Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.68 (tissue plasminogen activator)
 11,311 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present study we examined the existence of receptors for basic fibroblast growth factor (bFGF) and its regulation in rat granulosa cells. The binding of labeled bFGF to rat granulosa cells was dose-dependently displaced by unlabeled bFGF, but not other growth factors. FSH induced a dose-dependent increase in specific binding for bFGF to cultured rat granulosa cells. FSH treatment did not change the binding affinity (Kd, 2.8-3.0 x 10(-10) M) of the bFGF receptor, but increased the total number of bFGF-binding sites, whereas treatment with several steroid hormones had no effect on the specific binding of bFGF. Since cycloheximide, a protein synthesis inhibitor, inhibited the increase in bFGF binding induced by FSH, it is suggested that protein synthesis might be involved in the FSH stimulation of bFGF receptor induction. Furthermore, bFGF stimulated tissue plasminogen activator activity in a dose-dependent manner, and FSH-primed granulosa cells were more responsive to bFGF action, with a decrease in the ED50 from 5.0 to 1.5 ng/ml. The antibody against human bFGF neutralized the stimulatory effect of bFGF on tissue plasminogen activator secretion. The present study suggests that FSH induces functional receptors for bFGF in granulosa cells and that bFGF may play a role in the process of differentiation under the influence of FSH.
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PMID:Follicle-stimulating hormone induces functional receptors for basic fibroblast growth factor in rat granulosa cells. 132 47

Testicular peritubular cells produce a paracrine factor termed PModS that has dramatic effects on Sertoli cell function in vitro. The current study was designed to examine the actions of PModS and hormones on Sertoli cell aromatase activity and plasminogen activator production at various stages of pubertal development. Sertoli cells were isolated from 10-, 20-, and 35-day-old rats (ages correspond to prepubertal, midpubertal, and late-pubertal stages of development). Aromatase activity was found to be high and hormone-responsive in prepubertal Sertoli cells and to decline and be nonresponsive to hormones in late-pubertal Sertoli cells. FSH was the only hormone found to influence aromatase activity and estrogen production. PModS alone was not found to affect aromatase activity at any of the developmental stages examined. Interestingly, PModS was found to suppress the ability of FSH to stimulate aromatase activity and estrogen production in midpubertal Sertoli cells. Results imply that PModS may promote Sertoli cell differentiation to a more adult stage of development that is less responsive to FSH in stimulating aromatase activity. In contrast to aromatase activity, plasminogen activator production was found to increase during pubertal development. Production of Sertoli cell tissue-type plasminogen activator (tPa) was stimulated by FSH at each of the developmental stages examined, whereas production of urokinase-type plasminogen activator (uPa) was influenced by FSH only in prepubertal Sertoli cells. Insulin also stimulated uPa and tPa production by prepubertal Sertoli cells, and retinol significantly suppressed uPa production and the ability of FSH to stimulate tPa production by midpubertal Sertoli cells.
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PMID:Developmental regulation of Sertoli cell aromatase activity and plasminogen activator production by hormones, retinoids and the testicular paracrine factor, PModS. 157 55

FSH plays an important role in testicular Sertoli cell differentiation and function in spermatogenesis. Previous studies using rat androgen-binding protein (ABP) as a marker of FSH action on Sertoli cells have demonstrated in vivo and in vitro regulation of ABP. We now have extended these studies to examine FSH regulation of ABP mRNA using Northern blot hybridization. In the immature rat testicular ABP mRNA [1.7- and 2.3-kilobase (kb) species] increased with age and reached a maximum 20 days postpartum, coincident with an increased plasma FSH concentration. To determine the direct effect of FSH on Sertoli cells, we examined ABP mRNA in vitro. In Sertoli cell-enriched cultures FSH was found to maintain the major 1.7-kb ABP RNA transcript level over 5 days of treatment in a dose-dependent manner, whereas in the absence of FSH, ABP mRNA declined with time in culture. The ABP mRNA maintenance by FSH was accompanied by higher concentrations of secreted immunoreactive ABP, which declined in the absence of FSH. This FSH effect on ABP mRNA and secreted ABP was mimicked by the cAMP analog (Bu)2cAMP. After the decline of ABP mRNA during culture, administration of FSH did not result in a detectable increase in the 1.7-kb ABP mRNA within 3 days, whereas cAMP and c-fos mRNA were rapidly induced within 15 min. On the contrary, the level of the minor hybridizing ABP mRNA (2.3 kb) was altered by FSH, indicating differential regulation of the 1.7- and 2.3-kb hybridizing species. Also, after FSH deprivation, tissue plasminogen activator and inhibin alpha mRNA were substantially increased within 6 h of FSH treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Follicle-stimulating hormone regulation of androgen-binding protein messenger RNA in sertoli cell cultures. 210 26

