Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The influence of co-cultures of rat testicular macrophages and Leydig cells (LC) on LC morphology and steroidogenesis was investigated with and without macrophage stimulation by a bacterial lipopolysaccharide (LPS). LC showed an elongated form in the presence of stimulated testicular macrophages. In the presence of non-stimulated testicular macrophages a significant inhibition of testosterone production was observed (decrease of 33%) from 48 h in co-culture while an increase of 16% was obtained at the same culture time, after stimulation of macrophages by LPS. When LC were treated with testicular macrophage-conditioned media (MCM) obtained from LPS-treated macrophages, they became fusiform and there was stimulation (78%) of steroid production. After human FSH stimulation (1-1000 mIU ml-1), MCM from testicular macrophages was no more effective in enhancing testosterone production by LC than was media from untreated LC. Similar experiments with LPS were conducted with macrophages of peritoneal origin. Peritoneal macrophages stimulated or not by LPS in co-cultures with LC or peritoneal MCM did not significantly modify testosterone production. However, these cells were able to modify LC morphology when LPS-MCM was added to LC-culture medium. The present results suggest strongly that testicular macrophage-LC interactions could be important in the control of LC steroidogenesis.
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PMID:Influence of rat testicular macrophages on Leydig cell function in vitro. 157 28

Alterations of immune activity are often accompanied by reproductive disorders. Because interleukins mediate the host's response to immune activation, we first examined the effect of the central injection of several lymphokines on LH secretion by gonadectomized rats. We then studied the ability of the most potent lymphokine in this system, interleukin-1 beta (Il-1 beta), to interfere with the proestrous LH surge and ovulation in the intact female rat as well as the dependence of this effect on the activation of opiate receptors. Finally, we investigated the possibility that increased brain levels of Ils, as induced by the central administration of a bacterial endotoxin, might also alter the normal ovulatory process. After intracerebroventricular (icv) injection, Il-1 beta, Il-6, and tumor necrosis factor all lowered plasma LH levels in castrated rats. On a molar basis, Il-1 beta was the most potent inhibitor of LH secretion. In gonadectomized animals, 2.5 and 10 ng Il-1 beta administered icv significantly (P less than or equal to 0.01) decreased plasma LH levels for 6 h, while the effect of 40 ng lasted up to 12 h. By contrast, FSH secretion was only measurably altered by 40 ng Il-1 beta 8 and 12 h posttreatment. In intact cycling female rats, icv injection of 40 ng Il-1 beta or 400 ng Il-1 alpha at 0830 h on the morning of proestrus significantly (P less than 0.01 and P less than 0.05, respectively) interfered with the proestrous surge of LH. In contrast, the peripheral administration of either lymphokine was without measurable effect. Centrally injected Il-1 beta (40 ng at 0830 h on proestrus) also blocked ovulation in most animals, while a dose of 25 ng injected iv was ineffective. Finally, we observed that the icv injection of endotoxin (a lipopolysaccharide), also interfered with ovulation. The possible involvement of opiate-dependent pathways in mediating the inhibitory action of Il-1 beta on reproductive processes was tested by implanting naloxone pellets 16-24 h before lymphokine treatment. The pellets, which released 200, 400, or 800 micrograms naloxone/h (corresponding to approximately 0.6, 1.32, or 2.64 mg/kg BW.h), had no effect on ovulation by themselves. When given before icv Il-1 beta, all naloxone regimens countered the effect of the cytokine, with the 800-micrograms/h dose restoring ovulation in eight of nine rats.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cytokines act within the brain to inhibit luteinizing hormone secretion and ovulation in the rat. 211 35

The potential for immunizing against gonadotropins without using Freund's complete adjuvant was explored in bonnet monkeys by using tetanus toxoid (TT) as carrier and Salmonella lipopolysaccharide (LPS) as adjuvant. Pure hCG beta subunit and or sheep LH beta subunit was coupled with TT by employing N-succinimidyl-pyridyl-dithio-propionate reagent. Fertile female bonnet monkeys were injected with 50 mcg gonadotropin equivalent monthly. 1 mg sodium phthalyl derivative of LPS was added to the 1st injection. Animals with low titers were also given a booster on Day 145 with Leiras adjuvant. 3 of 5 monkeys immunized with ovine beta-LH subunit bonded to TT had strong responses, and 2 produced high antibody titers after a booster with Leiras adjuvant. A 2nd group of 3 monkeys treated with both ovine beta LH and beta hCG conjugated to a common carrier, TT, showed high titers, between 750 and 1300 ng/ml, which were sustained for nearly a year. Scathard analysis indicated that the combined antigens raised antibodies of high affinity, with Ka values ranging from 5 x 109 to 6 x 1010 per M. There were no cross reactions with either human FSH or TSH. 2 of the monkeys immunized against the combined antigens remained infertile for 6 and 3 cycles respectively, or until their antibody titers fell to 35 and 5 Monkeys in the 1st group also were infertile for several cycles before their antibody levels fell below 120 ng/ml against hCG.
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PMID:Enhancement of antigonadotropin response to the beta-subunit of ovine luteinizing hormone by carrier conjugation and combination with the beta-subunit of human chorionic gonadotropin. 242 91

