Testosterone Secretion In Rats Research Articles

Fine particle matter disrupts the blood-testis barrier by activating TGF-β3/p38 MAPK pathway and decreasing testosterone secretion in rat.

Fine particle matter (PM) is correlated with male reproductive dysfunction in animals and humans, but the underlying mechanisms remain unknown. To investigate the toxic mechanism of PM, 32 male Sprague-Dawley (SD) rats were exposed to saline or PM2.5 with the doses of 1.8, 5.4, and 16.2 mg/kg.b.w. via intratracheal instillation, respectively, one time every 3 days, in total times for 30 days. Sperm concentration, hormone level, the expressions of BTB-associated protein and the mitogen-activated protein kinase (MAPK) pathway, tumor necrosis factor α and transforming growth factor β3 levels were detected. The results showed a decrease in sperm number, testosterone and luteinizing hormone levels and altered ultrastructure of BTB in testis of rat after exposure to PM2.5 . The protein levels of N-Cadherin, Occludin, Claudin-11, and Connexin-43 were significantly decreased in the testes. TGF-β3 content in testes showed increase, with the p-p38/p38 MAPK ratio also increasing after PM2.5 exposure. These results demonstrate that PM2.5 restrained the expressions of BTB-associated proteins through activating TGF-β3/p38 MAPK pathway and decreasing testosterone secretion, and therefore lead to the damage of BTB resulting in the decrease of sperm quality, which might be the potential reasons for its negative effects on spermatogenesis and male reproduction.

Yoga stretching for improving salivary immune function and mental stress in middle-aged and older adults

ABSTRACTProtection against age-related immune suppression is important in elderly individuals. This study determined the effect of yoga on mucosal immune function and mental stress. Saliva samples were collected from 23 adult women (age: 60.4 ± 10.4 years) before and after 90 minutes of yoga stretching or rest to measure secretory immunoglobulin A (SIgA), cortisol, and testosterone. The SIgA concentration and secretion rate were significantly higher after yoga than before (p < .05). The cortisol concentration and secretion rate were lower and testosterone secretion rate higher after yoga (p < .05). Yoga stretching can reduce stress and enhance mucosal immune function in elderly women.

Sympathetic nerve to the ovary regulates ovarian testosterone secretion in female rats

Previously, we demonstrated that electrical stimulation of the superior ovarian nerve (SON), but not the ovarian nerve plexus (ONP), reduces the secretion rate of estradiol from the ovary via activation of alpha 2-adrenoceptors in rats. The inhibitory effect of SON on estradiol secretion may be due to reduced production of testosterone, a direct precursor of estradiol. Here, we examined the effects of electrical stimulation of the SON and the ONP on ovarian testosterone secretion in rats. On the day of estrous, ovarian venous blood was collected intermittently from the ovarian vein. The secretion rate of testosterone from the ovary was calculated from the difference in the testosterone concentration between ovarian venous plasma and systemic arterial blood plasma, and the rate of ovarian venous plasma flow. Stimulation of either the SON or ONP reduced the secretion rate of testosterone from the ovary. The reduction of the testosterone secretion rate by SON stimulation was not influenced by an alpha 2-adrenoceptor antagonist (yohimbine), but it was abolished by an alpha 1-adrenoceptor antagonist (prazosin). Our results show that ovarian nerves have an inhibitory role in ovarian testosterone secretion, via activation of alpha 1-adrenoceptors, but not alpha 2- adrenoceptors. This, therefore, indicates that the reduction of estradiol secretion by SON stimulation is independent of the reduction of testosterone secretion.

Salivary Immuno Factors, Cortisol and Testosterone Responses in Athletes of a Competitive 5,000 m Race.

