Dihydrotestosterone Levels Research Articles

Effects of testosterone on skin structure and factors related to androgen conversion and binding in Hetian sheep.

The effects of androgens on human skin mainly include the regulation of growth and differentiation of hair follicles and sebaceous glands. Androgens may have some physiological roles in sheep skin that are similar to those of humans, but further confirmation is needed. Therefore, Hetian sheep were chosen in this study as an animal model to explore the effects of testosterone on skin structure and factors related to androgen conversion and binding in Hetian sheep. The sheep were treated with different concentrations of testosterone for 42days. Skin tissue sections were prepared and then subjected to hematoxylin-eosin, Sacpic, Masson's trichrome, and Oil Red O staining to observe changes in skin morphology. Changes in the content of blood-related factors were also detected using ELISA kits. The skin tissue distribution of androgen receptor was explored by immunohistochemistry and immunofluorescence assays. The results showed that testosterone significantly increases the sebaceous gland area and stimulates the formation of new sebaceous glands. Further exploration revealed that testosterone promotes the proliferation of sebaceous gland juvenile cells. However, testosterone was found to have no significant effect on hair follicle density and hair follicle structure. Testosterone increased dihydrotestosterone levels but decreased 5α-reductase 1 and 5α-reductase 2 levels. The androgen receptors were distributed in the hair follicles, sebaceous glands, and some major skin appendages of Hetian sheep. This study suggests that androgens can be effective in regulating sebum production in sheep. This study will help advance research efforts to further explore the molecular and cellular mechanisms by which androgens modify sheep follicles and sebaceous glands.

Origanum majorana L. Extract Attenuated Benign Prostatic Hyperplasia in Rat Model: Effect on Oxidative Stress, Apoptosis, and Proliferation.

Benign prostatic hyperplasia (BPH) is a widespread androgenic illness influencing elderly men. It is distinguished by prostatic epithelial and stromal muscle cell proliferation. Inflammation, oxidative stress, and apoptosis have all been interrelated to the development of BPH. Marjoram (Origanum majorana L.) is a herb with reported antiproliferative, proapoptotic, and antioxidative properties, which have not yet been studied in relation to BPH. Consequently, in this work, an ethanolic extract of O. majorana was prepared in two doses (250 and 500 mg/kg/day) to be injected into castrated rats after induction of a testosterone-BPH model. Testosterone propionate (TP) was subcutaneously injected (0.5 mg/kg/day) for one week after castration to induce BPH. Forty adult Wistar male rats were randomly allocated into five groups: control, BPH model, high and low O. majorana doses (250, 500 mg/kg/day), and finasteride (FN) (0.8 mg/kg/day) as a positive control. Treatment was continued with drugs/normal saline for 28 days. Rat’s body and prostate were weighed, prostate index (PI) and % of prostate growth inhibition were calculated, serum dihydrotestosterone (DHT), prostatic content of superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (TAC), and malondialdehyde (MDA), DN damage, histopathological changes, immune expression of proliferating cell nuclear antigen (PCNA), caspase-3, α-SMA, and TGF-β1 were assessed. In addition, molecular quantitative PCR and ELISA analyses were performed to identify the expression of mRNAs and related proteins of both caspase-3 and TGF-β1 in prostate tissue from O. majorana-treated and untreated groups. Rats with BPH had significantly higher prostate weights and PI, higher DHT, DNA damage (8-hydroxyguanine, 8-OH-dG), and MDA levels with prominent PCNA, α-SMA, and TGF-β expression, but lower SOD, CAT, and TAC activity and caspase-3 expression. O. majorana (250 and 500 mg/kg/day)-treated groups revealed a decrease in prostate weights and PI, lower levels of DHT, suppressed oxidative stress, reduced tissue proliferation and fibrosis, and restored antioxidant and proapoptotic activity. Additionally, quantitative PCR and ELISA analysis showed that treatment with O. majorana significantly upregulated the expression of caspase-3 and downregulated the expression of TGF-β in prostate tissues of BPH rats. The data were confirmed by the immunohistological reactivity of these targeted markers in the prostate tissues. These effects were more significant with O. majorana 500 mg/mL/rat. In conclusion, the current study indicates the efficient use of O. majorana in the treatment of testosterone-induced BPH through its antiproliferative, proapoptotic, and antioxidative mechanisms.

