Blood Plasma Testosterone Levels Research Articles

Developmental, behavioral and endocrine alterations in male rats at early and late postnatal life following in utero exposure to low dose di-n-butylphthalate.

Environmental chemical pollutants that interfere with hormonal homeostasis or hormone signaling are the relevant agents inducing congenital or postnatally developed reproductive abnormalities in human beings, wild and domestic animals. In this study, we are examining reproductive effects of prenatal exposure of male rats to a low dose di-n-butylphthalate (DBP). Wistar female rats were given intragastrically DBP at a daily dose of 100mg/kg b.w. during 15th-21st days of pregnancy. Anogenital distance(AGD) in male offspring decreased on postnatal day (PND) 2 followed by its normalization on PND 7 and 10. There were no other visible teratogenic lesions in the newborns. The testicle descent into scrotum of control males occurred on PND 38.5 ± 0.1, while in DBP group it accelerated by 5.3days on the average. At the age of 6months, DBP-exposed animals exhibited double increase of blood plasma testosterone level as compared to controls, and hyperactive male sexual behavior in the presence of receptive female. The duration of latent periods of the first mount and the first intromission, as well as post-ejaculatory refractory period, have been shortened; the number of mounts with intromission and the number of ejaculations increased significantly. Histological examination of the testes indicated activation of Leydig cells. The female-type sexual behavior as evaluated by appearance of lordosis of orchidectomized and primed with estradiol and progesterone 10-month-old males in response to mount or approach of sexually active normal male was enhanced in DBP-group. Both 10-month-old and aging males (18months), castrated and hormone-primed, displayed homosexual type of behavior. Prenatal low dose DBP caused in 18-month-old males premature atrophy of the testes and accessory sexual glands, increased number of Leydig cell adenomas, a twice decrease of plasma testosterone level and exhausting of sexual potency. We concluded that prenatal exposition of male rats to low dose DBP determines epigenetic alterations of programming of sex brain differentiation and regulation of testicular steroidogenesis that leads to reproductive disorders and accelerated aging of reproductive system.

The effect of pre- and postnatal exposure to a mixture of daidzein and genistein on the reproductive system of male rats

Abstract Introduction: There is growing interest in the risk or benefits soybean food known as rich in isoflavones, due to their interactions with endogenous estrogen signal transduction pathway. Recent studies provide evidence that isoflavones can affect the reproductive and endocrine system under regular diet. The aim of this study was to determine how the long-lasting administration of the key isoflavones, genistein and daidzein, may change morphology of the testis and the function of the epididymal antioxidant system of male rats. Materials and methods: Male rats were treated by genistein and daidzein, in combination 2 (S2) or 20 (S20) mg/kg body weight per day for 5 days weekly mixed with regular rat chow from prenatal life until to sexual maturity. The control groups were fed without isoflavones. Results: The findings show that the body, testis and cauda epididymis weights, testosterone level in blood plasma were significantly lower than controls in the S20 group (p < 0.05). Also, superoxide dismutase activity in the epididymis, catalase activity in the testis, and glutathione peroxidase activity in the caput epididymis were significantly decreased (p < 0.05). Treating with these isoflavones significantly suppressed lipid peroxides levels in the epididymis (p < 0.05). Furthermore, presence of prematurely exfoliated gametogenic cells was observed in seminiferous tubules as well as the architectural disorganization of the seminiferous epithelium. Conclusions: These findings suggest that isoflavones, if consumed chronically at a dose as for the S20 group may act not only as antioxidants, but they can be a risk for the male rats reproductive system dysfunction.

Пренатальне застосування порогової дози ендокринного дизраптора дибутилфталату викликає передчасну вікову інволюцію органів репродуктивної системи самців щурів

