adrenosterone and 11-ketotestosterone

Whether serum androgen levels can identify women with "androgen insufficiency" or "androgen excess" is unresolved; thus, what constitutes "normal" remains uncertain. We sought to determine whether androgens, including 11-oxygenated C19 steroids, vary with age, menstrual cycle, or body mass index (BMI), during the reproductive years.. Cross-sectional study recruited from eastern Australian states.. A total of 588 women, aged 18 to 39 years, who were not pregnant, lactating, or using systemic hormone therapy, with regular menstrual cycles and no previous diagnosis of polycystic ovarian syndrome.. Sex steroids measured using liquid chromatography-tandem mass spectrometry.. Testosterone and androstenedione concentrations were significantly higher during the menstrual cycle mid- and luteal phases than in the early follicular phase, with median values across the cycle of 0.34 nmol/L (range, 0.04 to 1.01) and 1.97 nmol/L (range, 0.53 to 7.89), respectively. No cyclical variations were found in dehydroepiandrosterone (DHEA; 4.91 nmol/L; range, 0.08 to 23.51), 11-ketoandrostenedione (11KA; 7.99 nmol/L; range, 0.07 to 31.67), or 11-ketotestosterone (11KT; 1.27 nmol/L; range, 0.03 to 7.61). Overweight women had lower median testosterone (P < 0.05), DHEA (P < 0.05), and 11KA (P < 0.01) levels than normal-weight women. All C19 steroids were significantly lower (P < 0.01) in those aged 35 to 39 years than in those aged 18 to 25 years. The median 11KA/androstenedione (4.3:1) and 11KT/testosterone (3.9:1) ratios did not change with age, after adjustment for BMI and cycle stage.. We have demonstrated that 11KA and 11KT are stable across the menstrual cycle and make major quantitative contributions to the circulating androgen pool. All C19 androgens declined with age before menopause; hence, age-specific reference ranges are required for the interpretation of androgen levels in premenopausal women.

Topics: Adolescent; Adult; Androgens; Androstenes; Body Mass Index; Chromatography, Liquid; Cross-Sectional Studies; Female; Humans; Menstrual Cycle; Premenopause; Reproductive Physiological Phenomena; Testosterone; Young Adult

The 11β-hydroxysteroid dehydrogenase (11βHSD) types 1 and 2 are primarily associated with glucocorticoid inactivation and reactivation. Several adrenal C11-oxy C

Topics: 11-beta-Hydroxysteroid Dehydrogenase Type 1; 11-beta-Hydroxysteroid Dehydrogenase Type 2; Androstenes; Biosynthetic Pathways; Cell Line, Tumor; HEK293 Cells; Humans; Male; Progesterone; Prostatic Neoplasms; Protein Isoforms; Substrate Specificity; Testosterone

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 biological activity of androgens, important for male sexual differentiation and development, is mediated by the androgen receptor (AR) that binds to specific DNA recognition sites regulating the transcription of androgen target genes. We investigated androgen production by adult zebrafish testis tissue, and identified 11beta-hydroxyandrostenedione, 11-ketoandrostenedione (OA), and 11-ketotestosterone (11-KT) as main products, and hence potential ligands, for the zebrafish Ar. These androgens were then included in the pharmacological characterization of the zebrafish Ar. The zebrafish Ar responded well in terms of binding and transactivation to synthetic androgens as well as to testosterone and 11-KT, and reasonably well to OA and androstenedione. In situ hybridization analysis of zebrafish testis revealed that ar mRNA expression was detected in the subpopulation of Sertoli cells contacting early spermatogonia.

Topics: Androstenes; Animals; Binding, Competitive; Gene Expression; In Situ Hybridization; Ligands; Male; Receptors, Androgen; RNA, Messenger; Sertoli Cells; Testis; Testosterone; Transcriptional Activation; Zebrafish

The effect of 11-ketoandrostenedione (OA) on plasma concentrations of sexual steroids and spermatogenesis of Senegalese sole (Solea senegalensis) implanted with gonadotropin-releasing hormone agonist (GnRHa) was investigated. Males were treated with saline (control) or with GnRHa implants (50 mug kg(-1)) in the presence or absence of OA (2 or 7 mg kg(-1)) during twenty eight days. Treatment with GnRHa alone slightly stimulated spermatogenesis and milt production with respect to controls, and this was associated with a transient elevation of plasma 11-ketotestosterone (11-KT) at day seven and an increase of 5beta-reduced metabolite(s) of 17,20beta-dihydroxy-pregn-4-en-3-one (17,20betaP) at day twenty eight. However, treatment with GnRHa+OA increased plasma concentrations of 11-KT and free+sulphated 5beta-reduced metabolites of 17,20betaP at days seven, fourteen and twenty one. After twenty eight days, the testis of GnRHa+OA-treated fish showed a lower number of spermatogonia B and spermatocytes I, and a higher number of spermatids, than fish treated with GnRHa alone. In addition, the motility of spermatozoa produced by GnRHa+OA males was enhanced by 2-fold with respect to controls or GnRHa males. These results suggest that treatment of Senegalese sole with GnRHa+OA stimulates spermatogenesis resulting in more motile sperm. Such effects could be mediated by an increased synthesis of 11-KT and/or 17,20betaP in the testis but further studies will be required to elucidate the specific mechanism involved.