Effect of virgin coconut oil, lauric acid and myristic acid on serum and prostatic markers of benign prostatic hyperplasia

Purpose: To investigate the effect of virgin coconut oil, lauric acid and myristic acid on serum and prostatic androgens in testosterone-induced prostatic hyperplasia.Methods: Benign prostatic hyperplasia (BPH) was induced in the animals by repeated subcutaneous injection of testosterone propionate (5 mg/kg) at the inguinal region once a day for 28 days. Thereafter, BPH was treated for 56 days by oral administration of virgin coconut oil, lauric acid and myristic acid. Following the treatment period, the rats were sacrificed and blood samples were collected through cardiac puncture for biochemical analysis.Results: Virgin coconut oil, lauric acid and myristic acid led to a significant reduction (p < 0.05) in serum prostatic acid phosphatase (PAcP), prostate specific antigen (PSA) and dihydrotestosterone (DHT) levels, and also in prostatic DHT level.Conclusion: This study provides evidence that virgin coconut oil, lauric acid and myristic acid may be useful in the management of BPH because they exerted some anti-proliferative effects in the development and progression of BPH. Therefore, coconut may be a potential functional food for the management of BPH patients because it is rich in both lauric and myristic acid. However, further investigations, including clinical trials are required to buttress this.

Comparative application of testosterone undecanoate and/or testosterone propionate in induction of benign prostatic hyperplasia in Wistar rats.

Testosterone undecanoate is a hormone agent with long-acting potential and is used for testosterone replacement therapy for hypogonadism. This study was designed to investigate application of testosterone undecanoate in maintaining high androgen levels for inducing benign prostatic hyperplasia more conveniently than that for testosterone propionate. We conducted two-part studies to determine the optimal dosage and dosing cycle for efficient and stable induction of benign prostatic hyperplasia using testosterone undecanoate. In the injection dosage substudy, single testosterone undecanoate dose (125, 250, 500, 750, or 1000 mg/kg body weight) was administered, and the optimal concentration was determined for 8weeks by measuring changes in testosterone, dihydrotestosterone, and 5-alpha reductase levels. And then, testosterone undecanoate was administered at the optimal dose at intervals of 1, 2, 3, or 4 weeks for 12weeks to induce benign prostatic hyperplasia. The injection dosage substudy showed dose-dependently higher and more stable levels of testosterone in groups administrated testosterone undecanoate than in groups administered testosterone propionate. In the injection cycle substudy, testosterone undecanoate-administered group stably maintained high levels of testosterone, dihydrotestosterone, and 5-alpha reductase compared with testosterone propionate-administered group for the same injection cycle; moreover, the prostate measurements, an important sign of benign prostatic hyperplasia, were significantly increased. Based on these two substudies, we determined the optimal conditions for inducing benign prostatic hyperplasia stably and more conveniently than that for testosterone propionate. This study suggests an extended application of testosterone undecanoate for inducing benign prostatic hyperplasia that can improve research reliability considering the half-life of testosterone as well as injection dosage and concentration.

DHT Induces Arterial Stiffening in Female Wild Type Mice

Testosterone is the predominant sex hormone in men and is increased in women with polycystic ovarian syndrome (PCOS). PCOS patients also experience an increased risk for cardiovascular diseases including hypertension and arterial stiffness. Our previous work showed significant downregulation of the G protein‐coupled estrogen receptor (GPER) as well as the nuclear estrogen receptor ERα in cultured vascular smooth muscle cells in response to the testosterone metabolite dihydrotestosterone (DHT), which cannot be aromatized to estrogen. Therefore, we hypothesized that DHT may induce arterial stiffness in female mice via downregulation of vascular estrogen receptors. Two groups of female wildtype mice were treated with DHT via silastic capsule for 4 weeks; one group received a dose designed to mimic DHT levels in men while the other group received twice this dose. While post‐treatment systolic blood pressure was not different between the control, single dose, and double dose groups (111 ± 10, 106 ± 3, 110 ± 7, n=8 per group; P=0.22), intracarotid vascular stiffness measured via pulse wave velocity showed a more than two‐fold increase in single dose (4.3 ± 0.8 m/s) and double dose (4.8 ± 1.0 m/s) DHT treated mice when compared with non‐treated controls (1.9 ± 0.3 m/s; P<0.0001). These findings suggest that high testosterone levels in females may promote arterial stiffening and cardiovascular damage independent of changes in blood pressure. Future studies will include histological analysis of aortic sections using Masson’s trichrome to assess changes in the extracellular matrix as well as droplet digital polymerase chain reaction to assess changes in estrogen receptor expression. In conclusion, these findings of arterial stiffening in response to increased DHT levels in females are important for not only PCOS patients but also women using testosterone for fitness, gender transitioning, or reduced libido.

