Study of Regulation of Steroidogenesis by Phytochemicals
Date Issued
2014
Date
2014
Author(s)
Wang, Jyun-Yuan
Abstract
Animals use endocrine system to regulate physiological mechanisms. Leydig cell, granulosa cell, luteum cell and adrenal cortical cell producing steroid hormones controlled by endrocrine system through steroidogenesis. However, specific peptides, chemicals and phytochemicals extract from plants are found can regulate steroidogenesis. The purpose of this study is to clearify the mechanism of how steroidogenesis be effected under specific condition. Androgen is necessary for prostate cancer growth so decreasing androgen level is important in prostate cancer treatment. Curcumin was found inhibiting proliferation and metastasis of prostate cancer cell lines. Here we found that curcumin inhibits testosterone production in Leydig cell via suppressing expression of sterodiogenic genes. These results provide more evidences on curcumin as an effective drug for the treatment of prostate cancer. Metabolic syndrome is closely links to many symptoms including hypertension, hypercholesterolemia and diabetes. Erectile dysfunction is one symptoms of diabetes. With diabetic mice models, we comfirmed that hyperglycemia induced oxidative stress decrease testosterone level through suppressing steroidogenic genes expressionn in testis. Support quercetin as antioxidant restores testosterone production under insulin resistance. The other hand, leptin elevated in obese individual suppresses adrenal response to ACTH stimulation also glucocorticoid secretion. In this study, we confirm high leptin level in high-fat diet-induced obese mice cause poor adrenal response to ACTH while quercetin restores adrenal response. We hypothesize that quercetin interfere JAK2-PI3K pathway to restore adrenal steroidogenesis suppressed by leptin, more evidences are need to prove this hypothesis. Consumption of ponderosa pine needles causes late-term abortions in cattle and isocupressic acid (IA) responsible for the effect. With murine Leydig cell MA-10, we found that IA does not affect enzyme activities of steroidogenic genes but inhibits their expression through attenuating cAMP-PKA signaling. Thus, steroid production was suppressed. Since testes are essential for male reproduction and recent studies show that Kiss1 and Kiss1r are expressed in testes. To investigate their function in testes, primary mice Leydig cell was used in this study. Our results showed that Kiss1 did not affect testosterone production in primary Leydig cells, but suggest that expression pattern of KISS1 follows the stages of testicular development. Future studies are need to determine if kisspeptin regulates testicular development during puberty. In general, steroidogenesis is important to physiological regulation, this report demonstrate that some phytochemicals can effect steroids production directly, these results provide new direction on new food additives development and new drog discovery.
Subjects
Steroidogenesis
Phytochemicals
Testosterone
Glucocorticoids
Metabolic Syndrome
SDGs
Type
thesis
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