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. 2025 Apr 22;110(5):1398-1403.
doi: 10.1210/clinem/dgae420.

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

Suranut Charoensri  1   2 , Juilee Rege  3 , Chaelin Lee  1 , Xhorlina Marko  4 , William Sherk  4 , Julieta Sholinyan  1 , William E Rainey  3 , Adina F Turcu  1
Affiliations

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

Suranut Charoensri et al. J Clin Endocrinol Metab. .

Abstract

Context: Androstenedione (A4) and testosterone (T) are produced by both the adrenal glands and the gonads. The adrenal enzyme 11β-hydroxylase (CYP11B1) executes the final step in cortisol synthesis; CYP11B1 also uses A4 and T as substrates, generating 11-hydroxyandrostenedione and 11-hydroxytestosterone, respectively. It has been suggested that CYP11B1 is expressed in the gonads, yet the circulating levels of all 11-oxygenated androgens (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-oxyandrogens in: (i) paired gonadal and peripheral vein blood samples obtained during gonadal venograms from 11 patients (7 women), median age 37 (range, 31-51 years); and (ii) 17 women, median age 57 (range, 41-81 years) before and after bilateral salpingo-oophorectomy (BSO). We also compared CYP11B1, 17α-hydroxylase/17,20-lyase (CYP17A1), and 3β-hydroxysteroid dehydrogenase type 2 (HSD3B2) mRNA expression in adrenal, ovarian, and testicular tissue.

Results: A4, T, estradiol, estrone, progesterone, 17α- and 16α-hydroxyprogesterone were all higher in gonadal veins vs periphery (P < .05 for all), while four 11-oxyandrogens were similar between matched gonadal and peripheral vein samples. Equally, in women who underwent BSO, A4 (median [interquartile range]: 59.7 [47.7-67.6] ng/dL vs 32.7 [27.4-47.8] ng/dL, P < .001) and T (24.1 [16.4-32.3] vs 15.5 [13.7-19.0] ng/dL, P < .001) declined, while 11-oxyandrogens remained stable. Gonadal tissue displayed negligible CYP11B1 mRNA.

Conclusion: Despite producing substantial amounts of A4 and T, human gonads are not relevant sources of 11-oxyandrogens.

Keywords: 11-ketotestosterone; 11-oxygenated androgen; adrenal; androgen; gonad; steroidogenesis.

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Figures

Figure 1.
Figure 1.
Adrenal steroid hormone synthesis. Abbreviations: 11-DOC, 11-deoxycorticosterone; 11KA4, 11-ketoandrostenedione; 11KT, 11-ketotestosterone; 11OHA4, 11-hydroxyandrostenedione; 11OHT, 11-hydroxytestosterone; 11oxC19, 11-oxygenated androgens, CYP11A1, cholesterol side-chain cleavage enzyme; CYP11B1, 11β-hydroxylase; CYP11B2, aldosterone synthase; CYP17A1, 17α-hydroxylase/17,20-lyase; CYP21A2, 21-hydroxylase; CYB5, cytochrome b5; DHEA, dehydroepiandrosterone; DHEA-S, dehydroepiandrosterone-sulfate; HSD11B2, 11β-hydroxysteroid dehydrogenase type 2; HSD17B5, 17β-hydroxysteroid dehydrogenase type 5; HSD3B2, 3β-hydroxysteroid dehydrogenase type 2; SULT2A1, sulfotransferase family 2A member 1.
Figure 2.
Figure 2.
Comparison of 11-oxygenated androgen concentrations between paired gonadal veins and peripheral circulation in 7 women (continuous lines) and 4 men (dotted lines). Abbreviations: 11KA4, 11-ketoandrostenedione; 11KT, 11-ketotestosterone; 11OHA4, 11-hydroxyandrostenedione; 11OHT, 11-hydroxytestosterone; A4, androstenedione; T, testosterone.
Figure 3.
Figure 3.
Steroid concentrations before and after bilateral salpingo-oophorectomy (BSO) in 17 women. Abbreviations: 11KA4, 11-ketoandrostenedione; 11KT, 11-ketotestosterone; 11OHA4, 11-hydroxyandrostenedione; 11OHT, 11-hydroxytestosterone; A4, androstenedione; T, testosterone.
Figure 4.
Figure 4.
Real-time analyses of HSD3B2, CYP17A1, and CYP11B1 transcript levels in gonads and adrenal gland. Adrenals, n = 8; Testes, n = 6, Ovarian follicles, n = 6; Corpus luteum, n = 6. #P < .005, testes vs adrenal; @P < .005, ovarian follicle vs adrenal; **P < .005, Corpus luteum vs adrenal; *P < .05, Corpus luteum vs adrenal.
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