Peripheral Testosterone Levels Research Articles

Photoperiod manipulation corrects the negative effect of low dietary crude protein levels during weeks 12 to 26 on bone quality and fertility of male Guinea fowl (Numida meleagris)

Improving the reproductive performance of guinea fowl (Numida meleagris) based on the management of environmental factors is important for developing meleagriculture. Thus, the present study was conducted to evaluate the effect of dietary crude protein levels and photoperiod during the 12th to 26th wk of age on growth performance, calcium and phosphorus mobilization, and fertility of local Pearl Gray male guinea fowl. In total, 120 twelve-week-old male guinea fowl were divided into 3 groups with 8 replicates each and 5 birds per replicate using a completely random design. The experimental groups included: a group fed a diet containing 15% crude protein and subjected to 16 h of light and 8 h of darkness (16LL), a group fed a diet containing 19% crude protein and subjected to 16 h of light and 8 h of darkness (16HL), and a group fed a diet containing 15% crude protein and subjected to 18 h of light and 6 h of darkness (18LL) during the 12th to 26th wk of age. The results showed that guinea fowl in the 16HL treatment had a significantly (P = 0.003) lower feed conversion ratio than those in the 16LL and 18LL groups. Calcium and phosphorus levels in the tibia and femur were significantly higher (P < 0.05) in guinea fowl of the 16HL and 18LL groups than in that of the 16LL group. Birds in the 16HL and 18LL treatments had significantly higher peripheral testosterone levels (P < 0.00001) than those in the 16LL treatment. The 16HL and 18LL treatments had significantly higher (P < 0.05) sperm volume, sperm concentration and motility, and fertility rate than the 16LL group. Therefore, a decrease in crude protein level from 19 to 15% in the diet of male guinea fowl between the 12th and 26th wk of age negatively affects the growth performance and fertility of these birds, but this is corrected by an increase in the photoperiod before sexual maturity.

Long-term effects of the mmune cells introduction on the recipients endocrine system functional activity: experimental study

The plasticity of the main homeostatic systems immune and neuroendocrine allows the body to resist the actions of adverse factors, but, nevertheless, the latter can cause pathological changes or lead to a limitation in the function of these systems. The paper presents data demonstrating the long-term effects of the immune cells with different functional phenotypes transplantation performed during early postnatal ontogenesis on the syngeneic recipients endocrine system functional activity, assessed by the neuroactive steroid hormones level in the CNS and in blood serum. The relevance of this study is due to the active development of cellular technologies and their successful use in the treatment of many nosological forms of immunological, oncological and hematological diseases, which has significantly improved the survival rate and quality of patient’s life; however the mechanisms of the transplanted cells effect on the body as a whole remain insufficiently studied, especially in childhood, when the formation of regulatory connections of the main homeostatic systems of the body that maintain dynamic homeostasis is taking place, and it is difficult to predict the long-term effect of therapy, because, even with a directed effect on one of them, influence is exerted on the interconnected functioning of all these systems. Previously, we have shown that immune cells with different functional activities, which is characteristic of individuals with an active or passive type of behavior, after transplantation performed at different stages of ontogenesis, in a cytokine-mediated manner affect the change/formation of a certain neuroimmune status in syngeneic recipients, including the behavioral phenotype. The presented study shows that after a threefold administration of immune cells in the juvenile period, a certain hormonal status is formed in syngeneic recipients by puberty: in all recipients, after cell transplantation, the level of corticosterone in the brain and its separate structures, as well as in the peripheral blood serum, was relatively higher than that in animals raised without adoptive cell transfer; at the same time, there was a pronounced tendency to increase the level of testosterone in the blood serum, and different levels of testosterone were recorded in the hypothalamus, hippocampus, striatum, and frontal cortex. Distinctive features of the central and peripheral levels of corticosterone and testosterone in recipients after multiple transplantation of splenocytes in the late period of maturity are determined by the different functional phenotype of the injected immune cells.

