Plasma Testosterone Concentrations Research Articles

Effect of tonophosphan, zinc oxide, and ascorbic acid on semen, sexual desire, and the fertility rate of Egyptian buffalo bulls

A twenty weeks experimental trial was conducted to evaluate the effects of using tonophosphan (8 ml injection), zinc oxide (ZnO) at 0.8 g oral dose and ascorbic acid (AA) at 0.5% oral dose of live body weight on reproductive performance of Egyptian buffalo bulls (n = 20, 550–600 kg). The overall mean of all treated groups yielded marked improvement in all semen physical characteristics. Reaction time (RT), scrotal circumference, testicular volume, the concentration of semen fructose, testosterone, total proteins, and albumin in blood plasma were significantly (P ≤ 0.05) improved in all treatment groups compared with the control, but were greater in tonophosphan group. The highest concentrations of phosphorus and zinc in blood or semen were observed in tonophosphan and zinc treatments, respectively as compared to other groups. Overall mean of all semen physical characteristics and sperm outputs were not affected by advancing collection weeks. Meanwhile, the testosterone concentration and testicular volume increased (P ≤ 0.05), whereas the reaction time did not vary. The conception rate of buffalo cows was the highest (P ≤ 0.05) in tonophosphan (82.8%), followed by ascorbic acid and zinc (77.1 and 74.2%) as compared to the control group (60%). These findings suggested that tonophosphan, zinc oxide, and ascorbic acid supplementation improved the reproductive performance of Egyptian buffalo bulls; however, tonophosphan showed better performance.

Is the current-use flame retardant, DBE-DBCH, a potential obesogen? Effects on body mass, fat content and associated behaviors in American kestrels

The current-use brominated flame retardant, 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane (DBE-DBCH), is capable of perturbing sex steroid and thyroid hormone pathways in vitro and in vivo. Chemicals with this capability may also disrupt metabolic processes and are candidate obesogens, but this potential has not yet been determined for DBE-DBCH. Our objective was to examine gross biomarkers of metabolic disruption in captive American kestrels. Birds were exposed by diet to the β isomer at the environmentally relevant dose of 0.239 ng β-DBE-DBCH/g kestrel/day, from 30 days (d) prior to pairing through until chicks hatched (82 d) (n = 30 breeding pairs) or for 28 d (n = 16 pre-breeding pairs), and were compared with vehicle-only exposed controls. Body mass was assessed throughout the breeding season at biologically relevant time points, flight and feeding behavior was measured in 5-min samples daily, and plasma triglycerides and cholesterol were assessed at d10 of brood rearing. Treated males were heavier than controls at pairing (p = 0.051), the final week of courtship (p = 0.061), and at d10 (p = 0.012) and d20 of brood rearing (p = 0.051); β-DBE-DBCH-exposed breeding females were similar in weight to control females. Treated birds tended to have higher plasma triglycerides (p = 0.078), which for females, was positively associated with body mass (p = 0.019). Heavier breeding males had higher plasma concentrations of testosterone and total thyroxine (p ≤ 0.046). Overall, both sexes exposed to β-DBE-DBCH demonstrated reduced flight behavior and increased feeding behavior during courtship. In the pre-breeding pairs, treated male and female kestrels had a higher percentage of body fat than respective controls (p = 0.045). These results demonstrate that β-DBE-DBCH elicited inappropriate fat and weight gain in adult American kestrels, consistent with their increased feeding, reduced flight activity and endocrine changes, and suggests that DBE-DBCH may be an obesogen warranting further research to test this hypothesis.

Hypothalamic Gliosis by MRI and Visceral Fat Mass Negatively Correlate with Plasma Testosterone Concentrations in Healthy Men.

