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Nutrients Oct 2022Background: Chronic kidney disease (CKD) is associated with an accelerated risk of cardiovascular mortality. Hormonal and metabolic disorders in CKD may constitute novel...
Background: Chronic kidney disease (CKD) is associated with an accelerated risk of cardiovascular mortality. Hormonal and metabolic disorders in CKD may constitute novel risk factors. Our objective was to characterize and evaluate prognostic implications of circulating sex steroids and selected nutritional parameters in patients at different stages of CKD. Methods: Studied groups were composed of 78 men: 31 on hemodialysis (HD), 17 on peritoneal dialysis (PD), 30 with CKD stage G3-G4. Total testosterone (TT), dehydroepiandrosterone sulphate (DHEA-S), androstenedione, luteinizing hormone (LH), prolactin (PRL), and biochemical parameters were measured; Free testosterone (FT) was calculated. Results: The lowest TT and FT were observed in HD, the highest- in CKD (p = 0.006 for TT, p = 0.005 for FT). TT positively correlated with total cholesterol in HD (p = 0.012), FT negatively correlated with BMI in CKD (p = 0.023). During the 12 months, 9 patients died (5 in the HD, 4 in the PD group). The deceased group had significantly lower concentrations of albumin (p = 0.006) and prealbumin (p = 0.001), and a significantly higher concentration of androstenedione (p = 0.019) than the surviving group. In the group of men on dialysis, a serum TT concentration <2.55 ng/mL (Q1-first quartile) was associated with a 3.7-fold higher risk of death, although statistical significance was not achieved (p = 0.198). After analysis of the ROC curves, the FT level was the best prognostic marker in HD (AUC = 0.788; 95% CI: 0.581−0.996; p = 0.006) Conclusions: Total and free testosterone levels were lower in the HD group than in the CKD group. The nutritional status undoubtedly affects the survival of dialysis patients but also the concentrations of testosterone significantly contributes to further worsening the prognosis.
Topics: Humans; Male; Renal Dialysis; Androstenedione; Peritoneal Dialysis; Testosterone; Renal Insufficiency, Chronic
PubMed: 36364724
DOI: 10.3390/nu14214461 -
Physiological Research Nov 2018The androgens dehydroepiandrosterone sulfate, dehydro-epiandrosterone, androstenedione and testosterone are routinely assessed in women, and circulating levels of these... (Review)
Review
The androgens dehydroepiandrosterone sulfate, dehydro-epiandrosterone, androstenedione and testosterone are routinely assessed in women, and circulating levels of these androgens reflect their production. These androgens are measured in most laboratories using various immuno-analytical methods. Recently, however, androgen assays have begun to be performed using gas or liquid chromatography combined with mass spectrometry. To better understand the difficulties and issues of androgen laboratory diagnostics, it is important to assess each of the methods used, how and why they were introduced into practice, and their advantages, limits, historic milestones and current status. It is also necessary to understand how reference ranges are determined and specifics arising from the physiology of individual androgens. Here we present a summary and discussion of these issues.
Topics: Androgens; Androstenedione; Biomarkers; Chromatography, Liquid; Dehydroepiandrosterone; Endocrine System Diseases; Female; Humans; Mass Spectrometry; Reference Values; Testosterone
PubMed: 30484665
DOI: 10.33549/physiolres.933964 -
Scientific Reports Feb 2020The blubber steroid hormone profiles of 52 female humpback whales migrating along the east coast of Australia were investigated for seasonal endocrine changes associated...
The blubber steroid hormone profiles of 52 female humpback whales migrating along the east coast of Australia were investigated for seasonal endocrine changes associated with reproduction. Individuals were randomly sampled during two stages of the annual migration: before reaching the breeding grounds (northward migration; June/July), and after departing from the breeding grounds (southward migration; September/October). Assignment of reproductive status of the sampled individuals was based on season, single-hormone ranks and multi-variate analysis of the hormonal profiles. High concentrations of progesterone (>19 ng/g, wet weight), recognised as an indicator of pregnancy in this species, were only detected in one sample. However, the androgens, testosterone and androstenedione were measured in unusually high concentrations (1.6-12 and 7.8-40 ng/g wet weight, respectively) in 36% of the females approaching the breeding grounds. The absence of a strong accompanying progesterone signal in these animals raises the possibility of progesterone withdrawal prior to parturition. As seen with other cetacean species, testosterone and androstenedione could be markers of near-term pregnancy in humpback whales. Confirmation of these androgens as alternate biomarkers of near-term pregnancy would carry implications for improved monitoring of the annual fecundity of humpback whales via non-lethal and minimally invasive methods.