In the present study we examined the influence of FSH as well as a number of well-established cytokines on interleukin (IL)-6 by rat granulosa cells in culture. Increasing concentrations of FSH, IL-1 alpha, IL-1 beta, tumor necrosis factor alpha (TNF alpha), and lipopolysaccharide (LPS) were incubated for 48 h with undifferentiated granulosa cells obtained from diethylstilbestrol-primed immature rats. The results demonstrate that FSH, IL-1 alpha, IL-1 beta, and LPS, but not TNF alpha, caused significant concentration-dependent increases in IL-6 release. We also examined the effects of dibutyryl-cAMP, forskolin, and 3-isobutyl-1-methyl-xanthine (IBMX) on IL-6 release by granulosa cells. Each of these agents caused a significant concentration-dependent increase in IL-6 production by granulosa cells in either the absence or presence of FSH. Taken together, these results show that the granulosa cell is not only a likely source of IL-6 but that the release of IL-6 can be regulated. Moreover, evidence suggests that cAMP may serve as a second messenger for the stimulated secretion of IL-6 by undifferentiated granulosa cells.
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PMID:Interleukin-6 production by rat granulosa cells in vitro: effects of cytokines, follicle-stimulating hormone, and cyclic 3',5'-adenosine monophosphate. 768 Sep 7

Monoclonal antibody to TSH-receptor binds to the cells of human thyroid gland and to Chinese hamster ovary cell cultures. Pretreatments with TSH can decrease the binding of antibody, which effect is more expressed in CHO than in thyroid cells. Gonadotropin (FSH + LH) cannot influence the binding of antibody to thyroid, but there is an effect on CHO cells. Endotoxin (lipopolysaccharide, LPS) can depress the binding of antibodies on both objects and abolishes the difference between thyrotropin and gonadotropin receptors in their binding capacity, on both cell types. The experiments prove the similarity of thyrotropin and gonadotropin receptors which is responsible for the hormonal overlap.
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PMID:Changes in binding of monoclonal antibodies to TSH receptor following thyrotropin (TSH) and gonadotropin (GTH) pretreatments (studies on human thyroid and CHO cell lines). 778 44

Endotoxin, known as lipopolysaccharide (LPS), is a component of gram-negative bacterial cell walls and is a potent immunostimulator, inducing the release of several cytokines, such as tumor necrosis factor alpha (TNF alpha) and interleukins (IL) 1, 6, and 8. A previous study with immature rats revealed that exogenous administration of LPS inhibits ovarian estradiol secretion in response to eCG. The present study was undertaken in order to determine whether LPS could directly inhibit rat granulosa cell (GC) steroid secretion. GC were collected and purified from 26-day-old hypophysectomized female rats (hypophysectomy on Day 23). Purified GC were highly responsive to FSH (1-100 ng/ml), leading to increased estradiol, progesterone, and cAMP accumulation in culture media. GC were also capable of binding 125I-labeled hCG and were responsive to LH stimulation. Treatment of GC with LPS (1-100 ng/ml) led to a significant (p < 0.01) dose-dependent decrease in LH-stimulated estradiol accumulation in culture media (maximum 75% inhibition). However, treatment of GC with LPS had no significant effect on FSH-stimulated progesterone or estradiol, or LH-stimulated progesterone accumulation in culture media. GC stimulated with 8-bromo cAMP were also insensitive to the effects of LPS. LPS had no significant effect on 125I-labeled hCG binding to GC homogenates, nor did it have any significant effect on FSH or LH-stimulated cAMP accumulation. Treatment of both FSH and LH-stimulated GC with LPS was associated with an increase in IL-6 bioactivity in culture media. This effect could be blocked with the nonreceptor tyrosine kinase inhibitor herbimycin A. TNF alpha bioactivity was undetectable with or without LPS challenge. Direct challenge of GC with recombinant murine IL-6 had no effect on either FSH or LH-stimulated estradiol whereas TNF alpha inhibited FSH-stimulated estradiol secretion. Collectively, these results suggest that the inhibitory effects of LPS were not mediated by either IL-6 or TNF alpha. Treatment of GC with the epidermal growth factor receptor tyrosine kinase inhibitor, tyrphostin A46, blocked the inhibitory effects of LPS on steroid secretion and was associated with an increased cAMP accumulation in culture media. The results indicate that LPS inhibits in vitro GC estradiol secretion. This effect appears to be restricted to the LH-stimulated aromatization of androgens to estrogen and may involve a tyrosine kinase signaling pathway.
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PMID:Lipopolysaccharide inhibits in vitro luteinizing hormone-stimulated rat ovarian granulosa cell estradiol but not progesterone secretion. 872 69

