Significant Decrease In Testosterone Research Articles

The soy phytoestrogens genistein and daidzein as neuroprotective agents against anoxia-glucopenia and reperfusion damage in rat urinary bladder

Some bladder disorders, such as obstructive bladder and hyperactivity, may be caused partly by ischemia/reperfusion injury (I/R). The neuroprotective effects of estrogens were demonstrated in in vitro studies and a great interest in soy isoflavones (genistein and daidzein) as alternative to the synthetic estrogen receptor modulators for therapeutic use has been pointed out. The aim of this study was to investigate the effect of genistein and daidzein, on rat detrusor smooth muscle contractility and their possible neuroprotective role against I/R-like condition.Whole rat urinary bladders were subjected to in vitro anoxia-glucopenia (A-G) and reperfusion (R) in the absence or presence of drugs and response to electrical field stimulation (EFS) of intrinsic nerves evaluated. Furthermore rats were treated in vivo for 1week with the phytoestrogens and the same in vitro protocol was applied to the ex vivo bladders. Antioxidant activity of genistein and daidzein on the A-G/R model was determined by measuring malonyldialdehyde (MDA). Moreover, hormones plasma levels were determined by radioimmunoassay.Genistein and daidzein administered either in vitro or in vivo showed significant neuroprotective effect and antioxidant activity. Testosterone and 17β-estradiol plasma levels were not modified by daidzein, while a significant decrease of testosterone in genistein treated rats was evident. Moreover both phytoestrogens significantly decreased detrusor contractions induced by EFS in a concentration-dependent manner. For being either neuroprotective and myorelaxant, genistein and daidzein could be considered a good lead for new therapeutic agents to protect the urinary bladder from hyperactivity and nerve damage.

Time-course response in serum markers of bone turnover to a single-bout of electrical stimulation in patients with recent spinal cord injury

The objective of the present repeat-measures study was to determine whether plasma serum levels of testosterone, cortisol, osteocalcin or type I collagen C-telopeptide (CT) are acutely affected following an electro-myostimulation (EMS) bout, and their relation to bone mineral density and muscle mass. Ten men with recent (8 weeks) thoracic spinal cord injury (SCI) (ASIA A) and 10 age-matched able-bodied (AB) men performed one EMS bout on the quadriceps femoris muscle. Blood samples were drawn at basal condition, immediately after EMS, and 15 min, 30 min, 24 h and 48 h post-EMS. Muscle cross-sectional area was measured by magnetic resonance imaging. Bone mineral density (BMD) was determined by dual-energy X-ray absorptiometry. In the SCI group, a significant decrease in testosterone, cortisol and CT together with a significant increase in testosterone/cortisol ratio and osteocalcin/CT ratio was observed after EMS. For the AB subjects, only testosterone and CT decreased significantly following EMS. Muscle size was only related to testosterone/cortisol ratio in the SCI sample (R = 0.659, p < 0.05), whereas BMD did not show any relation to any biomarker. Acute EMS in recent spinal cord injured men seems to induce positive effects on bone turnover biomarkers, and anabolic and catabolic hormones.

Diamel Therapy in Polycystic Ovary Syndrome Reduces Hyperinsulinaemia, Insulin Resistance, and Hyperandrogenaemia

For to determine the effect of Diamel on the insulin resistance, insulin sensitivity, and sexual hormones results in women with polycystic ovary syndrome (PCOS). A study was carried out on 37 patients with this disorder. A triple-blind clinical trial was designed in which the Diamel food supplement was compared with a placebo. The women with reproductive ages were randomly distributed in two groups, with 18 and 19 women respectively, and they took Diamel or placebo and were followed up during 6 months with clinical and biochemical evaluation. A significant decrease in the HOMA-IR from the initial value at six months was observed in the group with Diamel. The insulin sensitivity improved considerably in this group. The rate of menstrual recovery was higher in the group with Diamel, and two patients from this group obtained pregnancy. The hormone levels shows a significant decrease in testosterone at 3 months in the group with Diamel compared with the control group. The LH also decreases in the same group when comparing the start with 6 months.We concluded that the Diamel decreases insulin resistance and improves sensitivity to this hormone in women with PCOS, with improvement in the levels of LH and testosterone.