Antidepressants’ effects on testosterone and estrogens: What do we know?

Various antidepressants are commonly used to treat depression and anxiety disorders, and sex differences have been identified in their efficacy and side effects. Steroids, such as estrogens and testosterone, both in the periphery and locally in the brain, are regarded as important modulators of these sex differences. This review presents published data from preclinical and clinical studies that measure testosterone and estrogen level changes during and/or after acute or chronic administration of different antidepressants. The majority of studies show an interaction between sex hormones and antidepressants on sexual function and behavior, or in depressive symptom alleviation. However, most of the studies omit to investigate antidepressants’ effects on circulating levels of gonadal hormones. From data reviewed herein, it is evident that most antidepressants can influence testosterone and estrogen levels. Still, the evidence is conflicting with some studies showing an increase, others decrease or no effect. Most studies are conducted in male animals or humans, underscoring the importance of considering sex as an important variable in such investigations, especially as depression and anxiety disorders are more common in women than men. Therefore, research is needed to elucidate the extent to which antidepressants can influence both peripheral and brain levels of testosterone and estrogens, in males and females, and whether this impacts the effectiveness or side effects of antidepressants.

Child sexual offenders show prenatal and epigenetic alterations of the androgen system

Child sexual offending (CSO) places a serious burden on society and medicine and pedophilia (P) is considered a major risk factor for CSO. The androgen system is closely linked to sexual development and behavior. This study assessed markers of prenatal brain androgenization, genetic parameters of androgen receptor function, epigenetic regulation, and peripheral hormones in a 2 × 2 factorial design comprising the factors Offense (yes/no) and Pedophilia (yes/no) in analyzing blood samples from 194 subjects (57 P+CSO, 45 P−CSO, 20 CSO−P, and 72 controls) matched for age and intelligence. Subjects also received a comprehensive clinical screening. Independent of their sexual preference, child sexual offenders showed signs of elevated prenatal androgen exposure compared with non-offending pedophiles and controls. The methylation status of the androgen receptor gene was also higher in child sexual offenders, indicating lower functionality of the testosterone system, accompanied by lower peripheral testosterone levels. In addition, there was an interaction effect on methylation levels between offense status and androgen receptor functionality. Notably, markers of prenatal androgenization and the methylation status of the androgen receptor gene were correlated with the total number of sexual offenses committed. This study demonstrates alterations of the androgen system on a prenatal, epigenetic, and endocrine level. None of the major findings was specific for pedophilia, but they were for CSO. The findings support theories of testosterone-linked abnormalities in early brain development in delinquent behavior and suggest possible interactions of testosterone receptor gene methylation and plasma testosterone with environmental factors.

Testosterone levels in healthy men correlate negatively with serotonin 4 receptor binding

The serotonergic system integrates sex steroid information and plays a central role in mood and stress regulation, cognition, appetite and sleep. This interplay may be critical for likelihood of developing depressive episodes, at least in a subgroup of sensitive individuals. The serotonin 4 receptor (5-HT4R) indexes central serotonergic tonus, which may be related to endogenous sex-steroid levels in the mentally healthy state even though this remains elusive. Here we evaluate if peripheral levels of estradiol and testosterone are associated with 5-HT4R binding as imaged by [11C]SB207145 positron emission tomography in a group of 41 healthy men. We estimated global 5-HT4R binding using a latent variable model framework, which models shared correlation between 5-HT4R across multiple brain regions (hippocampus, amygdala, posterior and anterior cingulate, thalamus, pallidostriatum and neocortex). We tested whether testosterone and estradiol predict global 5-HT4R, adjusting for age. We found that testosterone, but not estradiol, correlated negatively with global 5-HT4R levels (p=0.02) suggesting that men with high levels of testosterone have higher cerebral serotonergic tonus. Our findings corroborate the link between sex hormone levels and serotonin signalling. Future longitudinal studies in clinical relevant populations are needed to elucidate the potential importance of testosterone in the pathophysiology of e.g. major depression and its treatment.

