156. EFFECTS OF ALBENDAZOLE ON OVARIAN OESTROGEN SYNTHESIS IN THE RAT

2009 ◽  
Vol 21 (9) ◽  
pp. 74
Author(s):  
I. S. Zulkafli ◽  
P. J. Mark ◽  
G. B. Martin ◽  
B. J. Waddell
Keyword(s):  
Mating Behaviour ◽  
Regulatory Protein ◽  
Reproductive Function ◽  
Hydroxysteroid Dehydrogenase ◽  
Side Chain ◽  
Chain Cleavage ◽  
Rat Ovary ◽  
Steroidogenic Acute Regulatory ◽  
Ovarian Follicular Fluid ◽  
Steroidogenic Genes

Albendazole is a drug commonly used for treatment of helminth infestation in human and livestock populations. Recent studies show that albendazole reduces ovarian follicular fluid oestrogen levels in sheep1, but the mechanism involved is unknown. The aims of this study were to determine whether albendazole exerts similar effects on ovarian oestrogen levels in the rat, and to assess the effects of albendazole on expression of key steroidogenic genes in the rat ovary. Oestrus cycles were continuously monitored in Wistar rats by vaginal smears. Commencing at proestrus, albendazole was administered for 12 days in drinking water (approximate dose 15 mg/kg/day). Plasma and whole ovaries were collected on the fourth proestrus (1500–1600h). A second group of rats were treated similarly except that pseudopregnancy (PSP) was induced by mating with a vasectomised male at the second proestrus. Plasma and the non-luteal ovary were collected on day 8 of PSP. Oestradiol was extracted from plasma and ovaries with ethyl acetate and concentrations measured by a chemiluminescent assay. Expression of steroidogenic acute regulatory protein (StAR), P450 side chain cleavage (P450scc), 3β-hydroxysteroid dehydrogenase (3β-HSD), aromatase and 20α-hydroxysteroid dehydrogenase (20α-HSD) mRNAs were measured by RT-PCR. Oestrus cyclicity, ovarian weight and mating behaviour were all unaffected by albendazole in cycling and PSP rats, although as expected levels of oestradiol were lower in PSP. In ovaries of cycling rats albendazole did not affect oestradiol concentrations but reduced ovarian P450scc mRNA expression (by 65%; P=0.024) and there was a trend for an increase in 3β-HSD (P=0.09) and aromatase expression (P=0.12). Expression of the other steroidogenic genes was unaffected and no changes in gene expression were observed in PSP rats. In conclusion, albendazole treatment reduced ovarian P450scc in cycling rats but did not inhibit ovarian oestradiol synthesis or reproductive function.

scholarly journals Growth Differentiation Factor 9 Reverses Activin A Suppression of Steroidogenic Acute Regulatory Protein Expression and Progesterone Production in Human Granulosa-Lutein Cells

2010 ◽  
Vol 24 (8) ◽  
pp. 1676-1677
Author(s):  
Feng-Tao Shi ◽  
Anthony P. Cheung ◽  
Christian Klausen ◽  
He-Feng Huang ◽  
Peter C. K. Leung
Keyword(s):  
Regulatory Protein ◽  
Hydroxysteroid Dehydrogenase ◽  
Activin A ◽  
Inhibin B ◽  
Steroidogenic Acute Regulatory Protein ◽  
Side Chain ◽  
Progesterone Production ◽  
Chain Cleavage ◽  
Cleavage Enzyme ◽  
Steroidogenic Acute Regulatory

