The Experts below are selected from a list of 3975 Experts worldwide ranked by ideXlab platform

Paulus S. Wang - One of the best experts on this subject based on the ideXlab platform.

  • Downregulation of Testosterone production through luteinizing hormone receptor regulation in male rats exposed to 17α-ethynylestradiol.
    Scientific Reports, 2020
    Co-Authors: Po-han Lin, Shih Min Hsia, Kai-lee Wang, Tsung Hsien Kuo, Chih Chieh Chen, Cai Yun Jian, Chien Wei Chen, Yuh Chen Kuo, Heng Yi Shen, Paulus S. Wang
    Abstract:

    The pharmaceutical 17α-ethynylestradiol (EE2) is considered as an endocrine-disrupting chemical that interferes with male reproduction and hormonal activation. In this study, we investigated the molecular mechanism underlying EE2-regulatory Testosterone Release in vitro and in vivo. The results show that EE2 treatment decreased Testosterone Release from rat Leydig cells. Treatment of rats with EE2 reduced plasma Testosterone levels and decreased the sensitivity of human chorionic gonadotropin (hCG). EE2 reduced luteinizing hormone receptor (LHR) expression associated with decreased cAMP generation by downregulation of adenylyl cyclase activity and decreased intracellular calcium-mediated pathways. The expression levels of StAR and P450scc were decreased in Leydig cells by treatment of rats with EE2 for 7 days. The sperm motility in the vas deferens and epididymis was reduced, but the histopathological features of the testis and the total sperm number of the vas deferens were not affected. Moreover, the serum dihydroTestosterone (DHT) level was decreased by treatment with EE2. The prostate gland and seminal vesicle atrophied significantly, and their expression level of 5α-reductase type II was reduced after EE2 exposure. Taken together, these results demonstrate an underlying mechanism of EE2 to downregulate Testosterone production in Leydig cells, explaining the damaging effects of EE2 on male reproduction.

  • the effects of anti tnf α antibody on hyperprolactinemia related suppression of hcg induced Testosterone Release in male rats
    The Journal of Sexual Medicine, 2012
    Co-Authors: Ling-yu Yang, William J.s. Huang, Yi-ting Tsai, Paulus S. Wang
    Abstract:

    ABSTRACT Introduction Hyperprolactinemia (hyperPRL)‐related hypogonadism or suppression of human chorionic gonadotropin (hCG)‐induced Testosterone (T) Release is hypothesized to be mediated by a testicular interstitial macrophage and tumor necrosis factor alpha (TNF‐α)‐involved blockage. Aim To test if the lower T response after hCG challenge in the hyperPRL rats is reversed by administrating anti‐TNF‐α antibody (Ab). Methods HyperPRL was induced by allografting two anterior pituitary (AP) glands per rat. Control rats were grafted with similar amount of cerebral cortex. The testicular interstitial cells (TIC) were isolated from the testis 6 weeks after grafting. TIC was treated with anti‐TNF‐α Ab with or without hCG. The other groups of rats received intra‐testicular or intra‐muscular anti‐TNF‐α Ab 7 days before in vitro study. The TIC isolated from each testis was incubated and T Release with or without hCG challenge were measured. Main Outcome Measures Prolactin (PRL) and T were measured by radioimmunoassay. TNF‐α was measured by enzyme‐linked immunosorbent assay (ELISA). Results When low dose of anti‐TNF‐α Ab was administered to the TIC incubation, the effects of PRL‐related suppression of hCG‐stimulated T Release were not significant. While a higher dose of anti‐TNF‐α Ab almost abolished the suppressive effects of PRL to hCG‐stimulated T Release. Prior intra‐testicular or intra‐muscular administration of anti‐TNF‐α Ab reversed the suppressive effects of AP grafting on TIC's T Release. This was demonstrated in groups with anti‐TNF‐α Ab injection both 7 and 1 day prior to TIC incubations. Conclusions The data support the hypothesis that the suppression of hCG‐induced T Release associated with hyperPRL is through a TNF‐α‐mediated mechanism to suppress the Leydig cells. The effect of anti‐TNF‐α Ab is durable for at least 7 days. Besides intra‐testicular injection, there might be other ways available for administrating Ab. Anti‐TNF‐α Ab has a potential therapeutic application on hyperPRL‐induced hypogonadism or suppression of hCG‐induced T Release. Huang WJS, Yang L‐Y, Pu H‐F, Tsai Y‐T, and Wang PS. The effects of anti‐TNF‐α antibody on hyperprolactinemia‐related suppression of hCG‐induced Testosterone Release in male rats. J Sex Med 2012;9:1005–1014.