In utero exposure to dietary emulsifier alters the behavioral activity in offspring

ObjectivePediatric mental health disorder is a combination of neuroinflammatory conditions with unknown etiology and currently, there are less awareness on the impacts of food additives on pediatric neuroinflammatory conditions and adolescent mental health disorders. Food additives such as dietary emulsifier (DE) (polysorbate 80, carrageenan and maltodextrin) are added to a variety of processed foods, and their consumption has increased dramatically worldwide which could be a risk factor for pediatric mental health disorders. Therefore, there is a critical need to understand the impact of maternal exposure to food additives associated pediatric mental health and the underlying mechanism.Materials and MethodsBehavioral testing such as tail flick assay, radial arm, rotarod and hot plate assay was done on the offspring from both control and DE exposed mice for the impaired motor activity, pain sensitivity and cognitive behavior. Colonic microbial composition was determined through 16sRNA pyrosequencing of fecal DNA samples from control and in utero DE‐exposed offspring. Level of pro inflammatory cytokines in the colon tissue as well as the serum sample was measured using Multianalyte cytokine assay kit from Qiagen.Summary of ResultsOur results show that in utero exposure to DE leads to decreased brain sizes and impaired motor learning in the offspring. Additionally, in utero exposure to DE leads to decreased pain sensitivity as a sign of stress in offspring. In utero exposure to DE shows on onset of cognitive impairment in offspring. In utero exposure to DE leads to an elevated M1 macrophage cytokine profile and CLGI symptoms in the gastrointestinal tract of offspring. In utero exposure to DE leads to gut dysbiosis in offspring. Among the DE‐exposed adolescents, the male offspring had significantly higher impact on these parameters compared to the DE‐exposed female offspring. In utero exposure to DE leads to imbalance in serum levels of dihydrotestosterone (DHT) and estradiol (E2) in the Offspring.ConclusionOur data suggest that maternal exposure to food additive is associated with the male biased cognitive impairment and neurobehavioral changes in the offspring. In future, we will determine the specific mechanism responsible for the sex specific alternation in offspring born to DE exposed mother to develop a preventative and therapeutic strategies.

Naftopidil enantiomers suppress androgen accumulation and induce cell apoptosis via the UDP-glucuronosyltransferase 2B15 in benign prostate hyperplasia

Accumulation of androgens mediate alterations in prostate growth and has emerged as an essential factor in benign prostate hyperplasia (BPH). Dihydrotestosterone (DHT), the most potent natural androgen, binds to androgen receptors (AR) and regulates the prostate growth. Many inhibitors of DHT synthesis have been developed to reduce DHT levels and used in the treatment of prostate diseases. However, therapies targeting the elimination of the DHT remain limited. The DHT in prostate is metabolized by UDP-glucuronosyltransferase 2B (UGT2B) and transforms into inactive products. In this study, we analyzed and demonstrated that two enantiomers of naftopidil (NAF), an α1D/1A-adrenoceptor blocker, induced expression and activity of UGT2B in BPH rat prostate models as well as UGT2B15 in human prostate cells, BPH-1. The NAF enantiomers reduced intraprostatic and intracellular DHT levels, thus promoting cell apoptosis. Besides, assays with siRNA UGT2B15 transfection showed that UGT2B15 played an essential role in mediating the effects of the NAF enantiomers. The UGT2B15 mediated the inhibition of AR and PSA expression by NAF enantiomers. The data showed that the mechanism of upregulating UGT2B15 by the NAF enantiomers might differ from that of AR antagonists and 5α-reductase inhibitors. Together, our results demonstrated that NAF enantiomers could be potential and novel UGT2B15 regulators, which accelerated the DHT elimination and promoted apoptosis of BPH-1 cells. This study could help expand the clinical application of NAF and support the development of new therapeutic strategies targeting the elimination of androgens for the treatment of BPH and other androgen-sensitive diseases.

