• Title/Summary/Keyword: Steroidogenic factor 1

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Expression of Fas and TNFR1 in the Luteal Cell Types Isolated from the Ovarian Corpus Luteum

  • Kim, Minseong;Lee, Sang-Hee;Lee, Seunghyung;Kim, Gur-Yoo
    • Biomedical Science Letters
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    • v.25 no.1
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    • pp.107-112
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    • 2019
  • The corpus luteum (CL) is composed to various cells, such as luteal steroidogenic cells (LSCs), luteal thecal steroidogenic cells (LTCs), luteal endothelial cells (LECs), fibroblast, immune cells and blood cells. The life span of CL is controlled by proliferation and apoptosis of luteal cells. Therefore, this study investigated apoptotic factors in luteal cells derived from bovine CL. The CL tissues were collected from bovine ovaries and luteal cells were isolated from middle phase CL. Then, LTCs and LECs were separated according to cellular morphology from LSCs. The expression of Bax, Bcl-2, Fas and tumor necrosis factor 1 receptor (TNF1R) mRNA and protein were analyzed using quantitative RT-PCR and western blot. Results show that, Bax and TNFR1 mRNA expression were significantly increased at late group than early and middle groups, otherwise Bcl-2 were significantly decreased at late group than early group (P<0.05). Fas mRNA expression were significantly decreased in middle group compared to early and late groups (P<0.05). In addition, Bax and Bcl-2 mRNA in LTCs was lower than LSCs, Fas mRNA was higher than LSCs. The Bcl-2 protein expression was lower at LTCs than LSCs, especially Fas protein in LTCs was significantly lower than LSCs and LECs (P<0.05). Otherwise, TNFR1 protein of LTCs were similar with LSCs but higher compared with LECs. In conclusion, we suggest that the results may help understanding of apoptosis ability in luteal cells according to cell type during CL regression of estrous cycle.

Differential Activities of FOXL2 and Its Mutants on SF-1-Induced CYP19 Transcriptional Activation (SF-1을 매개한 CYP19의 전사활성에 미치는 FOXL2 야생형과 돌연변이형의 차별적 영향)

  • Park, Mi-Ra;Kim, Ah-Young;Na, Soon-Young;Kim, Hong-Man;Lee, Kang-Seok;Bae, Jee-Hyeon;Ko, Jeong-Jae
    • Development and Reproduction
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    • v.14 no.2
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    • pp.91-97
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    • 2010
  • FOXL2 is a winged-helix/forkhead (FH) domain transcription factor, and mutations in FOXL2 gene are responsible for blepharophimosis-ptosis-epicanthus inversus syndrome (BPES). BPES is an autosomal dominant genetic disease. BPES type I patients exhibit both premature ovarian failure (POF) and eyelid malformation, while only the eyelid defect is observed in BPES type II. FOXL2-null ovaries showed a blockage of granulosa cell differentiation, suggesting that FOXL2 plays an essential role for proper ovarian folliculogenesis. Previously, we screened for FOXL2-interacting proteins and identified steroidogenic factor-1 (SF-1) which is known to be required for gonad development and transactivates steroidogenic enzymes including CYP19. In the present study, we demonstrated that FOXL2 transactivates CYP19 and stimulated the transcriptional activation of CYP19 induced by SF-1. In contrast, FOXL2 mutants found in BPES type I and II exhibited compromised abilities to enhance CYP19 induction mediated by SF-1. Thus, this study provides a functional difference between wild-type FOXL2 and its mutants which may aid to understand pathophysiology of BPES elicited by FOXL2 mutations.

Immunohistochemical Study of Steroidogenesis, Proliferation, and Hypoxia-related Proteins in Caprine Corpora Lutea during the Estrous Cycle

  • Chiu, C.H.;Srinivasan, R.;Tseng, T.H.;Chuang, R.F.;Wu, L.S.
    • Asian-Australasian Journal of Animal Sciences
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    • v.22 no.5
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    • pp.636-642
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    • 2009
  • The corpus luteum (CL) is a transient endocrine gland that produces progesterone, a product required for the establishment and maintenance of pregnancy. In the absence of pregnancy, the production of progesterone in the CL decreases and the structure itself regresses in size. The life span and function of the CL are regulated by complex interactions between stimulatory (luteotrophic) and inhibitory (luteolytic) mediators. When an ovum is released from a mature follicle, angiogenesis and rapid growth of follicular cells form the CL. The purpose of the present study was to determine whether steroidogenesis, proliferation, and hypoxiarelated proteins are expressed in caprine CL. The expression of proliferating cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor $1{\alpha}$ (HIF-$1{\alpha}$) were determined in caprine CL during the estrous cycle. Cytochrome P450 side chain cleavage protein did not vary significantly during the estrous cycle; however, there was an increased expression of $3{\beta}$ -hydroxysteroid dehydrogenase in the early and middle stages, which rapidly decreased in the late stage. The same observations were made with respect to steroidogenic acute regulatory protein. Variations in progesterone content and expression of PCNA, HIF-$1{\alpha}$, and VEGF were consistent with this result. Thus, the steroidogenic proteins, PCNA, HIF-$1{\alpha}$, and VEGF in caprine CL are dependent on the stage of the estrous cycle.

