Search Results (16)

Background: Male patients with congenital hypogonadotropic hypogonadism (CHH) have impaired postnatal activation of the hypothalamic–pituitary–gonadal axis that occurs during mini-puberty. The aim of this study was to report our experience using gonadotropin replacement therapy for mini-puberty in male infants with CHH and to establish treatment recommendations. Methods: The patients included in this retrospective case series (n = 9) were diagnosed in the postnatal period due to micropenis, with two being accompanied by cryptorchidism and four with other associated hormonal deficits. All patients started treatment with gonadotropins early after diagnosis, between 2 weeks and 5 months of age, with a schedule of discontinuous injections with subcutaneous human chorionic gonadotropin (62.5–500 IU) two times per week and recombinant follicle-stimulating hormone-alpha (37.5–75 IU) three times per week. Results: The data from our study show an early response, ranging from almost undetectable levels of testosterone at diagnosis to elevated levels after starting treatment, as well as a positive clinical response with increases in testicular volume and penis size in all cases without requiring complementary treatment with testosterone esters and without adverse effects. Conclusions: Our results show that gonadotropin replacement therapy is a well-tolerated and effective treatment for testicular and penile problems in male patients with CHH. Full article

Androgen production primarily occurs in Leydig cells located in the interstitial compartment of the testis. In aging males, testosterone is crucial for maintaining muscle mass and strength, bone density, sexual function, metabolic health, energy levels, cognitive function, as well as overall well-being. As men age, testosterone production by Leydig cells of the testes begins to decline at a rate of approximately 1% per year starting from their 30s. This review highlights recent findings concerning the use of natural polyphenolics compounds, such as flavonoids, resveratrol, and phenolic acids, to enhance testosterone production, thereby preventing age-related degenerative conditions associated with testosterone insufficiency. Interestingly, most of the natural polyphenolic antioxidants having beneficial effects on testosterone production tend to enhance the expression of the steroidogenic acute regulatory protein (Star) gene in Leydig cells. The STAR protein facilitates the entry of the steroid precursor cholesterol inside mitochondria, a rate-limiting step for androgen biosynthesis. Natural polyphenolic compounds can also improve the activities of steroidogenic enzymes, hypothalamus-pituitary gland axis signaling, and testosterone bioavailability. Thus, many polyphenolic compounds such as luteolin, quercetin, resveratrol, ferulic acid phenethyl ester or gigantol may be promising in delaying the initiation of late-onset hypogonadism accompanying aging in males. Full article

Introduction: Doping and steroid use represent a serious threat to animal health and can even lead to their untimely and painful death. However, doping is an acute problem in today’s animal racing world, particularly in camel racing. Testosterone and its ten esters (benzoate, valerate, isocaproate, hexahydrobenzoate, decanoate, undecanoate, laurate, enanthate, cypionate, and caproate) are of utmost importance, because when they are administered to animals it is difficult to measure them efficiently. The levels of testosterone and its esters in camels and other animals are typically determined using urine and blood tests. The aim of this study was to develop and validate a liquid chromatographic–mass spectrometric (LC-MS/MS) method to determine testosterone esters in camel hair, and to apply the validated method to determine testosterone esters in collected samples. To our knowledge, this is the first report of such research. Results and Discussion: The levels of testosterone and its ten derivatives, along with the cortisol-D4 internal standard, were optimised for LC–MS/MS analysis; however, only testosterone along with its seven esters (namely benzoate, valerate, isocaproate, hexahydrobenzoate, decanoate, undecanoate and laurate) could be validated in camel hair. Only five testosterone esters could be determined in camel hair samples; the concentrations were obtained as 10.5–14.9 pg/mg for valerate (in three camels), 12.5–151.6 pg/mg for hexahydrobenzoate (in six camels), 4.8–32.1 pg/mg for laurate (in five camels), 5.1 pg/mg decanoate (in one camel), and 8.35–169 pg/mg for testosterone (in all 24 camels). Interestingly, the three racing camels displayed high concentrations of testosterone (59.2–169 pg/mg, all three camels), laurate (4.8–14.5 pg/mg, two camels), hexahydrobenzoate (116 pg/mg, one camel), decanoate (5.1 pg/mg, one camel), and valerate (11.7 pg/mg, one camel). Methods: Camel hair samples were collected from 21 non-racing dromedary camels along with three racing camels in Al Ain, UAE; these were decontaminated, pulverised, sonicated, and extracted prior to analysis. An LC–MS/MS method was employed to determine the levels of testosterone esters in the hair samples. Conclusions: This novel camel-hair test procedure is accurate, sensitive, rapid, and robust. The findings reported in this study could be significant to evaluate racing camels for suspected doping offenses. Further controlled testosterone supplementation studies are required to evaluate individual esters’ effects on camel health and diseases and on performance enhancement levels. This new hair test could promote further studies in doping control, toxicology, and pharmacology, as well as having other clinical applications relating to camel health, injury, and disease. Full article