Reproductive hormone levels, androgen receptor CAG repeat length and their longitudinal relationships with decline in cognitive subdomains in men: The European Male Ageing Study.

ObjectiveIt has been proposed that endogenous sex hormone levels may present a modifiable risk factor for cognitive decline. However, the evidence for effects of sex steroids on cognitive ageing is conflicting. We therefore investigated associations between endogenous hormone levels, androgen receptor CAG repeat length, and cognitive domains including visuoconstructional abilities, visual memory, and processing speed in a large-scale longitudinal study of middle-aged and older men. MethodsMen aged 40-79 years from the European Male Ageing Study (EMAS) underwent cognitive assessments and measurements of hormone levels at baseline and follow-up (mean = 4.4 years, SD ± 0.3 years). Hormone levels measured included total and calculated free testosterone and estradiol, dihydrotestosterone, luteinizing hormone, follicle-stimulating hormone, dehydroepiandrosterone sulphate and sex hormone-binding globulin. Cognitive function was assessed using the Rey-Osterrieth Complex Figure Copy and Recall, the Camden Topographical Recognition Memory and the Digit Symbol Substitution Test. Multivariate linear regressions were used to examine associations between baseline and change hormone levels, androgen receptor CAG repeat length, and cognitive decline. ResultsStatistical analyses included 1,827 and 1,423 participants for models investigating relationships of cognition with hormone levels and CAG repeat length, respectively. In age-adjusted models, we found a significant association of higher baseline free testosterone (β=-0.001, p=0.005) and dihydrotestosterone levels (β=-0.065, p=0.003) with greater decline on Rey-Osterrieth Complex Figure Recall over time. However, these effects were no longer significant following adjustment for centre, health, and lifestyle factors. No relationships were observed between any other baseline hormone levels, change in hormone levels, or androgen receptor CAG repeat length with cognitive decline in the measured domains. ConclusionsIn this large-scale prospective study there was no evidence for an association between endogenous sex hormone levels or CAG repeat length and cognitive ageing in men. These data suggest that sex steroid levels do not affect visuospatial function, visual memory, or processing speed in middle-aged and older men.

Hypercortisolism on the background of recovery of COVID-19 (сase report)

Damage to the lung tissue is a predominant complication of the viral disease COVID-19. Recently, there have been complications from other organs, including highly vascularized endocrine glands. Regarding the adrenal glands, there are reports of their damage with a decrease in their function. Сhanging the function of the adrenal glands (AG) in patients with or after COVID-19 is important. A few adrenal autopsy studies in patients have revealed vascular thrombosis, cortical lipid degeneration, ischemic necrosis, parenchymal infarcts, and other lesions leading to a decrease in AG function. The central mechanism of adrenal dysfunction through hemorrhage and necrosis of the pituitary gland is also possible. This paper presents a rare case of the development of hypercortisolism in a young woman after recovering from COVID-19. Based on high ACTH levels (157 and 122pg/ml), a negative nocturnal dexamethasone test, and high 24-hour urinary free (daily) cortisol excretion rates, we tentatively suspected Cushing’s disease. Chromogranin A was within the normal range of 21.35 (reference value <100). Other tests showed an elevated dihydrotestosterone level of 780.6 pg/ml (reference values 24–368 pg/ml). The levels of other anterior pituitary hormones tested were within the normal range. According to clinical guidelines, the drug of choice for the short-term treatment of this disease is steroidogenesis inhibitors— ketoconazole. The effectiveness of such a treatment regimen was previously brought to light by others. In our case, ketoconazole was prescribed at a dose of 400 mg 2 times a day and cabergoline (dostinex) at an initial dose of 1 mg per day. Given the low levels of vitamin D in the blood serum, it was recommended to continue taking vitamin D at a dose of 4000 IU per day. It was recommended to control blood laboratory parameters— serum cortisol, ACTH, AST, ALT, electrolytes, 25(OH)D, blood glucose level after 2 months and decide on further tactics for managing the patient.