Sex hormones aging and Alzheimer s disease

A promising strategy to delay and perhaps prevent Alzheimer's disease (AD) is to identify the age-related changes that put the brain at risk for the disease. A significant normal age change known to result in tissue-specific dysfunction is the depletion of sex hormones. In women, menopause results in a relatively rapid loss of estradiol and progesterone. In men, aging is associated with a comparatively gradual yet significant decrease in testosterone. We review a broad literature that indicates age-related losses of estrogens in women and testosterone in men are risk factors for AD. Both estrogens and androgens exert a wide range of protective actions that improve multiple aspects of neural health, suggesting that hormone therapies have the potential to combat AD pathogenesis. However, translation of experimental findings into effective therapies has proven challenging. One emerging treatment option is the development of novel hormone mimetics termed selective estrogen and androgen receptor modulators. Continued research of sex hormones and their roles in the aging brain is expected to yield valuable approaches to reducing the risk of AD.

Effect of ovarian aging on androgen biosynthesis in a cynomolgus macaque model

Objective The role of androgens in chronic disease pathogenesis, cognitive function and libido during menopause is of increasing interest. The aim of this study was to characterize the distribution and expression of androgenic proteins in the macaque ovary and to investigate the relationship between serum androgen concentrations, follicle number, and the persistence of androgenesis in the aging macaque ovary.Methods The subjects were 26 adult female cynomolgus macaques. Ovaries were immunostained for cytochrome P450 17α-hydroxylase/17–20 lyase (P450c17), 3β-hydroxysteroid dehydrogenase (3βHSD), and cytochrome b5 (cytb5). Based on primordial follicle counts, animals were divided into tertiles (low (≤200), intermediate (226–1232), and high (2372–4356)) to evaluate differences in androgen staining and changes in serum androgen concentrations following ovariectomy.Results Positive immunostaining for P450c17 and cytb5 within the theca interna layer of growing follicles persisted in advanced atretic follicles and secondary interstitial cells (residual stromal cells). Ovaries with low follicle numbers had less staining for all androgenic proteins compared to ovaries with higher numbers of growing follicles. Immunostaining for cytb5 was the most reliable marker for persistent androgenesis in ovaries with minimal primordial follicle numbers (<100) and residual stromal cells. Following ovariectomy, a significant decrease in testosterone (−27.7%, −30.8%, −27.5%; p < 0.01) and androstenedione (−33.4%, −35.7%, −46.0%; p < 0.01) was observed in monkeys with low, intermediate, and high primordial follicle counts, respectively.Conclusions Despite low follicle numbers, the aging macaque ovary retains the necessary proteins for androgenesis within residual stromal cells and contributes to peripheral androgen concentrations.

The therapeutic effect of a pulsed electromagnetic field on the reproductive patterns of male Wistar rats exposed to a 2.45-GHz microwave field

INTRODUCTION:Environmental exposure to man-made electromagnetic fields has been steadily increasing with the growing demand for electronic items that are operational at various frequencies. Testicular function is particularly susceptible to radiation emitted by electromagnetic fields.OBJECTIVES:This study aimed to examine the therapeutic effects of a pulsed electromagnetic field (100 Hz) on the reproductive systems of male Wistar rats (70 days old).METHODS:The experiments were divided into five groups: microwave sham, microwave exposure (2.45 GHz), pulsed electromagnetic field sham, pulsed electromagnetic field (100 Hz) exposure, and microwave/pulsed electromagnetic field exposure. The animals were exposed for 2 hours/day for 60 days. After exposure, the animals were sacrificed, their sperm was used for creatine and caspase assays, and their serum was used for melatonin and testosterone assays.RESULTS:The results showed significant increases in caspase and creatine kinase and significant decreases in testosterone and melatonin in the exposed groups. This finding emphasizes that reactive oxygen species (a potential inducer of cancer) are the primary cause of DNA damage. However, pulsed electromagnetic field exposure relieves the effect of microwave exposure by inducing Faraday currents.CONCLUSIONS:Electromagnetic fields are recognized as hazards that affect testicular function by generating reactive oxygen species and reduce the bioavailability of androgen to maturing spermatozoa. Thus, microwave exposure adversely affects male fertility, whereas pulsed electromagnetic field therapy is a non-invasive, simple technique that can be used as a scavenger agent to combat oxidative stress.