Objective:To determine whether a relationship was evident between gliosis in the mediobasal hypothalamus (MBH) and plasma testosterone concentrations in menMethods:41 adult men (ages 18–50 years) from 23 twin pairs underwent fasting morning blood draw and brain MRI. T2 relaxation time was used to quantify gliosis in the MBH and control areas in the putamen and amygdala. Plasma concentrations of testosterone and 17β-estradiol were measured by LC-MS/MS. Body composition including visceral adiposity was measured by dual X-ray absorptiometry.Results:A negative association was found between MBH T2 relaxation time and plasma concentrations of both free and total testosterone (r = −0.29, P<0.05 and r = −0.37, P<0.01, respectively). Visceral adiposity exhibited a negative correlation with plasma total testosterone concentration (r = −0.45, P=0.001) but a positive correlation with MBH T2 relaxation time (r = 0.24, P=0.03). The negative correlation between plasma total testosterone and MBH T2 relaxation time remained significant after adjustment for visceral adiposity, age, BMI, and insulin resistance.Conclusions:In healthy men across a range of BMIs, MBH gliosis was associated with higher visceral adiposity but lower endogenous testosterone. These findings suggest that MBH gliosis could provide novel mechanistic insights into gonadal dysfunction in men with obesity.

Testosterone mediates hyperthermic response of mice to heat exposure

AimsTestosterone is implicated as a potential contributing factor to heat-induced injury. We examined effects of testosterone on thermal response of mice to heat exposure. Main methodsAdult C57BL/6J male mice received gonadectomy or sham surgery subsequent vehicle (Gnx) or testosterone implants (Gnx+T). Body core temperature (Tc) of mice was recorded telemetrically during acute heat exposure. Thermal responses to heat exposure were also examined in age-matched female mice at each stage of the estrous cycle. Key findingsBasal Tc was lower in sham male mice than females, but did not differ among sham, Gnx or Gnx+T males. No alterations in expression of uncoupling proteins 2 and 3 in the gastrocnemius muscle were found in either Gnx or Gnx+T mice compared to sham males. During heat exposure, sham male mice had a faster and greater rise in Tc, compared to females. This rapid hyperthermic response to heat was abolished in Gnx males, but not in Gnx+T males. No significant correlation was revealed between peak Tc values and plasma testosterone concentrations in Gnx+T males treated with either low- or high-dose testosterone. No effects of estrous cycle phase on the thermal response to heat exposure were detected in female mice. SignificanceWe found that male mice were more susceptible to development of heat-induced hyperthermia than females and this was prevented by castration, not by castration with testosterone replacement. These results suggest that testosterone mediates heat-induced hyperthermia and is a heat stress susceptibility factor.

Spermatogenesis and steroid hormone profile in puberty of laboratory-reared common snook (Centropomus undecimalis)

The common snook, Centropomus undecimalis, is a protandrous hermaphrodite and considered an emerging species for intensive fish culture on the American continent. This study describes the onset of puberty in this species, correlating growth parameters, gonadal morphology (histology) and plasma concentrations of testosterone (T), 11-ketotestosterone (11-KT) and estradiol (E2) under two rearing conditions. Two experimental groups with 500 fish each were conducted until fish reached puberty, the first in a net cage (28 m3) inside an earthen estuarine pond (Exp. 1) and the second in a thermal-controlled tank (9.6 m3) in a recirculation aquaculture system (Exp. 2). The fish in Exp.1 initiated puberty in the second year (305.35 ± 91.78 g and 34.31 ± 3.48 cm). The fish in Exp. 2 initiated puberty in the first year (303.05 ± 40.38 g and 35.11 ± 1.34 cm), influenced mainly by the higher somatic growth. Only the fish in Exp. 1 reached the most advanced stage of spermatogenesis with the release of semen, probably due to the maturation of the reproductive system. Variations in gonadal steroids (T, 11-KT and E2) regulated the progression of spermatogenesis during the reproductive season, and these variations demonstrated a relevant role in the development of the testes. Plasma levels of T and E2 were higher (P < .05) in Exp. 2, indicating influence of the culture environment. However, plasma concentrations of 11-KT were not influenced by the environment, suggesting an important role of this androgen in the regulation of spermatogenesis. The results of this study show that in a controlled environment common snook can initiate puberty with one year old, which normally occurs in two-year-old in an environment with seasonal variations. This indicates a plasticity in the onset of puberty in the common snook, mostly related to body size than age.