The use of anabolic–androgenic steroids (AASs) as growth promoters in farm animals is banned in the European Union, representing both an illicit practice and a risk for consumer health. However, these compounds are still illegally administered, often in the form of synthetic esters. This work aimed to characterize significant coding RNA perturbations related to the illicit administration of testosterone and nandrolone esters in fattening pigs. A total of 27 clinically healthy 90-day-old pigs were randomly assigned to test and control groups. Nine animals were treated with testosterone esters (Sustanon^®) and other nine with nandrolone esters (Myodine^®). At the end of the trial, liver samples were collected and analyzed using RNAseq, allowing the identification of 491 differentially expressed genes (DEGs). The transcriptional signature was further characterized by a smaller sub-cluster of 143 DEGs, from which a selection of 16 genes was made. The qPCR analysis confirmed that the identified cluster could still give good discrimination between untreated gilt and barrows compared to the relative testosterone-treated counterparts. A conclusive field survey on 67 liver samples collected from pigs of different breeds and weight categories confirmed, in agreement with testosterone residue profiles, the specificity of selected transcriptional biomarkers, showing their potential applications for screening purposes when AAS treatment is suspected, allowing to focus further investigations of competent authorities and confirmatory analysis where needed. Full article

Nandrolone (Estr-4-en-17β-ol-3-one) is a derivative of testosterone and a naturally occurring anabolic–androgenic agent which belongs to the steroid group. Crystal structures of four short, medium and long esterified forms of nandrolone, including propionate, phenylpropionate, cypionate and undecanoate were determined using single-crystal X-ray diffraction. Crystal packing, supramolecular features and intermolecular interactions were described based on a quantitative and qualitative Hirshfeld surfaces analysis accompanied by evaluation of crystal energies and intermolecular interactions computation. Also, the solubility of the esters was investigated from a pharmaceutical perspective. Full article

Testosterone (17β-Hydroxyandrost-4-en-3-one) is the primary male anabolic-androgenic steroid. The crystal structures of two medium and two long esterified forms of testosterone, including enanthate, cypionate, decanoate and undecanoate, were determined by X-ray single crystal diffraction. The samples were also characterized by powder X-ray diffraction, FT-IR spectroscopy and thermal analysis (DTA, TG). Crystal packings and supramolecular features were described. The analysis of structural features was accomplished by computational methods in terms of the type of intermolecular interactions, crystal energies and Hirshfeld surfaces analysis. From a pharmaceutical point of view, the solubility of compounds was investigated. Full article

Understanding the regulation of the testicular endocrine function leading to testosterone production is a major objective as the alteration of endocrine function is associated with the development of many diseases such as infertility. In the last decades, it has been demonstrated that several endogenous molecules regulate the steroidogenic pathway. Among them, bile acids have recently emerged as local regulators of testicular physiology and particularly endocrine function. Bile acids act through the nuclear receptor FXRα (Farnesoid-X-receptor alpha; NR1H4) and the G-protein-coupled bile acid receptor (GPBAR-1; TGR5). While FXRα has been demonstrated to regulate testosterone synthesis within Leydig cells, no data are available regarding TGR5. Here, we investigated the potential role of TGR5 within Leydig cells using cell culture approaches combined with pharmacological exposure to the TGR5 agonist INT-777. The data show that activation of TGR5 results in a decrease in testosterone levels. TGR5 acts through the PKA pathway to regulate steroidogenesis. In addition, our data show that TGR5 activation leads to an increase in cholesterol ester levels. This suggests that altered lipid homeostasis may be a mechanism explaining the TGR5-induced decrease in testosterone levels. In conclusion, the present work highlights the impact of the TGR5 signaling pathway on testosterone production and reinforces the links between bile acid signaling pathways and the testicular endocrine function. The testicular bile acid pathways need to be further explored to increase our knowledge of pathologies associated with impaired testicular endocrine function, such as fertility disorders. Full article

