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.

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.

Transcriptional Regulation of Steroidogenic Genes: STARD1, CYP11A1 and HSD3B

2009 ◽  
Vol 234 (8) ◽  
pp. 880-907 ◽  
Author(s):  
Holly A. LaVoie ◽  
Steven R. King
Keyword(s):  
Transcriptional Regulation ◽  
Current Knowledge ◽  
Regulatory Protein ◽  
Side Chain ◽  
Combinatorial Regulation ◽  
Cytochrome P450scc ◽  
Chain Cleavage ◽  
Cleavage Enzyme ◽  
Steroidogenic Acute Regulatory ◽  
Species Specific

Expression of the genes that mediate the first steps in steroidogenesis, the steroidogenic acute regulatory protein (STARD1), the cholesterol side-chain cleavage enzyme, cytochrome P450scc (CYP11A1) and 3β-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase (HSD3B), is tightly controlled by a battery of transcription factors in the adrenal cortex, the gonads and the placenta. These genes generally respond to the same hormones that stimulate steroid production through common pathways such as cAMP signaling and common actions on their promoters by proteins such as NR5A and GATA family members. However, there are distinct temporal, tissue and species-specific differences in expression between the genes that are defined by combinatorial regulation and unique promoter elements. This review will provide an overview of the hormonal and transcriptional regulation of the STARD1, CYP11A1 and specific steroidogenic HSD3B genes in the adrenal, testis, ovary and placenta and discuss the current knowledge regarding the key transcriptional factors involved.

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