Мета — виявити морфологічні кореляти гіперандрогенного стану молодих статевозрілих самців щурів, матері яких зазнали експозиції до порогової дози дибутилфталату протягом останнього тижня вагітності, а також дослідити морфофункціональний стан органів репродуктивної системи цих тварин у процесі старіння. Матеріал і методи. Дибутилфталат (ДБФ) вводили самицям щурів Вістар перорально в щоденній дозі 100 мг/кг м.т. упродовж 15-21-го днів вагітності. У 6- та 18-місячних нащадків чоловічої статі визначали масу та гістологічну будову органів репродуктивної системи, кількість сперматозоїдів в епідидимісах і вміст тестостерону в плазмі крові. Результати. У 6-місячних тварин дослідної групи маса органів статевої системи та гістологічна будова простати й сперматогенного епітелію сім’яників не відрізнялись від контролю. Морфологічні ознаки клітин Лейдіга в сім’яниках цих тварин свідчили про їх функціональне напруження, що корелювало з підвищеним удвічі рівнем тестостерону. Натомість у 18-місячнихдослідних тварин порівняно з контролем відповідного віку маса додаткових статевих залоз, епідидимісів і кількість сперматозоїдів вірогідно зменшувались, більше ніж дворазове зниження вмісту тестостерону було на межі вірогідності. Морфологічна будова простати та сім’яників свідчила про посилення вікових інволютивних змін цих органів, кількість мікролейдігом в інтерстиціальному просторі збільшувалась удвічі. Висновок. Гіперандрогенний стан у молодих самців щурів, які зазнали пренатального впливу низьких доз ДБФ протягом критичного періоду статевої диференціації мозку, характеризується морфологічними ознаками функціональної активації клітин Лейдіга. У старіючих піддослідних щурів відбувається передчасна інволюція гормональної та генеративної функцій гонад.

Characterization of β-Nerve Growth Factor-TrkA system in male reproductive tract of rabbit and the relationship between β-NGF and testosterone levels with seminal quality during sexual maturation

β-Nerve Growth Factor (β-NGF) is a neurotrophin which acts through its receptors TrkA and p75, performing important actions in male reproductive physiology and its presence in seminal plasma (SP) has been related to male fertility. The aim of the present study was to evaluate the gene expression profile and the immunolocalization of β-NGF and its high-affinity receptor TrkA in sex organs in rabbits during sexual maturation period. β-NGF concentration for both SP and blood plasma (BP) and BP testosterone levels were determined as well as the seminal parameters during such period. Ten New Zealand White x California young rabbits were trained to semen collection since 20 weeks of age and routinely done once a week with two ejaculations per session. At 22 and 37 weeks of age, semen collection was carried out three times a week and seminal parameters were evaluated. Four males were randomly assigned and slaughtered in each age (n = 8); sex organs (prostate, bulbourethral glands and epididymis) were dissected and collected to determine β-NGF and TrkA gene expression and immunolocalization. SP and BP were also taken at each semen collection session to evaluate β-NGF concentration, and testosterone levels were also assessed in BP. The highest β-NGF mRNA expression was observed in prostate compared to bulbourethral glands and epididymis. These two last tissues showed residual β-NGF mRNA expression and limited localization of the neurotrophin. The prostate epithelial cells and lumen were strongly stained with regard to the other sex organs indicating that immunolocalization of β-NGF rely mainly in the prostate. TrkA gene expression was lower but constant and differentially immunolocalized in the sex organ tissues. Finally, β-NGF concentration in SP and BP remained unchanged in accordance to age, while some seminal characteristics such as sperm concentration, percentage of live sperm and mass and progressive motility were enhanced as endowed by BP testosterone variation. β-NGF and its cognate TrkA receptor are expressed and immunolocalized in the male reproductive tract in the two ages studied, independently of the circulating levels of testosterone and β-NGF.

Effectiveness of the GnRH agonist Deslorelin as a tool to decrease levels of circulating testosterone in zebra finches

Songbirds are widely used in studies of the neurobiology underlying learning, memory and performance of the sounds used in vocal communication. Development and activity of neurons in many brain sites implicated in those behaviors are closely related to levels of circulating testosterone. Approaches to understand the effects of testosterone in songbirds are presently limited to testosterone implants, which elevate testosterone levels to supraphysiological values, or castration, which eliminates gonadal production of testosterone. Previous studies in mammals indicate that GnRH agonists may be an effective tool to reduce testosterone within that range of extremes and without invasive surgery. To evaluate the effectiveness of the GnRH agonist Deslorelin as a tool to modulate levels of testosterone in songbirds, we recorded the effects of Deslorelin in adult male zebra finches. We recorded songs, body mass and blood testosterone levels pre-treatment, then we gave each bird a small subcutaneous implant of Deslorelin. We measured blood plasma testosterone levels weekly and recorded song behavior and gross morphology of brain, testes and heart at the end of each experiment. Testosterone levels were reduced at the 5mg/kg dose, and the very slight song changes we observed at that dose were like those reported for castrated zebra finches. As expected, there were no changes in the number of cells in androgen-sensitive brain structures. Suppression of testosterone at the 5mg/kg dose was reversible through implant removal. Thus, Deslorelin is a new tool to transiently suppress testosterone levels without the invasiveness and undesirable aftereffects of surgical castration.