Pollutant discharge causing the deterioration of the watershed environment has seriously threatened human health and ecosystem function. The importance of improving the risk warning system is becoming more and more prominent. Traditional chemical risk assessment methods focused on toxicity and the exposure of pollutants without considering the impact of persistent pollutants in different environmental media. In this study, a new approach was proposed to reflect multi-dimensional evaluation with a synthetic risk factor (SRF) of pollutants. The integrating parameters of SRF include toxicity endpoint values, environmental exposure level, persistent properties, and compartment features. Selected pesticides, perfluorinated compounds, organophosphate esters and endocrine disruptors were analyzed by the proposed and traditional methods. The results showed a higher risk outcome using SRF analysis for PFOS, imazalil, testosterone, androstenedione and bisphenol A, which were different from those obtained by the traditional method, which were consistent with existing risk management. The study demonstrated that the SRF method improved the risk assessment of various pollutants in different environmental media in a more robust fashion, and also provided a more accurate decision basis for ecological environment protection. Full article

Testosterone (17β-hydroxyandrost-4-en-3-one) is the primary naturally occurring anabolic–androgenic steroid. The crystal structures of three short esterified forms of testosterone, including propionate, phenylpropionate, and isocaproate ester, were determined via single-crystal X-ray diffraction. Furthermore, all the samples were investigated using powder X-ray diffraction, and their structural features were described and evaluated in terms of crystal energies and Hirshfeld surfaces. They were also compared with the base form of testosterone (without ester) and the acetate ester. Moreover, from a pharmaceutical perspective, their solubility was evaluated and correlated with the length of the ester. Full article

Androgens are an important and diverse group of steroid hormone molecular species. They play varied functional roles, such as the control of metabolic energy fate and partition, the maintenance of skeletal and body protein and integrity and the development of brain capabilities and behavioral setup (including those factors defining maleness). In addition, androgens are the precursors of estrogens, with which they share an extensive control of the reproductive mechanisms (in both sexes). In this review, the types of androgens, their functions and signaling are tabulated and described, including some less-known functions. The close interrelationship between corticosteroids and androgens is also analyzed, centered in the adrenal cortex, together with the main feedback control systems of the hypothalamic–hypophysis–gonads axis, and its modulation by the metabolic environment, sex, age and health. Testosterone (T) is singled out because of its high synthesis rate and turnover, but also because age-related hypogonadism is a key signal for the biologically planned early obsolescence of men, and the delayed onset of a faster rate of functional losses in women after menopause. The close collaboration of T with estradiol (E2) active in the maintenance of body metabolic systems is also presented Their parallel insufficiency has been directly related to the ravages of senescence and the metabolic syndrome constellation of disorders. The clinical use of T to correct hypoandrogenism helps maintain the functionality of core metabolism, limiting excess fat deposition, sarcopenia and cognoscitive frailty (part of these effects are due to the E2 generated from T). The effectiveness of using lipophilic T esters for T replacement treatments is analyzed in depth, and the main problems derived from their application are discussed. Full article

In hypertensive individuals, platelet morphology and function have been discovered to be altered, and this has been linked to the development of vascular disease, including erectile dysfunction (ED). The impact of nutritional supplementation with Cyperus esculentus (tiger nut, TN) and Tetracarpidium conophorum (walnut, WN) on androgen levels, ectonucleotidases, and adenosine deaminase (ADA) activities in platelets from L-NAME (Nω-nitro-L-arginine methyl ester hydrochloride) challenged rats were investigated. We hypothesized that these nuts may show a protective effect on platelets aggregation and possibly enhance the sex hormones, thereby reverting vasoconstriction. Wistar rats (male; 250–300 g; n = 10) were grouped into seven groups as follows: basal diet control group (I); basal diet/L-NAME/Viagra (5 mg/kg/day) as positive control group (II); ED-induced group (basal diet/L-NAME) (III); diet supplemented processed TN (20%)/L-NAME (IV); diet supplemented raw TN (20%)/L-NAME (V); diet supplemented processed WN (20%)/L-NAME (VI); and diet supplemented raw WN (20%)/L-NAME (VII). The rats were given their regular diet for 2 weeks prior to actually receiving L-NAME (40 mg/kg/day) for ten days to induce hypertension. Platelet androgen levels, ectonucleotidases, and ADA were all measured. L-NAME considerably lowers testosterone levels (54.5 ± 2.2; p < 0.05). Supplementing the TN and WN diets revealed improved testosterone levels as compared to the control (306.7 ± 5.7), but luteinizing hormone levels remained unchanged. Compared to control groups, the L-NAME-treated group showed a rise in ATP (127.5%) hydrolysis and ADA (116.7%) activity, and also a decrease in ADP (76%) and AMP (45%) hydrolysis. Both TN and WN supplemented diets resulted in substantial (p < 0.05) reversal effects. Enhanced testosterone levels and modulation of the purinergic system in platelets by TN and WN could be one of the mechanisms by which they aid in vasoconstriction control. Full article

