• 한국수정란이식학회지
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• 제25권4호
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• pp.273-279
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• 2010

Follicular cystic follicles (FCFs) show delayed regression with persistent follicle growth. However, the mechanism by which follicles are persistently grown remains unclear. Glutathione S-transferases (GSTs) are drug-metabolizing and detoxification enzymes that are involved in the intracellular transport and metabolism of steroid hormones. In this study, a proteomic analysis was performed to identify whether GST expression is changed in bovine FCFs and to predict the interactions between GST and other proteins. Normal follicles and FCFs were classified based on their sizes (5 to 10 mm and 25 mm). In bovine follicles, GST mu 1 (GSTM1) was detected as a differentially expressed protein (DEP) and significantly up-regulated in FCFs compared to normal follicles (p<0.05). Consistent with the proteomic results, semi-quantitative PCR data and western blot analysis revealed an up-regulation of GSTM1 in FCFs. Expression levels of aromatase and dehydrogenase proteins were changed in FCFs. These results show that the up-regulation of GSTM1 that is observed in bovine FCFs is likely to be responsible for the persistent follicle growth in FCFs as the activity of aromatase and the dehydrogenases.

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2003년도 추계학술대회
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• pp.137-137
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• 2003

• 한국독성학회:학술대회논문집
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• 한국독성학회 2003년도 추계학술대회
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• pp.137-137
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• 2003

Dichlorodiphenyltrichloroethane (DDT) is a widespread environmental pollutant. Earlier reports have demonstrated that DDT is an endocrine-active compound capable of affecting early-stage sexual differentiation in male rats. Experiments based on receptor binding affinity and receptor-mediated transcriptional activation have identified DDE as an androgen receptor antagonist.(omitted)

• Animal cells and systems
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• 제16권2호
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• pp.127-134
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• 2012

We investigated the effects of fadrozol, an aromatase inhibitor (AI), and $17{\alpha}$-methyltestosterone (MT) on the induction of sex change in juvenile longtooth grouper $Epinephelus$ $bruneus$, via histological observation of gonads. Changes in the mRNA expression of GtH subunits (FSH-${\beta}$ and LH-${\beta}$) in the pituitary, and estradiol-$17{\beta}$ (E2) and 11-ketotestosterone (11-KT) levels in the blood were also surveyed after AI and MT treatment. Juvenile longtooth groupers ($113{\pm}17g\;body\;weight$; $16.2{\pm}1.2cm\;body\;length$) received intramuscular injections of AI at 3 (3-AI) and 5 (5-AI) mg/kg BWdoses and MT at a 5 mg/kg BW (5-MT) dose. At week 7 post-injection, 3-AI and 5-MT oocytes were degenerated, and gonads of the 5-AI group initiated spermatogenesis. At week 21 post-injection, 3-AI- and 5-MT-treated gonads contained spermatogonia and spermatocytes, while 5-AI treatment induced advanced stages of spermatogenesis. The serum E2 level showed no significant differences throughout the experimental period, whereas that of 11-KT was significantly elevated in the 5-AI group at weeks 7 and 21 post-injection. A significant increase in the expression of FSH-${\beta}$ mRNA was evident in the 5-AI group at week 21 post-injection. In contrast, LH-${\beta}$ mRNA expression did not significantly differ among groups during the experimental period. These results imply that sex change has two stages in the longtooth grouper. In the first stage, oocytes are degenerated by the stimulation by 11-KT, and in the second stage spermatogenesis occurs, owing to the co-effects of 11-KT and FSH-${\beta}$.

• Fisheries and Aquatic Sciences
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• 제18권2호
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• pp.211-220
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• 2015

We investigated the differences in the expression of the neurohormones kisspeptin (Kiss) and gonadotropin-inhibitory hormone (GnIH) and cytochrome P450 aromatase (P450arom), gonadotropin hormones (GTHs), and sex steroids in the goldfish Carassius auratus exposed to light-emitting diodes (LEDs). The expression levels of Kiss1, Kiss2, G-protein-coupled receptor 54 (GPR54), GTHs, GnIH, and P450arom were compared between the control (white light) and LED-treated goldfish. Furthermore, we measured the plasma levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The levels of Kiss1 mRNA and protein; Kiss2, GPR54, and $GTH{\alpha}$ protein; GTH mRNA; and plasma FSH and LH in the hypothalamus and cultured hypothalamus cells were significantly higher in the green and purple LED treatment groups than in the other groups. These results suggested that red LEDs inhibit the sex maturation hormones, Kiss, GPR54, GTHs, and P450arom, and that GnIH plays a role in the negative regulation of reproductive function in goldfish.