Joint effects of chronic exposure to environmentally relevant levels of nonylphenol and cadmium on the reproductive functions in male rockfish Sebastiscus marmoratus

Nonylphenol (NP) and Cadmium (Cd) are two common contaminants that can be detected in aquatic environments. Nevertheless, the combined toxicity of NP and Cd at environmentally relevant concentrations in aquatic organisms has not been thoroughly characterized to date. In the present study, the interactions between NP and Cd on male Sebastiscus marmoratus were studied. After 21 days of exposure, the brain aromatase activity was observed to be significantly induced by 100 ng/L NP and 40 μg/L Cd, whereas all of the concentrations of co-treatment resulted in an increase in brain aromatase activity. Additionally, NP could also reduce plasma testosterone concentration, while NP, Cd and their mixture could induce plasma 17β-estradiol (E2) concentration and VTG concentration. The interactions between NP and Cd on the reproductive physiology were antagonism. Our results also support the notion of using these indicators as biomarkers for exposure to EDCs and further extend the boundary of biomonitoring to environmental levels.

Prospective Study of Endogenous Hormones and Incidence of Venous Thromboembolism: The Atherosclerosis Risk in Communities Study.

Exogenous hormone treatments in women (oral contraceptives and hormone replacement therapy [HRT]) are established risk factors for venous thromboembolism (VTE), but less is known about associations between plasma levels of endogenous hormones and VTE risk. We examined the association of baseline dehydroepiandrosterone sulphate (DHEAS), testosterone and sex hormone-binding globulin (SHBG) with risk of future VTE in men and post-menopausal women in the Atherosclerosis Risk in Communities Study. Testosterone, DHEAS and SHBG were measured in plasma samples collected in 1996 to 1998. Cox proportional hazards models were used to estimate hazard ratios for incident VTE adjusting for age, race/ethnicity, body mass index, height, smoking, estimated glomerular filtration rate and C-reactive protein. All analyses were stratified by sex and by current HRT use in women. Among 3,051 non-HRT-using women, 1,414 HRT-using women and 3,925 men at risk at baseline, 184, 62 and 206 experienced incident VTE after a median follow-up of 17.6 years. Plasma hormones were not associated with incidence of VTE among men and non-HRT-using women, although lower plasma DHEAS, when modelled using quartiles or restricted cubic splines, was associated with higher risk of VTE among HRT-using women. This study does not support the existence of an important association between plasma concentrations of endogenous testosterone, DHEAS or SHBG with risk of VTE in middle-aged to older men or post-menopausal women not using HRT.

Environmental Exposure to Endocrine Disruptor of Bisphenol A and Semen Quality of Men

Background: The reproductive health disorders in men are one of the urgent problems of international medicine. The prevalence of idiopathic male infertility has the highest rate. Oxidative stress, genetic factor, and endocrine disruptors are considered to be the most probable causes for the idiopathic male infertility. In this regard, studying the effect of endocrine disruptors, in particular bisphenol A on male reproductive health, becomes actual and relevant. Aims: The aim of the study was to reveal the relationship between the concentration level of bisphenol A (BPA) in seminal fluid and semen quality in men with normo- or pathozoospermia, as well as between the concentration level of bisphenol A and the level of total testosterone and estradiol in plasma. Materials and methods: 53 samples of seminal fluid of men with normo- or pathoospermia were studied. In seminal fluid the concentration of bisphenol A was determined by gas chromatography with mass spectrometry (GC-MS). The spermiological analysis was performed according to the WHO recommendations (2010) including the evaluation of sperm count/concentration, motility and morphology, and DNA fragmentation index. In addition, the concentration of total testosterone and estradiol in plasma was determined. The results were statistically processed using the Mann–Whitney U test, the correlation analysis, the paired regression method, and the ROC curves to determine the cut-off point for BPA in the seminal fluid. The results were considered statistically significant at p0.05. Results: In 100% of the ejaculate samples BPA with a median concentration of 0.15 (0.06–0.31) ng/ml was detected. Using the Spearman rank correlation coefficient, statistically significant correlations between the concentration of BPA and the total count (r=-0.330, p=0.016), concentration (r=-0.309; p=0.024), the proportion of progressively motile spermatozoa (r=-0.575; p=0.001), the proportion of spermatozoa with normal morphology (r=-0.397, p=0.003), the degree of sperm DNA fragmentation (r=0.349, p=0.025), and the concentration of total testosterone (r =-0.616; p0.001) were registered. A statistically significant inverse linear relationship (r=-0.406, p=0.003) and (r =-0.364, p=0.048) was determined by a paired linear regression between the BPA concentration in the seminal fluid and the proportion of progressively motile spermatozoa, and the total testosterone level respectively. To assess the risk of pathozoospermia, the threshold value of seminal BPA concentration was determined using the analysis of ROC-curves; the cut-off point was 0.1025 ng/ml. Conclusions: BPA in the seminal fluid influences negatively on the quality of the sperm and suppress the level of total testosterone in plasma.