Extracellular matrix components as well as enzymes and enzyme-inhibitors controlling the turn-over of these components play an important role in the local control of testicular function. Zymographic analysis was used to study the secretion and the control of the secretion of gelatinase A (MMP-2) and B (MMP-9) by primary cultures of rat Sertoli cells and by subcultures of peritubular cells. Data on gelatinase A were complemented by measurement of the corresponding mRNA by Northern blot analysis. The agonists investigated included hormones (FSH, testosterone), second messengers (dbcAMP, phorbolester and a Ca(2+)- ionophore), interleukin-1 beta (IL-1 beta) and inducers of cytokine production (Concanavalin A: ConA; lipopolysaccharide: LPS; double stranded RNA: PIC). It is demonstrated that Sertoli cells originally secrete both gelatinase A and B. When maintained in serum-free medium, however, they rapidly lose the ability to secrete gelatinase B. After 3 days of culture gelatinase A remains the only measurable gelatinase in both Sertoli and peritubular cell cultures. The production in peritubular cells, however, exceeds that in Sertoli cells some 25-fold. This was confirmed by a 30-fold difference in the level of steady-state gelatinase A mRNA levels. Gelatinase A secretion and gelatinase A mRNA were stimulated by ovine FSH in Sertoli cells and by dbcAMP and ConA in both Sertoli and peritubular cells. IL-1 beta displayed measurable but limited stimulatory effects in both cell types. Interestingly, in peritubular cells but not in Sertoli cells, ConA stimulated the production of a lower MW species probably representing an activated form of gelatinase A. It is concluded that both the amounts of gelatinase A produced, the levels of the corresponding mRNA and the regulation differ in cultured peritubular cells and Sertoli cells. The lectin concanavalin A is a novel and potent inducer of gelatinase A. It resembles cytochalasin D in selectively inducing an activated form of gelatinase A in peritubular cells. The mechanism responsible for this selective effect warrants further investigation.
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PMID:Gelatinase A secretion and its control in peritubular and Sertoli cell cultures: effects of hormones, second messengers and inducers of cytokine production. 873 89

In cultured granulosa cells, interleukin-1 beta (IL-1 beta) induced a time-dependent (16-72 h) and dose-related (0.3-30 ng/ml) stimulation of nitric oxide (NO) synthase (NOS) activity, as determined by the catalytic conversion of [3H]arginine to [3H]citrulline and NO2- accumulation in the culture medium. Although FSH alone failed to stimulate NOS activity, concomitant treatment with the gonadotropin (200 ng/ ml) or the cell-permeant cAMP analog (Bu)2cAMP (0.5 mM) markedly enhanced IL-1 beta-induced NO generation in cultured granulosa cells. The effect of IL-1 beta on citrulline biosynthesis and NO2- accumulation was abrogated by the NOS inhibitor NG-methyl-L-arginine or the IL-1-receptor antagonist protein. In contrast bacterial endotoxin (lipopolysaccharide), interferon-gamma, or tumor necrosis factor-alpha, which are well known inducers of inducible NOS (iNOS) in a variety of immunocompetent and nonimmunocompetent cell types, failed to increase [3H]citrulline formation or NO2- accumulation in untreated or FSH-stimulated cells. As demonstrated by reverse transcriptase-PCR analysis, IL-1 beta-stimulated NO generation was accompanied by a time-dependent increase in messenger RNA levels for iNOS and GTP-cyclohydrolase (GTPCH), the rate-limiting step for de novo tetrahydrobiopterin (BH4) biosynthesis. Treatment with FSH augmented only GTPCH messenger RNA expression, and a more than additive GTPCH signal was observed when cells were simultaneously challenged with IL-1 beta and FSH. Treatment with the GTPCH inhibitor 2,4-diamino-6-hydroxypyrimidine prevented IL-1 beta-induced NOS activity in untreated or FSH-stimulated cells, and this inhibition was completely reversed by sepiapterin, a substrate for BH4 biosynthesis, via an alternative pterin salvage pathway present in many cell types. As BH4 is an essential cofactor for NOS catalytic activity, these observations strongly suggest that FSH-induced biosynthesis of endogenous BH4 is essential for full iNOS biosynthetic capacity in IL-1 beta-stimulated granulosa cells.
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PMID:Induction of guanosine triphosphate-cyclohydrolase by follicle-stimulating hormone enhances interleukin-1 beta-stimulated nitric oxide synthase activity in granulosa cells. 897