• Genomics & Informatics
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• 제21권2호
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• pp.20.1-20.10
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• 2023

Aromatase inhibitors (AI) are drugs that are widely used in treating estrogen receptor (ER)-positive breast cancer patients. Drug resistance is a major obstacle to aromatase inhibition therapy. There are diverse reasons behind acquired AI resistance. This study aims at identifying the plausible cause of acquired AI resistance in patients administered with non-steroidal AIs (anastrozole and letrozole). We used genomic, transcriptomic, epigenetic, and mutation data of breast invasive carcinoma from The Cancer Genomic Atlas database. The data was then separated into sensitive and resistant sets based on patients' responsiveness to the non-steroidal AIs. A sensitive set of 150 patients and a resistant set of 172 patients were included for the study. These data were collectively analyzed to probe into the factors that might be responsible for AI resistance. We identified 17 differentially regulated genes (DEGs) among the two groups. Then, methylation, mutation, miRNA, copy number variation, and pathway analyses were performed for these DEGs. The top mutated genes (FGFR3, CDKN2A, RNF208, MAPK4, MAPK15, HSD3B1, CRYBB2, CDC20B, TP53TG5, and MAPK8IP3) were predicted. We also identified a key miRNA - hsa-mir-1264 regulating the expression of CDC20B. Pathway analysis revealed HSD3B1 to be involved in estrogen biosynthesis. This study reveals the involvement of key genes that might be associated with the development of AI resistance in ER-positive breast cancers and hence may act as a potential prognostic and diagnostic biomarker for these patients.

• 한국동물학회:학술대회논문집
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• 한국동물학회 2003년도 한국생물과학협회 학술발표대회
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• pp.197.3-197
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• 2003

No Abstract, See Full Text

• 한국발생생물학회지:발생과생식
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• 제11권3호
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• pp.187-193
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• 2007

Ethane 1,2-dimethane sulfonate(EDS)는 Leydig 세포의 선별적 사멸을 유도하는 약물로서 가역적인 테스토스테론 결핍 흰쥐를 만드는데 널리 사용된다. 부정소의 구조와 기능 유지는 크게 보아 정소에서 분비되는 테스토스테론에 의존적이지만, 테스토스테론으로부터 유도되는 dihydroxytestosterone(DHT)와 에스트로겐도 중요한 역할을 한다. 본 연구에서는 EDS 주사 후 7주까지 부정소에서의 스테로이드 호르몬 수용체, cyctochrome P450aromatase(P450arom)와 $5{\alpha}$-reductase의 유전자 발현 양상을 조사하였다. 성숙한 수컷 흰쥐($350{\sim}400\;g$)에 EDS를 1회 복강 주사하고(75 mg/kg i.p.) 주사 후 0, 1, 2, 3, 4, 5, 6, 7주가 경과한 날에 희생하였다. 표적 유전자들의 전사 활성은 반 정량적 역전사 중합효소 반응법(semi-quantitative RT-PCRs)으로 측정하였다. Estrogen receptor alpha($ER{\alpha}$) 전사 수준은 EDS 실험군에서 대조군에 비해 주사 1주후에 유의하게 상승했으나(P<0.01) 2주 후부터는 대조군과 유의적인 차이를 보이지 않았다. Estrogen receptor beta($ER{\beta}$)의 전사 수준은 주사 1주후 EDS 실험군에서 대조군에 비해 유의하게 증가했다가(P<0.05), 2주와 3주에는 감소하였고(P<0.05와 P<0.01), 4주와 6주까지는 변동폭을 보이다가 7주 후에는 대조군에 비해 증가하였다(P<0.05). Androgen receptor(AR) 전사 수준은 주사 2주 후에 유의하게 증가하다가(P<0.01) 3주 후부터는 대조군 수준으로 회복하였다. 반면, P450arom는 주사 1주 후부터 3주까지 급격하게 감소했다가(P<0.01 1주와 2주; P<0.05 3주), 4주에 대조군 수준으로 회복하였다. $5{\alpha}$-reductase type 2($5{\alpha}$-RT2)의 mRNA 수준은 4주 후 유의하게 증가했다가(P<0.01), 이후 대조군 수준으로 회복하였다. 본 연구는 EDS 주사가 성 스테로이드 호르몬 수용체들과 안드로겐 전환 효소들의 전사 활성에 가역적인 변화를 유도함을 보여준 것이다. EDS 주사 모델은 부정소의 생리 조절 기작을 이해하는데 유용할 것으로 사료된다.