46, XY 5-Alpha Reductase Deficiency in a 36-Year-Old Phenotypic Female Patient

46, XY 5-Alpha Reductase Deficiency in a 36-Year-Old Phenotypic Female Patient

Comparison of efficacy of diode laser in patients of facial hirsutism with normal dehydroepiandrosterone sulfate and dihydrotestosterone versus deranged dehydroepiandrosterone sulfate and dihydrotestosterone level-A longitudinal study.

Hirsutism is defined as an excessive terminal hair growth in female over male pattern distribution areas. Traditional methods of hair removal have been replaced by lasers. The aim of the study was to observe the effect of diode laser in hirsutism patient with normal and deranged dehydroepiandrosterone sulfate (DHEAS) and dihydrotestosterone (DHT) level. Fifty patients of facial hirsutism with skin type IV and V were enrolled. Eighteen patients with deranged DHEAS and DHT level were allocated in group A whereas 16 patients with normal level were allocated in group B. Three sittings of diode laser was done in all subjects with varying session within a period of 6 months. At first follow-up visit, the percentage of hair reduction was fair in 62.5% of patients in group B and 16.7% of patients in group A, whereas at second follow-up visit, it was good in 56.3% of patients in group B and 11.1% of patients in group A. Increase in vellus hair and reduction in percentage of terminal hair were more significant in group B. Hair free interval and satisfaction level was significantly higher in group B. Diode laser is effective mode of treatment in hirsutism patient irrespective of hormone level. But, the effect is observed to be more efficacious in patients with normal DHEAS and DHT level.

Delayed Puberty and Its Association With Hormonal Changes in Children With Chronic Renal Insufficiency

Chronic kidney diseases affect sex hormones, and thus it is now hypothesized abnormal puberty phenomenon in adolescents suffering renal failure. The primary study endpoint was to assess the frequency of disorders related to the clinical incidence of puberty symptoms among children suffering chronic kidney disease, and the secondary endpoint was also to assess the relationship between such manifestations and the serum level of sexual hormones. This cross-sectional study was performed on children with chronic renal failure (more than three months after the onset of the disease). Al baseline characteristics were retrospectively extracted from the hospital recorded files. The pieces of evidence of anemia and acidosis also appeared more in those with delayed puberty. Comparing the groups with delayed puberty and normal puberty showed significantly lower mean body weight and lower mean height in the group with delayed puberty as compared to those with normal status. Comparing serum hormonal conditions between the groups with normal and delayed puberty also showed significantly reduced serum levels of FSH, LH, testosterone, and dihydrotestosterone, as well as increased the serum level of prolactin in the group suffering delayed puberty. The main determinants for delayed puberty in patients suffering chronic renal insufficiency included abnormality in serum hormonal status, along with pieces of evidence of anemia or acidosis. Children with chronic renal insufficiency suffer from delayed puberty. Such phenomenon might be closely linked to abnormal changes in sex hormones due to the nature of renal dysfunction and hemodialysis.

Fenofibrate mitigates testosterone induced benign prostatic hyperplasia via regulation of Akt/FOXO3a pathway and modulation of apoptosis and proliferation in rats