  • Effects of maneb on Testosterone Release in male rats.
    Drug and chemical toxicology, 2011
    Co-Authors: Faustin Pascal Tsagué Manfo, Wen-fang Chao, Paul F. Moundipa, M. Pugeat, Paulus S. Wang
    Abstract:

    Maneb (Manganese ethylene-bis-dithiocarbamate) is a widely used fungicide in agriculture. In order to investigate its effect on male reproductive function, rats were intraperitonealy injected with maneb (1 and 4 mg/kg) for 9 or 18 days. After 6 and 14 days of treatment, the animals received human chorionic gonadotropin (hCG) via a jugular catheter and blood samples were collected at several intervals subsequent to the challenge. They were thereafter decapitated after 9 or 18 days, and organs (i.e., liver, seminal vesicles, and kidneys) were weighed. Leydig cells prepared from rats after 18 days of treatment were incubated with or without different stimulators or precursors [hCG, A23187, 25-OH-cholesterol (25-OH-C), or androstenedione] for 1 hour, and the media were analyzed for Testosterone or pregnenolone. Liver glutathione and thiobarbituric acid reactive substances (TBARS) as well as serum alanine aminotransferase (ALT) activity were also measured. Further, Leydig cells and testicular interstitial cells (TICs) prepared from normal rats were incubated with maneb (3-100 µM) for 1 or 2 hours, and Testosterone Release was assessed. The results showed that administration of maneb (4 mg/kg) for 9 and 18 days did not alter liver function, but resulted in a decrease of basal level of plasma Testosterone (P < 0.01). In addition, basal Testosterone and pregnenolone Release by Leydig cells prepared from maneb 18-day treated animals were significantly reduced (P < 0.05). However, acute in vitro exposure of TIC or Leydig cells to maneb did not alter their Testosterone Release. These results suggested that maneb alters Testosterone production, at least in part, through inhibition of CYP11A1 activitiy.

  • The Effects of Anti‐TNF‐α Antibody on Hyperprolactinemia‐Related Suppression of hCG‐Induced Testosterone Release in Male Rats
    The journal of sexual medicine, 2010
    Co-Authors: William J.s. Huang, Ling-yu Yang, Yi-ting Tsai, Paulus S. Wang
    Abstract:

    ABSTRACT Introduction Hyperprolactinemia (hyperPRL)‐related hypogonadism or suppression of human chorionic gonadotropin (hCG)‐induced Testosterone (T) Release is hypothesized to be mediated by a testicular interstitial macrophage and tumor necrosis factor alpha (TNF‐α)‐involved blockage. Aim To test if the lower T response after hCG challenge in the hyperPRL rats is reversed by administrating anti‐TNF‐α antibody (Ab). Methods HyperPRL was induced by allografting two anterior pituitary (AP) glands per rat. Control rats were grafted with similar amount of cerebral cortex. The testicular interstitial cells (TIC) were isolated from the testis 6 weeks after grafting. TIC was treated with anti‐TNF‐α Ab with or without hCG. The other groups of rats received intra‐testicular or intra‐muscular anti‐TNF‐α Ab 7 days before in vitro study. The TIC isolated from each testis was incubated and T Release with or without hCG challenge were measured. Main Outcome Measures Prolactin (PRL) and T were measured by radioimmunoassay. TNF‐α was measured by enzyme‐linked immunosorbent assay (ELISA). Results When low dose of anti‐TNF‐α Ab was administered to the TIC incubation, the effects of PRL‐related suppression of hCG‐stimulated T Release were not significant. While a higher dose of anti‐TNF‐α Ab almost abolished the suppressive effects of PRL to hCG‐stimulated T Release. Prior intra‐testicular or intra‐muscular administration of anti‐TNF‐α Ab reversed the suppressive effects of AP grafting on TIC's T Release. This was demonstrated in groups with anti‐TNF‐α Ab injection both 7 and 1 day prior to TIC incubations. Conclusions The data support the hypothesis that the suppression of hCG‐induced T Release associated with hyperPRL is through a TNF‐α‐mediated mechanism to suppress the Leydig cells. The effect of anti‐TNF‐α Ab is durable for at least 7 days. Besides intra‐testicular injection, there might be other ways available for administrating Ab. Anti‐TNF‐α Ab has a potential therapeutic application on hyperPRL‐induced hypogonadism or suppression of hCG‐induced T Release. Huang WJS, Yang L‐Y, Pu H‐F, Tsai Y‐T, and Wang PS. The effects of anti‐TNF‐α antibody on hyperprolactinemia‐related suppression of hCG‐induced Testosterone Release in male rats. J Sex Med 2012;9:1005–1014.