Circadian variations in peripheral levels of growth hormone and testosterone in male Murrah buffaloes

The aim of this study was to investigate the endocrine profiles of growth hormone (GH), testosterone and their interrelationship in prepubertal, pubertal and orchiectomised male Murrah buffaloes under starving conditions. The prepubertal and pubertal buffaloes were subjected to frequent blood sampling over 24 h at an interval of 1 h, whereas in orchiectomised buffaloes, the blood samples were collected over 18 h. Irrespective of group, the GH concentrations fluctuated in an episodic manner over 24 h and the fluctuations did not exhibit a consistent pattern between the animals of each group. The mean basal and peak concentrations of GH did not differ significantly (p > 0.05) among the groups. A significant (p > 0.0001) difference in testosterone concentrations was observed between prepubertal and pubertal groups. The differences in mean basal and peak testosterone concentrations between the prepubertal and pubertal groups were also significant (p < 0.01). The associations between testosterone and GH levels in both prepubertal (r = 0.15; p > 0.05) and pubertal (r = −0.37; p > 0.05) buffaloes were non-significant. The possible reasons for erratic episodic pattern of GH secretion will be discussed.

Oxytocin but Not Testosterone Modulates Behavioral Patterns in Autism Spectrum Disorders

Autism spectrum disorder (ASD) is a neurodevelopmental disorder of unknown etiology. Social deficits represent one of the core symptoms of the diagnosis. The aim was to reveal possible correlations among peripheral levels of oxytocin and testosterone with behavioral and symptom characteristics in patients with ASD. 8 children with ASD were recruited and underwent psychological profiling. Blood oxytocin and testosterone levels were analyzed using ELISA method. Oxytocin levels positively correlated with Adaptation to change category of CARS-2 (P = 0.008, R = 0.848) and Vineland-II maladaptive behavior scores (P = 0.004, R = 0.884). No significant correlations were found among testosterone levels and behavioral parameters. Higher oxytocin levels were connected with more severe adaptive behavior in ASD patients. Increased oxytocin levels in children with more severe phenotype could be a result of compensatory mechanism of impaired oxytocin signaling. Oxytocin seems to employ distinct mechanisms in regulating social behavior in autism and healthy population.

Early sexual maturity in local boars of Northeastern India: Age-related changes in testicular growth, epididymal sperm characteristics and peripheral testosterone levels

The present study reports the age related changes in the peripheral testosterone levels, testicular and epididymal growth and development and cauda epididymal spermiogram in local pigs of Northeastern India, which attain sexual maturity around 3 months of age. Local boars (n = 20) were castrated at monthly intervals from 2 to 6 months of age (4 boars per month) to study the testicular growth and development and the epididymal spermiogram. Blood samples, collected from local boars (n = 6) at monthly intervals from 2 to 6 months of age, were analyzed for testosterone levels by radioimmunoassay. Compared to Hampshire boars, significantly (P < 0.05) high testosterone levels were observed in the local boars as early as 2 months of age. The mean (± SEM) level of testosterone in the local boars at 2, 3 and 4 months of age was 11.89 ± 1.52, 20.45 ± 1.33 and 20.38 ± 2.0 ngml −1, respectively. Though there was consistently significant (P < 0.05) difference in the body weight between Hampshire and local pigs, the same was not observed in case of testicular weight except at 3 and 6 months of age. In line with the above observation, the testis:body weight ratio (gram testis per kg body weight) was significantly (P < 0.05) higher in the local boars compared to the Hampshire boars at any time of observation, which ranged from 0.8 to 1.0 in case of Hampshire and from 2.3 to 3.0 in local boars. The sperm concentration in the cauda epididymal fluid of local boars at 2, 3 and 6 months of age was 2255 ± 186.6, 3685 ± 103.8 and 4325 ± 146.2 million/ml, respectively and the sperm motility, viability and total abnormality was 73.3, 75.2 and 6.2%, respectively at 3 months of age. Taken together, the testosterone level, testicular growth and development and epididymal spermiogram indicate the trait of early sexual maturity in the local pigs as compared to Hampshire.