Sperm quality in wild-caught and farmed males of the European eel (Anguilla anguilla)

Sperm density and performance of wild and farmed male European eels were evaluated to investigate the effect of maintenance in captivity on ejaculate quality. Hormonal stimulation (with human chorionic gonadotropin) lasted for 17 weeks. Different origins of the male European eels partially influenced the quality of the ejaculates. Indeed, wild animals (i.e., collected at a natural site) had greater sperm longevity during the hormonal stimulation, whereas there was no significant effect of the origin on sperm density, spermatocrit, the percentage of motile sperm, and plasma testosterone concentrations. The different origins of the males also affected fatty acid sperm content, with greater unsaturated fatty acid and omega-6 concentrations in wild eels and lesser concentrations of saturated fatty acids and omega-3 fatty acids in farmed eels. Regarding sperm quality of European eels, this is the first study that takes into account the effect of different origins of stimulated males (wild-caught compared with farmed) on sperm quality, and these findings may help to improve the production of high-quality gametes in this endangered species.

The effect of carob (Ceratonia siliqua) bean extract on male New Zealand White rabbit semen

&lt;p&gt;The carob tree (Ceratonia siliqua) grows naturally in the Mediterranean region. The empiric use of carob cures for their aphrodisiac properties is very common in Turkey. Thus, the experiment was conducted to determine the effects of carob bean extracts on some reproductive parameters in male New Zealand White rabbits. During the adaptation period (stage 1), 6-8 mo old rabbits were trained in semen collection for 30 d. At the beginning of the treatment period (stage 2), rabbits were assigned randomly to 2 groups of 8 animals each. For a period of 49 d (1 spermatogenesis duration), one group was treated with a daily oral dose (10 mL) of carob extract and the other group received the corresponding volume of tap water. Semen was collected weekly. Semen samples taken at week 1 and 7 were analysed separately. At the beginning of stage 2, no differences were observed in the volume and pH of the ejaculate, sperm concentration, percentage of motility, percentage of live spermatozoa, percentage of sperm plasma membrane integrity, plasma concentration of testosterone, and seminal plasma protein levels between the control and carob extract treated animals. Similarly, at the end of stage 2, there were no differences in the volume and pH of the ejaculate, motility percentage, the percentage of live spermatozoa, percentage of sperm plasma membrane integrity, and the seminal plasma protein levels between the control and the carob extract treated animals. However, sperm concentration (P&amp;lt;0.05), plasma concentration of testosterone (P&amp;lt;0.05), and percentage of change in spermatozoa concentration (P&amp;lt;0.02) between groups were affected at the end of stage 2. The data suggested that the use of carob cures prepared by boiling carob fruit could have beneficial influences on sperm concentration in rabbits.&lt;/p&gt;