  • Effects of catechin, epicatechin and epigallocatechin gallate on Testosterone production in rat leydig cells.
    Journal of cellular biochemistry, 2010
    Co-Authors: Sung‐yun Chen, Shyi Wu Wang, Paulus S. Wang
    Abstract:

    Catechins have been reported to have many pharmacological properties such as the effects of anti-oxidative, anti-inflammatory, anti-carcinogenic, anti-ultraviolet, and reduction of blood pressure as well as glucose and cholesterol levels. However, the effect of catechins on the reproductive mechanism is still unknown. In the present study, the effects of catechins on Testosterone secretion in rat testicular Leydig cells (LCs) were explored. Both in vivo and in vitro investigations were performed. Purified LCs were incubated with or without catechin (CCN), epicatechin (EC), epigallocatechin gallate (EGCG, 10(-10)-10(-8) M) under challenge with human chorionic gonadotropin (hCG, 0.01 IU/ml), forskolin, SQ22536 (an adenylyl cyclase inhibitor), 8-bromo-adenosine 3':5'-cyclic monophosphate (8-Br-cAMP), A23187 (a calcium ionophore), and nifedipine (10(-5) M), respectively. To study the effects of catechins on steroidogenesis, steroidogenic precursors-stimulated Testosterone Release was examined. The functions of the steroidogenic enzymes including protein expression of cytochrome P450 side chain cleavage enzyme (P450scc) and steroidogenic acute regulatory (StAR) protein were investigated and expressed by Western blotting. Catechins increased plasma Testosterone in vivo in male rats. In vitro, low-dose concentration of catechins increased gonadotropin releasing hormone (GnRH)-stimulated luteinizing hormone (LH) Release by anterior pituitary gland and hCG-stimulated Testosterone Release by LCs of male rats. These results suggested that catechins stimulated Testosterone production by acting on rat LCs via the mechanism of increasing the action of cAMP, but not P450scc, StAR protein or the activity of intracellular calcium. EC, one of the catechins increased the Testosterone secretion by rat LCs via the enzyme activities of 17beta-hydroxysteroid dehydrogenase (17beta-HSD).

Shyi Wu Wang - One of the best experts on this subject based on the ideXlab platform.

  • Effects of catechin, epicatechin and epigallocatechin gallate on Testosterone production in rat leydig cells.
    Journal of cellular biochemistry, 2010
    Co-Authors: Sung‐yun Chen, Shyi Wu Wang, Paulus S. Wang
    Abstract:

    Catechins have been reported to have many pharmacological properties such as the effects of anti-oxidative, anti-inflammatory, anti-carcinogenic, anti-ultraviolet, and reduction of blood pressure as well as glucose and cholesterol levels. However, the effect of catechins on the reproductive mechanism is still unknown. In the present study, the effects of catechins on Testosterone secretion in rat testicular Leydig cells (LCs) were explored. Both in vivo and in vitro investigations were performed. Purified LCs were incubated with or without catechin (CCN), epicatechin (EC), epigallocatechin gallate (EGCG, 10(-10)-10(-8) M) under challenge with human chorionic gonadotropin (hCG, 0.01 IU/ml), forskolin, SQ22536 (an adenylyl cyclase inhibitor), 8-bromo-adenosine 3':5'-cyclic monophosphate (8-Br-cAMP), A23187 (a calcium ionophore), and nifedipine (10(-5) M), respectively. To study the effects of catechins on steroidogenesis, steroidogenic precursors-stimulated Testosterone Release was examined. The functions of the steroidogenic enzymes including protein expression of cytochrome P450 side chain cleavage enzyme (P450scc) and steroidogenic acute regulatory (StAR) protein were investigated and expressed by Western blotting. Catechins increased plasma Testosterone in vivo in male rats. In vitro, low-dose concentration of catechins increased gonadotropin releasing hormone (GnRH)-stimulated luteinizing hormone (LH) Release by anterior pituitary gland and hCG-stimulated Testosterone Release by LCs of male rats. These results suggested that catechins stimulated Testosterone production by acting on rat LCs via the mechanism of increasing the action of cAMP, but not P450scc, StAR protein or the activity of intracellular calcium. EC, one of the catechins increased the Testosterone secretion by rat LCs via the enzyme activities of 17beta-hydroxysteroid dehydrogenase (17beta-HSD).

