Chemical and biological characterization of a steroidogenic protein from Dioscorea opposita Thunb

Menopause is the period during which the level of estrogen secreted by the ovaries gradually declines and patients of menopausal syndrome may experience osteoporosis, cognitive decline, hot flush, mood disorder, night sweat, depression, nervous tension and insomnia. The report published by the World Health Organization in 1990 stated that the total population of postmenopausal women in the world was 476 million. By 2030, the predicted population will reach 1200 million. The current way to relieve menopausal syndrome is hormone replacement therapy (HRT) which restores the endogenous estrogen level by administration of supplementary exogenous estrogen or estrogen plus progestin. However, various studies showed that HRT might increase the incidence of breast cancer and ovarian cancer. There is a potential risk of using HRT for menopausal syndrome. The novel protein DO isolated in this study could be a potential alternative of HRT for the treatment of menopausal syndrome. DO isolated from Chinese yam Dioscorea opposite Thunb. had adistinctive N-terminal sequence Gly-Ile-Gly-Lys-Ile-Thr-Thr- Tyr-Trp-Gly-Gln-Tyr-Ser-Asp-Glu-Pro-Ser-Leu-Thr-Glu-Ala, indicating that DO might be a novel protein.DO was an acid stable and thermal stable protein. As determined by electro-chemiluminescence immunoassay (ECLIA) detection, DO could stimulate estradiol biosynthesis in rat granulosa cells in vitro as well as inducing both estradiol and progesterone secretion in female aging Sprague Darley (SD)-rat model in vivo. From the results of real-time PCR and Western blot, the possible mechanism might be through up-regulating the expression of ovarian follicle stimulating hormone receptor(FSHR)and aromatase. DO also exerted a beneficial effect on the cognitive function through elevating the translational level of brain derived neurotrophic factor (BDNF)and TrkB gp 145 receptor in the prefrontal cortex of female aging SD-rat model. Though further pharmacological studies are required, the results in this study suggested that DO could be a safer potential alternative for HRT in the treatment of menopausal syndrome with beneficial effects on hormone levels and cognitive function.published_or_final_versionChinese MedicineMasterMaster of Philosoph