Aromatase and 5-alpha Reductase Gene Expression: Modulation by Pain and Morphine Treatment in Male Rats

BackgroundThe steroid hormone testosterone has been found to be greatly reduced by opioids in different experimental and clinical conditions. The purpose of this study on male rats was to determine the effects of a single injection of morphine (5 mg/Kg) on persistent pain (formalin test) and the single or combined effects on p450-aromatase and 5-alpha reductase type 1 mRNA expression in the brain, liver and testis. Testosterone was determined in the plasma and in the brain, morphine was assayed in the plasma.ResultsIn the morphine-treated rats, there were increases of 5-alpha reductase mRNA expression in the liver and aromatase mRNA expression in the brain and gonads. Morphine was detected in the blood of all morphine-treated rats even though there were no clear analgesic affects in the formalin-treated animals three hours after treatment. Testosterone was greatly reduced in the plasma and brain in morphine-treated subjects.ConclusionsIt appears that morphine administration can induce long-lasting genomic effects in different body areas which contribute to the strong central and peripheral testosterone levels. These changes were not always accompanied by behavioral modifications.

Effects of Dexamethasone and Testosterone Propionate on LH Response to Gonadoliberin (LRH) in Young Post-Pubertal Bulls

LH and testosterone responses to gonadoliberin (LRH) were studied after previous dexamethasone and testosterone propionate combined treatment (treated group) compared with a single dexamethasone previous treatment (control group) in 12 Montbéliarde bulls aged 15 months. This experiment was performed on two occaisions 6 months apart according to the same schedule. They included each time 6 bulls, treated with intramuscular injections of 400 mg testosterone propionate and 6 hours later 0.25 mg gonadoliberin together with the other 3 bulls. Testosterone propionate did not influence the mean LH response to gonadoliberin although mean testosterone levels before gonadoliberin injection was very low in the controls. These data suggest that (1) the previously reported depressing effect of dexamethasone on LH is not mediated by the low peripheral testosterone level and (2) under the conditions of this study, there is no short term effect of testosterone at the pituitary level.

Assessment of erectile dysfunction in diabetic patients

Erectile dysfunction (ED) aetiology is multifactorial, including endocrine, neurological, vascular, systemic disease, local penile disorders, nutrition, psychogenic factors, and drug-related. This study was performed to compare the relevant comprehensive biochemical parameters as well as the clinical characteristics in diabetic ED and healthy control subjects and to assess the occurrence of penile neuropathy in diabetic patients and thus the relationship between ED and diabetes. A total of 56 patients accepted to undergo assessment for penile vasculature using intracavernosal injection and colour Doppler ultrasonography. Of the 56 diabetic patients, 38 patients were found with normal blood flow and thus they were considered as the diabetic-ED group, whereas, ED diabetic patients with an arteriogenic component were excluded. These patients with an age range between 17 and 58 years, complaining of ED, with duration of diabetic illness ranging from 2 to 15 years. The Control group comprised of 30 healthy subject aged between 19 and 55 years. Peripheral venous levels of testosterone, prolactin, follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), malondialdehyde and glycosylated haemoglobin (HbA(1)c) were obtained in all subjects. Valsalva manoeuvre and neurophysiological tests were also determined. Testosterone, prolactine, FSH, LH, and TSH hormones of the diabetic patients were not significantly different from those of the control group. Diabetic patients with ED have higher HbA(1)c and oxidative stress levels while the R-R ratio was significantly decreased. Bulbocavernosus reflex latency was significantly prolonged, whereas its amplitude, the conduction velocity and amplitude of dorsal nerve of penis were significantly reduced in the diabetic patients. We concluded that although ED is a multifactorial disorder, yet, the present study revealed that in ED patients without arteriogenic ED a neurogenic component is present. Furthermore, the complex effect of the Valsalva manoeuvre on cardiovascular function is the basis of its usefulness as a measure of autonomic function. Thus, it can be of value in the diagnosis of ED although these hypotheses require follow-up in a large study cohort.