Benign prostatic hyperplasia (BPH) is one of the most age-related health problems that commonly affect men. Regrettably, many individuals may not respond to current medical therapies or develop resistance to them. Accordingly, this study aimed to uncover how potentially fenofibrate, a lipid lowering agent, can ameliorate the induced BPH in rats. Forty rats were categorized randomly into four groups; the control group was given the vehicle (olive oil); the BPH model received testosterone propionate (20 mg/kg daily; s.c.) for 4 weeks; BPH-induced group received finasteride (10 mg/kg daily; p.o.) and BPH-induced group received fenofibrate (80 mg/kg daily; p.o.). After testosterone administration, both weight and relative weight of the prostate increased. Additionally, testosterone upregulated androgen receptor (AR), 5α-reductase gene expression and increased prostate proliferation. Histopathological examination confirmed that testosterone disrupted the histo-architecture of the prostate and caused marked hyperplasia of glands and stroma. On the other hand, fenofibrate administration reverted most hyperplastic changes of testosterone, it significantly reduced weight, relative weight of the prostate and dihydrotestosterone (DHT) level compared to BPH group. Also fenofibrate significantly decreased AR and 5α-reductase gene expression. Fenofibrate significantly suppressed ps473 Akt expression causing FOXO3a nuclear inclusion, which triggered induction of apoptosis. As well, Bax/Bcl2 ratio and caspase 3 content were significantly enhanced. Fenofibrate significantly diminished cyclin D1 immunoexpression and restored normal histo-architecture. In conclusion, this study emphasizes the preventive effect of fenofibrate in BPH rat model. This can be accredited, at least partly, to inhibiting AR and 5α-reductase expressions, the anti-proliferative, and pro-apoptotic activity of fenofibrate via modulation of Akt/FOXO3a pathway.

Testosterone Deficiency is Not Protective Against the Development of Adenocarcinoma of the Prostate in a Type1 Diabetic Patient.

We present a case of prostate cancer (PC) developing in a hypogonadal patient with well-controlled type 1 diabetes. The purpose of reporting this case is to emphasize that regular prostate examinations and prostate-specific antigen (PSA) measurements should be preformed in the diabetic male, even though the incidence of PC is lower in this group of patients. In addition, these examinations and tests need to be preformed even in the hypogonadal patient with diabetes since the presence of a low serum testosterone (T) level does not preclude the development of PC. This is because the development of PC is not related to serum androgen levels but to the androgen levels within the prostate, and dihydrotestosterone (DHT) levels and not T levels within the prostate gland are responsible for the development of PC. In the hypogonadal male, intraprostatic DHT may be high since DHT can be formed from adrenal androgens, particularly androstenedione, through activation of 5α-reductase 2, which is the minority enzyme in the normal prostate but becomes the major enzyme in the formation and growth of PC.

Varicocele: An Endocrinological Perspective.

Varicocele affects 15% of male population but it is more frequently identified in patients searching medical care for infertility. The impact of varicocele on semen production and fertility is known, but the relationship between clinical varicocele and impaired hormonal production is not clear. In published literature there are some studies regarding hormonal alterations in patients with varicocele but no review in which all the hormonal findings are explained. The aim of this review is to evaluate, by most common search engine, what is known about hormonal alterations in varicocele-bearing patients, to verify if a cause-effect relationship is documented and to give a useful contribution to in clinical management of this kind of patients. We found contradictory results about hormonal status from literature. Some studies confirmed a decrease of testosterone levels and higher FSH and LH levels that normalize after varicocelectomy, others found lower than normal levels of dihydrotestosterone due to decreased activity of epididymal 5-α-reductase. Lower circulating Anti-Müllerian Hormone levels, accompanied by a decreased Inhibin-B level, were reported as indicators of the decreased Sertoli cells function in varicocele-bearing adult patients. The finding of higher basal 17-OH-progesterone concentrations in patients with varicocele was explained by some authors with a testicular C-17,20-lyase deficiency. There is no doubt that varicocele could led to hormonal alterations. This review proposes that the impaired free sexual steroid levels are the result of a slight, deep-rooted defect in the testes of a certain amount of men with varicocele but further multicentre, randomized controlled studies remain mandatory to better clarify the hormonal features of patients with varicocele and to assess the utility of hormonal evaluation for establishing the duration of varicocele and for better identifying patients who need surgical correction.

Protective Effects of Gallic Acid and Curcumin on Serum Levels of Hepatic Transaminases, Blood Plasma Parameters and Pituitary-testicular Hormones in Rats Treated Nickel Nanoparticles