Abstract Background: We have reported that growth differentiation factor (GDF) 9 can enhance activin A (βAβA)-induced inhibin B (αβB) secretion in human granulosa-lutein (hGL) cells, but its effects on steroidogenic acute regulatory protein (StAR), ovarian steroidogenic enzymes, and progesterone production are unknown. We undertook this study to further evaluate GDF9 in this regard. Methods: hGL cells from women undergoing in vitro fertilization treatment were cultured with and without small interfering RNA (siRNA) transfection targeted at inhibin α-subunit or GDF9 before treatment with GDF9, activin A, FSH, or combinations. We compared StAR, P450 side-chain cleavage enzyme, and 3β-hydroxysteroid dehydrogenase expression in hGL cells and progesterone levels in culture media after these treatments. mRNA, protein, and hormone levels were assessed with real-time RT-PCR, immunoblotting, and ELISA, respectively. Data were analyzed by ANOVA followed by Tukey’s test. Results: Activin A alone reduced basal and FSH-induced progesterone production by decreasing the expression of StAR protein, which regulates the rate-limiting step in steroidogenesis but not P450 side-chain cleavage enzyme and 3β-hydroxysteroid dehydrogenase. GDF9 attenuated these activin A effects on StAR and progesterone. After transfection of a-subunit siRNA, activin A level increased (P < 0.001), whereas basal and activin A-induced inhibin B levels (with and without GDF9) decreased. Furthermore, the effects of GDF9 in reversing activin A suppression of progesterone production were attenuated (P < 0.001). Transfection of GDF9 siRNA decreased GDF9 as expected and led to lower StAR expression and progesterone secretion than those observed with activin A treatment alone. Conclusion: GDF9 attenuates the suppressive effects of activin A on StAR expression and progesterone production by increasing the expression of inhibin B, which acts as an activin A competitor.

scholarly journals Molecular Mechanism of Isocupressic Acid Supresses MA-10 Cell Steroidogenesis

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Kuan-Hao Tsui ◽  
Jyun-Yuan Wang ◽  
Leang-Shin Wu ◽  
Chih-Hsien Chiu
Keyword(s):  
Molecular Mechanism ◽  
Ponderosa Pine ◽  
Molecular Mechanisms ◽  
Regulatory Protein ◽  
Pine Needles ◽  
Side Chain ◽  
Poisonous Plant ◽  
Chain Cleavage ◽  
Steroidogenic Acute Regulatory ◽  
Steroidogenic Genes

Consumption of ponderosa pine needles causes late-term abortions in cattle and is a serious poisonous plant problem in foothill and mountain rangelands. Isocupressic acid (IA) is the component of pine needles responsible for the abortifacient effect, its abortifacient effect may be due to inhibition of steroidogenesis. To investigate the more detail molecular mechanism, we used MA-10 cell, which is wild used to investigate molecular mechanism of steroidogenesis, to characterize the molecular mechanisms underlying the actions of IA in more detail. In this report, we focus on the function of IA on important steroidogenic genes, including steroidogenic acute regulatory protein (StAR), cytochrome P450 cholesterol side-chain cleavage (P450scc), and 3β-hydroxysteroid dehydrogenase (3β-HSD). We found that IA does not affect enzyme activities of these genes but inhibits transcription of P450scc and translation of StAR and P450scc through attenuating cAMP-PKA signaling. Thus, steroid productions of cells were suppressed.

In obese mice, exercise training increases 11β-HSD1 expression, contributing to glucocorticoid activation and suppression of pulmonary inflammation

2017 ◽  
Vol 123 (4) ◽  
pp. 717-727 ◽  
Author(s):  
Shu-Fang Du ◽  
Qing Yu ◽  
Kai Chuan ◽  
Chang-Lin Ye ◽  
Ze-Jia He ◽  
...  
Keyword(s):  
Exercise Training ◽  
Pulmonary Inflammation ◽  
Regulatory Protein ◽  
Hydroxysteroid Dehydrogenase ◽  
Mouse Lung ◽  
Obese Mice ◽  
Chain Cleavage ◽  
Anti Inflammatory ◽  
Steroidogenic Acute Regulatory

