Dietary Coconut Oil Mitigates Hyperandrogenemia in Obese Female Pigs Due to Suppression of Androgen Steroidogenesis in the Adrenal Cortex and Theca Externa

Abstract Western-style diets (WSD) cause cardiometabolic disease and hyperandrogenemia in reproductive-age women. A promising alternative for improved fertility in obese women may derive from the nutraceutical, coconut oil. We hypothesized that dietary coconut oil included in a high fat diet would mitigate hyperandrogenemia due to obesity through depression of androgen steroidogenesis in theca externa and adrenal cortex. Seventeen sexually mature female Ossabaw pigs were divided into 3 diet groups: control (n=6; C; 2200 kcal/pig/day), WSD (n=5; WSD; 5000 kcal/pig/day), or high fat coconut oil diet (n=6; COC; 5000 kcal/pig/day). Ingredients in WSD and COC diets were the same except 9% of calories in WSD were from lard and 9% of calories in COC were from coconut oil. Pigs were fed for 9 cycles (~ 8 mos) and fasting blood was collected at cycle 0 (baseline), 7, and 9. After cycle 7, ovarian steroidogenesis was suppressed by oral progestogen for 18 days. On day 18 while ovarian steroidogenesis was still suppressed, an ACTH stimulation was performed. On day 19, progestogen was withdrawn and 7.5 µg/kg IM dexamethasone was given every 12 hours to suppress adrenal steroidogenesis. On day 20, 3000 IU/m2 human chorionic gonadotropin (hCG) was given IV. Pigs underwent a washout cycle post-stimulations and were euthanized when they had dominant ovarian follicles in cycle 9 for collection of follicular fluid (FF), theca externa, and adrenal cortex. FF was assessed for steroid hormones by LC-MS/MS. Adrenal cortex and theca cells were cultured as follows for 48 hours after which cells and media were collected: 1) theca: control, insulin (I; 100 ng/ml), LH (10 ng/ml), or LH+I (10 ng/ml + 100 ng/ml); 2) adrenal: control or 1 µM ACTH. WSD pigs had a protracted estrous cycle length and increased FF testosterone, dehydroepiandrosterone sulfate, androstenedione (A4), androstenediol, and allo-pregnanolone (Allo-Preg) compared to C pigs. Both serum and cell culture media A4 concentrations were higher in response to ACTH in WSD pigs. By 72 hours post-hCG, COC pigs had higher serum A4 than C or WSD pigs, but in vitro LH yielded decreased cell culture media A4 in both WSD and COC pigs. COC pigs had increased FF dihydrotestosterone and Allo-Preg compared to C pigs. These results suggest that dietary coconut oil administration in obese females may depress excessive androgen steroidogenesis by adrenal cortex but may only partially mitigate excessive androgen production by theca externa.