  • Differential effects of nonylphenol on Testosterone secretion in rat Leydig cells.
    Toxicology, 2009
    Co-Authors: Kai-lee Wang, Shyi Wu Wang, Guey-shyang Hwang, I-fang Mao, Mei-lien Chen, Paulus S. Wang
    Abstract:

    Nonylphenol (NP), a final metabolite of nonylphenol polyethoxylate, has been reported to interfere with male reproduction. However, its mechanisms are not fully understood. In the present study, we examined the effects of NP on steroidogenesis of Testosterone in rat Leydig cells. The Testosterone concentrations in rat plasma were examined after intravenous injection of NP (100 microg/kg) at different time intervals. In addition, rat Leydig cells were challenged with different concentrations of NP (4.25-127.5 microM) to evaluate its influences on Testosterone steroidogenesis. Administration of NP showed a decrease of hCG-induced plasma Testosterone. Moreover, in vitro experiments revealed that NP (127.5 microM) alone stimulated Testosterone Release through increase of both protein levels and activities of the StAR and P450(SCC). In contrast, NP inhibited hCG-induced Testosterone Release in rat Leydig cells. The inhibitory effect was also observed after incubation of the Leydig cells in the presence of different precursors. These results suggested that NP had differential effects on Testosterone synthesis.

  • Effects of hypoxia on Testosterone Release in rat Leydig cells.
    American journal of physiology. Endocrinology and metabolism, 2009
    Co-Authors: Guey-shyang Hwang, Te-jung Chen, Szu-tah Chen, Shyi Wu Wang
    Abstract:

    The aim of this study was to explore the effect and action mechanisms of intermittent hypoxia on the production of Testosterone both in vivo and in vitro. Male rats were housed in a hypoxic chamber (12% O(2) + 88% N(2), 1.5 l/ml) 8 h/day for 4 days. Normoxic rats were used as control. In an in vivo experiment, hypoxic and normoxic rats were euthanized and the blood samples collected. In the in vitro experiment, the enzymatically dispersed rat Leydig cells were prepared and challenged with forskolin (an adenylyl cyclase activator, 10(-4) M), 8-Br-cAMP (a membrane-permeable analog of cAMP, 10(-4) M), hCG (0.05 IU), the precursors of the biosynthesis Testosterone, including 25-OH-C (10(-5) M), pregnenolone (10(-7) M), progesterone (10(-7) M), 17-OH-progesterone (10(-7) M), and androstendione (10(-7)-10(-5) M), nifedipine (L-type Ca(2+) channel blocker, 10(-6)-10(-4) M), nimodipine (L-type Ca(2+) channel blocker, 10(-5) M), tetrandrine (L-type Ca(2+) channel blocker, 10(-5) M), and NAADP (calcium-signaling messenger causing Release of calcium from intracellular stores, 10(-6)-10(-4) M). The concentrations of Testosterone in plasma and medium were measured by radioimmunoassay. The level of plasma Testosterone in hypoxic rats was higher than that in normoxic rats. Enhanced Testosterone production was observed in rat Leydig cells treated with hCG, 8-Br-cAMP, or forskolin in both normoxic and hypoxic conditions. Intermittent hypoxia resulted in a further increase of Testosterone production in response to the Testosterone precursors. The activity of 17β-hydroxysteroid dehydrogenase was stimulated by the treatment of intermittent hypoxia in vitro. The intermittent hypoxia-induced higher production of Testosterone was accompanied with the influx of calcium via L-type calcium channel and the increase of intracellular calcium via the mechanism of calcium mobilization. These results suggested that the intermittent hypoxia stimulated the secretion of Testosterone at least in part via stimulatory actions on the activities of adenylyl cyclase, cAMP, L-type calcium channel, and steroidogenic enzymes.

  • Effects of hypoxia on Testosterone Release in rat Leydig cells.
    American Journal of Physiology-endocrinology and Metabolism, 2009
    Co-Authors: Guey-shyang Hwang, Te-jung Chen, Szu-tah Chen, Shyi Wu Wang
    Abstract:

    The aim of this study was to explore the effect and action mechanisms of intermittent hypoxia on the production of Testosterone both in vivo and in vitro. Male rats were housed in a hypoxic chamber...

