scholarly journals A novel mechanism for the melatonin inhibition of testosterone secretion by rat Leydig cells: reduction of GnRH-induced increase in cytosolic Ca2+

1999 ◽  
Vol 23 (3) ◽  
pp. 299-306 ◽  
Author(s):  
S Valenti ◽  
S Thellung ◽  
T Florio ◽  
M Giusti ◽  
G Schettini ◽  
...  
Keyword(s):  
Leydig Cells ◽  
Calcium Concentration ◽  
Inhibitory Effect ◽  
Adult Rat ◽  
Testosterone Secretion ◽  
Gi Protein ◽  
Hydroxy Progesterone ◽  
Induced Changes ◽  
Cells Cultured

The site of inhibition, by melatonin, of GnRH-dependent testosterone secretion was investigated in adult rat Leydig cells cultured in vitro. The various effects downstream of the binding of GnRH to its own receptor were isolated and mimicked by specific drugs. Testosterone secretion was then evaluated after 3 h stimulation with GnRH, thapsigargin (1 microM), phorbol-12-myristate-13-acetate (100 nM), arachidonic acid (20 microM), and ionomycin (1 microM) in the presence or absence of melatonin (215 nM). The effect of melatonin on the GnRH-induced changes in cytoplasmic calcium concentration ([Ca(2+)](i)) was also studied, using Fura-2 as fluorescent Ca(2+) indicator. Melatonin attenuated the increase in [Ca(2+)](i) and inhibited the testosterone secretion induced by GnRH, but not that induced by ionomycin. Both ionomycin and thapsigargin potentiated GnRH-induced testosterone secretion; however, ionomycin, but not thapsigargin, partially prevented the inhibitory effect of melatonin on cells stimulated with GnRH. The effect of melatonin was probably dependent on the binding of melatonin to its Gi-protein-coupled receptor, as the inhibitory effect on GnRH-induced secretion was supressed in cells pretreated with pertussis toxin in a concentration of 180 ng/ml for 20 h. Assay of 17-hydroxy-progesterone showed that, irrespective of the treatment, cells cultured with melatonin secreted greater amounts than controls. We conclude that melatonin reduces GnRH-induced testosterone secretion by 1) decreasing [Ca(2+)](i), through impairment of the GnRH-dependent release of Ca(2+) from intracellular stores and 2) blocking 17-20 desmolase enzymatic activity, an effect that occurs irrespective of changes in [Ca(2+)](i).

Interleukin-1α-induced changes in androgen and cyclic adenosine 3′,5′-monophosphate release in adult rat Leydig cells in culture

1991 ◽  
Vol 129 (3) ◽  
pp. 381-390 ◽  
Author(s):  
C. Moore ◽  
W. H. Moger
Keyword(s):  
Leydig Cells ◽  
Culture Media ◽  
Interleukin 1 ◽  
Inhibitory Effect ◽  
Adult Rat ◽  
Cells In Culture ◽  
Similar Inhibitory Effect ◽  
Half Maximal Effective Concentration ◽  
Interleukin 1Α ◽  
Induced Changes

ABSTRACT Interleukin-1 (IL-1) has been proposed as a paracrine regulator of testicular function. The effect of this cytokine on adult rat Leydig cells in primary culture was investigated. Interstitial cells were purified on a two-step Percoll gradient and cultured in the presence or absence of recombinant human IL-1α (IL-1α). The presence of IL-1α in the culture media resulted in a dose-dependent increase in 24-h basal androgen release (half-maximal effective concentration = 40–50 U/ml). The stimulatory effect of IL-1α peaked on days 3 and 4, and was often still significant after 6 days of culture. Removal of IL-1α was followed by a return of basal androgen release to control levels within 3 days. In contrast, cells treated with IL-1α (100 U/ml) for 3 days released significantly less androgen (per 4 h) in response to 1–100 ng LH/ml than control cells. A similar inhibitory effect on the response to dibutyryl cAMP and pregnenolone was observed. Under basal conditions, IL-1α-treated cells released significantly more cAMP than did control cells. In contrast, the increase in cAMP release seen with LH-stimulated cells was significantly inhibited by treatment with IL-1α. These results suggest that IL-1α has a dual effect on adult rat Leydig cells in culture. It stimulates basal but inhibits LH-induced androgen release with parallel changes in cAMP levels. An additional inhibitory effect appears to lie at the level of the 17α-hydroxylase/C17–20 lyase enzyme. Journal of Endocrinology (1991) 129, 381–390

