UNIPROT:P05231 - FACTA Search

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Query: UNIPROT:P05231 (interleukin-6)
23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment of FSH-stimulated granulosa cells with increasing amounts of interleukin-6 (IL-6) caused a significant concentration-dependent suppression of progesterone biosynthesis. However, basal progesterone production in non-FSH-stimulated cells remained unresponsive to the cytokine. Quantitation of IL-6 in the conditioned media from untreated granulosa cells by the 7TD1 hybridoma cell bioassay revealed detectable levels of IL-6. Further, FSH treatment caused a significant concentration-dependent increase in IL-6 release. In contrast, both basal and FSH-stimulated IL-6 release could be significantly suppressed by interferon gamma (INF-gamma). The results of the present study suggest: 1) a role for IL-6 in the regulation of progesterone production, 2) that the granulosa cell is a source of IL-6 and 3) that the release of IL-6 by the granulosa cell is a regulated event.
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PMID:Interleukin-6: effects on and production by rat granulosa cells in vitro. 153 22

Intravenously administered interleukin-6 (IL-6), a monokine produced by activated monocytes and folliculostellate cells of the pituitary gland, has been recently reported to elevate plasma ACTH level and to stimulate PRL, GH and LH release from cultured pituitary cells. To determine the site(s) of action of IL-6 in the control of pituitary hormone release, we injected human recombinant IL-6 into the third brain ventricle (3V) of freely moving, conscious male rats. Both 0.05 and 0.25 pmol doses of IL-6 were ineffective to change plasma ACTH in comparison to the values in controls. The maximal IL-6 dose tested of 1.25 pmol increased plasma ACTH within 15 min and the response lasted over 180 min. Plasma TSH levels were significantly lowered by a dose of 0.25 pmol IL-6, but neither the lower dose of 0.05 pmol nor the higher dose of 1.25 pmol altered plasma TSH levels throughout the 180 min of the experiment. Plasma PRL and GH levels were not changed by any IL-6 dose tested. In ovariectomized rats plasma LH and FSH levels were also unaltered by IL-6. The effects of IL-6 on plasma ACTH and TSH were only partially paralleled by increased rectal temperature which suggests that hypothalamic temperature regulating centers were independent of these actions. To evaluate a possible direct effect on the pituitary, IL-6 was incubated in vitro with hemipituitaries under an atmosphere of 95% O2/5% CO2. After 1 h of incubation IL-6 failed to cause any change in the secretion of pituitary hormones throughout a concentration range of 10(-15)-10(-9) M.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of interleukin-6 on pituitary hormone release in vivo and in vitro. 165 74

Recent studies demonstrate that several cytokines are potent modulators of steroid release from the testis. In an attempt to determine whether these agents may influence other types of secreted substances, we used plaque assays to measure the effect of interleukin-6 (IL-6), interleukin-2 (IL-2), and tumor necrosis factor alpha on transferrin (TF) release from Sertoli cells in culture. Because Sertoli cells from different parts of the tubule respond differently to modulatory factors, we used cultures obtained by microdissection from stages III-V, VII, IX-XI, and XIII of the cycle of the seminiferous epithelium. Our results revealed that each agent increased the rate of TF plaque formation from cultures of IX-XI, and XIII staged segments but not from those staged III-V and VII. Moreover, IL-6, but not the other cytokines, modified the response of Sertoli cells to another regulator, FSH. This was evidenced by our findings that pretreatment with IL-6 for 1 h resulted in FSH-induced increases in the rate of plaque formation for cells from IX-XI segments, in addition to those segments which are normally responsive without pretreatment (III-V and VII segments). Further experiments revealed that IL-6 also had a chronic influence on the proportion of TF secretors present in certain staged cultures. Treatment for 24 h with IL-6 markedly reduced the percentage of TF secretors in cultures from stage XIII segments and resulted in a slight increase in TF cells for stage VII cultures. However, no chronic influences in TF secretors were detected with either IL-2 or tumor necrosis factor alpha treatment. Our results demonstrate very clearly that certain cytokines acting in a stage specific manner have acute and/or chronic influences on the release of TF from Sertoli cells. These findings, when viewed in light of reports of the presence of these factors in the testis, suggest strongly that cytokines or cytokine-like substances, by modulating the release of Sertoli cell substances, may play an important role in testis function.
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PMID:Effects of interleukin-6, interleukin-2, and tumor necrosis factor alpha on transferrin release from Sertoli cells in culture. 190 26