Nickel nanoparticles (NiNPs) have toxic effects on body cells due to the production of free radicals. The purpose of this research was to investigate the protective effects of Gallic acid (GA) and Curcumin (Cur) on hepatic transaminases, blood plasma parameters and pituitary-testicular hormones levels in NiNPs-treated rats. Seventy adult male Wistar rats were divided in 7 groups of 10 including control, Ni50 mg/kg, Ni50+GA150 mg/kg, Ni50+GA300 mg/kg, Ni50+Cur150 mg/kg, Ni50+Cur300 mg/kg and Ni50+GA300+CUR300 mg/kg. NiNPs, GA and Cur were administered orally by oral gavage for 28 days. At the last phase of the study, the samples of blood were taken directly from heart and serum levels of hepatic transaminases (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)), blood plasma parameters (Glucose, total protein (TP), bilirubin (Bil), albumin (Alb), creatinine (Cr), Blood urea nitrogen (BUN), triglyceride, cholesterol, HDL, LDL and alkaline phosphatase (ALP)) and pituitary-testicular hormones (FSH, LH, testosterone and dihydrotestosterone) were assessed. NiNPs administration increased serum levels of glucose, ALT, ALP, AST, Bil, BUN, Cr, triglyceride, cholesterol and LDL compared to the control group (p0.05) and in contrast, it decreased serum levels of FSH, LH, testosterone, dihydrotestosterone, Alb, TP and HDL (p0.05). However, co-administration of GA and Cur at doses of 300 ml/kg in NiNPs -treated rats improved all blood plasma parameters compared to the control group (p0.05). The findings of this study suggest that co-administration of GA and Cur at a dose of 300 mg/kg can reduce and improve the damaging effects of NiNPs on blood plasma parameters, hepatic transaminases and pituitary-testicular hormones in adult rats.

Preterm infant circulating sex steroid levels are not altered by transfusion with adult male plasma: a retrospective multicentre cohort study

ObjectiveTo determine if plasma transfusions with male donor plasma to very preterm infants affect circulatory levels of sex steroids.Design and patientsRetrospective multicentre cohort study in 19 infants born at gestational...

Effect of risk-reducing salpingo-oophorectomy on sex steroid hormone serum levels among postmenopausal women: an NRG Oncology/Gynecologic Oncology Group study

Risk-reducing salpingo-oophorectomy is an effective ovarian cancer risk reduction strategy. However, bilateral oophorectomy has also been associated with increased long-term nonneoplastic sequelae, effects suggested to be mediated through reductions in systemic sex steroid hormone levels. Currently, it is unclear whether the postmenopausal ovary contributes to the systemic hormonal milieu or whether postmenopausal ovarian volume or other factors, such as body mass index and age, affect systemic hormone levels. We examined the impact of oophorectomy on sex steroid hormone levels in postmenopausal women. Furthermore, we explored how well ovarian volume measured by transvaginal ultrasound correlated with direct ovarian measures obtained during surgical pathology evaluation and investigated the association between hormone levels and ovarian volumes. Postmenopausal women who underwent risk-reducing salpingo-oophorectomy (180 cases) or ovarian cancer screening (38 controls) enrolled in an international, prospective study of risk-reducing salpingo-oophorectomy and risk of ovarian cancer algorithm-based screening among women at increased risk of ovarian cancer (Gynecologic Oncology Group-0199) were included in this analysis. Controls were frequency matched to the cases on age at menopause, age at study entry, and time interval between blood draws. Ovarian volume was calculated using measurements obtained from transvaginal ultrasound in both cases and controls and measurements recorded in surgical pathology reports from cases. Serum hormone levels of testosterone, androstenedione, androstenediol, dihydrotestosterone, androsterone, dehydroepiandrosterone, estrone, estradiol, and sex hormone-binding globulin were measured at baseline and follow-up. Spearman correlation coefficients were used to compare ovarian volumes as measured on transvaginal ultrasound and pathology examinations. Correlations between ovarian volumes by transvaginal ultrasound and measured hormone levels were examined using linear regression models. All models were adjusted for age. Paired t tests were performed to evaluate individual differences in hormone levels before and after risk-reducing salpingo-oophorectomy. Ovarian volumes measured by transvaginal ultrasound were only moderately correlated with those reported on pathology reports (Spearman rho [ρ]=0.42). The median time interval between risk-reducing salpingo-oophorectomy and follow-up for the cases was 13.3 months (range, 6.0-19.3), and the median time interval between baseline and follow-up for the controls was 12.7 months (range, 8.7-13.4). Sex steroid levels decreased with age but were not correlated with transvaginal ultrasound ovarian volume, body mass index, or time since menopause. Estradiol levels were significantly lower after risk-reducing salpingo-oophorectomy (percentage change,-61.9 post-risk-reducing salpingo-oophorectomy vs+15.2 in controls; P=.02), but no significant differences were seen for the other hormones. Ovarian volumes measured by transvaginal ultrasound were moderately correlated with volumes directly measured on pathology specimens and were not correlated with sex steroid hormone levels in postmenopausal women. Estradiol was the only hormone that declined significantly after risk-reducing salpingo-oophorectomy. Thus, it remains unclear whether the limited post-risk-reducing salpingo-oophorectomy changes in sex steroid hormones among postmenopausal women impact long-term adverse outcomes.