  • effect of adlay coix lachryma jobi l var ma yuen stapf hull extracts on Testosterone Release from rat leydig cells
    Phytotherapy Research, 2009
    Co-Authors: Paulus S. Wang, Shih Min Hsia, Yi Wen Tseng, Shyi Wu Wang, Yueh-hsiung Kuo, Din Wen Huang, Wenchang Chiang
    Abstract:

    Adlay has been used as a traditional Chinese medicine for the treatment of many diseases. However, few studies have reported the effects of adlay seeds on the endocrine system. In the present study, the effects of methanol extracts of adlay hull (AHM) on Testosterone synthesis were studied. Rat Leydig cells were incubated with different reagents including human chorionic gonadotropin, 8-bromo-adenosine-3',5'-cyclic monophosphate, forskolin, A23187, progesterone and androstenedione in the presence or absence of AHM. The rat anterior pituitary (AP) gland was treated with gonadotropin-releasing hormone (GnRH) in vitro in the presence or absence of AHM, and the concentrations of luteinizing hormone (LH) in the media were measured. AHM decreased Testosterone Release via the inhibition of (1) the PKA and PKC signal transduction pathways, (2) 17β-HSD enzyme activity in rat Leydig cells, and (3) in vitro GnRH-induced LH secretion.

Shih Min Hsia - One of the best experts on this subject based on the ideXlab platform.

  • Downregulation of Testosterone production through luteinizing hormone receptor regulation in male rats exposed to 17α-ethynylestradiol.
    Scientific Reports, 2020
    Co-Authors: Po-han Lin, Shih Min Hsia, Kai-lee Wang, Tsung Hsien Kuo, Chih Chieh Chen, Cai Yun Jian, Chien Wei Chen, Yuh Chen Kuo, Heng Yi Shen, Paulus S. Wang
    Abstract:

    The pharmaceutical 17α-ethynylestradiol (EE2) is considered as an endocrine-disrupting chemical that interferes with male reproduction and hormonal activation. In this study, we investigated the molecular mechanism underlying EE2-regulatory Testosterone Release in vitro and in vivo. The results show that EE2 treatment decreased Testosterone Release from rat Leydig cells. Treatment of rats with EE2 reduced plasma Testosterone levels and decreased the sensitivity of human chorionic gonadotropin (hCG). EE2 reduced luteinizing hormone receptor (LHR) expression associated with decreased cAMP generation by downregulation of adenylyl cyclase activity and decreased intracellular calcium-mediated pathways. The expression levels of StAR and P450scc were decreased in Leydig cells by treatment of rats with EE2 for 7 days. The sperm motility in the vas deferens and epididymis was reduced, but the histopathological features of the testis and the total sperm number of the vas deferens were not affected. Moreover, the serum dihydroTestosterone (DHT) level was decreased by treatment with EE2. The prostate gland and seminal vesicle atrophied significantly, and their expression level of 5α-reductase type II was reduced after EE2 exposure. Taken together, these results demonstrate an underlying mechanism of EE2 to downregulate Testosterone production in Leydig cells, explaining the damaging effects of EE2 on male reproduction.

  • effect of adlay coix lachryma jobi l var ma yuen stapf hull extracts on Testosterone Release from rat leydig cells
    Phytotherapy Research, 2009
    Co-Authors: Paulus S. Wang, Shih Min Hsia, Yi Wen Tseng, Shyi Wu Wang, Yueh-hsiung Kuo, Din Wen Huang, Wenchang Chiang
    Abstract:

    Adlay has been used as a traditional Chinese medicine for the treatment of many diseases. However, few studies have reported the effects of adlay seeds on the endocrine system. In the present study, the effects of methanol extracts of adlay hull (AHM) on Testosterone synthesis were studied. Rat Leydig cells were incubated with different reagents including human chorionic gonadotropin, 8-bromo-adenosine-3',5'-cyclic monophosphate, forskolin, A23187, progesterone and androstenedione in the presence or absence of AHM. The rat anterior pituitary (AP) gland was treated with gonadotropin-releasing hormone (GnRH) in vitro in the presence or absence of AHM, and the concentrations of luteinizing hormone (LH) in the media were measured. AHM decreased Testosterone Release via the inhibition of (1) the PKA and PKC signal transduction pathways, (2) 17β-HSD enzyme activity in rat Leydig cells, and (3) in vitro GnRH-induced LH secretion.