• Asian-Australasian Journal of Animal Sciences
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• 제20권3호
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• pp.340-350
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• 2007

The objective of this study was to determine whether peroxisome proliferator-activated receptor ${\gamma}$(PPAR${\gamma}$ is involved in the regulation of weaning to estrus of primiparous sows. Twelve sows composed of 6 groups of 2 full-sibs in a similar age (325.2 d), body weight (BW; 152.4 kg) and backfat thickness (BFT; 27.0 mm) at start of lactation, were allocated to accept 31 MJ (restricted group, R-group) or 53 MJ (control group, C-group) DE/d treatment, respectively. The experimental results indicated that the low energy intake resulted in excessive losses of BW and BFT during lactation in R-group sows, which may be related to decrease of serum 15-deoxy-${\Delta}^{12,14}$-prostaglandin $J_2$ (15d-$PGJ_2$), a ligand of PPAR${\gamma}$ The obvious peak and the frequency of LH, FSH and estradiol ($E_2$) were only observed in C-group sows. Except for $E_2$ at d 1 and 2, serum FSH, LH and $E_2$ concentrations in R-group were lower than those in C-group sows after weaning. However, the serum progesterone ($P_4$) level in R-group sows was always more than that in C-group. The expression abundances of PPAR${\gamma}$and GnRH receptor (GnRH-R) in pituitary, FSH receptor (FSH-R), LH receptor (LH-R), estrogen receptor (ES-R) and aromatase in ovary of anestrous sows were lower than those of estrous sows. Neither the BFT nor the BW was associated with the mRNA abundance of PPAR${\gamma}$in hypothalamus during lactation. Expressions of PPAR${\gamma}$in pituitary and ovary were affected evidently by the BFT changes and only by the loss of BW of sows during and after lactation. Furthermore, PPAR${\gamma}$mRNA level in ovary was significantly related to the expression abundances of GnRH-R, FSH-R, ES-R and aromatase, and GnRH-R was obviously associated with PPAR${\gamma}$expression in pituitary. However, PPAR${\gamma}$expression in hypothalamus likely has no effects on these genes expression and no obvious difference for all sows. Not serum $E_2$ or $P_4$ alone but the ratios of $E_2$ to $P_4$ and 15d-$PGJ_2$ to $P_4$, and serum FSH and LH were evidently related to PPAR${\gamma}$expression in pituitary and ovary. It is concluded that PPAR${\gamma}$is associated with body conditions, reproduction hormones and their receptor expression, which affected the functions of pituitary and ovary and ultimately the estrus after weaning of primiparous sows.

• 대한한의학회지
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• 제43권1호
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• pp.18-32
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• 2022

Objectives: This study aimed to examine the safety, effects on proliferation of hair papilla cells, and anti-inflammatory and antioxidant mechanisms of Artemisia sieversiana Ehrh. ex Willd. (AS) extract. Methods: Safety tests through purity testing, acute toxicity tests, and repeated toxicity tests were performed using AS extract (ASE) which had been dried for over two years. Cell culture and proliferation tests were conducted; VEGF (vascular endothelial growth factor), bFGF (basic fibroblast growth factor), and EGF (epidermal growth factor) and protein expression analyses were performed for mechanistic evaluation; and inhibitory effects of ASE on the RNA expression of testosterone, 5𝛼-reductase, and aromatase was assessed. The anti-inflammatory and antioxidant efficacy of ASE was confirmed by measuring the levels of nitric oxide, inflammatory mediators (TNF-𝛼 and PGE2), inflammatory cytokines (IL-1𝛽, IL-6, and IL-8), and chemokine MCP-1. Results: The safety of ASE was confirmed. The mechanism of cell proliferation in human hair follicle dermal papilla cells involved the promotion of VEGF, bFGF, and EGF expression. ASE decreased mRNA expression of testosterone, 5𝛼-reductase, and aromatase-1 in a concentration-dependent manner. PGE2 and TNF-𝛼 production by inflammatory mediators was also significantly decreased in a concentration-dependent manner, and inflammatory cytokine and chemokine expression was inhibited. Conclusions: ASE is suggested to promote papillary cell growth at the cellular level, to suppress expression of various enzymes involved in hair cycle and cell death, and to inhibit hair loss through anti-androgen, anti-inflammatory, and antioxidant effects.