ABSTRACT
Hyperthecosis syndrome is a common endocrine system metabolic disorder in women of childbearing age. The main symptoms are elevated androgen levels, abnormal ovulation, and excessive oxidative stress. Currently, there is no effective treatment for hyperthecosis syndrome. α(1)-adrenergic receptor (ADRA1) is involved in the metabolic pathway of ovarian steroid hormone. This study studied the mechanism of the ADRA1 inhibitor terazosin in the LH-induced bovine theca cells in vitro. We found that terazosin regulates the expression of steroidogenic factor 1 (SF1) and downstream genes through the ERK1/2 pathway, reducing androgen content. Terazosin promotes the expression of HSP90 and reduces the activity of iNOS. In addition, Terazosin up-regulates the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream gene γ-GCS, which improves the ability of theca cells to resist oxidative stress. This study provides a reference for the treatment of human hyperthecosis syndrome.
Subject(s)
Steroid 17-alpha-Hydroxylase , Theca Cells , Animals , Cattle , Cells, Cultured , Female , Heat-Shock Proteins , Humans , Prazosin/analogs & derivatives , Steroidogenic Factor 1/geneticsABSTRACT
Endocrine disrupting chemicals (EDCs) are exogenous substances that interfere with the stability and regulation of the endocrine system of the body or its offspring. These substances are generally stable in chemical properties, not easy to be biodegraded, and can be enriched in organisms. In the past half century, EDCs have gradually entered the food chain, and these substances have been frequently found in maternal blood. Perinatal maternal hormone levels are unstable and vulnerable to EDCs. Some EDCs can affect embryonic development through the blood-fetal barrier and cause damage to the neuroendocrine system, liver function, and genital development. Some also effect cross-generational inheritance through epigenetic mechanisms. This article mainly elaborates the mechanism and detection methods of estrogenic endocrine disruptors, such as bisphenol A (BPA), organochlorine pesticides (OCPs), diethylstilbestrol (DES) and phthalates (PAEs), and their effects on placenta and fetal health in order to raise concerns about the proper use of products containing EDCs during pregnancy and provide a reference for human health.
Subject(s)
Endocrine Disruptors/adverse effects , Fetus/drug effects , Pesticides/adverse effects , Placenta/drug effects , Animals , Benzhydryl Compounds/adverse effects , Benzhydryl Compounds/blood , Body Fluids/chemistry , Diethylstilbestrol/adverse effects , Diethylstilbestrol/blood , Endocrine Disruptors/administration & dosage , Endocrine Disruptors/blood , Endocrine Disruptors/metabolism , Female , Humans , Hydrocarbons, Chlorinated/adverse effects , Hydrocarbons, Chlorinated/blood , Neurosecretory Systems/drug effects , Pesticides/blood , Pesticides/metabolism , Phenols/adverse effects , Phenols/blood , Phthalic Acids/adverse effects , Phthalic Acids/blood , PregnancyABSTRACT
Estrogen receptors (ER) include ER alpha, ER beta and new membrane receptor G protein-coupled receptor 30 (GPR30). Estrogen receptors are key receptors to maintain ovarian granulosa cell differentiation, follicle and oocyte growth and development, and ovulation function. The abnormal functions of estrogen, its receptors, and estradiol synthesis-related enzymes are closely related to clinical reproductive endocrine diseases, such as polycystic ovary syndrome (PCOS) and endometriosis (EMS). At present, hormone therapy is the main treatment for ovarian-related diseases, and a stable hormone environment is established by regulating ovarian function. In recent years, some estrogen-related drugs have made great progress, such as clomiphene, which is a nonsteroidal antiestrogen drug in clinical application. This article elaborates on the regulatory role of estrogen and its nuclear receptors and membrane receptors in oocyte development, especially female reproductive diseases related to the abnormal expression of estrogen and its receptors. We also highlighted the latest advances of treatment strategy for these diseases and the application of related targeted small molecule drugs in clinical research and treatment, so as to provide reference for the treatment of female reproductive diseases.