  • Effect of adlay (Coix lachryma‐jobi L. var. ma‐yuen Stapf.) hull extracts on Testosterone Release from rat Leydig cells
    Phytotherapy research : PTR, 2008
    Co-Authors: Shih Min Hsia, Paulus S. Wang, Yi Wen Tseng, Shyi Wu Wang, Yueh-hsiung Kuo, Din Wen Huang, Wenchang Chiang
    Abstract:

    Adlay has been used as a traditional Chinese medicine for the treatment of many diseases. However, few studies have reported the effects of adlay seeds on the endocrine system. In the present study, the effects of methanol extracts of adlay hull (AHM) on Testosterone synthesis were studied. Rat Leydig cells were incubated with different reagents including human chorionic gonadotropin, 8-bromo-adenosine-3',5'-cyclic monophosphate, forskolin, A23187, progesterone and androstenedione in the presence or absence of AHM. The rat anterior pituitary (AP) gland was treated with gonadotropin-releasing hormone (GnRH) in vitro in the presence or absence of AHM, and the concentrations of luteinizing hormone (LH) in the media were measured. AHM decreased Testosterone Release via the inhibition of (1) the PKA and PKC signal transduction pathways, (2) 17β-HSD enzyme activity in rat Leydig cells, and (3) in vitro GnRH-induced LH secretion.

Wenchang Chiang - One of the best experts on this subject based on the ideXlab platform.

  • effect of adlay coix lachryma jobi l var ma yuen stapf hull extracts on Testosterone Release from rat leydig cells
    Phytotherapy Research, 2009
    Co-Authors: Paulus S. Wang, Shih Min Hsia, Yi Wen Tseng, Shyi Wu Wang, Yueh-hsiung Kuo, Din Wen Huang, Wenchang Chiang
    Abstract:

    Adlay has been used as a traditional Chinese medicine for the treatment of many diseases. However, few studies have reported the effects of adlay seeds on the endocrine system. In the present study, the effects of methanol extracts of adlay hull (AHM) on Testosterone synthesis were studied. Rat Leydig cells were incubated with different reagents including human chorionic gonadotropin, 8-bromo-adenosine-3',5'-cyclic monophosphate, forskolin, A23187, progesterone and androstenedione in the presence or absence of AHM. The rat anterior pituitary (AP) gland was treated with gonadotropin-releasing hormone (GnRH) in vitro in the presence or absence of AHM, and the concentrations of luteinizing hormone (LH) in the media were measured. AHM decreased Testosterone Release via the inhibition of (1) the PKA and PKC signal transduction pathways, (2) 17β-HSD enzyme activity in rat Leydig cells, and (3) in vitro GnRH-induced LH secretion.

  • Effect of adlay (Coix lachryma‐jobi L. var. ma‐yuen Stapf.) hull extracts on Testosterone Release from rat Leydig cells
    Phytotherapy research : PTR, 2008
    Co-Authors: Shih Min Hsia, Paulus S. Wang, Yi Wen Tseng, Shyi Wu Wang, Yueh-hsiung Kuo, Din Wen Huang, Wenchang Chiang
    Abstract:

    Adlay has been used as a traditional Chinese medicine for the treatment of many diseases. However, few studies have reported the effects of adlay seeds on the endocrine system. In the present study, the effects of methanol extracts of adlay hull (AHM) on Testosterone synthesis were studied. Rat Leydig cells were incubated with different reagents including human chorionic gonadotropin, 8-bromo-adenosine-3',5'-cyclic monophosphate, forskolin, A23187, progesterone and androstenedione in the presence or absence of AHM. The rat anterior pituitary (AP) gland was treated with gonadotropin-releasing hormone (GnRH) in vitro in the presence or absence of AHM, and the concentrations of luteinizing hormone (LH) in the media were measured. AHM decreased Testosterone Release via the inhibition of (1) the PKA and PKC signal transduction pathways, (2) 17β-HSD enzyme activity in rat Leydig cells, and (3) in vitro GnRH-induced LH secretion.

William J.s. Huang - One of the best experts on this subject based on the ideXlab platform.

  • the effects of anti tnf α antibody on hyperprolactinemia related suppression of hcg induced Testosterone Release in male rats
    The Journal of Sexual Medicine, 2012
    Co-Authors: Ling-yu Yang, William J.s. Huang, Yi-ting Tsai, Paulus S. Wang
    Abstract:

    ABSTRACT Introduction Hyperprolactinemia (hyperPRL)‐related hypogonadism or suppression of human chorionic gonadotropin (hCG)‐induced Testosterone (T) Release is hypothesized to be mediated by a testicular interstitial macrophage and tumor necrosis factor alpha (TNF‐α)‐involved blockage. Aim To test if the lower T response after hCG challenge in the hyperPRL rats is reversed by administrating anti‐TNF‐α antibody (Ab). Methods HyperPRL was induced by allografting two anterior pituitary (AP) glands per rat. Control rats were grafted with similar amount of cerebral cortex. The testicular interstitial cells (TIC) were isolated from the testis 6 weeks after grafting. TIC was treated with anti‐TNF‐α Ab with or without hCG. The other groups of rats received intra‐testicular or intra‐muscular anti‐TNF‐α Ab 7 days before in vitro study. The TIC isolated from each testis was incubated and T Release with or without hCG challenge were measured. Main Outcome Measures Prolactin (PRL) and T were measured by radioimmunoassay. TNF‐α was measured by enzyme‐linked immunosorbent assay (ELISA). Results When low dose of anti‐TNF‐α Ab was administered to the TIC incubation, the effects of PRL‐related suppression of hCG‐stimulated T Release were not significant. While a higher dose of anti‐TNF‐α Ab almost abolished the suppressive effects of PRL to hCG‐stimulated T Release. Prior intra‐testicular or intra‐muscular administration of anti‐TNF‐α Ab reversed the suppressive effects of AP grafting on TIC's T Release. This was demonstrated in groups with anti‐TNF‐α Ab injection both 7 and 1 day prior to TIC incubations. Conclusions The data support the hypothesis that the suppression of hCG‐induced T Release associated with hyperPRL is through a TNF‐α‐mediated mechanism to suppress the Leydig cells. The effect of anti‐TNF‐α Ab is durable for at least 7 days. Besides intra‐testicular injection, there might be other ways available for administrating Ab. Anti‐TNF‐α Ab has a potential therapeutic application on hyperPRL‐induced hypogonadism or suppression of hCG‐induced T Release. Huang WJS, Yang L‐Y, Pu H‐F, Tsai Y‐T, and Wang PS. The effects of anti‐TNF‐α antibody on hyperprolactinemia‐related suppression of hCG‐induced Testosterone Release in male rats. J Sex Med 2012;9:1005–1014.

  • The Effects of Anti‐TNF‐α Antibody on Hyperprolactinemia‐Related Suppression of hCG‐Induced Testosterone Release in Male Rats
    The journal of sexual medicine, 2010
    Co-Authors: William J.s. Huang, Ling-yu Yang, Yi-ting Tsai, Paulus S. Wang
    Abstract:

    ABSTRACT Introduction Hyperprolactinemia (hyperPRL)‐related hypogonadism or suppression of human chorionic gonadotropin (hCG)‐induced Testosterone (T) Release is hypothesized to be mediated by a testicular interstitial macrophage and tumor necrosis factor alpha (TNF‐α)‐involved blockage. Aim To test if the lower T response after hCG challenge in the hyperPRL rats is reversed by administrating anti‐TNF‐α antibody (Ab). Methods HyperPRL was induced by allografting two anterior pituitary (AP) glands per rat. Control rats were grafted with similar amount of cerebral cortex. The testicular interstitial cells (TIC) were isolated from the testis 6 weeks after grafting. TIC was treated with anti‐TNF‐α Ab with or without hCG. The other groups of rats received intra‐testicular or intra‐muscular anti‐TNF‐α Ab 7 days before in vitro study. The TIC isolated from each testis was incubated and T Release with or without hCG challenge were measured. Main Outcome Measures Prolactin (PRL) and T were measured by radioimmunoassay. TNF‐α was measured by enzyme‐linked immunosorbent assay (ELISA). Results When low dose of anti‐TNF‐α Ab was administered to the TIC incubation, the effects of PRL‐related suppression of hCG‐stimulated T Release were not significant. While a higher dose of anti‐TNF‐α Ab almost abolished the suppressive effects of PRL to hCG‐stimulated T Release. Prior intra‐testicular or intra‐muscular administration of anti‐TNF‐α Ab reversed the suppressive effects of AP grafting on TIC's T Release. This was demonstrated in groups with anti‐TNF‐α Ab injection both 7 and 1 day prior to TIC incubations. Conclusions The data support the hypothesis that the suppression of hCG‐induced T Release associated with hyperPRL is through a TNF‐α‐mediated mechanism to suppress the Leydig cells. The effect of anti‐TNF‐α Ab is durable for at least 7 days. Besides intra‐testicular injection, there might be other ways available for administrating Ab. Anti‐TNF‐α Ab has a potential therapeutic application on hyperPRL‐induced hypogonadism or suppression of hCG‐induced T Release. Huang WJS, Yang L‐Y, Pu H‐F, Tsai Y‐T, and Wang PS. The effects of anti‐TNF‐α antibody on hyperprolactinemia‐related suppression of hCG‐induced Testosterone Release in male rats. J Sex Med 2012;9:1005–1014.