The rare case of 46,XX testicular disorder of sex development carrying a heterozygous p.Arg92Trp variant in NR5A1

  • Lia Kim;Hwa Young Kim;Jung Min Ko
    • Journal of Genetic Medicine
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    • v.19 no.2
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    • pp.115-119
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    • 2022
  • The 46,XX testicular disorder of sex development (DSD) is a rare condition in which 46,XX individuals develop testicular differentiation and virilization. Translocation of the sex-determining region Y (SRY) onto the X chromosome is the main cause of 46,XX testicular DSD, whereas dysregulation between pro-testis and pro-ovarian genes can induce SRY-negative 46,XX testicular DSD. Nuclear receptor subfamily 5 group A member 1 (NR5A1), a nuclear receptor transcription factor, plays an essential role in gonadal development in XY and XX embryos. Herein, we report the first Korean case of SRY-negative 46,XX testicular DSD with a heterozygous NR5A1 p.Arg92Trp variant. The patient presented with a small penis, bifid scrotum, and bilateral undescended testes. Whole exome sequencing revealed a heterozygous missense variant (c.274C>T) of NR5A1. Our case highlights that NR5A1 gene variants need to be considered important causative factors of SRY-negative non-syndromic 46,XX testicular DSD.

Metabolic Signatures of Adrenal Steroids in Preeclamptic Serum and Placenta Using Weighting Factor-Dependent Acquisitions

  • Lee, Chaelin;Oh, Min-Jeong;Cho, Geum Joon;Byun, Dong Jun;Seo, Hong Seog;Choi, Man Ho
    • Mass Spectrometry Letters
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    • v.13 no.1
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    • pp.11-19
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    • 2022
  • Although translational research is referred to clinical chemistry measures, correct weighting factors for linear and quadratic calibration curves with least-squares regression algorithm have not been carefully considered in bioanalytical assays yet. The objective of this study was to identify steroidogenic roles in preeclampsia and verify accuracy of quantitative results by comparing two different linear regression models with weighting factor of 1 and 1/x2. A liquid chromatography-mass spectrometry (LC-MS)-based adrenal steroid assay was conducted to reveal metabolic signatures of preeclampsia in both serum and placenta samples obtained 15 preeclamptic patients and 17 age-matched control pregnant women (33.9 ± 4.2 vs. 32.8 ± 5.6 yr, respectively) at 34~36 gestational weeks. Percent biases in the unweighted model (wi = 1) were inversely proportional to concentrations (-739.4 ~ 852.9%) while those of weighted regression (wi = 1/x2) were < 18% for all variables. The optimized LC-MS combined with the weighted linear regression resulted in significantly increased maternal serum levels of pregnenolone, 21-deoxycortisol, and tetrahydrocortisone (P < 0.05 for all) in preeclampsia. Serum metabolic ratio of (tetrahydrocortisol + allo-tetrahydrocortisol) / tetrahydrocortisone indicating 11β-hydroxysteroid dehydrogenase type 2 was decreased (P < 0.005) in patients. In placenta, local concentrations of androstenedione were changed while its metabolic ratio to 17α-hydroxyprogesterone responsible for 17,20-lyase activity was significantly decreased in patients (P = 0.002). The current bioanalytical LC-MS assay with corrected weighting factor of 1/x2 may provide reliable and accurate quantitative outcomes, suggesting altered steroidogenesis in preeclampsia patients at late gestational weeks in the third trimester.

Effect of Prostaglandin F2 Alpha on E-cadherin, N-cadherin and Cell Adhesion in Ovarian Luteal Theca Cells (난소의 황체협막세포에서 E-cadherin, N-cadherin과 세포부착에 미치는 Prostaglandin F2 Alpha의 영향)

  • Lee, Sang-Hee;Jung, Bae Dong;Lee, Seunghyung
    • Korean Journal of Clinical Laboratory Science
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    • v.51 no.3
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    • pp.360-369
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    • 2019
  • Cadherins are essential transmembrane proteins that promote cell-cell adhesion and maintain the corpus luteum structure in the ovary. This study examined the influence of prostaglandin F2 alpha ($PGF2{\alpha}$) on E-cadherin, N-cadherin, and adhesion in luteal theca cells (LTCs). The luteal cells were isolated from the mid-phase corpus luteum, and the LTCs were cultured separately from the luteal heterogeneous cells according to the morphology of the mesenchymal cells and to determine if steroidogenic and endothelial cells of LTCs, 3beta-hydroxysteroid dehydrogenase ($3{\beta}$-HSD), and vascular endothelial growth factor receptor 2 (VEGFR2) mRNA were used. The LTCs were then incubated in the culture medium supplemented with 0.01, 0.1, and 1.0 mM $PGF2{\alpha}$ for 24 h, and the E-cadherin and N-cadherin proteins in the LTCs were detected by confocal laser scanning microscopy. The results revealed $3{\beta}$-HSD mRNA expression in the LTC but no VEGF2R mRNA expression. The E-cadherin and N-cadherin proteins of the LTCs were damaged in the 0.01, 0.1, and 1.0 mM $PGF2{\alpha}$ treatment groups, and the expression of the N-cadherin protein was reduced significantly in 0.01 mM $PGF2{\alpha}$ compared to the 0 mM $PGF2{\alpha}$ treatment groups (P<0.05). In addition, the number of attached LTCs were significantly lower in the 0.01 mM $PGF2{\alpha}$ treatment group than in the 0 mM $PGF2{\alpha}$ treatment group (P<0.05). In conclusion, $PGF2{\alpha}$ affected the disruption of cadherin proteins and cell adhesion in LTCs. These results may help better understand the cadherin and adhesion mechanism during corpus luteum regression in the ovary.