Topics: Androstenes; Animals; Flatfishes; Gonadotropin-Releasing Hormone; Hydroxyprogesterones; Implants, Experimental; Male; Sodium Chloride; Sperm Motility; Spermatogenesis; Spermatozoa; Testis; Testosterone

The immunocompetence handicap hypothesis (ICHH) provides a functional explanation for how sexual ornaments can provide honest signals of male quality. A key aspect of this hypothesis is that testosterone (T) has a bimodal effect: a higher T level enhances the expression of ornaments (increasing mating success and, ultimately, fitness); however, at the same time, it suppresses immune function. Tests of the latter assumption, which have focused mainly on aspects of adaptive immunity in birds, led to equivocal results. We performed a hormone-implant experiment in male three-spined sticklebacks (Gasterosteus aculeatus) to test the key assumptions of the ICHH in a fish, where the dominant circulating androgen is 11-ketotestosterone (11kT) rather than T. Males were implanted with 11-ketoandrostenedione, which is a natural precursor of 11kT. Each individual's circulating 11kT level, ornamentation, and immunocompetence were measured 2 weeks later. In addition, we quantified oxidative tissue damage because the ICHH has been hypothesized to work via oxidative stress. We found that the males' 11kT levels correlated positively with ornamentation but negatively with immunocompetence, in particular, measures of innate immunity. Moreover, there was a trend for fish with high 11kT levels to suffer more from oxidative stress. Thus, our data provide support for the ICHH.

Topics: Acrolein; Androstenes; Animals; Body Size; Immunity, Innate; Immunocompetence; Leukocyte Count; Leukocytes; Liver; Male; Nesting Behavior; Organ Size; Oxidative Stress; Phagocytosis; Protein Binding; Respiratory Burst; Sex Characteristics; Smegmamorpha; Spleen; Testis; Testosterone

This paper reviews a series of recent studies on the effect of adaptation to chronic stress on pubertal development in the common carp. In pre-pubertal male common carp adaptation to temperature stress caused a retardation of testicular development. Stress-induced delay of the first wave of spermatogenesis could be prevented by treatment with a cortisol antagonist, indicating that the stress effect is mediated by cortisol. Chronically elevated cortisol levels affected all parts of the brain-pituitary-gonad (BPG)-axis. In the hypothalamus lower levels of sGnRH were observed, in the pituitary the steady state levels of FSHbeta-m RNA were decreased, while the testicular production of especially the 11-oxygenated androgens 11-ketoandrostenedione (OA) and 11keto-testosterone (11KT) was strongly diminished. OA and 11KT have been shown to promote testicular development in fish. The LH-induced androgen synthesis in vitro was strongly inhibited by cortisol and its agonist dexamethasone. Although cortisol was shown also to interfere with the synthesis of the 11-oxygenated androgens in vivo, the lower androgen levels induced by cortisol were mainly due to the reduced testicular mass. Restoration of the plasma concentrations of these androgens by implantation could not prevent the cortisol-induced retardation of testicular growth and the first wave of spermatogenesis. Therefore, it is suggested that cortisol acts directly on Sertoli cells and/or on germ cells, which is supported by the demonstration of GRs on germ cells. We have little indication that the cortisol-induced retardation of testicular development is mediated by a decreased secretion of LH, but a crucial role for FSH can not be excluded.

Topics: Adaptation, Physiological; Androstenes; Animals; Carps; Dexamethasone; Follicle Stimulating Hormone, beta Subunit; Glucocorticoids; Gonadotropin-Releasing Hormone; Hydrocortisone; Male; Sexual Maturation; Spermatogenesis; Temperature; Testis; Testosterone

