebagai fitoprogestin untuk alternatif terapi pada infertilitas melalui reseptor progesteron yaitu apigenin dan e-guggulsterone.

---

The prevalence of infertility conditions is high in women. Implantation failure is one of the causes of the low success of IVF as an assisted reproductive technology. Defects in endometrial receptivity result in inadequate development for the implantation process. Progesterone plays a role in increasing endometrial receptivity, therefore it is necessary to explore the potential of natural compounds as a basis for developing alternative infertility therapies. The aim of this study is to screen and evaluate natural compounds that potentially to be candidates for progesterone receptor modulators. The methods used are systematic literature screening, molecular docking, absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction analysis, molecular dynamics simulation, and competitive binding assay of progesterone receptors. Based on the results of the literature screening, information related to 12 compounds that have the ability to modulate progesterone receptors. The results of molecular docking simulations, ADMET analysis, and molecular dynamics simulations obtained six potential candidate compounds in terms of binding to the progesterone receptor in the active site, being stable with the progesterone receptor, and having a good pharmacokinetic profile. These compounds are apigenin, kaempferol, naringenin, baicalein, paeoniflorin and e-guggulsterone. The result of assay in confirming the binding to the human progesterone receptor showed that the compound with an IC50 value closest to the control progesterone was apigenin (1.10 μM) and e-guggulsterone (1.35 μM). The next compounds are Baicalein (13.85 μM), Kaempferol (16 μM) and Naringenin (47.97 μM). Paeoniflorin (0.98 μM) has the lowest IC50 value compared to other compounds, but the graph shows no change in polarization value to changes in compound concentration so that the data is considered invalid (R = 0.18). In conclusion, the candidate compounds which have the potential to be developed as a phytoprogestin for alternative therapy for infinfertility via the progesterone receptor are apigenin and e-guggulsterone."

"Latar belakang: Peran estrogen pada patofisiologi endometriosis sudah dikenal sejak lama. Namun, belum ada studi yang menganalisis rasio estradiol, estron dan estriol antara wanita dengan dan tanpa endometriosis. Tujuan: Menganalisis kadar estron (E1), estradiol (E2) dan estriol (E3) dalam darah dan rasio E2:E1, E2:E3 dan E1:E3 antara wanita dengan dan tanpa endometriosis. Metode: Penelitian dengan desain potong lintang analitik, dengan 27 wanita dengan endometriosis dan 27 wanita tanpa endometriosis yang memenuhi kriteria inklusi. Sampel didapatkan dari RS Cipto Mangunkusumo dan rumah sakit jejaring lainnya periode Oktober 2012 - April 2013. Kadar metabolit estrogen dalam darah diperiksa dengan uji enzyme-linked immunosorbent (ELISA). Perbandingan data antara dua kelompok dianalisis dengan uji Mann-Whitney. Hasil: Kadar estron ditemukan lebih rendah pada kelompok endometriosis dibandingkan kelompok kontrol (54,66 pg/ml vs 73,52 pg/ml, p 0,229). Demikian pula, kadar estradiol dan estriol lebih rendah pada kelompok endometriosis (29 pg/ml vs 35 pg/ml, p 0,815 dan 1,11 pg/ml vs 1,67 pg/ml, p 0.095, berturut-turut). Rasio E2:E1 lebih tinggi pada kelompok endometriosis (0,51 pg/ml vs 0,38 pg/ml, p 0,164), demikian pula dengan rasio E2: E3 (26,53 pg/ml vs 21,11 pg/ml , p 0,223) dan rasio E1:E3 (58,55 pg/ml vs 50,28 pg/ml, p 0,684). Namun, semua perbedaan itu tidak bermakna secara statistik. Kesimpulan: Kadar estron, estradiol, dan estriol pada wanita dengan kelompok endometriosis lebih rendah dibandingkan pada wanita tanpa endometriosis. Rasio E2: E1, E2: E3 dan E1: E3 lebih tinggi pada kelompok endometriosis. Namun, semua perbedaan itu tidak bermakna secara statistik.

---

Background: The role of estrogen in the pathophysiology of endometriosis has been well known. However, no study has observed the ratio of estradiol, estrone, and estriol between women with endometriosis and without endometriosis.

Objectives: To assess the estrone (E1), estradiol (E2) and estriol (E3) blood level and its ratio (E2:E1, E2:E3 and E1:E3) between women with and without endometriosis.

Methods: An analytical cross sectional study with 27 women with endometriosis and 27 women without endometriosis who met the inclusion criteria. The samples were recruited in Cipto Mangunkusumo hospital and other satellite hospitals from October 2012 to April 2013. The blood level of estrogen metabolites was examined by enzyme-linked immunosorbent assay (ELISA). The data comparison between two groups was analyzed by using Mann-Whitney test.

Result: The level of Estrone was found to be lower in endometriosis group compared to this in control group (54,66 pg/ml vs 73,52 pg/ml, p 0.229). Similarly, the level of estradiol and estriol were lower in endometriosis group (29 pg/ml vs 35 pg/ml, p 0.815 and 1,11 pg/ml vs 1,67 pg/ml, p 0.095, consecutively). The E2:E1 ratio was higher in endometriosis group (0,51 pg/ml vs 0,38 pg/ml, p 0.164), as well as E2:E3 ratio (26,53 pg/ml vs 21,11 pg/ml, p 0.223) and the E1:E3 ratio (58.55 vs 50.28, p 0.684). However, all those differences were not statistical significant.

Conclusion: The estrone, estradiol and estriol level in women with endometriosis group was lower compared to these in women without endometriosis group. The ratio E2:E1, E2:E3 and E1:E3 was higher in endometriosis group. However, all those differences were statistically insignificant."