Effects of glucocorticoid on the eye development in guinea pigs

Glucocorticoid (GC) has been widely used in clinic. However, the effect of GC on normal and myopic development of eyes is still unknown. In this study, 3-week-old guinea pigs were randomly divided into four groups: No-Lens (control), GC+No-Lens, negative lens-induced myopia (LIM), and GC+LIM. To induce myopia, right eyes were covered with a −10 D lens in GC+LIM and LIM groups. GC+No-Lens and GC+LIM groups received intraperitoneal injections of hydrocortisone (10 mg/kg) once daily for 2 weeks, and then received intragastric hydrocortisone (32.5 mg/kg) every other day for the next 4 weeks, while No-Lens (control) and LIM groups were injected intraperitoneally with saline for 2 weeks, and then given saline by intragastric administertion for the next 4 weeks. Several parameters were assessed: ocular axial length and refractive error, sclera thickness, matrix metalloprotein-2 (MMP-2) and tissue inhibitor metalloprotease-2 (TIMP-2) expressions and localization of the posterior sclera, plasma concentrations of free triiodothyronine (FT3), free thyroxine (FT4), testosterone (T), and oestradiol (E2). Results indicated that: (1) in normal eye development, hydrocortisone could inhibit both the axial elongation and the myopic shift; whereas (2) in LIM eye development, hydrocortisone (a) enhanced the axial elongation, myopic shift and sclera thinning; (b) enhanced the MMP-2 expression and decreased TIMP-2 expression, and (c) elevated the plasma concentration of E2 but decreased the levels of FT3, FT4, and T. In conclusion, glucocorticoid may influence both normal and LIM eye development. The balance of the hormones is fundamental for the eye development.

Follicular Development and Secretion of Ovarian Hormones during the Juvenile and Adult Reproductive Lives of the Myelin Mutant taiep Rat: An Animal Model of Demyelinating Diseases.

Infertility and reproductive problems have been reported in women with several neurological disorders, for example, demyelination. However, the physiology of such problems has remained unknown so far. The taiep rats are an animal neurological model that initially shows a hypomyelination followed by a progressive demyelination of the central nervous system. This animal has reproductive problems, and the aim of this work is to characterize the follicular development, secretion of ovarian hormones, and presence of noradrenaline in the ovaries of the female taiep rats in the juvenile and adult stages. The taiep rats have low body weight (approximately 19% less than that of SD rats), a delay of 4 days in the age of vaginal opening, and an irregularity in the estrous cycle by the absence or prolongation of some estral cycle stage. In the juvenile stage, we observed a decrease of approximately 44% in the total number of follicles with a 15% increase of atresia and an 80% decrease in the fluorescence intensity of catecholamines in the ovaries, with a 21% increment in plasma concentrations of testosterone. In the adult stage, we observed follicular cysts and a 50% decrease in fluorescence intensity of catecholamines in the ovaries, with changes in the secretion of ovarian hormones, an increase of 20 times in progesterone, and a decrement of a half in estradiol. The demyelination in taiep rats affects follicular development and steroidogenesis in the early stages of the animal's life, and this is maintained until adulthood.

Effect of seasonality on testicular blood flow as determined by color Doppler ultrasonography and hormonal profiles in Shiba goats

The objectives of this study were to determine if there is a seasonal pattern of testicular blood flow in male Shiba goats, and ascertaining whether or not there is a relationship among changes in testicular hemodynamics and circulating testosterone (T) and estradiol (E2). Twelve sexually mature male Shiba goats (Capra hircus), aged 19.5 ± 2.5 months were used in this study. Monitoring of the changes in testicular blood flow was performed once a week for 1 year, using color spectral Doppler ultrasonography. Plasma concentrations of testosterone (T) and estradiol (E2) were determined by radioimmunoassay. Among the four seasons, the greatest increases (P ≤ 0. 001) in the values for the resistive index (RI) and pulsatility index (PI) of the testicular artery were recorded in the summer. Also, PI and RI values recorded in spring were greater than those recorded in autumn, while for winter there were the least values for these indices. Likewise, concentrations of T and E2 showed seasonal changes. Concentrations of T and E2 were greater during the autumn and winter compared to those in spring and summer. Interestingly, E2 concentrations were negatively associated with Doppler indices of the testicular artery. In conclusion, although Shiba goats are considered to be non-seasonal breeding animals, there were distinct seasonal patterns of testicular blood flow as measured by color Doppler ultrasonography, especially in Doppler indices. These changes were coincident with the changes in the circulating E2 and may be attributable to the seasonal changes in ambient temperature or daylight length.

Antifertility effect of methanolic leaf extract of Chenopodium ambrosioides Hook. in male Sprague Dawley rats.

