• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2007년도 Proceedings of The Convention
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• pp.57-64
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• 2007

Metabolic interactions of the three major cannabinoids, ${\Delta}^9$-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol (CBN) with steroid hormones were investigated. These cannabioids concentration-dependently inhibited $3{\beta}$-hydroxysteroid dehydrogenase and $17{\alpha}$-hydroxylase in rat adrenal and testis microsomes. CBD and CBN were the most potent inhibitors of $3{\beta}$-phydroxysteroid dehydrogenase and progesterone $17{\alpha}$-hydroxylase, respectively, in rat testis microsomes. Three cannabinoids highly attenuated hCG-stimulated testosterone production in rat testicular interstitial cells. These cannabinoids also decreased in levels of mRNA and protein of StAR in the rat testis cells. These results indicate that the cannabinoids could interact with steroid hormones, and exert their modulatory effects on endocrine and testicular functions. Metabolic interaction of a THC metabolite, $7{\beta}$-hydroxy-${\Delta}^8$-THC with steroids is also investigated. Monkey liver microsomes catalyzed the stereoselective oxidation of $7{\beta}$-hydroxy-${\Delta}^8$-THC to 7-oxo-${\Delta}^8$-THC, so-called microsomal alcohol oxygenase (MALCO). The reaction is catalyzed by CYP3A8 in the monkey liver microsomes, and required NADH as well as NADPH as an efficient cofactor, and its activity is stimulated by some steroids such as testosterone and progesterone. Kinetic analyses revealed that MALCO-catalyze reaction showed positive cooperativity. In order to explain the metabolic interaction between the cannabinoid metabolite and testosterone, we propose a novel kinetic model involving at least three binding sites for mechanism of the metabolic interactions.

• 환경생물
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• 제22권4호
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• pp.550-558
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• 2004

The effects of postnatal exposure to octylphenol(OP) on the expressions of the steroidogenic enzymes and testosterone production were evaluated. Postnatal male mice (15-day-old) were injected with 2 or 20mg $kg^{-l}$ body weight (BW) of OP for 5 days and sacrificed on postnatal day 21. Testosterone concentration was measured by radioimmunoassay and the expressions of the testicular genes were determined by RT-PCR analyses. Significant reductions in the mean body and testis weight were observed in the OP treated animals. No marked alteration in the histological structure of the testis were observed, however, slight reduction in the seminiferous tubule diameter and the number of Leydig cells and several pyknotic cells could be identified in the 20 mg $kg^{-l}$ BW of the OP treated animals. Serum testosterone concentration was dramatically reduced and the mRNA expressions of the steroidogenic acute regulatory protein (StAR), cholesterol side-chain cleavage enzyme (P450scc) and $17\beta$-hydroxylase/Cl7-20 lyase $(P450_{17\alpha})$ were decreased. No significant changes of the gene expressions of the steroidogenic factor-l (SF-I) and estrogen and androgen receptor after the OP treatment showed that the decreased expressions of the steroidogenic enzymes in the present study did not correlate with these genes. Altogether, the present study demonstrates that postnatal treatment of OP inhibits steroidogenesis by decreasing the transcriptional expressions of the StAR and steroidogenic enzymes. The alteration in steroidogenesis may adversely affect the normal development of the testis and sper- matogenesis.

• Reproductive and Developmental Biology
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• 제40권2호
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• pp.15-22
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• 2016