The exercise-stress model can be a model of temporary immunosuppression that occurs after severe physical and psychological stress. It also allows for the study of interactions between the endocrine and the immune systems. This study examined changes in salivary hormonal and immune factors in athletes in response to physical and psychological stress in a 5,000 m running competition. Eighteen endurance-trained runners (9 males and 9 females) participated in this study. All participants completed a competitive 5,000 m race. Saliva samples were collected 10 min before (PRE) and 10 min after (POST) the competition. Saliva was analyzed for α-amylase activity, concentrations of salivary immunoglobulin A (SIgA), lactoferrin, cortisol, testosterone and total protein. Although the concentrations of salivary TP, SIgA, lactoferrin, cortisol and α-amylase activity were significantly increased immediately after a competitive 5,000 m race, the secretion rates of these factors were not significantly altered in both male and female groups. Additionally, basal levels of SIgA and α-amylase activity were significantly higher in female runners than in male runners. This gender difference still existed after the race. The secretion rates of testosterone decreased significantly after the race in the male, but not in the female group. Moreover, testosterone-to-cortisol (T/C) ratios were significantly lower post-competition compared to pre-competition in both male and female athletes. The T/C ratio had been used as a performance index for athletes. Whether there are correlations between these changes of their physiological characteristics and better running performance need further investigations.

Effects of electrical stimulation of autonomic nerves to the ovary on the ovarian testosterone secretion rate in rats

Previously, we demonstrated that electrical stimulation of the superior ovarian nerve (SON), but not the ovarian nerve plexus (ONP), reduces the secretion rate of estradiol from the ovary via activation of alpha 2-adrenoceptors in rats. The inhibitory effect of SON on estradiol secretion may be due to reduced production of testosterone, a direct precursor of estradiol. Here, we examined the effects of electrical stimulation of the SON and the ONP on ovarian testosterone secretion in rats. On the day of estrous, ovarian venous blood samples were collected intermittently from the ovarian vein. The secretion rate of testosterone from the ovary was calculated from the difference in the testosterone concentration between ovarian venous plasma and systemic arterial blood plasma, and the rate of ovarian venous plasma flow. Stimulation of either the SON or ONP reduced the secretion rate of testosterone from the ovary. The reduction of the testosterone secretion rate by SON stimulation was not influenced by an alpha 2-adrenoceptor antagonist (yohimbine), but it was abolished by an alpha 1-adrenoceptor antagonist (prazosin). Our results show that ovarian nerves have an inhibitory role in ovarian testosterone secretion, via activation of alpha 1-adrenoceptors, but not alpha 2-adrenoceptors. This, therefore, indicates that the reduction of estradiol secretion by SON stimulation is independent of the reduction of testosterone secretion.

Integration of new regulatory strategies into the network of an endocrine control system: limitation of androgen secretion by rat testis is achieved by substrate-dependent modulation of P450XVII enzyme concentration and catalytic efficiency.

In addition to the well-known control circuits involved in the regulation and adaptation of testicular androgen biosynthesis, it is proposed that two new control strategies are involved in the maintenance of steady-state testosterone secretion rates by testicular Leydig cells. Cytochrome P450XVII (steroid-17 alpha-monooxygenase/steroid-17,20-lyase), one key enzyme in steroid hormone biosynthesis, responds to external human choriogonadotropin stimulation with an oxygen-dependent and substrate flux-dependent inactivation and decomposition, and increased substrate availability decreases the efficiency of androgen formation in favour of abortive intermediate leakage. These results are discussed as a paradigm of substrate-dependent modulation of cytochrome P450 activities.

Involvement of Pyruvate in the Exercise-Induced Testosterone Secretion in Rats.

Involvement of Pyruvate in the Exercise-Induced Testosterone Secretion in Rats.