In the present work we explored cellular sites of interleukin-6 (IL-6) biosynthesis in human follicular aspirates from patients undergoing in vitro fertilization therapy and the effects of this cytokine on oocyte fertilization and granulosa cell (GC) steroidogenesis. Biological IL-6 activity from 20-40 IU/mL was present in follicular fluids from 22 patients; it was also detected in 10 of 22 supernatants of cultured oocyte-cumulus complexes and in cumulus cell and GC cultures. Biological IL-6 activity in oocyte-cumulus complex cultures was not related to fertilization rates. Total ribonucleic acid was isolated from follicular aspirates and GC-enriched preparations. After reverse transcriptase and polymerase chain reaction cycles using oligonucleotide primers corresponding to known cDNA sequences for IL-6, a 126-basepair band characterized the amplification product of IL-6 transcripts on gel electrophoresis. To localize IL-6 messenger ribonucleic acid, in situ hybridization analysis was performed using a [35S]IL-6 riboprobe. The distribution of transcripts was more dense (15% vs. 3% stained cells) in GC-enriched preparations, which contained more than 95% GCs, than in original follicular preparations, which contained 20-40% viable GCs; it was not significantly modified by the presence of macrophage contaminants. The expression of IL-6 protein was assessed by positive immunohistological stainings. Biological IL-6 activity was higher, and in situ hybridization signals were more dense and more intense in 24-h GC cultures than in 72-h GC cultures, suggesting that IL-6 biosynthesis was transiently induced. Under experimental conditions of low IL-6 endogenous levels in cultures, adding recombinant human IL-6 from 10-200 IU/mL had no effect on progesterone production or aromatase activity in GC cultures free of macrophages, whereas in GC cultures including macrophage contaminants, stimulatory effects on basal and hCG-stimulated progesterone production and on basal and FSH-stimulated aromatase activities were observed. The present study provides strong support for the view that IL-6 is produced by GCs in the preovulatory follicle at the time of ovulation. In addition, we showed that IL-6 might be an intraovarian regulatory factor concerned with steroidogenesis.
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PMID:Interleukin-6 biosynthesis in human preovulatory follicles: some of its potential roles at ovulation. 751 93

Cytokines are not only mediators of inflammation and the immune system but are also important factors in cell proliferation, differentiation, and cell-to-cell communication. Cytokines have been identified within follicular fluid and some authors indicated that they are playing some roles in ovulation and ovarian steroidogenesis. Interleukin-2 (IL-2), mainly secreted by activated T-cells, influences other T-cells, B-cells, Macrophages, NKcells, etc. and is a major proliferating and differentiation factor of lymphocytes. Interleukin-6 (IL-6) is known to be secreted from and influence immune cells and/or non-immune cells such as fibroblasts, hepatic cells, endothelial cells, etc. The in vitro ovarian perfusion system has some advantages, compared with in vivo study, that is, it is devoid of systemic or unnecessary factors which are not focused on. In this study, the effects of IL-2 and IL-6 on ovulation and steroidogenesis were examined using the newly developed in vitro ovarian perfusion system and the culture of follicular granulosa cells. In the perfusion experiment, 100 ng/ml of IL-6 suppressed LH (100ng/ml)-induced estradiol (E2) secretion but did not influence progesterone (P4) secretion, while IL-2 had no effect on steroid secretion. Both IL-2 (100ng/ml) and IL-6 (100ng/ml) significantly suppressed LH-induced ovulation (ovulation rate; 8.3 +/- 1.5, mean +/- SE), to 2.2 +/- 1.1 and 3.2 +/- 1.0, respectively. Addition of 1.0, 3.0, 10 ng/ml of IL-6 decreased FSH (50ng/ml)-induced E2 secretion dose-dependently in the culture experiments of granulosa cells. IL-6 also suppressed FSH-induced P4 secretion in concentrations of 3.0 and 10 ng/ml. On the other hand, IL-2 concentrations of 10 and 30 ng/ml increased FSH-induced P4 secretion although 100 ng/ml of IL-2 showed no effect. Any dosage of IL-2 did not influence E2 secretion induced by FSH. All of these results obtained in the present study suggest that IL-2 and IL-6 may directly and/or indirectly suppress some mechanisms of ovulation, but with still unclarified different pathways.
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PMID:[Effect of interleukin-2 and interleukin-6 on ovary in the ovulatory period--establishment of the new ovarian perfusion system and influence of interleukins on ovulation rate and steroid secretion]. 759 Jun 3

