adrenosterone and 11-hydroxytestosterone

Patients with 21-hydroxylase deficiency (21OHD) have long-term complications, resulting from poor disease control and/or glucocorticoid overtreatment. Lack of optimal biomarkers has made it challenging to tailor therapy and predict long-term outcomes.. To identify biomarkers of disease control and long-term complications in 21OHD.. Cross-sectional study of 114 patients (70 males), ages 2 to 67 years (median, 15 years), seen in a tertiary referral center.. We correlated a mass-spectrometry panel of 23 steroids, obtained before first morning medication, with bone age advancement (children), adrenal volume (adults), testicular adrenal rest tumors (TART), hirsutism, menstrual disorders, and pituitary hormones.. Total adrenal volume correlated positively with 18 steroids, most prominently 21-deoxycortisol and four 11-oxygenated-C19 (11oxC19) steroids: 11β-hydroxyandrostenedione (11OHA4), 11-ketoandrostenedione (11ketoA4), 11β-hydroxytestosterone (11OHT), and 11-ketotestosterone (11ketoT) (r ≈ 0.7, P < 0.0001). Nine steroids were significantly higher (P ≤ 0.01) in males with TART compared with those without TART, including 11OHA4 (6.8-fold), 11OHT (4.9-fold), 11ketoT (3.6-fold), 11ketoA4 (3.3-fold), and pregnenolone sulfate (PregS; 4.8-fold). PregS (28.5-fold) and 17-hydroxypregnenolone sulfate (19-fold) levels were higher (P < 0.01) in postpubertal females with menstrual disorders. In males, testosterone levels correlated positively with all 11oxC19 steroids in Tanner stages 1 and 2 (r ≈ 0.7; P < 0.001) but negatively in Tanner stage 5 (r = -0.3 and P < 0.05 for 11ketoA4 and 11ketoT). In females, testosterone level correlated positively with all four 11oxC19 steroids across all Tanner stages (r ≈ 0.8; P < 0.0001).. 11oxC19 steroids and PregS might serve as clinically useful biomarkers of disease control and long-term complications in 21OHD.

Topics: 17-alpha-Hydroxypregnenolone; Adolescent; Adrenal Glands; Adrenal Hyperplasia, Congenital; Adrenal Rest Tumor; Adult; Age Determination by Skeleton; Aged; Androgens; Androstenedione; Androstenes; Child; Child, Preschool; Cortodoxone; Cross-Sectional Studies; Female; Hirsutism; Humans; Hydroxytestosterones; Male; Menstruation Disturbances; Middle Aged; Organ Size; Pregnenolone; Testicular Neoplasms; Testosterone; Young Adult

Androgen excess is a defining feature of polycystic ovary syndrome (PCOS), but the exact origin of hyperandrogenemia remains a matter of debate. Recent studies have highlighted the importance of the 11-oxygenated C19 steroid pathway to androgen metabolism in humans. In this study, we analyzed the contribution of 11-oxygenated androgens to androgen excess in women with PCOS.. One hundred fourteen women with PCOS and 49 healthy control subjects underwent measurement of serum androgens by liquid chromatography-tandem mass spectrometry. Twenty-four-hour urinary androgen excretion was analyzed by gas chromatography-mass spectrometry. Fasting plasma insulin and glucose were measured for homeostatic model assessment of insulin resistance. Baseline demographic data, including body mass index, were recorded.. As expected, serum concentrations of the classic androgens testosterone (P < 0.001), androstenedione (P < 0.001), and dehydroepiandrosterone (P < 0.01) were significantly increased in PCOS. Mirroring this, serum 11-oxygenated androgens 11β-hydroxyandrostenedione, 11-ketoandrostenedione, 11β-hydroxytestosterone, and 11-ketotestosterone were significantly higher in PCOS than in control subjects, as was the urinary 11-oxygenated androgen metabolite 11β-hydroxyandrosterone. The proportionate contribution of 11-oxygenated to total serum androgens was significantly higher in patients with PCOS compared with control subjects [53.0% (interquartile range, 48.7 to 60.3) vs 44.0% (interquartile range, 32.9 to 54.9); P < 0.0001]. Obese (n = 51) and nonobese (n = 63) patients with PCOS had significantly increased 11-oxygenated androgens. Serum 11β-hydroxyandrostenedione and 11-ketoandrostenedione correlated significantly with markers of insulin resistance.. We show that 11-oxygenated androgens represent the majority of circulating androgens in women with PCOS, with close correlation to markers of metabolic risk.