Role of endothelial cells in regulating hemoglobin-induced changes in lymphatic pumping

1992 ◽  
Vol 263 (6) ◽  
pp. H1880-H1887 ◽  
Author(s):  
R. M. Elias ◽  
J. Eisenhoffer ◽  
M. G. Johnston
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Inhibitory Effect ◽  
Direct Inhibitory Effect ◽  
Induced Changes ◽  
Lymphatic Pumping ◽  
Pumping Activity

Studies with a sheep isolated duct preparation in vivo demonstrated that the route of administration of hemoglobin was important in demonstrating its inhibitory effect on lymphatic pumping. With autologous oxyhemoglobin administered intravenously (final plasma concentration 5 x 10(-5) M), pumping was not inhibited. However, the addition of oxyhemoglobin (5 x 10(-5) M) into the reservoir (lumen of the duct) resulted in > 95% inhibition of pumping. The extraluminal administration of oxyhemoglobin (10(-5) M) to bovine mesenteric lymphatics in vitro resulted in a 40% inhibition of pumping, whereas the introduction of oxyhemoglobin (10(-5) M) into the lumen of the vessels suppressed pumping 95%. In vessels mechanically denuded of endothelium, intraluminal oxyhemoglobin inhibited pumping 50%. These results suggested that oxyhemoglobin depressed pumping through an effect on both smooth muscle and endothelium. Once pumping was inhibited with oxyhemoglobin administration, stimulation of the duct with elevations in transmural pressure restored pumping activity when endothelial cells were present. However, in the absence of endothelium, pumping decreased with increases in distending pressures. We conclude that oxyhemoglobin has a direct inhibitory effect on lymphatic smooth muscle. The ability of oxyhemoglobin to alter the pressure range over which the lymph pump operates appears to be dependent on an intact endothelium.

scholarly journals In vitro pituitary and testicular effects of the leptin-related synthetic peptide leptin(116-130) amide involve actions both similar to and distinct from those of the native leptin molecule in the adult rat

2000 ◽  
pp. 406-410 ◽  
Author(s):  
M Tena-Sempere ◽  
L Pinilla ◽  
LC Gonzalez ◽  
J Navarro ◽  
C Dieguez ◽  
...  
Keyword(s):  
Body Weight ◽  
Adult Male ◽  
Body Weight Gain ◽  
Biologically Active ◽  
Male Rats ◽  
Male Rat ◽  
Gh Secretion ◽  
Adult Rat ◽  
Testosterone Secretion

The obese gene (ob) product, leptin, has recently emerged as a key element in body weight homeostasis, neuroendocrine function and fertility. Identification of biologically active, readily synthesized fragments of the leptin molecule has drawn considerable attention, as they may provide a powerful tool for detailed characterization of the biological actions of leptin in different experimental settings. Recently, a fragment of mouse leptin protein comprising amino acids 116-130, termed leptin(116-130) amide, was shown to mimic the effects of the native molecule in terms of body weight gain and food intake, and to elicit LH and prolactin (PRL) secretion in vivo. As a continuation of our previous experimental work, the present study reports on the effects of leptin(116-130) amide on basal and stimulated testosterone secretion by adult rat testis in vitro. In addition, a comparison of the effects of human recombinant leptin and leptin(116-130) amide at the pituitary level on the patterns of LH, FSH, PRL and GH secretion is presented. As reported previously by our group, human recombinant leptin(10(-9)-10(-7)M) significantly inhibited both basal and human chorionic gonadotrophin (hCG)-stimulated testosterone secretion in vitro. Similarly, incubation of testicular tissue in the presence of increasing concentrations of leptin(116-130) amide (10(-9)-10(-5)M) resulted in a dose-dependent inhibition of basal and hCG-stimulated testosterone secretion; a reduction that was significant from a dose of 10(-7)M upwards. In addition, leptin(116-130) amide, at all doses tested (10(-9)-10(-5)M), significantly decreased LH and FSH secretion by incubated hemi-pituitaries from adult male rats. In contrast, in the same experimental protocol, recombinant leptin(10(-9)-10(-7)M) was ineffective in modulating LH and FSH release. Finally, neither recombinant leptin nor leptin(116-130) amide were able to change basal PRL and GH secretion in vitro. Our results confirm the ability of leptin, acting at the testicular level, to inhibit testosterone secretion, and map the effect to a domain of the leptin molecule that lies between amino acid residues 116 and 130. In addition, we provide evidence for a direct inhibitory action of leptin(116-130) amide on pituitary LH and FSH secretion, a phenomenon not observed for the native leptin molecule, in the adult male rat.