Previous studies in the placental viviparous bonnethead shark, Sphyrna tiburo, have correlated 17 beta-estradiol, progesterone, testosterone, and dihydrotestosterone with reproductive events in both males and females. However, several key reproductive events, including implantation, maintenance of pregnancy, and parturition, did not correlate with these four steroid hormones. Therefore, the present study investigated three steroid hormones, 11-ketotestosterone, 11-ketoandrostenedione, and dihydroprogesterone, which have demonstrably important roles in the reproductive cycles of teleosts. It was hypothesized that one or more of these three hormones would correlate with specific reproductive events in S. tiburo. Concurrently, developmental (growth and/or maturation) analyses of these three steroids plus 17 beta-estradiol, progesterone, testosterone, and dihydrotestosterone were investigated in juvenile bonnethead sharks. Serum dihydroprogesterone concentrations were highest in mature females and 11-ketotestosterone concentrations were highest in mature males. In mature females, 11-ketoandrostenedione levels were elevated from the time of mating, through six months of sperm storage and another four months of gestation. At parturition concentrations became significantly lower and remained lower until mating occurred again in another two to three months. Serum 11-ketotestosterone concentrations were the highest at implantation though not significant. In mature males, significantly elevated serum levels of dihydroprogesterone occurred in April and May, near the start of annual testicular development. During growth in males, testosterone and dihydrotestosterone increased progressively and in females, testosterone increased progressively. At maturity in males, significant increases occurred in testosterone and 11-ketotestosterone concentrations while, in females, dihydroprogesterone, 11-ketotestosterone, 17 beta-estradiol, progesterone, testosterone, and dihydrotestosterone concentrations increased. This study shows that although testosterone may be the primary androgen in the bonnethead shark, other derived androgens may have important functions in growth, maturation, and reproduction. J. Exp. Zool. 284:595-603, 1999.

Topics: 20-alpha-Dihydroprogesterone; Androstenes; Animals; Chromatography, High Pressure Liquid; Copulation; Dihydrotestosterone; Estradiol; Female; Male; Pregnancy; Pregnancy, Animal; Progesterone; Radioimmunoassay; Sex Characteristics; Sexual Maturation; Sharks; Testosterone

Despite the existence of several protocols, problems appear to persist in the small scale chemical synthesis of radiolabeled 11-ketotestosterone from cortisol. We investigated the possibilities of using the mild oxidant pyridinium dichromate for the oxidative cleavage of the dihydroxyacetone side chain of cortisol and 17 beta-hydroxysteroid dehydrogenase for the subsequent reduction of the resulting 17-keto group. Our protocol has resulted in consistently high yields of both the intermediate, adrenosterone (70-80%), and the product, 11-ketotestosterone (up to 60%). This, taken together with the convenience and relatively low cost of our method, recommends the protocol for its use for the synthesis of [3H]-11-ketotestosterone for endocrine studies.

Topics: Androstenes; Hydrocortisone; Hydroxysteroid Dehydrogenases; Oxidation-Reduction; Pyridinium Compounds; Testosterone; Tritium

Blood cells of male and female rainbow trout showed 17 beta-hydroxysteroid dehydrogenase (17 beta HSD) activity in vitro, reducing 11 beta-hydroxyandrostenedione and 11-ketoandrostenedione (OA) to 11 beta-hydroxytestosterone and 11-ketotestosterone (OT), respectively. Enzyme activity did not vary with gonadal development in either sex. The conversion of tritiated precursors was partly inhibited in the presence of steroid-free serum or radioinert steroid, but inhibition was less strong when radioinert androgens were added to steroid-free serum or when the serum contained endogenous steroids. Treatment of male trout with salmon gonadotropin in vivo and/or incubation with a pituitary extract of mature salmon in vitro did not affect OA conversion when blood cells were incubated in the absence of serum, whereas it was slightly but significantly higher when they were incubated in the presence of serum and pituitary extract. In addition to blood cells and steroidogenic tissues, spleen, intestine, brain, liver, excretory kidney, and skin tissue also produced an OA metabolite isopolar to OT in vitro, so that 17 beta HSD appears to be present in a variety of trout issues. With respect to the biological significance of extragonadal steroid metabolism in vivo, the ligand binding characteristics of circulating steroid binding proteins may be of primary relevance in regulating substrate availability.

Topics: 17-Hydroxysteroid Dehydrogenases; Androstenes; Animals; Female; Gonadotropins; Gonads; Male; Pituitary Gland; Seasons; Serum Albumin, Bovine; Testosterone; Tissue Distribution; Tissue Extracts; Trout

Blood cells from Baltic salmon, Salmo salar, three-spined stickleback, Gasterosteus aculeatus, eel pout, Zoarces viviparus, crucian carp, Carassius carassius, African catfish, Clarias gariepinus, and reedfish, Calamoichthys calabaricus, were incubated with tritiated 11 beta-hydroxyandrostenedione (OHA) or 11-ketoandrostenedione (OA). In all fish there was conversion of OA to 11-ketotestosterone (OT), indicating that 17 beta-hydroxysteroid dehydrogenase activity was present in the blood cells. On the other hand, OHA was not converted to 11 beta-hydroxytestosterone in any fish. The addition of serum to the incubates largely prevented the OA-OT conversion by salmon blood cells.

Topics: Androstenes; Animals; Biotransformation; Carps; Catfishes; Eels; Fishes; In Vitro Techniques; Salmon; Species Specificity; Testosterone

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