Effects of BDE-99 on hormone homeostasis and biochemical parameters in adult male rats

In this study, we evaluated the effects of BDE-99 on hormone homeostasis, as well as in urinary and serum biochemical parameters of adult male rats. Animals (10 per group) received BDE-99 by gavage at single doses of 0, 0.6 and 1.2 mg/kg. Forty-five days after BDE-99 exposure, urine and serum samples were collected for hormonal and biochemical analysis. Oxidative stress (OS) markers in erythrocytes, plasma and urine were also evaluated. Urinary excretion of total protein significantly increased following BDE-99 exposure, while lactate dehydrogenase (LDH), γ-glutamil transferase (GGT), and N-acetylglucosaminidase (NAG) activities significantly decreased. Liver toxicity was evidenced by elevated serum activities of the enzymes glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) and alkaline phosphatase (ALP). Following BDE-99 administration, OS markers in erythrocytes showed an increase in superoxide dismutase (SOD) activity, and a reduction in glutathione reductase (GR) activity. In urine, isoprostane levels increased after BDE-99 exposure. The hormonal analysis showed a significant decrease in testosterone and progesterone levels. These results support the hypothesis that BDE-99 interacts with hormonal response. Moreover, BDE-99 administration to adult male rats showed signs of renal and hepatic toxicity.

Effect of food restriction on ghrelin in adult male rats and its relation to male reproductive hormones

Ghrelin is an endogenous ligand for growth hormone secretagogue (GHS) receptor (GHS-R). It has recently emerged as an orexigenic food intake controlling signal acting upon hypothalamic centres. To study the effect of food restriction on ghrelin level and its relation to male reproductive hormones, 32 adult male albino rats divided into two groups: Group I (8 rats as a control group) fed ad libitum for 21 days and 24 rats as Group II (food-restricted group) fed 30% of ad libitum intake of food consumed by the control group. Rats were weighed every 3 days. Group II rats were further subdivided into three subgroups: IIa, IIb and IIc that were killed at days 8, 16 and 21 from the start of food restriction respectively. Ghrelin level was assayed by ELISA technique in serum samples and tissue homogenates prepared from the stomach and hypothalamus. In addition, male reproductive hormones: testosterone, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were assayed in serum by chemiluminescence. Mean body weight of food restricted rats was observed to decrease during the period of the experiment. Food restriction produced a significant increase of serum ghrelin and a significant decrease of both gastric and hypothalamic ghrelin in group II when compared with group I. The changes in ghrelin level varied with the duration of food restriction. Significant inverse correlation was found between serum ghrelin and each of gastric and hypothalamic ghrelin in group II. A significant decrease of testosterone, FSH and LH were found in food restricted rats compared with controls. The decrease was significantly related to the duration of food restriction. Significant inverse correlation was detected between serum ghrelin and each of the male reproductive hormones in food restricted group II rats. Thus ghrelin could be one of the hormones responsible for the suppression of male reproductive axis in case of negative energy balance.

The inhibitory effects on adult male reproductive functions of crude garlic (Allium sativum) feeding

to investigate the effects of crude garlic on adult male rat reproductive functions. Thirty male rats were divided into five groups: group 1 (untreated) and groups 2, 3, 4 and 5 were fed for 30 days with 5%, 10%, 15% and 30% crude garlic, respectively. Testes and accessory organs were weighed and some markers were assessed. Light and electron microscopy observations were also performed. A significant decrease was observed in the body weight of groups 4 (14%; P < 0.01) and 5 (20%; P < 0.01); of the prostate weight in group 5 (29.1%; P < 0.05) and of seminal vesicle weight in groups 3 (14.4%; P < 0.01), 4 (18.3%; P < 0.01) and 5 (27.3%; P < 0.01). In contrast, testis and epididymis weights were unchanged. In epididymis tissue, the alpha glucosidase activity and the spermatozoa density were unchanged. The treatment resulted in a significant decrease in testosterone serum levels in groups 3 (77.3%; P < 0.01), 4 (77.3%; P < 0.01) and 5 (90.9%; P < 0.01), associated with a significant increase in LH serum levels (P < 0.01). Testicular histology showed a dose-dependent increase in the percentage of empty seminiferous tubules. Moreover, testicular function was affected; a significant decrease in phosphatase acid activity (P < 0.01) and testosterone (P < 0.05) contents were observed. Crude garlic consumption during 1 month reduced testosterone secretion and altered spermatogenesis at 10%, 15% and 30% doses.