Immune system disorders are often accompanied by alterations in the reproductive axis. The bacterial endotoxin (lipopolysaccharide or LPS) has central inflammatory effects, and activates cytokine release (immune system mediatory factors) in the hypothalamus, where the luteinizing hormone-releasing hormone neurons are located. The present study was designed to investigate the effect of LPS on the pulsatile release of LH and FSH in adult male rats. With this aim, orchidectomized male rats were implanted with an atrial catheter and received, after two basal blood collections, LPS (250 microg/kg i.v.) or saline. Subsequently, blood samples were taken at regular intervals during 110 min. As expected, LH release was markedly reduced following exposure to LPS. In order to quantify these effects objectively, we subjected these data to PC-pulsar analysis. Pulsatile LH release was clearly disrupted in LPS-treated animals as compared to control rats: pulse frequency 1.3 +/- 0.3 versus 0.43 +/- 0.2/110 min, p < 0.05; pulse amplitude 17.18 +/- 2.2 versus 8.33 +/- 0.66 ng/ml, p < 0.05; overall mean release 15.2 +/- 0.75 versus 7.08 +/- 1.11 ng/ml, p < 0.001; maximum values 27.5 +/- 3.08 versus 9.95 +/- 2.16 ng/ml, p < 0.001; baseline levels 13.83 +/- 0.77 versus 6.55 +/- 0.74 ng/ml, p < 0.001. Regarding FSH secretion, LPS administration significantly lowered baseline levels (p < 0.05) and overall mean release (p < 0.01); FSH pulsatility parameters showed no significant differences. These observations indicate that LPS decreases LH and FSH mean release rates and baseline levels and inhibits several pulsatility parameters of LH release (frequency, amplitude and maximum values); FSH pulsatility parameters are not altered by LPS administration. We speculate that this effect is exerted principally at the hypothalamic level by modifying GnRH secretion.
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PMID:Effect of bacterial endotoxin on in vivo pulsatile gonadotropin secretion in adult male rats. 958 97

Activins and follistatins regulate all levels of the reproductive axis, including the pituitary where they stimulate and inhibit FSH production, respectively. Gonadotropes are known to express inhibin/activin betaB and activin-B (betaBbetaB) functions as an autocrine modulator of FSH production. By contrast, the mRNA for the activin-binding protein, follistatin, is present in most pituitary cells and folliculo-stellate cells may be the major source of the protein secreted by the anterior pituitary. Interleukin-1beta (IL-1beta) is one of several cytokines known to also influence the reproductive axis. IL-1beta inhibits the hypothalamo-pituitary-gonadal (HPG) axis by suppressing GnRH and gonadal steroid production. Because several pituitary cell types, including follistatin-producing folliculo-stellate cells, are targets of IL-1beta, cytokine effects on gonadotrope function were evaluated using cultured rat anterior pituitary cells. Activin-A (0.01 to 1 nM; 24h) increased basal FSH secretion approximately 2-fold. IL-1beta (0.005 to 0.5 nM) by itself had no effect on basal FSH secretion. However, IL-1beta attenuated FSH secretion in response to all concentrations of activin-A. These results suggest that the cytokine might stimulate the local production of a factor, such as follistatin, that antagonizes the action of activin-A. RNase protection analysis indicated that IL-1beta (0.005 to 5 nM) stimulated follistatin and inhibin/activin betaB mRNA accumulation in a time-dependent manner. These in vitro effects of IL-1beta were blocked by the specific IL-1 receptor antagonist (IL-lra) and were not mimicked by either rhIL-6 or lipopolysaccharide (LPS). Treatment of intact male rats with LPS (50 microg, i.v.), which increases plasma IL-1beta and induces IL-1beta expression in many tissues, including the pituitary, produced similar time-dependent increases in pituitary follistatin and inhibin/activin subunit mRNA levels. These results suggest that IL-1beta can modulate gonadotrope responses to activins by influencing the local balance of activin-B and follistatin within the pituitary.
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PMID:Interleukin-1beta regulates pituitary follistatin and inhibin/activin betaB mRNA levels and attenuates FSH secretion in response to activin-A. 964 13


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