Male hypogonadism is often treated by testosterone (T) replacement therapy such as oral administration of the ester prodrug, testosterone undecanoate (TU). However, the systemic exposure to T following oral TU is very low due to esterase-mediated metabolism, particularly in the small intestine. The aim of this work was to examine the esterase-inhibitory effect of natural fruit extract of strawberry (STW) on the intestinal degradation of TU as a potential approach to increasing the oral bioavailability of T. Herein, the hydrolysis of TU was assessed in fasted state simulated intestinal fluid with added esterase activity (FaSSIF/ES) and Caco-2 cell homogenates in the presence of STW extract. It is noteworthy that STW substantially inhibited the degradation of TU in FaSSIF/ES and Caco-2 cell homogenates at concentrations that could be achieved following oral consumption of less than one serving of STW fruit. This can significantly increase the fraction of unhydrolyzed TU in the intestinal lumen as well as in enterocytes. In addition, it was demonstrated that TU has high intestinal lymphatic transport potential as the association of TU with plasma-derived human chylomicrons was in the range of 84%. Therefore, oral co-administration of TU with STW could potentially increase the intestinal stability of TU and consequently the contribution of lymphatically delivered TU to the systemic exposure of T in vivo. Full article

The bioavailability of orally administered drugs could be impacted by intestinal and hepatic first-pass metabolism. Testosterone undecanoate (TU), an orally administered ester prodrug of testosterone, is significantly subjected to first-pass metabolism. However, the individual contribution of intestinal and hepatic first-pass metabolism is not well determined. Therefore, the aim of the current study was to predict the metabolic contribution of each site. The hydrolysis–time profiles of TU incubation in human liver microsomes and Caco-2 cell homogenate were used to predict hepatic and intestinal first-pass metabolism, respectively. The in vitro half-life (t_{1/2 inv}) for the hydrolysis of TU in microsomal mixtures was 28.31 ± 3.51 min. By applying the “well-stirred” model, the fraction of TU that could escape hepatic first-pass metabolism (F_H) was predicted as 0.915 ± 0.009. The incubation of TU in Caco-2 cell homogenate yielded t_{1/2 inv} of 109.28 ± 21.42 min, which was applied in a “Q gut” model to estimate the fraction of TU that would escape intestinal first-pass metabolism (F_G) as 0.114 ± 0.02. Accordingly, only 11% of the absorbed fraction of TU could escape intestinal metabolism, while 91% can pass through hepatic metabolism. Hence, compared to the liver, the intestinal wall is the main site where TU is significantly metabolised during first-pass effect. Full article

The use of anabolic steroid hormones as growth promoters in feed for farm animals has been banned in the European Union since 1988 on the basis of Council Directive 96/22/EC. However, there is still ongoing monitoring and reporting of positive findings of these banned substances in EU countries. The aim of this work was to investigate the efficacy and discriminatory ability of metabolic fingerprinting after the administration of 17β-testosterone esters to pigs. Plasma and urine samples were chromatographically separated on a Hypersil Gold C18 column. High resolution mass spectrometry metabolomic fingerprints were analysed on a hybrid mass spectrometer Q-Exactive. Three independent multivariate statistical methods, namely principal component analysis, clustre analysis, and orthogonal partial least squares discriminant analysis showed significant differences between the treated and control groups of pigs even 14 days after the administration of the hormonal drug. Plasma samples were also analysed by a conventional quantitative analysis using liquid chromatography with tandem mass spectrometry and a pharmacokinetic curve was constructed based on the results. In this case, no testosterone residue was detected 14 days after the administration. The results clearly showed that a metabolomics approach can be a useful and effective tool for the detection and monitoring of banned anabolic steroids used illegally in pig fattening. Full article

Great attention has been paid in recent years to the harmful effects of various chemicals that interfere with our natural hormone balance, collectively known as endocrine-disrupting chemicals (EDCs) or endocrine disruptors. The effects on the reproductive system of bisphenol A (BPA) and phthalates have received particular attention: while they have a short half-life, they are so widespread that human exposure can be considered as continuous. Evidence is often limited to the animal model, disregarding the likelihood of human exposure to a mixture of contaminants. Data from animal models show that maternal exposure probably has harmful effects on the male fetus, with an increased risk of urogenital developmental abnormalities. After birth, exposure is associated with changes in the hypothalamic-pituitary-testicular axis, hindering the development and function of the male genital pathways through the mediation of inflammatory mechanisms and oxidative stress. The epidemiological and clinical evidence, while generally confirming the association between reproductive abnormalities and some phthalate esters and BPA, is more contradictory, with wildly different findings. The aim of this review is therefore to provide an update of the potential mechanisms of the damage caused by BPA and phthalates to reproductive function and a review of the clinical evidence currently available in the literature. Full article