Selection for catatonia: Effect on sexual function and estrous cycle synchronization

Body, ovary, and uterus weights; estrous cycle; dopamine and norepinephrine levels in the hypothalamus; and testosterone levels in blood plasma have been recorded in 2- to 3-month-old GC female rats selected for elevated catatonia response and compared with the outbred Wistar stock. The body weights of GC rats are lower, and the cyclic linkage between the ovaries and the uterus is disrupted, as is apparent from a reduced diestrus ovary weight and a lower estrogen-dependent uterus weight increase in comparison to those of Wistar. A statistically significant synchronization of estrous cycles is observed in GC rats kept in standard cages, five to seven animals per cage. It includes a larger number of matches of individual estrus phases so as to form a group estrus phase of their 4- to 5-day-long estrous cycle. Synchronized estrus phases occur in 50–60% of GC rats, which is significantly more than in Wistar rats (30–40%). With reduced dopamine and norepinephrine levels in hypothalami of GC rats, the levels of these monoamines are higher in estrus and low in diestrus. Testosterone levels in diestrus GC females are higher than in estrous or Wistar ones.

Гормональні зміни у самиць щурів при дії хронічного стресу та надлишку андрогенів у період статевого дозрівання

The dynamics of blood plasma corticosterone, testosterone and androstenedione levels and their reaction to acute stress (30 min immobilization) in 35-, 40- and 45-day old female rats exposed to chronic stress (daily 30-min immobilization from 35th to 45th day of life) and/or to excess of exogenous androgens (implantation of capsules with testosterone to 33-day old animals) during pubescence was studied. Both control and experimental females in all age groups responded to acute stress by significant elevation of blood plasma corticosterone levels. At the end of the chronic stress session, the extent of adrenals activation in response to acute dosed stress was lowered in androgenized 45-day old females and increased gradually in stressed ones. After acute stress, the blood plasma testosterone level decreased in control 35-day old females and rose - in androgenized females against 10-fold rising of basal hormonal level. In 40-day old control females as well as in androgenized ones exposed to chronic stress during 5 days, the acute dosed stress did not result in significant changes of blood plasma testosterone and elevated blood plasma androstenedione. Stressed 40-day old females with increased basal androstenedione secretion did not respond to acute stress by the hormone level changes while blood plasma testosterone declined significantly. At the end ofpubescence (on the 45th day of life), acute stress did not affect the blood plasma testosterone level in control and androgenized animals, while decreased it in stressed females and increased - in androgenized rats exposed to chronic stress against elevated basal level of the hormone. The conclusion is made about possible functional relationship between the changes in hormonal homeostasis during pubescence and development of reproductive system in mature animals.

Effects of Chronic Stress during Puberty on Reproductive System of Female Rats with Experimental Hyperandrogenicity

Effects of chronic stress (daily 30-min immobilization) on 35-45 days of life and its combination with androgenization (implantation of testosterone-containing capsules on 33rd day of life) on reproductive system of 2.5 month old female rats were studied. The term of sexual maturation, estrous cycles regularity and structure, blood plasma levels of testosterone, progesterone and androstenedione as well as ovarian histology were examined. Androgenization resulted in the blood plasma testosterone level increase and the androstenedione level decrease, development of oligo- or anovulatory condition characterized by disorders or discontinuation in estrous cyclicity. We also detected abrupt reduction or absence of postovulatory luteal bodies, cysts formation and ovarian interstitial tissue overgrowth. All experimental animals had normal blood plasma corticosterone level. Stressed rats had no considerable changes in reproductive system except of some cyclicity disorders. Stressed against androgenization rats demonstrated delayed pubescence, an increased number of ovarian cysts along with attenuation ofandrogenization-caused negative effects on the sexual cyclicity.

