PSAT073 The Human Gonads Do Not Contribute to the Circulating Pool of 11-Oxygenated Androgens

BACKGROUND: Androstenedione (A4) and testosterone (T) are produced by both the adrenal glands and the gonads. The adrenal enzyme steroid 11β-hydroxylase (CYP11B1) executes the last step in cortisol synthesis; CYP11B1 also uses A4 and T as substrates, generating 11-hydroxyadrostenedione (11OHA4) and 11-hydroxytestosterone (11OHT), respectively. 11OHA4 and 11OHT are further metabolized, primarily in periphery, to 11-ketoandrostenedione and 11-ketotestosterone. It has been suggested that CYP11B1 is expressed in the gonads, yet the circulating levels of all 11-oxygenated C19 steroids (11-oxyandrogens) are similar in males and females of reproductive ages, despite enormous differences in T. OBJECTIVE: To assess the gonadal contribution to the circulating pool of 11-oxyandrogens. METHODS: We used liquid chromatography-tandem mass spectrometry to measure 13 steroids, including traditional and 11-oxy-androgens in: (I) paired peripheral and gonadal vein serum samples from 11 patients (7 women), median age 37 years (range 31-51); and (II) 17 women, median age 57 years (range 41-81) before and after bilateral salpingo-oophorectomy (BSO). We also performed CYP11B1, 17α-hydroxylase/17,20-lyase, and cytochrome b(5) immunohistochemistry in formalin-fixed paraffin-embedded ovaries and testes (10 each). RESULTS: A4, T, estradiol, estrone, progesterone, 17α- and 16α-hydroxyprogesterone were all higher in gonadal veins than in periphery (p<0.001 for all), while all 4 11-oxyandrogens were similar between matched peripheral and gonadal vein samples. Similarly, in women who underwent BSO, A4 (median [interquartile range]: 33 [24.5-49] ng/dL vs. 60 [47.5-71] ng/dL, p=0.0008) and T (15 [12.5-20] vs. 24 [15.5-33.5], p=0.0005) were lower after vs. before surgery, while the four 11-oxyandrogens were not significantly different. Immunohistochemistry staining for CYP11B1 was negative in both ovarian and testicular tissue. CONCLUSION: Our results indicate that despite producing substantial amounts of both A4 and T, the human gonads are not important sources of 11-oxyandrogens. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.