  • Role of testicular interstitial macrophages in regulating Testosterone Release in hyperprolactinemia.
    Journal of cellular biochemistry, 2003
    Co-Authors: William J.s. Huang, Jiun-yih Yeh, Shu-fen Kan, L.s. Chang, Paulus S. Wang
    Abstract:

    Hyperprolactinemia-induced hypogonadism has been linked to a dysfunction of the hypothalamus-pituitary-testis axis. The direct inhibitory effects of prolactin on the testicular Release of Testosterone have also been demonstrated, though their mechanisms remain unclear. Incubation of rat testicular interstitial cells (TICs) with prolactin stimulated the Release of Testosterone. TICs from rats with anterior pituitary-grafting-induced hyperprolactinemia Release lower amounts of Testosterone than controls. However, Leydig cells isolated from anterior pituitary-grafted rats Release a greater amount of Testosterone. These paradoxical observations have remained unexplained. This study examined the roles of testicular interstitial macrophages and of their product, tumor necrosis factor-alpha (TNF-alpha), in regulating Leydig cells under condition of hyperprolactinemia. Hyperprolactinemia was induced by grafting two anterior pituitary glands of rats under the renal capsule. Control animals were grafted with rat cortex tissue. The rats were sacrificed 6 weeks later. TICs and macrophages, and Leydig cells were isolated for in vitro incubation and drugs challenge. Testosterone Released by testicular interstitial or Leydig cells was measured by radioimmunoassay. TNF-alpha concentration in the medium of TICs or macrophages was measured by enzyme-linked immunosorbent assay (ELISA). A dose-dependent stimulation of TNF-alpha secretion in the medium of TICs or macrophages by the prolactin challenge was observed. Higher amounts of TNF-alpha were Released by TICs in the anterior pituitary-grafted rats than in the control group. In contrast, the Release of TNF-alpha by testicular interstitial macrophages isolated from the anterior pituitary- and cortex-grafted groups was quantitatively similar. Challenge with human chorionic gonadotropin did not modify the TNF-alpha Release by testicular interstitial macrophages in either group. Challenge of Leydig cells with TNF-alpha inhibited their Release of Testosterone stimulated by human chorionic gonadotropin, but not their basal Testosterone Release. These different patterns of Testosterone Release in TICs versus Leydig cells cultures in anterior pituitary-grafted rats may be due to the influence of testicular interstitial macrophages. These observations correlate with in vivo conditions, where prolactin increases the Release of TNF-alpha by testicular interstitial macrophages, which, in turn, decreases the human chorionic gonadotropin-stimulated Release of Testosterone by Leydig cells. In summary, hyperprolactinemia-induced hypogonadism involves a mechanism of prolactin-originated, macrophage-mediated inhibitory regulation of Testosterone Release by Leydig cells. TNF-alpha, one of the cytokines secreted by macrophages, may play a key role in this mechanism.

  • Regulation of Testosterone secretion by prolactin in male rats.
    Journal of cellular biochemistry, 1999
    Co-Authors: William J.s. Huang, Jiun-yih Yeh, Shyi Wu Wang, Yu-chung Chiao, Shiow-chwen Tsai, Ho Lin, Jiann-jong Chen, Seng-wong Hwang, L.s. Chang
    Abstract:

    The goal of this study was to characterize the mechanism by which hyperprolactinemia alters Testosterone production in rat testicular interstitial cells (TICs). Hyperprolactinemia was induced by grafting 2 anterior pituitary (AP) glands under the subcapsular space of the kidney in experimental rats. Control rats were grafted with brain cortex (CX). Six weeks post-grafting, rats were challenged with human chorionic gonadotropin (hCG) then, the changes in either plasma Testosterone or luteinizing hormone was measured. Additionally, TICs were isolated and challenged in vitro with hCG or prolactin, and the Testosterone Release measured by radioimmunoassay. Further investigation in signal transduction as intracellular 3′:5′ cyclic adenosine monophosphate (cAMP) production was observed under a regulation of forskolin or SQ22536. After the challenge of hCG or GnRH, the AP-grafted rats showed a suppressed response in Testosterone Release as compared to those in the CX-grafted group. The in vitro data from the AP-grafted rats compared to the CX-grafted animals showed a diminished response in Testosterone Release upon hCG stimulation. Administration of forskolin or SQ22536 disclosed dysfunction of adenylate cyclase in TICs from the AP-grafted rats. When 8-Br-cAMP was incubated with TICs, the Testosterone production was lower in the AP-grafted compared to the CX-grafted group. These results suggest that in addition to adenylate cyclase dysfunction, inefficiency of post-cAMP pathways are also involved in the hypogonadism elicited by hyperprolactinemia in rats. J. Cell. Biochem. 74:111–118, 1999. © 1999 Wiley-Liss, Inc.