Peculiarities of pathogenesis, diagnostics and treatment of erectile dysfunction in patients presenting with hypogonadism

Different authors estimate the prevalence of hypogonadism and erectile dysfunction at 1.7% to 35%. The contribution of androgens playing an important role in regulation of erection remains the subject of extensive investigations. To date, experimental and clinical studies have demonstrated that androgen deficiency leads to degeneration and apoptosis of smooth muscle cells followed by fibrosis of cavernous bodies, impaired expression of endothelial and neuronal NO synthase, decreased arterial inflow and increased venous drainage of the cavernous bodies, enhanced sensitivity to mediators of vasoconstriction, impaired NO-mediated relaxation of smooth muscles in response to sexual stimulation, reduced expression of type 5 phosphodiesterase (PDE-5). Moreover, hypogonadism and erectile dysfunction are frequently associated with cardiovascular disorders, diabetes mellitus, metabolic syndrome, dyslipidemia, hypercholesterolemia, hypertriglyceridemia, and obesity. The main purpose of hormonal substitution therapy is to maximally normalize the physiological concentration of plasma testosterone and to eliminate clinical manifestations of androgen deficiency. The treatment with testosterone-containing preparations is indicated only for patients with clinical symptoms and laboratory findings suggestive of hypogonadism. The testosterone-based preparations for intramuscular administration currently find wide application for this purpose. Testosterone substitution therapy enhances libido, increases the frequency of morning erection, and improves sexual quality of life at large. It is worthy of note that treatment with these preparations is well tolerated by the patients. Control over hormonal substitution therapy with testosterone preparations implies evaluation of the clinical response and achievement of the target testosterone level in blood plasma. Also. it is necessary to measure PSA, perform digital rectal examination, and determine the hematocrit level prior to the initiation of the treatment, 3 and 6 months after its termination, and every 6 months thereafter. To conclude, androgens are natural stimulators maintaining sexual function in men. Patients with hypogonadism and erectile dysfunction should be managed by combined therapy with androgens and PDE-5 inhibitors.

Level of neuroactive steroids in the brain and sex-related peculiarities of formation and extinction of conditioned reflex in rats

Sex-related peculiarities of dynamics of brain sex steroids in the process of learning and extinction of the conditioned reflex of passive avoidance have been studied in model experiment. Prior to learning of the conditioned reflex, female rats were found to be distinguished by manifestation of anxiety and fear as compared with male rats. At formation of the conditioned reflex, no significant sex-related differences were detected between males and females, whereas extinction of the conditioned reaction of passive avoidance in males occurred by 2–3 days faster than in females. At learning of conditioned reaction of passive avoidance, in sexually mature male rats there was revealed an increase of the testosterone content in various brain structures, especially in hippocampus and frontal cortex, while its level in blood plasma remained unchanged. Also shown was an elevation of estradiol concentration in female amygdale, whereas at extinction of the conditioned reaction of passive avoidance, a rise of estradiol values was noted in hippocampus and cingular cortex. At the same time, the testosterone level in blood plasma did not change, whereas after extinction of the conditioned reflex the estradiol concentration decreased statistically significantly. Different dynamics of changes of the sex steroid levels in brain and blood plasma can indicate a possibility of their formation in the nervous tissue. The performed correlation analysis confirms the concept of selective involvement of testosterone and estradiol of individual brain structures in realization of processes of learning and memory in sexually mature male and female rats.

Reproductive disorders in fish from Lake Molnbyggen and an adjacent stream contaminated by leakage water from a refuse dump

Fish were examined in Lake Molnbyggen, a remote Swedish lake with a refuse dump in the vicinity, and an adjacent stream which drains the refuse dump area. The results showed significantly decreased gonadosomatic index (GSI) in females of four teleost species: perch ( Perca fluviatilis), northern pike ( Esox lucius), roach ( Rutilus rutilus) and brook trout ( Salvelinus fontinalis). Results show that female perch and female brook trout with decreased GSI have a low brain aromatase activity (CYP 19), close to the activity found in juvenile fish. The testosterone levels in blood plasma were also significantly lower in female perch with decreased GSI values. A frequent occurrence of fin deformations and open wounds were also found on perch, pike and roach. The biomarkers ethoxyresorufin O-deethylase, glutathione reductase and hydrophobic DNA adducts indicated a low general exposure to anthropogenic substances, although glutathione- S-transferase and catalase were induced in female perch. In conclusion, these results suggest serious adverse impairment of endocrine functions caused by specific organic pollutants in leakage water from the refuse dump.

Involvement of the catecholamine mechanisms in the activation of mouse hypophyseotesticular complex induced by the female presence effect.

We have studied the role of the adrenergic and dopaminergic mechanisms in the activation of the endocrine testicular function of CBA/Lac and A/He male mice induced by the presence of a female in estrus without any tactile contact with a male. The alpha-adrenoreceptor blocker phentolamine inhibited an increase in the peripheral blood plasma testosterone level caused by the receptive female challenge. Propranolol blockade of beta-adrenoreceptors abruptly increased the stimulating effect of the receptive female presence on the blood testosterone level. The expression of the adrenoblocker action on the blood male sex hormone level depended on a male genotype. The dopamine receptor blocker pimozide produced a moderate effect on the blood testosterone but an attempt to separate its influence into the male sex hormone tonic secretion and the blood testosterone level against a background of sexual activation failed. It was concluded that the adrenergic mechanisms were involved in the activation of the hypothalamo-hypophyseotesticular complex induced by the presence of the receptive female.