As a one of unsaturated fatty acid, polyunsaturated fatty acids (PUFAs) have multiple actions: as precursor of prostaglandins (PGs), steroid hormone synthesis and energy production in animal reproduction. PUFAs, which include omega-3 (n-3) and omega-6 (n-6), are derived from the diet and changed by diet, species, breed and season. The plasma membrane of spermatozoa in mammals contain various PUFAs. These composition of PUFAs regulate the membrane fluidity and cause lipid peroxidation via generation of reactive oxygen species (ROS). Induced lipid peroxidation by ROS decreased viability and motility of spermatozoa, and it is reduced by addition of antioxidant and low concentration of PUFAs. Because oocytes of animal have a high lipid components, process of oocyte maturation and embryo development are influenced by PUFAs. In in vitro study, oocyte maturation, embryo development, intracellular cAMP and MAPK activity were increased by treatment of n-3 ${\alpha}$-linolenic acid (ALA) during maturation, whereas n-6 linoleic acid (LA) negatively influenced. Also, inhibition of fatty acid metabolism in oocyte influenced blastocyst formation of cattle. PGs are synthesized from PUFAs and various PUFAs influence PGs via regulation of PG-endoperoxide synthase (PTGS). Steroid hormone synthesis from cholesterol is regulated by expression of steroid acute regulator (StAR) protein and mRNA. Exogenous n-3 and n-6 PUFAs altered sex hormone in animal through stimulate or inhibit StAR activity. Because PUFAs altered PG and steroid hormone synthesis, follicular development was influenced by PUFAs. This effect of unsaturated fatty acid could provide information for improvement of reproductive ability in animals.

• Molecules and Cells
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• 제26권1호
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• pp.74-80
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• 2008

Bisphenol A bis (2,3-dihydroxypropyl) ether ($BADGE.2H_2O$) is a component of commercial liquid epoxy resins commonly used in the food-packing industry and in dental sealants. There is evidence that it has significant estrogenic activity. Nur77 plays a crucial role in the regulation of certain genes involved in LH-mediated steroidogenesis in testicular Leydig cells. It was previously demonstrated that Bisphenol A (BPA) stimulates Nur77 gene induction and steroidogenesis. In this study, we investigated the effects of $BADGE.2H_2O$ on Nur77 gene expression and steroidogenesis. Northern blot analysis showed that it increased the expression of Nur77 mRNA and protein, and transient transfection assays demonstrated that it increased the promoter activity and transactivation of Nur77. It also increased the expression of certain steroidogenic genes, such as StAR and $3{\beta}$-HSD. Finally, over-expression of a dominant negative Nur77 cDNA via adenoviral infection reduced $BADGE.2H_2O$-mediated progesterone biosynthesis. These results indicate that $BADGE.2H_2O$ disrupts testicular steroidogenesis by increasing Nur77 gene expression.

• Animal Bioscience
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• 제34권8호
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• pp.1290-1302
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• 2021

Objective: Follicle selection is an important process in chicken egg laying. Among several small yellow (SY) follicles, the one exhibiting the highest expression of follicle stimulation hormone receptor (FSHR) will be selected to become a hierarchal follicle. The role of lncRNA, miRNA and other non-coding RNA in chicken follicle selection is unclear. Methods: In this study, the whole transcriptome sequencing of SY follicles with different expression levels of FSHR in Jining Bairi hens was performed, and the expression of 30 randomly selected mRNAs, lncRNAs and miRNAs was validated by quantitative real-time polymerase chain reaction. Preliminary studies and bioinformatics analysis were performed on the selected mRNA, lncRNA, miRNA and their target genes. The effect of identified gene was examined in the granulosa cells of chicken follicles. Results: Integrated transcriptomic analysis on chicken SY follicles differing in FSHR expression revealed 467 differentially expressed mRNA genes, 134 differentially expressed lncRNA genes and 34 differentially expressed miRNA genes, and sosondowah ankyrin repeat domain family member A (SOWAHA) was the common target gene of three miRNAs and one lncRNA. SOWAHA was mainly expressed in small white (SW) and SY follicles and was affected by follicle stimulation hormone (FSH) treatment in the granulosa cells. Knockdown of SOWAHA inhibited the expression of Wnt family member 4 (Wnt4) and steroidogenic acute regulatory protein (StAR) in the granulosa cells of prehierarchal follicles, while stimulated Wnt4 in hierarchal follicles. Overexpression of SOWAHA increased the expression of Wnt4 in the granulosa cells of prehierarchal follicles, decreased that of StAR and cytochrome P450 family 11 subfamily A member 1 in the granulosa cells of hierarchal follicles and inhibited the proliferation of granulosa cells. Conclusion: Integrated analysis of chicken SY follicle transcriptomes identified SOWAHA as a network gene that is affected by FSH in granulosa cells of ovarian follicles. SOWAHA affected the expression of genes involved in chicken follicle selection and inhibited the proliferation of granulosa cells, suggesting an inhibitory role in chicken follicle selection.