Ovulation in mammals is preceded by surges of the two pituitary gonadotropins, LH and FSH. Although previous studies have shown that purified FSH induces ovulation when administered to hypophysectomized rats, proof that FSH has inherent ovulatory potential is lacking because all FSH preparations have varying degrees of residual LH. To determine if FSH alone can induce ovulation, we generated LH-free recombinant FSH (RCFSH) by culturing eukaryotic cells transfected with the human common alpha- and FSH beta-subunit genes. Immature hypophysectomized rats were implanted with estrogen and then primed with PMSG (15 IU, sc). Fifty-two hours later, either RCFSH or hCG was injected (sc) to induce ovulation. A dose-dependent increase in the ovulation rate was stimulated by RCFSH, reaching 100% ovulation at 18 IU/rat, comparable to that achieved with 12 IU hCG. The maximum number of oocytes ovulated per ovary was similar for both groups. Ovulation induced by either RCFSH or hCG was time dependent and associated with a periovulatory increase in the ovarian activity and message levels of tissue-type plasminogen activator, a protease important in the preovulatory degradation of the follicle wall. Because PMSG has inherent LH-like activity in rats, we also implanted hypophysectomized rats with a minipump (sc) that released RCFSH (4 IU/day) to induce follicle growth. Fifty-two hours later, a single sc injection of a surge dose (20 IU) of RCFSH also induced ovulation, further indicating the ability of FSH alone to induce both follicle growth and ovulation. To test whether FSH can also induce ovulation in adult animals, rats were hypophysectomized on proestrous morning and treated with increasing doses of RCFSH (ip) to induce ovulation. At 7.8 IU RCFSH, all rats ovulated, with about 10 oocytes/rat. These results demonstrate that RCFSH is capable of inducing ovulation in hypophysectomized immature and adult rats, with associated increases in ovarian tissue-type plasminogen activator gene expression. Thus, FSH may be involved in follicular rupture in addition to its role in follicle recruitment and maturation. The preovulatory surges of both LH and FSH may represent a protective mechanism to ensure an optimal ovulatory stimulus. The present finding also serves as the basis to formulate new ovulation induction protocols.
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PMID:Recombinant follicle-stimulating hormone induces ovulation and tissue plasminogen activator expression in hypophysectomized rats. 212 46

Pro-opiomelanocortin-derived peptides, alpha-MSH and beta-endorphin, are synthesized and secreted by Leydig cells, and are believed to have paracrine effects on Sertoli cells in the testis. Peptides with MSH activity stimulate adenylate cyclase and cAMP accumulation in Sertoli cell-enriched cultures. The purpose of the present study was to determine whether such peptides would affect Sertoli cell parameters, such as aromatase and plasminogen activator activities, that are known to be regulated by cAMP. alpha-MSH stimulated aromatase activity in Sertoli cell-enriched cultures prepared from 10-day-old rats and this effect was potentiated by methyl isobutylxanthine (MIX). The combination of alpha-MSH plus MIX was not as potent as FSH. alpha-MSH, des-acetyl-alpha-MSH, beta-MSH, ACTH(1-13), and ACTH(1-24) stimulated aromatase activity to a similar extent, suggesting that Sertoli cells do not distinguish between the activities of these peptides. alpha-MSH potentiated the action of dbcAMP and forskolin on Sertoli cell aromatase, but unexpectedly had no effect on the action of either half-maximal or maximal doses of FSH. The regulation of plasminogen activator was examined next; urokinase was markedly suppressed by FSH in 10-day-old Sertoli cells. Although neither alpha-MSH nor MIX alone had an effect on urokinase secretion, in combination they were as effective as FSH. In 10-day-old Sertoli cells each of these peptides had little or no effect on tissue plasminogen activator.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Estradiol and plasminogen activator secretion by cultured rat Sertoli cells in response to melanocyte-stimulating hormones. 247 57