This study evaluated the antifertility activity of methanolic extract of Chenopodium ambrosioides leaf on male rats. During the experiment, different doses of extract (0, 50, 100 and 150mg/kg) were orally administered to rats for 28days. Analysis of sperm parameters revealed a dose-dependent decrease in sperm motility, viability and daily sperm production (DSP). While, increased oxidative stress in reproductive organs; and impaired testicular and epididymal histology was also evident in high dose regimen. Furthermore, a reduction in concentrations of plasma testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) was also recorded. Reduced pregnancy outcome and small litter size in the females paired with treated male rats after 30days of treatment withdrawn was noted in higher doses. From these findings, it is concluded that the methanolic leaf extract of C.ambrosioides is quite effective in reversible suppression of male fertility.

Impact of low-dose chronic exposure to bisphenol A and its analogue bisphenol B, bisphenol F and bisphenol S on hypothalamo-pituitary-testicular activities in adult rats: A focus on the possible hormonal mode of action

Bisphenol A an estrogen-mimic endocrine disrupting chemical, used to manufacture polycarbonate plastics and epoxy resins with toxic effects for male reproduction. Due to its toxicity, industries have started to replace it with other bisphenols. In this study, the toxicity of BPA analogues (BPB, BPF and BPS) was evaluated in a chronic study. We investigated whether the chronic exposure to low bisphenols doses affects spermatogenesis with outcomes on oxidative stress and male reproductive system. Male rats (22 day old) were exposed to water containing 0.1% ethanol for control or different concentrations of BPA and its analogues BPB, BPF and BPS (5, 25 and 50 μg/L) in drinking water for 48 weeks. Results of the present study showed a significant alteration in the gonadosomatic index (GSI) and relative reproductive organs weights. Oxidative stress in the testis was significantly elevated while sperm motility, Daily sperm production (DSP) and number of sperm in epididymis were reduced. Plasma testosterone, LH and FSH concentrations were reduced and estradiol levels were high in 50 μg/L exposed group. These results suggest that exposure to BPA and its analogues for chronic duration can induce structural changes in testicular tissue and endocrine alterations in the male reproductive system.

Urbanization alters the relationship between coloration and territorial aggression, but not hormones, in song sparrows

Melanin-based coloration is associated with aspects of phenotype, including conspecific aggression and hormone concentrations. These relationships could arise as a result of genetic and/or biochemical links between melanin production and other traits. Additionally, anthropogenic change, including urbanization, exposes animals to novel conditions that can alter pigmentation, behaviour or hormones, potentially disrupting relationships between coloration and other traits. We examined relationships among the extent and darkness of melanin spotting on the breast of male song sparrows, Melospiza melodia, territorial behaviour, plasma testosterone and corticosterone concentrations to determine whether coloration was reliably associated with phenotype in this species. We conducted this study in urban and rural populations to determine whether relationships between coloration, behaviour and hormones varied between habitats. Males in urban habitat had more extensive brown spotting than rural males. The relationship between melanin coloration and territoriality differed in urban and rural habitats. In rural sparrows, territoriality was negatively correlated with spotting area, while in urban sparrows territoriality was positively associated with spotting darkness. Regardless of habitat, males with more extensive spotting increased testosterone secretion more in response to gonadotropin-releasing hormone administration and males with darker spotting had greater handling restraint-induced release of corticosterone. This suggests that plumage coloration is associated with underlying physiology, but the relationship between coloration and behaviour may shift between habitats.

Effect of anti-androgen and progesterone on development of regrowth antlers in 6 year old sika deer