Free testosterone levels and implications on clinical outcomes in elderly men

Aging is accompanied by a progressive decline in serum testosterone. Evidence concerning the clinical manifestations of low serum testosterone levels is contradictory. We aimed to examine the age-related decline in testosterone and the possible clinical outcomes, including erectile dysfunction, prostatism, cognitive function, daily life activities, depression, and osteoporosis. One hundred and twenty men underwent comprehensive geriatric assessment. Testosterone and free testosterone levels were measured, geriatric assessment scales, International Index of Erectile Function (IIEF) and International Prostate Symptom Scale (IPSS) were performed, and bone mineral densities were determined. The mean age of the 120 men was 73.8+/-5.90. A significant decrease in testosterone and free testosterone levels with increasing age was determined (p=0.021). It was also found that erectile dysfunction, as determined by IIEF (r=0.66, p<0.001), and symptoms of prostatism determined by IPSS (r=-0.23, p=0.016), were significantly associated with low free testosterone levels. Laboratory parameters, obesity, osteoporosis, cognitive function, daily life activities, and cardiovascular diseases were not significantly different between groups with low and normal free testosterone levels. Age-related decrease in free testosterone may lead to erectile dysfunction and symptoms of prostatism in elderly men.

Adverse Effects of Propranolol on Reproductive Function in Adult Male Mice

Ingestion of propranolol at 10 and 15 mg kg(-1) body weight for 35 days by adult male mice was investigated for its effects on fertility. Body weight and absolute and relative testes weights were reduced and the average weights of epididymis, ventral prostate and seminal vesicle decreased significantly. A significant decline of spermatogenesis in testes due to a decrease in the number of primary, secondary spermatocytes and spermatids in the treatment group 2 (15 mg kg(-1)) is attributed to a significant decrease in testosterone, LH and FSH. Sperm motility and density were also significantly decreased in the cauda epididymis and in the testes of group 2 treated male mice. In addition, the treatment markedly increased the number of fetal resorptions in female mice impregnated by the group 2 males, thereby reducing their fertility.

Hormonal responses to a 160-km race across frozen Alaska

Background:Severe physical and environmental stress seems to have a suppressive effect on the hypothalamic–pituitary–gonadal (HPG) axis in men. Examining hormonal responses to an extreme 160-km competition across frozen Alaska provides...

Adverse effects of rosemary (Rosmarinus officinalis L.) on reproductive function in adult male rats.

Ingestion of rosemary (Rosmarinus officinalis L.) by two groups of adult Sprague-Dawley rats at levels of 250 and 500 mg/kg body wt for 63 days was investigated for its effects on fertility. Body weight and absolute and relative testes weights were not affected, but the average weights of epididymides, ventral prostates, seminal vesicles, and preputial glands decreased significantly. A significant decline in spermatogenesis in testes due to a decrease in the number of primary and secondary spermatocytes and spermatids in treatment group 2 (500 mg/kg) is attributed to a significant decrease in testosterone. Sperm motility and density were also significantly decreased in the cauda epididymis and in the testes of rosemary-treated male rats in group 2. In addition, the treatment markedly increased the number of fetal resorptions in female rats impregnated by group 2 males, thereby reducing their fertility.