alpha 2-Macroglobulin and clusterin are two putative Sertoli cell secretory products; however, the regulator(s) modulating their secretion by Sertoli cells is not known. Recent studies from this laboratory have shown that the testicular alpha 2-macroglobulin, unlike its liver homologue, is not an acute-phase reactant and its concentration is not affected by acute inflammation. We sought to determine whether FSH, testosterone, and other biomolecules would affect the secretion of alpha 2-macroglobulin and clusterin by Sertoli cells as well as whether peritubular myoid cells would affect the secretion of these proteins by Sertoli cells. It was noted that Sertoli cells cultured in vitro secreted increasing amounts of alpha 2-macroglobulin and clusterin as a function of time. FSH (50-1000 ng/ml) and testosterone (10(-11)-10(-5) M) had no apparent effect on the secretion of alpha 2-macroglobulin and clusterin by Sertoli cells. Addition of interleukin-6 to Sertoli cell-enriched cultures, in doses known to stimulate alpha 2-macroglobulin secretion by hepatocytes, did not affect the alpha 2-macroglobulin secretion. However, dexamethasone at 10(-7)-10(-5) M stimulated alpha 2-macroglobulin secretion by Sertoli cells dose-dependently while the addition of interleukin-6 had no synergistic effect on dexamethasone-stimulated alpha 2-macroglobulin secretion. These findings suggest that the synthesis and/or secretion of alpha 2-macroglobulin by Sertoli cells is regulated by a mechanism distinct from that of the liver.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of Sertoli cell alpha 2-macroglobulin and clusterin (SGP-2) secretion by peritubular myoid cells. 767 1

Interleukin-6 bioactivity (IL-6) has been shown to be present in Sertoli cells. To further characterize the IL-6 in the seminiferous epithelium, the IL-6 like-antigen was detected, stage-specific basal distribution of IL-6-like bioactivity and its regulation by FSH, cAMP and TPA was characterized in isolated, rat seminiferous tubule segments. In addition, the effects of human recombinant IL-6 on stage-specific DNA synthesis was investigated. Both monoclonal and polyclonal antibodies recognized M(r) 22 and 23 kDa of IL-6 like immunoreactivity in the seminiferous epithelium. The basal IL-6 production showed high levels during stages XIII-XIV-I-V, low during VII and VIII. FSH stimulated IL-6 production at nearly all stages and most significantly at stage VII of the cycle. Human recombinant IL-6 dose-dependently inhibited the onset of meiotic DNA synthesis of preleptotene spermatocytes, and a minor inhibition was found on advanced (A3-type B) spermatogonia. These results support the hypothesis that IL-6 is a stage-specific paracrine regulator of the seminiferous epithelium exerting a specific inhibitory action on meiotic DNA synthesis.
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PMID:Function of interleukin-6 as an inhibitor of meiotic DNA synthesis in the rat seminiferous epithelium. 775 35

The expression and function of gonadotropin receptors, and the secretion of steroids, transferrin, and cytokines were investigated in three immortalized (single transfection with v-myc) mouse granulosa cell lines (GRM01, GRM01L, and GRM02). A dose-dependent increase in progesterone production was obtained in GRM01 and GRM02 cells after addition of LH, FSH, modulators of the adenylate cyclase enzyme system, and cAMP analogues. The LH-induced release of progesterone was already detectable in GRM02 cells after 8 h and was related to incubation time and cell number. Both epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) induced the secretion of progesterone in GRM02 cells, while no effect was obtained with TGF beta. LH receptor concentration was highest in the GRM02 cell line. FSH receptor mRNA was visualized in GRM01 and GRM02 cells. Aromatase activity in GRM02 cells was induced by androgens and inhibited by aromatase inhibitors. Whereas all cell lines were able to secrete transferrin, only in GRM01 cells was transferrin secretion increased significantly by LH. FSH did not affect transferrin secretion in the three cell lines, in contrast to forskolin or 8-bromo-cAMP. The immortalized mouse granulosa cell lines were able to express and release several growth factors. The expression and secretion of activin, inhibin, TGF beta, EGF, TGF alpha, insulin-like growth factor II, fibroblast growth factor (acidic and basic), platelet-derived growth factor, and interleukin-6 suggest an autocrine or paracrine role for these factors in follicular differentiation and function. In conclusion, these cells, derived from mural granulosa cells and immortalized in a preovulatory state, can be used to study granulosa cell physiology or to study the role of granulosa cells and their derivatives in the process of follicular maturation, fertilization, and early embryonic development.
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PMID:Secretion of steroids, growth factors, and cytokines by immortalized mouse granulosa cell lines. 802 76