Topics: Androstenedione; Animals; Biomarkers; Female; Humpback Whale; Pregnancy; Pregnancy Tests; Progesterone; Seasons; Subcutaneous Fat; Testosterone
PubMed: 32075989
DOI: 10.1038/s41598-020-58933-4 -
European Journal of Endocrinology Dec 2022Differentiation of an adrenal from an ovarian source of hyperandrogenemia can be challenging. Recent studies have highlighted the importance of 11-oxygenated C19...
OBJECTIVE
Differentiation of an adrenal from an ovarian source of hyperandrogenemia can be challenging. Recent studies have highlighted the importance of 11-oxygenated C19 steroids to the androgen pool in humans. The aim of this study was to confirm the origin of 11-oxygenated androgens in females and to explore their potential use in the diagnostics of hyperandrogenic disorders.
METHODS
We measured testosterone and its precursors (dehydroepiandrosterone-sulfate and androstenedione) and 11-oxygenated androgens (11β-hydroxyandrostenedione (11-OHA4) and 11-ketotestosterone (11-KT)) in the periphery, adrenal and ovarian veins in four different cases of hyperandrogenism in females (polycystic ovary syndrome (PCOS), primary bilateral macronodular adrenal hyperplasia, Sertoli-Leydig cell tumor and ovarian steroid cell tumor).
RESULTS
Two patients demonstrate excessive testosterone secretion in neoplastic ovarian tumors which was not paralleled by a significant secretion of 11-oxygenated androgens as determined by adrenal and ovarian vein sampling. In androgen-secreting bilateral adrenal macronodular hyperplasia, steroid profiles were characterized by elevated 11-KT and 11-OHA4 concentrations in adrenal veins and the periphery. In the patient with PCOS, peripheral 11-KT concentrations were slightly elevated in comparison to the other patients, but the 11-KT and 11-OHA4 concentrations were comparable in ovarian veins and in the periphery.
CONCLUSION
This study confirms that 11-OHA4 and 11-KT are not biosynthesized by the ovary. We propose that the testosterone/11-KT ratio as well as 11-OHA4 could help identify predominant adrenal androgen excess and distinguish neoplastic and non-neoplastic ovarian androgen source.
SIGNIFICANCE STATEMENT
This study confirms that 11β-hydroxyandrostenedione (11-OHA4) and 11-ketotestosterone (11-KT) are not biosynthesized by the human ovary. We propose that the testosterone/11-KT ratio as well as 11-OHA4 could help to identify predominant adrenal androgen excess and distinguish neoplastic and non-neoplastic ovarian androgen source.
Topics: Female; Humans; Hyperandrogenism; Androgens; Polycystic Ovary Syndrome; Hyperplasia; Androstenedione; Testosterone; Ovarian Neoplasms; Steroids
PubMed: 36239921
DOI: 10.1530/EJE-22-0518 -
PloS One 2023Steroids play a crucial role in modulating brain and behavior. While traditionally it is thought that the brain is a target of sex steroids produced in endocrine glands...
Steroids play a crucial role in modulating brain and behavior. While traditionally it is thought that the brain is a target of sex steroids produced in endocrine glands (e.g. gonads), the brain itself produces steroids, known as neurosteroids. Neurosteroids can be produced in regions involved in the regulation of social behaviors and may act locally to regulate social behaviors, such as reproduction and aggression. Our model species, the weakly electric fish Gymnotus omarorum, displays non-breeding aggression in both sexes. This is a valuable natural behavior to understand neuroendocrine mechanisms that differ from those underlying breeding aggression. In the non-breeding season, circulating sex steroid levels are low, which facilitates the study of neurosteroids. Here, for the first time in a teleost fish, we used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to quantify a panel of 8 steroids in both plasma and brain to characterize steroid profiles in wild non-breeding adult males and females. We show that: 1) systemic steroid levels in the non-breeding season are similar in both sexes, although only males have detectable circulating 11-ketotestosterone, 2) brain steroid levels are sexually dimorphic, as females display higher levels of androstenedione, testosterone and estrone, and only males had detectable 11-ketotestosterone, 3) systemic androgens such as androstenedione and testosterone in the non-breeding season are potential precursors for neuroestrogen synthesis, and 4) estrogens, which play a key role in non-breeding aggression, are detectable in the brain (but not the plasma) in both sexes. These data are consistent with previous studies of G. omarorum that show non-breeding aggression is dependent on estrogen signaling, as has also been shown in bird and mammal models. Overall, our results provide a foundation for understanding the role of neurosteroids, the interplay between central and peripheral steroids and potential sex differences in the regulation of social behaviors.