The High-affinity Non-peptide CRH1Receptor Antagonist R121919 Attenuates Stress-induced Alterations in Plasma Oxytocin, Prolactin, and Testosterone Secretion in Rats

Evidence from basic and clinical research suggests that hyperactivity of central corticotropin-releasing hormone (CRH) circuits contributes to causality and course of affective disorders. Therefore, CRH receptor antagonists have attracted attention as potential therapeutics. We could previously show that the novel high-affinity non-peptide CRH 1 receptor antagonist R121919 significantly inhibits stress-induced corticotropin release and displays anxiolytic effects in rats selectively bred for high anxiety-related behavior. These animals are characterized by their innate hyper-reactivity of the hypothalamic-pituitary-adrenocortical system linked to an increased emotionality and therefore are suitable for the evaluation of CRH 1 receptor antagonists. Here we show that in addition to its effects on anxiety-related behavior and corticotropin secretion, R121919 attenuates the stress-induced release of corticosterone, prolactin, and oxytocin. Moreover, the decrease in plasma testosterone following exposure to stress is abolished by R121919. Our data indicate that antagonism of CRH 1 receptors may prevent stress-associated endocrine alterations.

Inhibitory Effect of Neurogenic and Immune Stressors on Testosterone Secretion in Rats

Objective: We investigated the ability of foot shocks, endotoxemia and turpentine-induced tissue injury, to interfere with luteinizing hormone (LH) and testosterone (T) secretion, and the putative role of β-adrenergic, opiate- and corticotropin-releasing factor (CRF) receptors in these responses. Methods: Adult male rats were exposed to mild intermittent foot shocks for 1 h, administered endotoxin [lipopolysaccharide (LPS)] intravenously (i.v., 5 µg/kg), or injected with turpentine intradermally (i.m., 400 µl/kg), prior to injection with human chorionic gonadotropin (hCG, 1 U/kg i.v.). In some cases, antagonists to CRF, adrenergic or opiate receptors, or their vehicle were administered prior to the stressors. Levels of LH, T, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), adrenocorticotropin (ACTH) and/or corticosterone were measured in serial blood samples. Results: All three challenges significantly lowered basal LH and T levels and blunted the T response to hCG, though the magnitude of this inhibition was significantly (p < 0.01) smaller in shocked rats (42%), compared to animals injected with LPS (92%) or turpentine (78%). Shocks, LPS and turpentine all significantly stimulated ACTH and corticosterone release, and the magnitude and time course of these responses were also stressor specific. While turpentine only increased circulating IL-6 concentrations, shocks and LPS both significantly increased circulating TNF-α and IL-6 levels, but the effect of shocks was markedly smaller. Pretreatment with propranolol did not restore T responses, while naloxone produced small and inconsistent effects. However, the CRF antagonist Astressin B, which significantly prevented stressor-induced increase in circulating levels of ACTH and corticosterone, partially reversed the inhibitory effect of LPS on hCG-induced T release. Conclusion: (1) Both neurogenic and systemic stressors lower basal plasma LH and T levels and blunt the T response to hCG. (2) LPS, whose ability to release ACTH and corticosterone was similar to that of shocks, but caused increases in circulating TNF-α and IL-6 levels that were significantly larger than those due to the other stressors, was the most potent inhibitor of the T response to hCG. (3) Neither β-adrenergic nor opiate receptors play a major role in the ability of the stressors we used to inhibit T release.

Effects of methanol extract of Chansu on hypothalamic-pituitary-testis function in rats.