Among vertebrates, there is an extreme conservation in amino acid sequence for the neuropeptide PACAP-38 and its C-terminal shortened derivative PACAP-27. The PACAP gene is assigned to chromosome 18 in man and its organization has been characterized. PACAP-38 and its minor derivative PACAP-27 are widely distributed in the central nervous system. PACAP-38 is particularly abundant in hypothalamus. The mapping of the afferentation and efferentation of PACAP systems are progressively delineated, including a search for the colocalization with other neurotransmitters. In several peripheral organs positive neuronal perikarya and fibers are also seen. PACAP acts through two types of receptors: (1) the highly selective type I that displays a 500 to 2000 selectivity for PACAP-38 and PACAP-27 as compared to VIP; (2) type II is the so-called VIP receptor showing similar high affinity for PACAP-38, PACAP-27 and VIP. It is less selective, therefore, than previously thought. This is why this second receptor, qualifying as an unspecific VIP-PACAP receptor, is hardly considered here. Type I receptors can stimulate two enzymes: the adenylate cyclase and phospholipase C (whose activation leads to the inositol phosphate-cytosolic Ca2+ cascade). This dual coupling may have several distal consequences including on gene expression, cell growth and differentiation. Although a relatively comprehensive spectrum of pharmacological activities has already been established we still need to limit the physiological roles of PACAP as neurotransmitter and/or neuromodulator. Concerning the hypothalamo-pituitary axis, PACAP reduces food intake in mice and raises plasma arginine vasopressin in rat, probably through PACAP-ir neurons in paraventricular and supraoptic nuclei projecting to the neurohypophysis. PACAP originating in the hypothalamus may also be transported to the anterior pituitary through portal vessels. Data on the antehypophysis suggest a role on i.a. reproduction and growth. PACAP stimulates adenylate cyclase and increases [Ca2+] in gonadotropes, somatotropes, and folliculo-stellate cells. It elevates the secretion of alpha-MSH from melanotropes, and that of interleukin-6 from pituitary folliculo-stellate cells. PACAP potentiates the effects of LHRH on LH and FSH secretion. More clearly perhaps, PACAP increases the synthesis of LH, GH, PRL and ACTH after 1-2 days. In human pathology, PACAP-27 and PACAP-38 stimulate adenylate cyclase activity in membranes from 'null'-, gonadotropin-, GH-, and ACTH-producing pituitary adenomas but are inactive in prolactinomas.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Type I receptors for PACAP (a neuropeptide even more important than VIP?). 821 37

The present study's aims are to search for the presence of interleukin-6 bioactivity (IL-6) in medium conditioned by various testicular cell types and to investigate the cellular and hormonal regulation of testicular IL-6 production. Sertoli cells prepared from rats of increasing ages (20, 35, and 45 days) secreted IL-6 in vitro, whereas medium conditioned by pachytene spermatocytes, early spermatids, and peritubular cells showed no activity. Lipopolysaccharide (LPS) and latex beads, two known stimulators of monocyte/macrophage IL-6 production, markedly stimulated IL-6 secretion by Sertoli cells at all the ages investigated. Maximum levels of IL-6 were reached after 6 h of culture of Sertoli cells with LPS and after 24 h with latex beads. When Sertoli cells were cocultured with pachytene spermatocytes, early spermatids, or fractions containing residual bodies and cytoplasts from elongated spermatids, only the latter significantly stimulated IL-6 levels. Maximum levels of IL-6 were attained by adding 2 x 10(6) residual bodies to Sertoli cells; a significant increase in IL-6 secretion was seen after 6 h, and maximum levels were observed after 24 h. The levels of IL-6 varied throughout different stages of the seminiferous epithelium cycle; highest levels were observed in stages II-VI and lowest in stages VII-VIII. IL-6 bioactivities induced by LPS and residual bodies and cytoplasts from elongated spermatids could be totally neutralized with a specific monoclonal antibody at all of the ages studied. FSH, phorbol myristate acetate, and IL-1 alpha augmented Sertoli cell IL-6 secretion in a dose-dependent manner. Furthermore, FSH and (Bu)2cAMP differentially stimulated IL-6 secretion during the seminiferous epithelial cycle. It is concluded that the release of IL-6 from Sertoli cells is regulated by a complex interplay between residual bodies and humoral factors.
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PMID:Identification, ontogeny, and regulation of an interleukin-6-like factor in the rat seminiferous tubule. 838 Mar 79

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