To investigate the effects of anti-androgen drugs and melengestrol acetate (MGA) on development of regrowth antlers in 6 year old sika deer, twenty healthysika deerwith similar body weight and antler weightwere randomly divided into five groups by using single factor test design: flutamide (n=4), bicalutamide (n=4), progesterone acetate (CPA, n=4), melengestrol acetate (MGA, n=4), control(n=4). All deer were fed with same diets and were housed outside together in an opened fence of 15 m×30 m with free access to water and feed. Treatment groups were injected subcutaneously sustained-release agents of the four drugs respectively when two-branched antlers were harvested. The control group had no special treatment. In the experiment period of 60 d, blood sampleswere collected for 4 times for each deer. The concentration of testosterone in plasma was tested and analyzed to compare the changes between different groups. Development of regrowth antlers was observed. At the end of the experiment, regrowth antlers were weighted and analyzed. The resultsshowed that the weights of regrowth antlers in treatment groups were significantly greater than those from control group and the weight gain (as compared with the control group) was 100.50%, 64.46%, 87.16% and 117.46% respectively in flutamide group, bicalutamide group, progesterone acetate group and melengestrol acetate group. For plasma testosterone concentration, it was not significantly different in the early stage (in the first 35 d), but at the end of the experimen, it was significantly higher than that of earlier stage (P<0.01) in various groups. Testosterone concentration of flutamide treated group was significantly lower than that of the other groups (P<0.01), while the level inbicalutamide and MGA treated groups was significantly higher than that in other groups (P<0.01). The results showed that both anti-androgen drugs and MGA treatment promoted the development of regrowth antlers and increased the weight of regrowth antlers, where the effect was most significant by MGA treatment. From the morphological observation of the antlers, it was found that anti-androgen and MGA treatments prolonged the growth period of regrowth antlers through delaying the ossification of antlers. However, plasma testosterone concentration was not affected by the treatments.

Sex steroids and risk of differentiated thyroid carcinoma: Results from the EPIC study

Introduction The incidence of thyroid carcinomas has been rapidly increasing over the last 20–30 years in many Westernized countries. Large part of the increase is due to diagnostic improvements, however other changes may be involved. The only well-established risk factors for differentiated thyroid carcinomas (TC) (the most common forms of TC) are history of benign thyroid disease, notably goiter and benign nodules, and exposure to ionizing radiations (especially during childhood). However, recent studies have shown consistent evidence that body mass, including height and weight, are also positively associated with differentiated TC risk. However, mechanisms that may explain this association are currently not known but can include sex hormones. We therefore investigated the role of sex steroids and sex hormones binding globulin (SHBG) in the etiology of differentiated thyroid cancer in a case-control study nested within the large European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods Within EPIC, during follow-up, we identified 329 primary incident cases of differentiated thyroid carcinoma (133 in pre-menopausal women, 118 in postmenopausal women, and 78 in men) among subjects who participated in the study and gave a blood sample at blood collection. To these cases, 710 controls, who did not develop any cancers, apart from non-melanoma skin cancer, at the time of the diagnosis of the case, were matched on study recruitment center, sex, age, date, time, fasting status at blood collection, duration of follow-up, and, in women, menopausal status and phase of the menstrual cycle. Women taking exogenous hormones at blood donation were excluded. Plasma concentrations of testosterone (T), androstenedione (D4), dehydroepiandrosterone (DHEA), estradiol, estrone and progesterone (in pre-menopausal women only) were performed by a highly sensitive high-resolution liquid chromatography/mass spectrometry (LC-HSMS/MS) method. SHBG concentrations were measured by a validated immunoassay. Odds ratios (ORs) of TC by levels of each biomarker were estimated using conditional logistic regression models adjusted for potential confounders (including height, waist circumference, physical activity, smoking status, alcohol consumption, education level, and for women, age at first full term pregnancy, number of full term pregnancies, and exogenous hormone use). Results In pre-menopausal women, controls had a lower BMI, a shorter waist circumference, and a higher alcohol intake than the cases (24.2 vs. 25.7 kg/m2 for BMI, 76.5 vs. 80.0 cm for waist, 3.2 vs. 1.8 g/day for alcohol intake, respectively). Preliminary conditional logistic regression analyses suggest positive associations of borderline statistical significance of differentiated thyroid cancer with the concentrations of T, D4 and DHEA in pre-menopausal women (ORT3vsT1: 1.83 (95% CI: 0.99–3.39) for T; 1.99 (95% CI: 1.02–3.87) for D4; 1.84 (95% CI: 0.95–3.56) for DHEA). No associations could be observed in postmenopausal women nor in men. No associations were found with estrogens or progesterone. Conclusions This study is the first prospective study conducted on sex steroids and differentiated TC risk and will provide insights on mechanisms relating overweight and obesity to TC risk. Our preliminary results suggest a possible positive association of differentiated TC risk with high androgen concentration in pre-menopausal women but no relationship with estrogens or progesterone.