scholarly journals Mumps Virus Decreases Testosterone Production and Gamma Interferon-Induced Protein 10 Secretion by Human Leydig Cells

2003 ◽  
Vol 77 (5) ◽  
pp. 3297-3300 ◽  
Author(s):  
Ronan Le Goffic ◽  
Thomas Mouchel ◽  
Annick Ruffault ◽  
Jean-Jacques Patard ◽  
Bernard Jégou ◽  
...  
Keyword(s):  
Cell Cultures ◽  
Leydig Cell ◽  
Leydig Cells ◽  
Mumps Virus ◽  
Gamma Interferon ◽  
Testosterone Secretion ◽  
Testosterone Production

ABSTRACT Mumps virus is responsible for sterility. Here, we show that the mumps virus infects Leydig cells in vitro and totally inhibits testosterone secretion and that ribavirin in mumps virus-infected Leydig cell cultures completely restores testosterone production. Moreover, we show that gamma interferon-induced protein 10 (IP-10) is highly expressed by mumps virus-infected Leydig cells and that ribavirin does not block IP-10 production.

Intragonadal regulation of immune system functions

1990 ◽  
Vol 2 (3) ◽  
pp. 263 ◽  
Author(s):  
MP Hedger ◽  
JX Qin ◽  
DM Robertson ◽  
Kretser DM de
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Germ Cell ◽  
Conditioned Medium ◽  
Leydig Cells ◽  
Seminiferous Tubules ◽  
Interstitial Tissue ◽  
Short Term ◽  
Adult Rat

Immune responses within the mammalian gonads, and in particular the testis, are deficient in spite of adequate lymphatic drainage and the presence of lymphocytes and MHC II+ macrophages. There is considerable evidence from in vivo and in vitro studies that this 'suppression' of the immune system may be due, at least in part, to localized inhibition or regulation of normal lymphocyte and/or macrophage functions within the gonads. In the testis, both steroidal and non-steroidal products of the Leydig cells, including androgens, endorphins, and inhibin-related proteins, have been implicated in mediating this activity. In turn, a number of immune cell cytokines affect steroidogenic cell function in vitro. The studies described in this paper indicated that [3H]-thymidine incorporation by adult rat thymocytes in vitro was inhibited by conditioned medium collected from short-term incubations of Percoll-purified adult rat Leydig cells, but stimulated by testicular interstitial fluid and by conditioned medium collected from short-term incubations of adult rat seminiferous tubules. The factors responsible for these effects on thymocyte function appeared to be of large molecular weight, as they were retained by ultrafiltration membranes with exclusion limits of 10,000 or 30,000 daltons. It is hypothesized that an 'immunosuppressive' mechanism, principally mediated by non-steroidal factors secreted by the steroidogenic cells of the gonadal interstitial tissue, exists within the gonads in order to prevent activation of the immune system by germ cell antigens and growth factors associated with germ cell proliferation and differentiation. This mechanism probably acts in parallel with normal antigen-specific tolerance mechanisms operating at the gonadal level. As immune responses to germ cells are believed to be a significant causative factor in infertility, particularly in men, this represents an important area for further study.