Selective venous sampling for androgen‐producing ovarian pathology

Multiple diagnostic modalities may be needed to establish the source of excessive androgen production in women. The role of selective venous catheterization in this process has not been established fully. A study of hyperandrogenaemic subjects and literature review. Four hyperandrogenaemic women and an additional 132 previously reported cases with available testing data and a pathological diagnosis were evaluated. Serum androgens, diagnostic imaging and ovarian venous effluent sampling. Criteria to distinguish ovarian tumours from other ovarian conditions and to localize the lesion(s) were evaluated. Basal peripheral testosterone levels >or= 4.51 nmol/l (>or= 130 ng/dl) discriminated ovarian tumours from benign causes of hyperandrogenism (sensitivity: 93.8%, 95% CI 85.0-98.2; specificity: 77.8%, 95% CI 66.4-86.7). Single lesions produced higher ipsilateral testosterone concentrations (612.6 +/- 162.0 nmol/l; 17 653 +/- 4670 ng/dl) compared to contralateral values (26.4 +/- 5.2 nmol/l; 761 +/- 150 ng/dl). In women with peripheral testosterone >or= 4.51 nmol/l, a right-to-left (R:L) ovarian testosterone ratio >or= 1.44 correctly identified all 18 women with right-sided tumours and misclassified two with bilateral lesions; 12 out of 14 women with left-sided or bilateral lesions had a lower R:L value. When this criterion was combined with a left-to-right (L:R) ovarian testosterone effluent ratio of > 15 to identify left-sided tumours, overall 66% of women were correctly categorized. Peripheral testosterone concentrations identified ovarian androgen-producing tumours, and venous sampling could correctly localize 66% of these, suggesting a role for sampling when imaging studies are not revealing.

Comparaison des taux d’estradiol et de testostérone dans le sang périphérique et dans le sang spermatique chez les patients avec azoospermie sécrétoire

Comparison of testosterone and oestradiol levels in spermatic cord blood and peripheral blood as a function of the results of testicular sperm extraction by surgical biopsy in a population of patients with nonobstructive azoospermia (NOA). Prospective, comparative, teaching hospital-sponsored, ethics committee-approved study of 30 patients with NOA. Plasma testosterone and oestradiol assays in peripheral blood and blood taken from the spermatic vein during testicular biopsy were performed simultaneously for each patient. Statistical analyses were performed with Mann-Whitney test and Spearman's correlation coefficient by univariate and multivariate analysis of variance (p<0.05). No significant correlation was demonstrated between spermatic and peripheral blood levels of testosterone and oestradiol, regardless of the biopsy results. The spermatic oestradiol/testosterone ratio was significantly increased when testicular sperm extraction was negative (p=0.018). The increase of the oestradiol/testosterone ratio in spermatic cord blood in the case of negative testicular sperm extraction suggests the hypothesis of greater conversion of testosterone to oestradiol in the testes. This could reflect increased aromatase activity in the absence of germ cells. Further studies using tissue markers of spermatogenesis should provide a better understanding of the physiological role of oestrogens in spermatogenesis and to refine the indications for testicular biopsy in patients with NOA.