Topics: Animals; Female; Male; Electric Fish; Androstenedione; Neurosteroids; Chromatography, Liquid; Tandem Mass Spectrometry; Aggression; Gonadal Steroid Hormones; Testosterone; Steroids; Estrogens; Brain; Seasons; Mammals
PubMed: 37816021
DOI: 10.1371/journal.pone.0289461 -
Annales de Biologie Clinique Aug 2016Androstenedione is an androgen hormone and a precursor for testosterone and estrone synthesis. It is produced in both gonadal (testes and ovaries) and extragonadal...
Androstenedione is an androgen hormone and a precursor for testosterone and estrone synthesis. It is produced in both gonadal (testes and ovaries) and extragonadal levels (peripheral conversion of dehydroepiandrosterone). This hormone is useful in the assessment of virilism and hirsutism in women. In this paper, after a brief physiological reminder, the author presents the preanalytical and analytical considerations and the clinical utility of this hormone.
Topics: Adult; Androstenedione; Blood Chemical Analysis; Child; Female; Hirsutism; Humans; Immunoassay; Male; Polycystic Ovary Syndrome; Research Design
PubMed: 27492704
DOI: 10.1684/abc.2016.1171 -
Fertility and Sterility Sep 1982
Review
Topics: Androstenedione; Animals; Clomiphene; Corpus Luteum; Estradiol; Female; Follicle Stimulating Hormone; Humans; Inhibins; Menstruation; Ovarian Follicle; Pituitary Gland; Progesterone; Time Factors
PubMed: 6811331
DOI: No ID Found -
International Journal of Molecular... Jan 2021The peripheral zone (PZ) and transition zone (TZ) represent about 70% of the human prostate gland with each zone having differential ability to develop prostate cancer....
The peripheral zone (PZ) and transition zone (TZ) represent about 70% of the human prostate gland with each zone having differential ability to develop prostate cancer. Androgens and their receptor are the primary driving cause of prostate cancer growth and eventually castration-resistant prostate cancer (CRPC). De novo steroidogenesis has been identified as a key mechanism that develops during CRPC. Currently, there is very limited information available on human prostate tissue steroidogenesis. The purpose of the present study was to investigate steroid metabolism in human prostate cancer tissues with comparison between PZ and TZ. Human prostate cancer tumors were procured from the patients who underwent radical prostatectomy without any neoadjuvant therapy. Human prostate homogenates were used to quantify steroid levels intrinsically present in the tissues as well as formed after incubation with 2 µg/mL of 17-hydroxypregnenolone (17-OH-pregnenolone) or progesterone. A Waters Acquity ultraperformance liquid chromatography coupled to a Quattro Premier XE tandem quadrupole mass spectrometer using a C column was used to measure thirteen steroids from the classical and backdoor steroidogenesis pathways. The intrinsic prostate tissue steroid levels were similar between PZ and TZ with dehydroepiandrosterone (DHEA), dihydrotestosterone (DHT), pregnenolone and 17-OH-pregnenolone levels higher than the other steroids measured. Interestingly, 5-pregnan-3,20-dione, 5-pregnan-3-ol-20-one, and 5-pregnan-17-ol-3,20-dione formation was significantly higher in both the zones of prostate tissues, whereas, androstenedione, testosterone, DHT, and progesterone levels were significantly lower after 60 min incubation compared to the 0 min control incubations. The incubations with progesterone had a similar outcome with 5-pregnan-3,20-dione and 5-pregnan-3-ol-20-one levels were elevated and the levels of DHT were lower in both PZ and TZ tissues. The net changes in steroid formation after the incubation were more observable with 17-OH-pregnenolone than with progesterone. In our knowledge, this is the first report of comprehensive analyses of intrinsic prostate tissue steroids and precursor-driven steroid metabolism using a sensitive liquid chromatography-mass spectrometry assay. In summary, the PZ and TZ of human prostate exhibited similar steroidogenic ability with distinction in the manner each zone utilizes the steroid precursors to divert the activity towards backdoor pathway through a complex matrix of steroidogenic mechanisms.