Effect of glucocorticoids on testosterone production by porcine Leydig cells in primary culture

1984 ◽  
Vol 62 (9) ◽  
pp. 1166-1169 ◽  
Author(s):  
M. Bernier ◽  
W. Gibb ◽  
R. Collu ◽  
J. R. Ducharme
Keyword(s):  
Primary Culture ◽  
Chorionic Gonadotropin ◽  
Leydig Cells ◽  
Inhibitory Effect ◽  
Time Dependent ◽  
Testosterone Production ◽  
Direct Inhibitory Effect ◽  
The Media ◽  
Synthetic Glucocorticoids

For this study, purified immature porcine Leydig cells in primary culture were used. After 2 days of culture, the cells were incubated with dexamethasone (5 × 10−9, 1 × 10−7 M) for various periods of time (3–45 h). The media were discarded and treatment was repeated with or without the addition of human chorionic gonadotropin (HCG, 10 mIU/mL) for 3 h. Dexamethasone (10−7 M) decreased testosterone production of HCG-treated cells (up to 40%) in a time-dependent fashion while the lower dose was ineffective. The effect of varying doses (10−8 and 10−6 M) of natural glucocorticoids (corticosterone, cortisol) or synthetic glucocorticoids (triamcinolone, triamcinolone acetonide, betamethasone, dexamethasone) and that of a synthetic progestin (R-5020) on cultured Leydig cells was also studied. After 18 h of preincubation, the various synthetic but not the natural steroids nor R-5020, were able to decrease testosterone production of control and HCG-treated cells by 20–40%. Of a number of other hormonal and nonhormonal substances studied at concentrations of 10−9 – 10−5 M, only lysine8-vasopressin at a concentration of 10−6 M was able to inhibit testosterone production by these cells. These results indicate that dexamethasone and other synthetic glucocorticoids, and to a lesser degree lysine8-vasopressin, may exert a direct inhibitory effect on testosterone production by purified porcine immature Leydig cells in vitro.

scholarly journals Xylazine regulates the release of glycine and aspartic acid in rat brain

2018 ◽  
Vol 62 (1) ◽  
pp. 121-128
Author(s):  
Yi-Ming Zhang ◽  
Dong-Xu Yu ◽  
Bai-Shuang Yin ◽  
Xin-Ran Li ◽  
Li-Na Li ◽  
...  
Keyword(s):  
Aspartic Acid ◽  
Brain Area ◽  
Brain Regions ◽  
Inhibitory Effect ◽  
Test Methods ◽  
Control Group ◽  
Clinical Anaesthesia ◽  
Induced Changes ◽  
Dose Dependent

AbstractIntroductionXylazine, a type of α2-adrenoceptors, is a commonly used drug in veterinary medicine. Xylazine-induced changes in the content of amino acid neurotransmitters – glycine (Gly) and aspartic acid (Asp), in different brain regions and neurons were studied.Material and MethodsWistar rats were administered 50 mg/kg or 70 mg/kg of xylazine by intraperitoneal injection. In addition, in vitro experiments were conducted, in which neurons were treated with 15 μg/mL, 25 μg/mL, 35μg/mL, and 45 μg/mL of xylazine. Test methods were based on the enzyme-linked immunosorbent assays (ELISA).ResultsDuring anaesthesia, Asp levels in each brain area were significantly lower compared to the control group. Except for the cerebrum, levels of Gly in other brain areas were significantly increased during the anaesthesia period. In vitro, xylazine-related neuron secretion of Gly increased significantly compared to the control group at 60 min and 90 min. Moreover, xylazine caused a significant decrease in the levels of Asp secreted by neurons at 20 min, but gradually returned to the level of the control group.ConclusionThe data showed that during anaesthesia the overall levels of Asp decreased and overall levels of Gly increased. In addition, the inhibitory effect of xylazine on Asp and the promotion of Gly were dose-dependent. Our data showed that different effects of xylazine on excitatory and inhibitory neurotransmitters provided a theoretical basis for the mechanism of xylazine activity in clinical anaesthesia.

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