The endocrine system and ageing

Complex changes occur within the endocrine system of ageing individuals. This article explores the changes that occur in the metabolism and production of various hormones and discusses the resulting clinical consequences. As individuals age there is a decline in the peripheral levels of oestrogen and testosterone, with an increase in luteinizing hormone, follicle-stimulating hormone and sex hormone-binding globulin. Additionally there is a decline in serum concentrations of growth hormone, insulin-like growth factor-I and dehydroepiandrosterone and its sulphate-bound form. Even though there are complex changes within the hypothalmo-pituitary-adrenal/thyroid axis, there is minimal change in adrenal and thyroid function with ageing. The clinical significance of these deficiencies with age are variable and include reduced protein synthesis, decrease in lean body mass and bone mass, increased fat mass, insulin resistance, higher cardiovascular disease risk, increase in vasomotor symptoms, fatigue, depression, anaemia, poor libido, erectile deficiency and a decline in immune function. For each endocrine system, studies have been carried out in an attempt to reverse the effects of ageing by altering the serum hormonal levels of older individuals. However, the real benefits of hormonal treatment in older individuals are still being evaluated.

Horn growth related to testosterone secretion in two wild Mediterranean ruminant species: The Spanish ibex ( Capra pyrenaica hispanica) and European mouflon ( Ovis orientalis musimon)

Seasonal variations in the horn development and testicular activity of the Spanish ibex ( Capra pyrenaica hispanica) ( n = 6) and European mouflon ( Ovis orientalis musimon) ( n = 5) were monitored to determine the role of increasing testosterone concentration on the arrest of horn growth during the rutting season. Marked seasonal variations in the rate of horn growth ( P < 0.01) and testicular activity ( P < 0.001) were seen in both species, although the magnitude and timing of these changes were different ( P < 0.01). Horn growth rate was inversely correlated to seasonal levels in testosterone plasma concentration in both species (ibex: R = −0.45, P < 0.01; mouflon R = −0.51, P < 0.01). In the mouflon, the increase in plasma testosterone concentration recorded in September ( P < 0.05 compared with the lowest concentration) coincided with a significant reduction in horn growth ( P < 0.05). In the ibex, the increase in plasma testosterone concentration in October ( P < 0.05 compared with the lowest concentration) was associated with a significant arrest of horn growth in November ( P < 0.05). These results appear to support the hypothesis that high peripheral plasma levels of testosterone are linked with the seasonal arrest of horn growth during the rutting period.

In Men, Peripheral Estradiol Levels Directly Reflect the Action of Estrogens at the Hypothalamo-Pituitary Level to Inhibit Gonadotropin Secretion

Estradiol inhibits gonadotropin release in men by an action at the hypothalamus and pituitary. Because of the tissue-specific regulation of aromatase, peripheral estradiol levels may not reflect brain estradiol concentrations. We evaluated whether local aromatization of testosterone in the hypothalamus or pituitary is important for gonadotropin release and to what extent circulating estrogens affect gonadotropin levels and peripheral testosterone levels. DESIGN, SUBJECTS, AND INTERVENTIONS: We suppressed aromatase activity in 10 young healthy men with letrozole 2.5 mg once daily, restored plasma estradiol levels with estradiol patches (100 microg/d for the first week, 50 microg/d the second week, 25 microg/d the third week, and no estradiol patch the fourth week) and measured plasma testosterone, estradiol, LH, FSH, and SHBG levels. The mean estradiol and testosterone levels during the study ranged between 68.6 +/- 38.3 and 12.6 +/- 7.21 pg/ml for estradiol and 179 +/- 91 and 955 +/- 292 ng/dl (mean +/- sd) for testosterone. Levels of testosterone, LH, and FSH were inversely related to peripheral estradiol levels. During letrozole use, the mean plasma estradiol level needed to restore testosterone, LH, and FSH levels to baseline levels was not significantly different from the baseline mean estradiol level. Local aromatization of testosterone in the hypothalamo-pituitary compartment is not a prerequisite for expression of the inhibitory action of estrogens on gonadotropin secretion in men. Peripheral estradiol levels directly reflect the inhibitory tone exerted by estrogens on gonadotropin release and are a major determinant of peripheral testosterone, LH, and FSH levels.

Effects of medroxyprogesterone and estradiol on the recovery of spermatogenesis in irradiated rats.