Chansu, a galenical preparation of the dried white venom of Chinese Bufo bufo gargarizans, is one of the major components of Kyushin, a traditional Chinese medicine. Kyushin is reported to have a cardiotonic effect that has been suggested to be due to the action of bufadienolides such as bufalin and cinobufagin. Recently, we found that administration of bufalin in male rats diminished the luteinizing hormone (LH) response to gonadotropin-releasing hormone (GnRH) and the secretion of testosterone both in vivo and in vitro. These observations suggest that Chansu may possess hypogonadal effects in male rats. In the present study, the effects of the methanol extract of Chansu on hypothalamic-pituitary-testicular function in male rats were examined. Crude Chansu was extracted by methanol and purified by a Sep-Pak C18 column. No activity of bufalin, cinobufagin, estradiol, or digoxin in purified methanol extract was detected; all Chansu used in this study was the purified methanol extract. A single intravenous injection of Chansu resulted in a decrease of the basal (20% to 55%) and human chorionic gonadotropin (hCG)-induced (35% to 40%) levels of plasma testosterone and the GnRH-induced level of plasma LH (25% to 30%). Administration of Chansu in vitro decreased basal and hCG-stimulated testosterone production by 60% to 70% and 40% to 60%, respectively, as well as spontaneous and forskolin- or 3-isobutyl-1-methylxanthine (IBMX)-induced accumulation of adenosine 3',5'-cyclic monophosphate (cAMP) by 30% to 45% in rat testicular interstitial cells. Although LH release by rat anterior pituitary glands was diminished, GnRH release by the rat mediobasal hypothalamus was enhanced by administration of Chansu in vitro. These results suggest that the bufalin-free extracts of Chansu inhibit testosterone secretion in rats, in part, due to (1) a decreased production of testicular cAMP, (2) a decreased response of testosterone to gonadotropin, and (3) a reduction of the LH response to GnRH.

Aging alters feed-forward and feedback linkages between LH and testosterone in healthy men.

To discern the effect of aging on coordinate luteinizing hormone (LH) and testosterone secretion, we sampled healthy older men (age 62-74 yr, n = 11) and young controls (age 21-34 yr, n = 13) every 2.5 min overnight. Deconvolution analysis and cross-correlation were used to relate serum LH concentrations to calculated testosterone secretion rates (feed-forward stimulation), as well as serum testosterone concentrations to computed LH secretion rates (feedback inhibition). Despite statistically similar mean serum LH and testosterone concentrations in the young and older men, older individuals had diminished feed-forward stimulation of LH concentrations on calculated testosterone secretion rates, as well as delayed feedback inhibition of testosterone concentrations on computed LH secretion rates.

Interactions Between Alcohol‐ and Opioid‐Induced Suppression of Rat Testicular Steroidogenesis In Vivo

To examine interactions between alcohol and endogenous opioids in their suppressive effects on rat testicular function, the opioid antagonist naltrexone or the opioid agonist morphine was administered to adult male rats alone or in combination with alcohol. Serum testosterone, testicular interstitial fluid (TIF) testosterone, and TIF volumes were measured to assess testicular function. Naltrexone induced dose-dependent increases in serum and TIF testosterone levels without changes in TIF volume. Alcohol (0.5 g/kg) inhibited naltrexone-induced stimulation of testosterone secretion and shifted the naltrexone dose-response curve to the right. Conversely, naltrexone (0.05 mg/kg) inhibited alcohol-induced suppression of testosterone secretion and shifted the alcohol dose-response curve to the right. Relatively high doses of naltrexone (5 to 30 mg/kg) were needed to stimulate testosterone secretion maximally in rats treated with a low dose of alcohol (0.5 g/kg) and to stimulate normal levels of testosterone secretion in rats treated with a high dose of alcohol (2 g/kg). In addition, combined treatment with 1 and 30 mg/kg of naltrexone and 0.5 to 2 g/kg of alcohol did not alter blood alcohol concentrations significantly, suggesting that the interactions between alcohol and naltrexone were unrelated to gross changes in alcohol metabolism or bioavailability factors. Simultaneous treatments with a low dose of alcohol (0.3 g/kg), near the threshold of efficacy, and low-moderate doses of morphine (0.3 to 3 mg/kg) were not additive in suppressing testosterone secretion, compared with either agent alone. These results support the hypothesis that opioid antagonists can reverse the suppressive effect of alcohol on testicular steroidogenesis, but the results also suggest that endogenous opioids do not exclusively mediate alcohol's effects on testosterone secretion.

Heritable testicular hypoplasia in Nguni (Bos indicus) bulls: vascular characteristics and testosterone production.