• 한국발생생물학회지:발생과생식
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• 제20권2호
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• pp.91-99
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• 2016

Lipopolysaccharide (LPS), an endotoxin, elicits strong immune responses in mammals. Several lines of evidence demonstrate that LPS challenge profoundly affects female reproductive function. For example, LPS exposure affects steroidogenesis and folliculogenesis, resulting in delayed puberty onset. The present study was conducted to clarify the mechanism underlying the adverse effect of LPS on the delayed puberty in female rats. LPS was daily injected for 5 days ($50{\mu}g/kg$, PND 25-29) to treated animals and the date at VO was evaluated through daily visual examination. At PND 39, animals were sacrificed, and the tissues were immediately removed and weighed. Among the reproductive organs, the weights of the ovaries and oviduct from LPS-treated animals were significantly lower than those of control animals. There were no changes in the weights of uterus and vagina between the LPS-treated and their control animals. immunological challenge by LPS delayed VO. Multiple corpora lutea were found in the control ovaries, indicating ovulations were occurred. However, none of corpus luteum was present in the LPS-treated ovary. The transcription level of steroidogenic acute regulatory protein (StAR), CYP11A1, CYP17A1 and CYP19 were significantly increased by LPS treatment. On the other hand, the levels of $3{\beta}$-HSD, $17{\beta}$-HSD and LH receptor were not changed by LPS challenge. In conclusion, the present study demonstrated that the repeated LPS exposure during the prepubertal period could induce multiple alterations in the steroidogenic machinery in ovary, and in turn, delayed puberty onset. The prepubertal LPS challenge model used in our study is useful to understand the reciprocal regulation of immune (stress) - reproductive function in early life.

• Asian-Australasian Journal of Animal Sciences
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• 제28권11호
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• pp.1573-1582
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• 2015

This study was to investigate the effect of soyabean isoflavones (SIF) on onset of puberty, serum hormone concentration, and gene expression in hypothalamus, pituitary and ovary of female Bama miniature pigs. Fifty five, 35-days old pigs were randomly assigned into 5 treatment groups consisting of 11 pigs per treatment. Results showed that dietary supplementation of varying dosage (0, 250, 500, and 1,250 mg/kg) of SIF induced puberty delay of the pigs with the age of puberty of pigs fed basal diet supplemented with 1,250 mg/kg SIF was significantly higher (p<0.05) compared to control. Supplementation of SIF or estradiol valerate (EV) reduced (p<0.05) serum gonadotrophin releasing hormone and luteinizing hormone concentration, but increased follicle-stimulating hormone concentration in pigs at 4 months of age. The expression of KiSS-1 metastasis-suppressor (KISS1), steroidogenic acute regulatory protein (StAR) and 3-beta-hydroxysteroid dehydrogenase/delta-5-delta-4 isomerase ($3{\beta}-HSD$) was reduced (p<0.01) in SIF-supplemented groups. Expression of gonadotropin-releasing hormone receptor in the pituitary of miniature pigs was reduced (p<0.05) compared to the control when exposed to 250, 1,250 mg/kg SIF and EV. Pigs on 250 mg/kg SIF and EV also showed reduced (p<0.05) expression of cytochrome P450 19A1 compared to the control. Our results indicated that dietary supplementation of SIF induced puberty delay, which may be due to down-regulation of key genes that play vital roles in the synthesis of steroid hormones.