Topics: Androstenedione; Androsterone; Chromatography, High Pressure Liquid; Humans; Male; Mass Spectrometry; Progesterone; Prostate; Prostatic Neoplasms; Steroids; Testosterone
PubMed: 33418978
DOI: 10.3390/ijms22020487 -
Biochimica Et Biophysica Acta Jul 2002Breast cancer is the leading cause of death among women and the contribution of circulating oestrogens to the growth of some mammary tumours has been recognized.... (Review)
Review
Breast cancer is the leading cause of death among women and the contribution of circulating oestrogens to the growth of some mammary tumours has been recognized. Consequently, suppression of oestrogen action by inhibition of their biosynthesis at the androstenedione-oestrone aromatization step, by means of selective inhibitors of the enzyme aromatase, has become an effective therapeutic option for the treatment of hormone-dependent breast cancer. Exemestane (6-methylenandrosta-1,4-diene-3,17-dione) is a novel steroidal irreversible aromatase inhibitor recently approved and introduced into the global market under the name Aromasin. The design, laboratory and viable syntheses of exemestane, starting from a variety of steroidal precursors, are presented and discussed. Data from biochemical and pharmacological studies as well as the clinical impact of the compound are briefly reviewed. The drug is an orally active and well-tolerated hormonal therapy for postmenopausal patients with advanced breast cancer that has become refractory to standard current hormonal therapies.
Topics: Androstadienes; Androstenedione; Antineoplastic Agents; Aromatase Inhibitors; Breast Neoplasms; Enzyme Inhibitors; Estrogen Receptor Modulators; Estrogens; Female; Humans; Neoplasms, Hormone-Dependent
PubMed: 12084475
DOI: 10.1016/s0925-4439(02)00096-0 -
The Journal of Reproduction and... 2013Steroid hormones are produced by the porcine uterus. We hypothesized that the uterus in pigs possesses active 3β-hydroxysteroid dehydrogenase/Δ(5)-Δ(4) isomerase...
The activity and localization of 3β-hydroxysteroid dehydrogenase/Δ(5)-Δ(4) isomerase and release of androstenedione and progesterone by uterine tissues during early pregnancy and the estrous cycle in pigs.
Steroid hormones are produced by the porcine uterus. We hypothesized that the uterus in pigs possesses active 3β-hydroxysteroid dehydrogenase/Δ(5)-Δ(4) isomerase (3β-HSD) responsible for progesterone and androstenedione production, that uterine steroids may supplement the amount of steroid hormones produced by embryos and corpus luteum and that these steroids are necessary for maintenance of pregnancy. In this study, we examined 1) endometrial and myometrial expression of 3β-HSD mRNA, 2) uterine 3β-HSD protein activity and 3) in vitro production of A(4) and P(4) by uterine slices harvested from pigs on days 10 to 11, 12 to 13 and 15 to 16 of pregnancy and the estrous cycle. The expression of 3β-HSD and the presence and activity of 3β-HSD protein were different in the endometrium and the myometrium during the examined periods of pregnancy and the estrous cycle. Production of A(4) by the endometrium and myometrium was highest on days 12 to 13 of pregnancy and the estrous cycle. Endometrial secretion of P(4) did not differ in the course of early pregnancy and on the respective days of the estrous cycle. The gravid myometrium was the highest source of P(4) in pregnant pigs on days 12 to 13. The release of P(4) by the cyclic myometrium rose during the examined days of the estrous cycle. The steroidogenic activity of the uterus, as described in this study, may support early pregnancy or the luteal phase of the estrous cycle in pigs.
Topics: 17-Hydroxysteroid Dehydrogenases; Androstenedione; Animals; Endometrium; Estrous Cycle; Female; Gene Expression Regulation, Developmental; Gene Expression Regulation, Enzymologic; Myometrium; Pregnancy; Pregnancy, Animal; Progesterone; RNA, Messenger; Swine; Time Factors; Uterus
PubMed: 23095516
DOI: 10.1262/jrd.2012-099