The biased unilateral occurrence of heritable gonadal hypoplasia was investigated by examining the gross- and microanatomy of the testicular artery and vein, testicular blood flow and testicular testosterone secretion in normal Nguni bulls and in Nguni bulls showing unilateral left, unilateral right and bilateral hypoplasia of the testis. A high incidence of branching of the testicular artery was found ipsilateral to hypoplastic testes. The branching occurs a short distance from the dorsal aorta: one branch proceeds to the testis, the other to the ipsilateral kidney. The association between arterial branching to the kidney and ipsilateral hypoplasia of the testis held for both unilaterally left and unilaterally right hypoplastic bulls. Variations in the anatomy of the testicular vein occurred in both normal and hypoplastic bulls but there was no specific association between the variations and ipsilateral hypoplasia. The lumen diameter of the testicular artery or branch correlated with testis mass. Wall thickness of the artery ipsilateral to hypoplastic testes was not different from that in normal bulls, discounting hyperplasia of the endothelium. Total blood flow to the testis correlated with testis mass. The secretion rate of testosterone from hypoplastic testes was lower than that of normal testes but there was no difference when compared on a unit mass basis.

Acute effects of anticonvulsant drugs on gonadotropin-stimulated and precursor-supported androgen production in the rat testis

The possibility of direct inhibition of testicular endocrine function by carbamazepine, phenytoin, or valproate was tested using the rat Leydig cell model in vitro in order to find whether such an effect could contribute to the reduction of plasma free testosterone levels reported in male patients who take antiepileptic medications. With maximally stimulating concentrations of human choriogonadotropin (hCG) or cyclic AMP, testosterone formation was inhibited by 50% in the presence of 40 μM carbamazepine, 350 μM phenytoin, or > 1 mM valproate. With submaximally stimulating concentrations of hCG, leading to physiological testosterone secretion rates, half-maximal inhibition occured in the presence of 15 μM carbamazepine, 180 μM phenytoin, or 900 μM valproate. Only the values for carbamazepine were in the clinically therapeutic range. Further investigation revealed that carbamazepine acted primarily at a target between cyclic AMP formation and cholesterol conversion to androgens. In contrast, phenytoin acted by competitive interaction at the cytochrome P450XVII which converts progesterone to androgens. Valproate had by far the lowest potential to generate adverse effects in this endocrine system.

Effect of uni- and bilateral cryptorchidism on testicular inhibin and testosterone secretion in rats.

The effect of uni- and bilateral cryptorchidism on testicular inhibin and testosterone secretion and their relationships to gonadotropins were studied in rats. Mature Wistar male rats weighing approximately 300 g were made either uni- or bilaterally cryptorchid. Testicular inhibin and testosterone content and plasma levels of LH and FSH were examined 2 weeks later. A similar remarkable decrease in testicular inhibin content was found in uni- and bilaterally cryptorchid testes. On the other hand, the testicular testosterone content was significantly decreased only in unilaterally cryptorchid testis with an inverse increase in the contralateral testis. Plasma testosterone levels were normal and plasma LH and FSH increased significantly in both of the cryptorchid groups. These results showed that cryptorchidism impairs both Sertoli and Leydig cell functions. While testosterone production was compensated by increased LH for 2 weeks, neither inhibin secretion nor storage changed in cryptorchid or contralateral testes during the same period.

Adrenocorticotropin administration increases testosterone secretion in adult male rats

It appears that the effect of acute administration of pituitary-adrenal hormones on the pituitary-gonadal axis is species-dependent. However, no information is available with regard to the effect of acute adrenocorticotropin (ACTH) administration on testosterone secretion in rats. The present data indicate that acute ACTH administration can increase serum testosterone levels without modifying luteinizing hormone (LH) levels. Since this rise was not observed in castrated rats, it must be assumed that increased serum testosterone was of gonadal origin. The action of ACTH on testosterone secretion was likely an indirect one since there is no evidence at present for a direct, short-term action of the pituitary-adrenal axis on Leydig cell function.

