Hyperandrogenism induced Through a pulsatile release system induces proinflammatory Cytokines an evidence on the regulatory role of dht on Chronic inflammation in pcos subjects

Abstract

newlineBACKGROUND: The incidence of chronic inflammation in individuals with polycystic ovarian syndrome (PCOS) is a cause for concern. To understand this, it was planned to utilize a hyperandrogenised model system using dihydrotestosterone (DHT). DHT model system displayed enhanced circulatory cytokines, increased leukocyte intrusion to ovary liver and bone along with induction of oxidative stress and pro-inflammatory genes. These changes obtained could be attributed to the DHT levels. To strengthen the in vivo findings and to assess the impact of DHT on immune cell viability and cytokine gene expression, in vitro studies were planned using THP1 monocytes. In silico studies were performed to identify the possible targets for androgen induced immune signaling. newlineOBJECTIVES: Considering the role of hormonal imbalance in chronic inflammation, the present investigation is focused on delineating the effect of non-aromatizable androgen on the inflammatory cytokines in vivo using rat model system, in vitro using THP-1 monocytes and in silico using computational tools. newlineMATERIAL AND METHODS: Twelve female Wistar albino rats, 21 days old, were split into two groups (control and hyperandrogenised group), comprising 6 rats per each group. Control group rats were sham-operated and implanted with an empty osmotic pump filled with sterile vehicle. Hyperandrogenised group of rats were surgically implanted with a DHT-filled osmotic pump capable of releasing a total of 83and#956;g of DHT per day to mimic the hyperandrogenic state in women with PCOS. The DHT was administered to rats for a total of 90 days. The animals were monitored weekly to record the bodyweight. The estrous cycle phases of rats were monitored through the routine examination of vaginal smears for the presence of cornfield cells. The animals were euthanized after 90 days of post-implantation and their ovaries, liver, femur, and blood were collected for further analyses.