Health on the Factory Floor: Occupational Phthalate Exposure Reduces Testosterone

Human studies have shown widespread exposure to phthalates, compounds used in the manufacture of household, consumer, and medical products. The metabolites mono-2-ethylhexyl phthalate (MEHP) and mono-n-butyl phthalate (MBP) have shown testicular toxicity in rats, specifically damage to the cells that produce testosterone and sperm. But animal studies involve higher phthalate exposures than humans typically experience, and there is inconclusive evidence that low exposures affect testicular cells in men. Occupational phthalate exposure tends to be greater and more consistent than the highly variable low levels seen in the general population, however, and research at a Chinese manufacturing plant now reveals that such exposure can be significantly related to decreased blood testosterone concentration [EHP 114:1643–1648; Pan et al.]. The study participants included 74 men who manufactured polyvinyl chloride (PVC) flooring at a plant in Liaoning Province and 63 men employed at a construction company. All the men completed a questionnaire about lifestyle factors and provided blood and urine samples. Blood samples were analyzed for circulating amounts of free testosterone, luteinizing hormone, follicle-stimulating hormone, and estradiol. Urine analysis provided data on concentrations of MBP and MEHP, which served as biomarkers of exposure. Due to the materials involved in flooring manufacture, the men at the flooring plant were assumed to have dermal and inhalational exposure to dibutyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP), the parent compounds of MBP and MEHP. Indeed, all the participants except one construction worker had detectable levels of urinary MBP and MEHP, demonstrating that phthalate exposure was pervasive. However, PVC plant workers had up to 100-fold higher levels of MBP and MEHP and significantly lower blood testosterone concentrations, compared with construction workers. Regression analysis revealed a modest but significant decrease in testosterone as total phthalate esters increased. Based on MEHP concentrations, the investigators estimated that 40.5% of the PVC plant workers had DEHP exposure exceeding the European Union’s tolerable daily intake standard of 37.0 μg/kg body weight. The team concluded that high levels of DEHP and DBP exposure seemed to suppress testosterone production in the PVC plant workers, but it is not clear from this study what effect, if any, that might have on their fertility.

Sirolimus Impairs Gonadal Function in Heart Transplant Recipients

The impact of sirolimus on hormone levels involved in the hypothalamus-pituitary-gonad axis in male heart transplant recipients was investigated.A pair-matched analysis with 132 male heart transplant recipients on either sirolimus based- or calcineurin inhibitor-based immunosuppression was performed. Matching criteria were age, years after transplantation and creatinine levels. Measured parameters were testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), sexual hormone-binding globulin (SHBG) and free androgen index (FAI).Mean testosterone was 3.86 ± 1.41 ng/mL in the sirolimus group and 4.55 ± 1.94 ng/mL in the controls (p = 0.025). Serum LH was 12.82 ± 11.19 mlU/mL in the sirolimus patients and 6.2 ± 5.25 mlU/mL in the controls (p = 0.015). Follicle stimulating hormone levels were 13.31 ± 18.4 mlU/mL vs. 7.32 ± 5.53 mlU/mL, respectively (p = 0.015). The analysis revealed a significant decrease in testosterone and a significant increase in FSH and LH in the sirolimus group. The duration of sirolimus treatment correlated positively with SHBG (p < 0.01), LH (p < 0.05) and FSH (p < 0.05) and negative with the FAI (p < 0.05). Sirolimus trough levels correlated with LH and FSH levels (p < 0.01).Heart transplant recipients treated with sirolimus revealed significantly lower testosterone levels and a significant increase in gonadotropic hormones. These effects were trough-level dependent. All candidates awaiting organ transplantation should be informed about these adverse effects.