Suppression of intratesticular testosterone (ITT) levels is required for spermatogenic recovery in rats after irradiation, but maintenance of peripheral testosterone (T) levels is important for many male functions. Considering the preservation of peripheral T while suppressing ITT, we tested the effects of a combination of a progestin, medroxyprogesterone acetate (MPA), plus T on spermatogenic recovery after irradiation, and compared its effects to those of T alone or T combined with estradiol (E2). Rats were given testicular irradiation (6 Gy) and treated during wk 3-7 after irradiation with MPA + T, or the individual steroids with or without GnRH antagonist (GnRH-ant), or GnRH-ant alone, or T + E2. Whereas GnRH-ant alone stimulated differentiation in 55% of tubules 13 wk after irradiation compared with 0% in irradiated-only rats, the addition of MPA reduced the percentage of tubules showing differentiation to 18%. However, T or MPA alone or the combination of the two induced germ cell differentiation in only 2-4% of tubules. In contrast, E2 stimulated differentiation in 88% of tubules, and T combined with E2 still resulted in differentiation in 30% of tubules. Although both MPA and E2 suppressed ITT levels to approximately 2% of control (2 ng/g testis), MPA was a less effective stimulator of spermatogenic recovery than E2 or GnRH-ant alone. MPA's function as a weak androgen was likely responsible for inhibiting spermatogenic recovery, as was the case for all other tested androgens. Thus, for clinical protection or restoration of spermatogenesis after radiation or chemotherapy by suppressing T production, MPA, at least in the doses used in the present study, is suboptimal. The combination of an estrogen with T appears to be most effective for stimulating such recovery.

Pineal control of immune status and hematological changes in blood and bone marrow of male squirrels ( Funambulus pennanti) during their reproductively active phase

In addition to pineal control of reproduction in seasonal breeders, melatonin is also known to influence various immune parameters. In the present experiment, we assessed the effect of exogenous melatonin treatment on different hematological parameters of peripheral blood and bone marrow cells, together with histological observations of spleen and thymus blastogenic response and stimulation ratio, and hormonal assays (melatonin and testosterone) of Indian palm squirrel ( Funambulus pennanti) during their reproductively active phase when endogenous melatonin levels are low. Daily subcutaneous injection of melatonin (25 μg/100 g body mass.) at 17.30–18.00 h to adult male squirrels for 60 consecutive days during May–June significantly increased the lymphocyte count of blood and bone marrow and the blastogenic response/percent stimulation ratio of spleen and thymus. Histological observation showed densely packed thymocytes and splenocytes. During this period, peripheral testosterone level was high and melatonin was low establishing an inverse relationship as noted earlier for this squirrel. In pinealectomized squirrels, decreased total leukocyte count and percent lymphocyte count in peripheral blood and bone marrow, along with a decreased cell density in spleen and thymus was observed histologically. Further, melatonin treatment of pinealectomized squirrels resulted in restoration of the immune parameters in line with a normal control level. We suggest that during the reproductively active period of male Indian palm squirrels the lymphoid organs were sensitive to melatonin; hence, the exogenous melatonin treatment had an immuno-enhancing effect.

Androgen therapy in the aging male.