Exercise training is advocated for treating chronic inflammation and obesity-related metabolic syndromes. Glucocorticoids (GCs), the anti-inflammatory hormones, are synthesized or metabolized in extra-adrenal organs. This study aims to examine whether exercise training affects obesity-associated pulmonary inflammation by regulating local GC synthesis or metabolism. We found that sedentary obese ( ob/ob) mice exhibited increased levels of interleukin (IL)-1β, IL-18, monocyte chemotactic protein (MCP)-1, and leukocyte infiltration in lung tissues compared with lean mice, which was alleviated by 6 wk of exercise training. Pulmonary corticosterone levels were decreased in ob/ob mice. Exercise training increased pulmonary corticosterone levels in both lean and ob/ob mice. Pulmonary corticosterone levels were negatively correlated with IL-1β, IL-18, and MCP-1. Immunohistochemical staining of the adult mouse lung sections revealed positive immunoreactivities for the steroidogenic acute regulatory protein, the cholesterol side-chain cleavage enzyme (CYP11A1), the steroid 21-hydroxylase (CYP21), 3β-hydroxysteroid dehydrogenase (3β-HSD), and type 1 and type 2 11β-hydroxysteroid dehydrogenase (11β-HSD) but not for 11β-hydroxylase (CYP11B1). Exercise training significantly increased pulmonary 11β-HSD1 expression in both lean and ob/ob mice. In contrast, exercise training per se had no effect on pulmonary 11β-HSD2 expression, although pulmonary 11β-HSD2 levels in ob/ob mice were significantly higher than in lean mice. RU486, a glucocorticoid receptor antagonist, blocked the anti-inflammatory effects of exercise training in lung tissues of obese mice and increased inflammatory cytokines in lean exercised mice. These findings indicate that exercise training increases pulmonary expression of 11β-HSD1, thus contributing to local GC activation and suppression of pulmonary inflammation in obese mice. NEW & NOTEWORTHY Treadmill training leads to a significant increase in pulmonary corticosterone levels in ob/ob mice, which is in parallel with the favorable effects of exercise on obesity-associated pulmonary inflammation. Exercise training increases pulmonary 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) expression but has no significant effect on 11β-HSD2 expression in both lean and ob/ob mice. These findings indicate that exercise training increases pulmonary expression of 11β-HSD1, thus contributing to local glucocorticoid activation and suppression of pulmonary inflammation in obese mice.

scholarly journals Prostaglandin E2 Via Steroidogenic Factor-1 Coordinately Regulates Transcription of Steroidogenic Genes Necessary for Estrogen Synthesis in Endometriosis

2009 ◽  
Vol 94 (2) ◽  
pp. 623-631 ◽  
Author(s):  
Erkut Attar ◽  
Hideki Tokunaga ◽  
Gonca Imir ◽  
M. Bertan Yilmaz ◽  
David Redwine ◽  
...  
Keyword(s):  
Prostaglandin E2 ◽  
Promoter Activity ◽  
Hydroxysteroid Dehydrogenase ◽  
Side Chain ◽  
Mrna Levels ◽  
Steroidogenic Factor 1 ◽  
Side Chain Cleavage ◽  
Chain Cleavage ◽  
Estrogen Synthesis ◽  
Steroidogenic Genes

Abstract Context: Products of at least five specific steroidogenic genes, including steroidogenic acute regulatory protein (StAR), which facilitates the entry of cytosolic cholesterol into the mitochondrion, side chain cleavage P450 enzyme, 3β-hydroxysteroid-dehydrogenase-2, 17-hydroxylase/17-20-lyase, and aromatase, which catalyzes the final step, are necessary for the conversion of cholesterol to estrogen. Expression and biological activity of StAR and aromatase were previously demonstrated in endometriosis but not in normal endometrium. Prostaglandin E2 (PGE2) induces aromatase expression via the transcriptional factor steroidogenic factor-1 (SF1) in endometriosis, which is opposed by chicken-ovalbumin upstream-transcription factor (COUP-TF) and Wilms’ tumor-1 (WT1) in endometrium. Objective: The aim of the study was to demonstrate a complete steroidogenic pathway leading to estrogen biosynthesis in endometriotic cells and the transcriptional mechanisms that regulate basal and PGE2-stimulated estrogen production in endometriotic cells and endometrium. Results: Compared with normal endometrial tissues, mRNA levels of StAR, side chain cleavage P450, 3β-hydroxysteroid-dehydrogenase-2, 17-hydroxylase/17-20-lyase, aromatase, and SF1 were significantly higher in endometriotic tissues. PGE2 induced the expression of all steroidogenic genes; production of progesterone, estrone, and estradiol; and StAR promoter activity in endometriotic cells. Overexpression of SF1 induced, whereas COUP-TFII or WT1 suppressed, StAR promoter activity. PGE2 induced coordinate binding of SF1 to StAR and aromatase promoters but decreased COUP-TFII binding in endometriotic cells. COUP-TFII or WT1 binding to both promoters was significantly higher in endometrial compared with endometriotic cells. Conclusion: Endometriotic cells contain the full complement of steroidogenic genes for de novo synthesis of estradiol from cholesterol, which is stimulated by PGE2 via enhanced binding of SF1 to promoters of StAR and aromatase genes in a synchronous fashion.

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