Topics: Adult; Androgens; Androstenedione; Androstenes; Blood Glucose; Case-Control Studies; Chromatography, Liquid; Dehydroepiandrosterone; Female; Gas Chromatography-Mass Spectrometry; Humans; Hydroxytestosterones; Hyperandrogenism; Insulin; Insulin Resistance; Obesity; Polycystic Ovary Syndrome; Tandem Mass Spectrometry; Testosterone; Young Adult

The seasonal changes in plasma levels of the androgens 11-ketotestosterone (OT), testosterone (T), 11 beta-hydroxytestosterone (OHT), 11-ketoandrostenedione (OA), and 11 beta-hydroxyandrostenedione (OHA) were measured in the male three-spined stickleback (Gasterosteus aculeatus L). OT was the dominant plasma androgen in the breeding season in summer and was the only androgen that peaked during this period. The levels of OT correlated closely with the development of male secondary sexual characters and reproductive behavior. T and OHT were low in all seasons, whereas OHA and OA displayed the highest levels in early winter. During the postbreeding period, the time of active spermatogenesis, all measured steroids were low. Castration resulted in an almost complete loss of plasma OT and reduced T, whereas OHT, OHA, and OA were not reliably influenced. Androstenedione implants in castrated fish increased plasma T and OA implants increased plasma OT, suggesting a nontesticular site of conversion.

Topics: Androgens; Androstenedione; Androstenes; Animals; Fishes; Hydroxytestosterones; Male; Orchiectomy; Reproduction; Seasons; Sexual Maturation; Testosterone

Male rainbow trout show high plasma androgen levels beginning with the period of full spermatogenesis until the end of spermiation. The difficulties in explaining the steroid levels in regard to the concomitant changes of the plasma GTH concentrations prompted investigations into whether the steroid demand may be met in part by extragonadal steroid metabolism. The results of in vitro experiments with liver tissue fit into the concept of an interrenal-liver-gonad axis of androgen production, since increased amounts of C-19 steroids were detected in the media after incubation of hepatic tissue with cortisol. 17 beta-Hydroxysteroid dehydrogenase and hydroxysteroid glucuronyltransferase activities were shown to be associated with blood cells of mature males. The fact that unidentified products from incubations with 17 beta-estradiol, testosterone, and 17 alpha-hydroxyprogesterone were also found suggests that other steroid metabolizing enzymes are also associated with blood cells. The possibility is discussed that, assuming the blood cell activities are relevant in vivo, a production of potent androgens or the formation of water soluble steroid derivatives could proceed in the blood (e.g., 11-ketoandrostenedione----11-ketotestosterone; testosterone----testosterone glucuronide), possibly affecting the organism's steroid balance.

Topics: 17-alpha-Hydroxyprogesterone; Androgens; Androstenedione; Androstenes; Animals; Blood Cells; Estradiol; Hydroxyprogesterones; Hydroxytestosterones; Liver; Male; Salmonidae; Testosterone; Trout

Testes of sexually mature Sarotherodon mossambicus were incubated at 15, 22, 30, and 40 degrees with (a) tritiated testosterone and (b) salmon pituitary extract. Formation of 11-keto- and 11 beta-hydroxytestosterone from the tritiated precursor showed little change in yield between 15 and 30 degrees but yields of glucuronides rose dramatically between 22 and 30 degrees and a significant rise was observed for formation of 5 beta-androstane-3 alpha, 17 beta-diol between 15 and 40 degrees. Yields of 3 alpha, 17 beta-dihydroxy-5 beta-androstan-11-one followed a pattern similar to that of 11-ketotestosterone. With endogenous precursors under the stimulation of salmon pituitary extract, yields of testosterone, 11-ketotestosterone, and 11 beta-hydroxytestosterone were maximal at 22 degrees after which they declined to very low levels at 40 degrees. Yields of testosterone and 11-ketotestosterone glucuronides while showing a peak at 22 degrees declined much more slowly at higher temperatures than did those of the free steroids. In the absence of pituitary stimulation, levels of all steroids were below the limits of detection. Plasma levels of testosterone (15.3 +/- 1.5 ng/ml), 11-ketotestosterone (5.3 +/- 2.7 ng/ml), 11 beta-hydroxytestosterone (5.5 +/- 2.6 ng/ml), and their glucuromides (1.5 +/- 0.5, 0.14 +/- 0.1, and 1.5 +/- 0.5 ng/ml, respectively) were measured in fish held at 25 degrees. A rapid conchromatographic method for the assay of the three free steroids is described and the results are shown to be comparable to those obtained after chromatography.

Topics: Androgens; Androstenes; Animals; Fishes; Glucuronates; Gonadotropins; Hydroxytestosterones; Male; Temperature; Testis; Testosterone