Serum Testosterone, Cortisol and Biochemistry During a Cycling Stage- Race

0992 Previous research has characterized the effects of multi-day stage races on resting blood biochemistry and hormonal status in cyclists. Whether the effects of racing on markers of training stress are unique in those cyclists that achieve the highest overall rankings is unknown. PURPOSE: To compare common biochemical and hormone parameters used to monitor severity of exercise in cyclists placing top10 and those not placing top10 in a 6-D stage race. METHODS: Venous blood was collected on each race day (D1-D6) in the morning from 14 Australian male road cyclists competing in the Tour of Tasmania. Serum was analyzed for Creatine Kinase (CK), Urea and Urate using automated photometric techniques and serum Cortisol and Testosterone were quantified using a competitive immunoassay. Seven cyclists finished in the top 10 overall and 7 cyclists did not achieve a top 10 result. Plasma volume shifts were estimated based on hematocrit and hemoglobin concentration. Data were analyzed using a 2 × 6 (group × day) ANOVA with repeated measures over time and a series of unpaired t-tests to examine daily group differences. Data are presented as Mean ± SD. RESULTS: On D1 there were no significant differences between top 10 and non-top 10 finishers: CK (175 ± 88 vs 109 ± 28 IU.L−1, p = 0.08), Urea (6.2 ± 0.8 vs 5.8 ± 1.3 mM, p = 0.51), Urate (0.26 ± 0.4 vs 0.27 ± 0.4 mM, p = 0.52), Cortisol (409 ± 69 vs 439 ± 80 mM, p = 0.48), Testosterone (14.5 ± 6.1 vs 18.6 ± 10.5 mM, p = 0.39). Racing was associated with a significant decrease in Testosterone (−19%) and a significant increase in Plasma Volume (17%), Cortisol (25%), CK (70%), Urea (36%) and Urate (21%). Interestingly, cyclists placing top 10 had less of a plasma volume expansion (D3) and a greater increase in CK (D4-D6) and Cortisol (D5) than cyclists that did not achieve a top 10 result. Both top 10 and non-top 10 cyclists had a similar Urea, Urate and Testosteone response to racing. CONCLUSIONS: The higher concentration of serum CK and Cortisol in top10 cyclists may reflect that a greater relative effort is required to achieve a competitive result. Further research is needed to understand why resting CK and Cortisol, but not Urea, Urate or Testosterone are unique in cyclists placing well in a 6-day stage race.

Di(n-butyl) phthalate impairs cholesterol transport and steroidogenesis in the fetal rat testis through a rapid and reversible mechanism.

In utero exposure to di(n-butyl) phthalate (DBP) leads to a variety of male reproductive abnormalities similar to those caused by androgen receptor antagonists. DBP demonstrates no affinity for the androgen receptor, but rather leads to diminished testosterone production by the fetal testis. The purpose of this study was to determine the onset and reversibility of DBP effects on the fetal testis and to determine at a functional level the points in the cholesterol transport and steroidogenesis pathways affected by DBP. Starting at gestational day (gd) 12, pregnant rats were gavaged daily with 500 mg/kg DBP or corn oil control. Significant decreases in testosterone production and mRNA expression of scavenger receptor B1, P450(SCC), steroidogenic acute regulatory protein, and cytochrome p450c17 were observed as early as gd 17. Testosterone, mRNA, and protein levels remained low 24 h after withdrawal of DBP treatment but increased 48 h after cessation of DBP exposure. In another experiment, pregnant dams were treated with DBP until gd 19, with the start of DBP treatment moved 1 d later into gestation for each treatment group, with the final group dosed only on gd 19. Significant decreases in testosterone, mRNA expression, and protein expression were evident as early as 3 h after treatment with DBP, with full repression apparent 24 h after treatment. Using a testis explant system, we determined that DBP treatment led to diminished transport of cholesterol across the mitochondrial membrane as well as diminished function at each point in the testosterone biosynthesis pathway except 17 beta-hydroxysteroid dehydrogenase. The transcriptional repression caused by DBP does not appear to be mediated via interference with steroidogenic factor-1 as determined by reporter assays. We conclude that high-dose DBP exposure leads to rapid and reversible diminution of the expression of several proteins required for cholesterol transport and steroidogenesis in the fetal testis, resulting in decreased testosterone synthesis and consequent male reproductive maldevelopment.

HORMONAL RESPONSES TO A 160KM RACE (SUSITNA 100) ACROSS FROZEN ALASKA.