PO-259 Identification of a clinically meaningful site-specific steroid roadmap in prostate cancer

IntroductionIn prostate cancer the genotype of the tumour does not always predict clinical behaviour and disease aggressiveness after castration therapy. Additional factors might be important. Here we hypothesise that there is a site-specific steroid profile roadmap after castration that is of clinical significance.Material and methodsSteroid profiles in blood plasma (BP) and bone marrow aspirate plasma (BMA) from 120 castrated patients with prostate cancer were evaluated with mass spectrometry. We studied the steroid ligand-receptor interactions in prostate cancer adrenal metastases (PCAM) because they represent a steroid-rich environment. Adrenalectomy specimens from 3 castrated patients with PCAM were analysed.Results and discussionsIt is known that normally BP/Adrenal vein plasma testosterone (T) concentration ratio is approximately 1:1 and cortisol (C) ratio is roughly1:3. We measured similar T levels in BP and BMA. The levels of C were significantly lower in BMA compared to BP. Our data suggest that T levels are uniform but there is a C concentration gradient between the different compartments. Cortisol acts through GR and in the presence of T is a partial AR inhibitor.All PCAM samples had functional androgen receptor (AR) (wild-type (wt), no copy number changes) and glucocorticoid (GR), but no progesterone receptor (PR). No DHT was detected. Patient 1 tumour was able to synthesise T and had above castrate intra-tumoral T levels. The tumour lacked enzymes to synthesise, but was able to catabolize C. The levels of C were within the normal BP range. Gene expression of AR was normal. Patient 2 and 3 samples had castrate T and high C levels (3-fold BP), but AR gene expression was remarkably high. All patients had PTEN and RB deletions, while patients 2 and 3 had mutant (m) p53.Addition of 40 ng/dl T increased growth in vitro in a xenograft PCAM model (propagated in matrigel) derived from patient 1. When C was concomitantly added at high levels such as those in patients 2 and 3, PCAM growth returned to baseline (no steroids), suggesting that almost all T or C activity were lost. Moreover, proliferation in VCAP cells (High AR/GR+) decreased when high C was added in low T, but remained well above baseline, generating the hypothesis that this steroid combination mostly inhibits AR/GR tumours with non-amplified AR (e.g. early in castration).ConclusionThere is a clinically meaningful site-specific steroid roadmap. The PCAM steroid profile may serve as a useful model to elucidate tumour interactions with the steroid environment.

Modulation of inflammatory and hormonal parameters in response to testosterone therapy: Effects on the ventral prostate of adult rats.

Testosterone is often recommended in the treatment of several aging-related conditions. However, there are still questions about the consequences of this therapy in terms of hormonal and inflammatory parameters that are crucial for prostate homeostasis. Thus, we investigate if the testosterone therapy (TT) modulates the hormone receptors and inflammatory cytokines in the ventral prostate of adult rats. Wistar rats aging 150 days were divided into two experimental groups (n = 10/group): T: received subcutaneous injections of testosterone cypionate (5 mg/kg body weight) diluted in corn oil every other day for 4 weeks; and C: received corn oil as vehicle. Animals were euthanized at 180 days old by decapitation. Blood was collected to obtain hormone and cytokines concentrations. The ventral prostate was dissected and processed for light microscope and molecular analyses. Relative ventral prostate weight and epithelial compartment were increased after TT. The number of intact and degranulated mast cells was reduced in the T group. Plasma testosterone, DHT and intraprostatic testosterone concentrations were higher in the T group. TT leads to an increase in cell proliferation and up-regulation of AR, ERβ, PAR-4, and NRF2. Importantly, plasma concentration and tissue expression of IL-10 and TNF-α were higher after TT. In summary, these results indicate that TT can regulate inflammatory response, with impacts in cytokines and mast cell population, and modulates steroids receptors, important parameters for prostatic homeostasis.