Influence of luliberin and chorionic gonadotropin on luteinizing hormone and testosterone in the blood of monkeys under conditions of acute stress.

1. A single administration of luliberin to intact animais in a dose of 100 μg leads to a pronounced transitory rise in the LH and testosterone levels in the peripheral blood plasma. 2. Administration of luliberin 30 min before stress stimulates the secretion of LH by the pituitary, but does not prevent the stress-induced decrease in the testosterone level in the blood. 3. A single administration of 4500 units of hCG leads, in intact animals, to a sharp rise in the testosterone concentration, which remains at a high level for three days after stimulation of the gonads. 4. Preliminary stimulation of the testes by hCG prevents the stress-induced suppression of the testosterone level in the blood plasma; however, the reaction of the testes to the stimulating effect of hCG is decreased in this case.

Synthesis of phospholipid-binding protein in the reproductive organs of the bull during ontogenesis

In bulls of the Czech red-spotted breed, the synthesis of phospholipid-binding protein (PBP) in the epithelial cells of the seminal vesicles and ampullary glands begins at the age of 20–24 weeks. Optimum production of the protein, characterized by intensive fluorescence of the productive epithelium in indirect immunofluorescence and by a high seminal vesicle and ampullary fluid titre in the erythrocyte haemolytic reaction, does not begin until the age of 25 weeks, however. PBP synthesis by the seminal vesicles and ampullary glands depends on the amount of testosterone in the blood. This is demonstrated by the absence of PBP synthesis in sexually immature bulls with a low blood plasma testosterone level and by low PBP synthesis in sexually adult bulls with severe orchitis accompanied by degeneration of the Leydig cells and a low blood testosterone level.

Seminal ribonuclease of bulls - biosynthesis in normal and orchitic bulls and correlation with blood plasma hormone levels

In sexually mature and healthy bulls, seminal ribonuclease (AS RNase) is synthesized in the distal part of the corpus epididymidis, the cauda epididymidis, the ampullary glands and the seminal vesicles. Indirect immunofluorescence demonstrated AS RNase binding to the cytoplasmic droplets of bull spermatozoa. In bulls with orchitis, AS RNase synthesis decreases in accordance with the degree of damage to the Leydig cells and the drop in the blood plasma testosterone level. The organ most sensitive to decreased testosterone levels, from the aspect of AS RNase synthesis, is the epididymis and the least sensitive are the seminal vesicles. Hypertrophy of the adrenal cortex (in particular of the zona fasciculata and the zona reticularis) and elevated adrenocortical secretion - demonstrated by a raised cortisol concentration in the blood plasma of severely orchitic bulls - failed to inhibit AS RNase synthesis. Injections of Gn RH-LH and HCG raised the blood plasma cortisol, but not testosterone, concentrations in bulls with very severe orchitis. This also indicates serious damage to the Leydig cells in these bulls.

Correlation Between Fluctuations of Testosterone Levels in Systemic Circulation and Sexual Behavior in Intact Female Japanese Monkeys in the Laboratory Condition

Heterosexual interactions of pairs of Japanese monkeys were studied in connection with fluctuations of testosterone concentrations in blood plasma of females, using seven intact adult females and two males. Blood was collected from the females daily or with a few days interruption. Testosterone, estradiol-17b, and progesterone in blood plasma were determined by radioimmunoassay. The behavioral records were obtained through heterosexual pairing tests of 30 minutes duration. Testosterone levels in blood plasma considerably fluctuated in each female from day to day, and statistically significant change could not be detected during the normal menstrual cycle. Male approach to females increased simultaneously with the increment of plasma testosterone level in three out of seven females. In seven normal menstrual cycles both copulation with ejaculation in the early follicular phase of the menstrual cycle and male approach in the late follicular phase of the cycle were observed in significantly higher frequencies on days of high level of testosterone, as compared with them on days of low level of testosterone in respective phase. These results suggest that testosterone enhances some types of sexual behavior of the male partner, at least, in the existence of estradiol-17s in the late follicular phase of the menstrual cycle.