Testicular blood flow in young and old rats and influence of hCG.

To evaluate the influence of age, testicular capillary blood flow (TCBF) was measured, using the microsphere technique, in rats 3 to 24 months old, under basal conditions and after hCG stimulation (10 IU/d for two days). Despite a decline in plasma T levels, testicular capillary blood flow did not decrease with age, and hCG stimulation resulted in similar increases of approximately 50% (P less than 0.01) in testicular capillary blood flow in all age groups. We concluded that the age-associated decrease in testosterone secretion in rats is not the consequence of a decreased testicular blood flow.

Effect of immunoneutralization of LH releasing hormone on LH, FSH and ovarian steroid secretion in the preovulatory phase of the oestrous cycle in the ewe.

Immunoneutralization of LH releasing hormone (LHRH) by the i.v. administration of LHRH antiserum in the preovulatory period in the ewe resulted in a prompt abolition of the pulsatile secretion of LH without alteration of basal plasma levels of LH. This resulted in an immediate cessation of the pulsatile secretion of ovarian oestradiol, with no change in the secretion rate of androstenedione or plasma levels of FSH. The ovarian secretion rate of testosterone increased significantly. Twenty to 22h after the injection of LHRH antiserum, pulsatile secretion of LH and ovarian oestradiol and androgen secretion remained suppressed while plasma levels of FSH had increased significantly. The bolus injection of ovine LH (10 micrograms, i.v.) at this time caused a significant increase in oestradiol, androstenedione and testosterone, these responses being inversely related to the titre of LHRH antiserum in the plasma at this time. These results show that (1) the secretion of oestradiol from the preovulatory sheep follicle is entirely dependent on the pulsatile secretion of LH and (2) since the secretion of ovarian androgens was not inhibited, LH may exert a short-term control over the aromatase enzyme system controlling the conversion of androgen to oestrogen in the granulosa cell of the preovulatory sheep follicle.

In vitro testosterone secretion by testicular tissue from young bulls and the effects of chronic and acute exposure to estradiol-17 beta.

The possibility that estradiol-17 beta may directly influence testicular steroidogenesis in bulls was investigated in vitro. Testicular tissues were incubated for 4 h and regression coefficients (b, ng X ml-1 X h-1) based on the increase in testosterone in the medium were used to describe testosterone secretion rates. In the first experiment, testicular tissues from control bulls and bulls chronically implanted with estradiol were incubated in the absence (basal conditions) or presence of 10 mIU/ml human chorionic gonadotropin (hCG). Under basal conditions, testosterone secretion rates were similar for tissues from control (b = 24.1 +/- 6.0) and implanted (b = 34.7 +/- 6.0) bulls. Testosterone secretion rates were increased approximately fourfold during incubation with hCG; tissues from implanted animals secreted testosterone at a higher rate (P less than .05) than control tissues (b = 120.7 +/- 6.0 vs 81.6 +/- 6.0). In a second experiment, testicular tissues were obtained from control bulls and incubated both with and without hCG (10 mIU/ml) and with and without estradiol (concentrations ranging from 3.7 nM to 37 microM). In this experiment, basal secretion rate (b = 12.6 +/- 3.6) was increased threefold during incubation with hCG (b = 37.8 +/- 3.6). Estradiol failed to inhibit hCG-stimulated testosterone secretion when bovine testicular tissue was incubated with 0, 3.7 and 370 nM estradiol. In contrast, 37 microM estradiol suppressed (P less than .05) testosterone secretion, perhaps reflecting a pharmacologic effect. The results suggest that neither chronic nor acute exposure to estradiol directly affects testosterone secretion by the bovine testis.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition and recovery of testosterone secretion in rats are tightly coupled to quantitative changes in Leydig cell smooth endoplasmic reticulum.

Inhibition and recovery of testosterone secretion in rats are tightly coupled to quantitative changes in Leydig cell smooth endoplasmic reticulum.