5-Alpha reductase inhibitors induce a prostate luminal to club cell transition in human benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a progressive expansion of peri-urethral prostate tissue common in aging men. Patients with enlarged prostates are treated with 5-alpha reductase inhibitors (5ARIs) to shrink prostate volume by blocking the conversion of testosterone to dihydrotestosterone (DHT). A reduction in DHT levels can elicit atrophy and apoptosis of prostate secretory luminal cells, which results in a favorable clinical response characterized by improved lower urinary tract symptoms. However, the histologic response to 5ARI treatment is often heterogeneous across prostate acini and lower urinary tract symptoms can persist to require surgical intervention. We used two spatial profiling approaches to characterize gene expression changes across histologically normal and atrophied regions in prostates from 5ARI-treated men. Objective transcriptomic profiling using the Visium spatial gene expression platform showed that 5ARI-induced atrophy of prostate luminal cells correlated with reduced androgen receptor signaling and increased expression of urethral club cell genes including LTF, PIGR, OLFM4, SCGB1A1, and SCGB3A1. Prostate luminal cells within atrophied acini adapted to decreased DHT conditions by increasing NF-κB signaling and anti-apoptotic BCL2 expression, which may explain their survival. Using GeoMx digital spatial profiling with a probe set to assess ~18 000 RNA targets, we confirmed that atrophied acini expressing SCGB3A1 displayed higher levels of club cell markers compared with histologically normal acini with NKX3-1 expression. In addition, club-like cells within regions of 5ARI-induced atrophy closely resembled true club cells from the prostatic urethra. A comparison of histologically normal regions from 5ARI-treated men and histologically normal regions from untreated men revealed few transcriptional differences. Taken together, our results describe a heterogeneous response to 5ARI treatment where cells in atrophied acini undergo an adaptation from a prostate secretory luminal to a club cell-like state in response to 5ARI treatment. © 2021 The Pathological Society of Great Britain and Ireland.

Leydig and Sertoli cell function in individuals with genital ambiguity, 46,XY karyotype, palpable gonads and normal testosterone secretion: a case-control study.

Because normal male sexual differentiation is more complex than normal female sexual differentiation, there are more cases of disorders of sex development (DSDs) with 46,XY karyotype that have unclear etiology. However, Leydig and Sertoli cell markers are rarely used in distinguishing such individuals. To evaluate the function of Leydig and Sertoli cells in individuals with genital ambiguity, 46,XY karyotype, palpable gonads and normal testosterone secretion. Case-control study with 77 patients, including eight with partial androgen insensitivity syndrome, eight with 5α-reductase deficiency type 2 (5ARD2) and 19 with idiopathic 46,XY DSD, and 42 healthy controls, from the Interdisciplinary Study Group for Sex Determination and Differentiation (GIEDDS), at the State University of Campinas (UNICAMP), Campinas, Brazil. Baseline levels of gonadotropins, anti-Müllerian hormone (AMH), inhibin B, insulin-like 3 (INSL3), testosterone and dihydrotestosterone in cases, and AMH, inhibin B, and INSL3 levels in controls, were assessed. There was no significant difference in age between cases and controls (P = 0.595). AMH and inhibin B levels were significantly lower in cases than in controls (P = 0.031 and P < 0.001, respectively). INSL3 levels were significantly higher in cases than in controls (P = 0.003). Inhibin B levels were lower in 5ARD2 patients (P = 0.045) and idiopathic patients (P = 0.001), in separate comparisons with the controls. According to our findings, we can speculate that inhibin B levels may be used to differentiate among DSD cases.