The world population is expanding rapidly; at the same time, life expectancy is increasing, and fertility rates are decreasing. Due to these facts, it is expected that the biggest increases of population growth will occur in the aging population. In the aging male, endocrine changes and a decline in endocrine function involve tissue responsiveness as well as reduced secretory output from peripheral glands and alterations in the central mechanism controlling the temporal organization of hormonal release. The latter are likely to be responsible for the dampened circadian hormonal and non-hormonal rhythms. These are in part responsible for the age-dependent decrease of the peripheral levels of testosterone, dehydroepiandrosterone (DHEA), the thyroid hormones, growth hormone (GH), IGF1 and melatonin. These hormonal changes, which develop in most men at about the age of 50, are in part responsible for endocrine deficiencies of some older men. One of the best-studied endocrine deficiencies is late-onset hypogonadism. This is a syndrome characterized by adverse effects on multiple organ systems and decreased quality of life, associated with advancing age and characterized by signs and symptoms of hypogonadism and a deficiency in serum androgen levels with or without a decreased genomic sensitivity to androgens. In cases of endocrine deficiencies, traditional endocrinology aims to replace the missing hormone or hormones with substitutes. It has been demonstrated that interventions such as hormone therapies may favorably influence some of the pathological conditions in aging men by preventing the preventable and delaying the inevitable. A comprehensive medical, psycho-social and life-style history, a physical examination and laboratory testing are essential for the diagnosis and management of late-onset hypogonadism. Acute, chronic or inter-current diseases must be taken into consideration prior to initiating any hormonal substitution therapy. In the era of evidence-based medicine, we have to acknowledge that data on testosterone therapy (HT) in the aging male is mostly circumstantial, based on experience in the treatment of transitional or chronic hypogonadism in young men resulting from disease or experiments of nature. However, over the past several years prospective studies on testosterone therapy in the aging male were performed and shown to be beneficial for certain older men in preventing or delaying some aspects of aging. Recommendations for algorithms for the diagnosis of late-onset hypogonadism and monitoring therapy for safety and efficacy are the subject of this paper.

Ultrastructural and Immunohistochemical Analysis of Leydig Cells in Patients with Non-Obstructive Azoospermia

Leydig cells are an important source of testosterone, the male sex hormone that stimulates spermatogenesis [1, 2]. These cells are situated in the testicular interstitial compartment, together with blood vessels and other cells of connective tissue. The structural integrity of Leydig cells is necessary for the normal sperm production [3, 4]. The purpose of the study was as follows: 1. to describe ultrastructural changes of Leydig cells in patients with a non-obstructive azoospermia ; 2. to check the testosterone production in situ in testicular biopsies of these patients and 3. to define the levels of this hormone in the blood serum. A total of 60 testicular biopsies from infertile patients with the non-obstructive azoospermia and 8 control biopsies were analysed. In control biopsies, Leydig cells displayed their normal ultrastructure. Round or oval nucleus was situated mostly in the centre of the cell. The chromatin of the nucleus was predominantly euchromatic, with a small presence of heterchromatin associated with the nuclear envelope. A prominent nucleolus was frequently observed. The cytoplasm of the cell was rich in cisternae of smooth endoplasmic reticulum and mitochondria with tubular cristae. Occasional cisternae of rough endoplasmic reticulum, glycogen, lipid droplets and Reinke's crystals were also observed. Leydig cells in infertile men with non-obstructive azoospermia had a significantly changed ultrastructure. The nucleus of such cells was often indented with the increased presence of heterochromatin. Within the cell cytoplasm, a lot of lipid droplets and vacuoles of the electron low-density content could be noticed. There was a reduction in the cisternae of smooth endoplasmic reticulum, glycogen and mitochondria. The presence of Reinke's crystals seemed to be reduced in the pathologically changed cells. However, it should be pointed out that all biopsies contained a limited number of Leydig cells with the normal fine structure. Immunohistochemical analysis (IHC) pointed out a decreased testosterone production in situ (assessed by stereological analysis of IHC positive cells) in testicular biopsies of infertile group. However, when blood serum testosterone levels were considered, 86% of patients with non-obstructive azoospermia had normal testosterone levels. In only 3% of cases testosterone levels were decreased. In conclusion, Leydig cells in patients with the non-obstructive azoospermia displayed a significant change in their ultrastructure. The cells with the normal (unchanged) morphology were also observed within the same biopsies, but were less numerous. IHC data indicated the decreased production of testosterone in situ. However, in the vast majority of cases with non-obstructive azoospermia the peripheral levels of testosterone were normal. Electron microscopic and IHC observations on the fine structure of Leydig cells could help in the understanding of factors contributing to the male-factor infertility.