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

Abstract

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 b5 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.