The year 2000 Susitna 100, formally named the Iditasport 100, provided a novel race in which to examine hormonal responses. The 160km race included an elevation gain of 2270m, the ambient temperature at the start of the race was 28oF and dropped to 20oF, accompanied by a wet snowfall, a few hours after starting. Furthermore it was mandatory that all racers carried survival gear weighing a minimum of 15lbs. PURPOSE To examine hormonal responses to a 160km race across frozen Alaska. METHOD Blood samples were obtained from sixteen men before and after racing, and analyzed for testosterone, interlukin-6 (IL-6), growth hormone(GH), and cortisol. Six of the subjects raced by bicycle and ten subjects raced by foot(runners); mean(±SD) finish times were 1310 ±376min and 2039 ±367min, respectively. RESULTS No differences were observed in the hormonal responses between the cyclists and runners. In the cyclists there was significant(p < .05) pre-to post-race increase in cortisol (mean ±SE, 138.89 ±14.86 to 440.64 ±48.15nmol/L), GH (0.12 ±0.00 to 3.22 ±1.05ng/ml), IL-6 (2.42 ±.25 to 12.25 ±0.56pg/ml), and a significant decrease in testosterone (12.32 ±1.41 to 6.96 ±1.00nmol/L). In the runners there was a significant pre- to post-race increase in cortisol (245.83 ±55.21 to535.98 ±94.80ng/ml), GH (0.1832 ±.00 to 3.73 ±0.53n/ml), IL-6 (2.42 ±0.21 to 12.25 ±0.56 pg/ml), and a significant decrease in testosterone (13.81 ±1.30 to 5.59 ±1.53nmol/L). CONCLUSION These data indicate a suppression of the hypopituitary gonadal axis potentially mediate by amplification of adrenal stress responses to such an ultra-endurance race.

Müllerian Inhibiting Substance lowers testosterone in luteinizing hormone-stimulated rodents.

Müllerian Inhibiting Substance (MIS) expression is inversely proportional to the serum concentration of testosterone in males after birth and in vitro studies have shown that MIS can lower testosterone production by Leydig cells. Also, mice overexpressing MIS exhibited Leydig cell hypoplasia and lower levels of serum testosterone, but it is not clear whether this is a result of MIS affecting the development of Leydig cells or their capacity to produce testosterone. To examine the hypothesis that MIS treatment will result in decreased testosterone production by mature Leydig cells in vivo, we treated luteinizing hormone (LH)-stimulated adult male rats and mice with MIS and demonstrated that it can lead to a several-fold reduction in testosterone in serum and in testicular extracts. There was also a slight decrease in 17-OH-progesterone compared to the more significant decrease in testosterone, suggesting that MIS might be regulating the lyase activity of cytochrome P450c17 hydroxylase/lyase (Cyp17), but not its hydroxylase activity. Northern analysis showed that, in both MIS-treated rats and mice, the mRNA for Cyp17, which catalyzes the committed step in androgen synthesis, was down-regulated. In rats, the mRNA for cytochrome P450 side-chain cleavage (P450scc) was also down-regulated by MIS. This was not observed in mice, indicating that there might be species-specific regulation by MIS of the enzymes involved in the testosterone biosynthetic pathway. Our results show that MIS can be used in vivo to lower testosterone production by mature rodent Leydig cells and suggest that MIS-mediated down-regulation of the expression of Cyp17, and perhaps P450scc, contributes to that effect.

Environmental and seasonal adaptations of the adrenocortical and gonadal responses to capture stress in two populations of the male garter snake, Thamnophis sirtalis.

Stress and reproduction are generally thought to work in opposition to one another. This is often manifested as reciprocal relationships between glucocorticoid stress hormones and sex steroid hormones. However, seasonal differences in how animals respond to stressors have been described in extreme environments. We tested the hypothesis that garter snakes, Thamnophis sirtalis, with limited reproductive opportunities will suppress their hormonal stress response during the breeding season relative to conspecifics with an extended breeding season. The red-sided garter snake, T.s. parietalis, of Manitoba, Canada, has a brief breeding season during which males displayed no change in either plasma levels of testosterone or corticosterone, which were both elevated above basal levels, in response to capture stress. During the summer, capture stress resulted in increased plasma corticosterone and decreased testosterone. During the fall, when mating can also occur, males exhibited a significant decrease in testosterone but no increase in corticosterone in response to capture stress. The red-spotted garter snake, T.s. concinnus, of western Oregon, has an extended breeding season during which males displayed a stress response of increased plasma corticosterone and decreased testosterone levels. The corticosterone response to capture stress was similar during the spring, summer, and fall. In contrast, the testosterone response was suppressed during the summer and fall when gametogenesis was occurring. These data suggest that male garter snakes, in both populations, seasonally adapt their stress response but for different reasons and by potentially different mechanisms. J. Exp. Zool. 289:99-108, 2001.