Expression of tissue plasminogen activator (tPA) gene is stimulated by gonadotropins in granulosa cells. Because adrenergic agents interact with specific granulosa cell receptors to increase progesterone biosynthesis, the effects of these pounds on tPA activity and mRNA levels were also investigated. Cells obtained from immature estrogen-treated rats were initially cultured with FSH or medium alone for 2 days. They were then reincubated with various adrenergic agents before measurement of medium tPA activity using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, followed by a fibrin overlay technique. In addition, cellular RNA was extracted, and tPA mRNA levels were analyzed using a specific rat cRNA probe. Isoproterenol, a beta-adrenergic agonist, stimulated the secretion of tPA activity in a dose-dependent manner, with FSH-pretreated cells secreting higher levels of the enzyme than cells without FSH priming. Northern blot hybridization of total RNA showed the accumulation of a 22S species tPA message in cells treated with isoproterenol, suggesting increased expression of the tPA gene. Furthermore, slot blot hybridization of RNA from these cells indicated a time-dependent increase in tPA mRNA, with maximal induction between 1-3 h of incubation. A selective beta 2-adrenergic agonist, terbutaline, but not the beta 1-agonist dobutamine, stimulated tPA activity. Also, the stimulatory effect of isoproterenol was blocked by a beta 2-antagonist (ICI-118,551) but not by a beta 1-antagonist (practolol), suggesting the involvement of a beta 2-receptor. Like FSH and LH, isoproterenol increased extra- and intracellular cAMP levels. Cotreatment of a saturating dose of isoproterenol with FSH or LH did not further stimulate tPA activity. Similar to that in cells treated with FSH, inhibition of protein synthesis by cycloheximide resulted in the superinduction of tPA mRNA in isoproterenol-treated cells. Thus, activation of beta 2-adrenergic receptors in granulosa cells induces tPA mRNA and activity, presumably through the protein kinase-A pathway shared by gonadotropins. Adrenergic neurotransmitters may be potential intraovarian regulators of this important protease.
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PMID:Beta-adrenergic agents stimulate tissue plasminogen activator activity and messenger ribonucleic acid levels in cultured rat granulosa cells. 247 32

Several studies indicate that substances synthesized by granulosa cells are capable of regulating oocyte activity. We have studied the effect of factors synthesized by granulosa cells on tPA activity of denuded oocytes using a co-culture system. The results show that an FSH-dependent factor(s) synthesized by granulosa cells (but not by theca-interstitial cells) is capable of stimulating tPA activity of denuded oocytes. This finding is important for understanding hormonal regulation of oocyte tPA activity by mediators synthesized in granulosa cells.
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PMID:A factor from granulosa cells can stimulate oocyte tissue plasminogen activator activity. 251 32

The secretion of plasminogen activator by seminiferous tubules at defined stages of the epithelial cycle is influenced both by neighboring spermatogenic cells and by hormones. We have used cRNA probes for urokinase-type (uPA) and tissue-type (tPA) plasminogen activators to analyze their mRNA levels in different stages of the epithelial cycle. Urokinase-type PA mRNA was most abundant in stages VII-VIII, while tPA mRNA levels showed smaller variations between the different stages. Both FSH and (Bu)2cAMP increased the steady-state level of tPA mRNA and tPA production without affecting those of uPA in stages VII-IX in vitro, whereas retinoic acid treatment selectively increased the concentration uPA mRNA and uPA production in stages II-VI. The results show that the expression of the uPA and tPA genes is differentially regulated in specific stages of the rat seminiferous epithelium.
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PMID:Regulation of urokinase- and tissue-type plasminogen activator gene expression in the rat seminiferous epithelium. 253 92

Recent reports suggest that epidermal growth factor (EGF) or related peptides may act as local hormones to regulate granulosa cell differentiation. While FSH and GnRH are known to stimulate accumulation of tissue-type plasminogen activator (tPA) mRNA in granulosa cells, studies using nonovarian cells have shown stimulation of tPA by EGF. In this study, the effect of EGF and its structural analog transforming growth factor-alpha (TGF alpha) on ovarian tPA mRNA and activity was investigated. Granulosa cells obtained from immature estrogen-treated rats were cultured with FSH or increasing doses of EGF or TGF alpha before analysis of tPA activity using sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by a fibrin overlay technique. Like FSH and GnRH, EGF and TGF alpha stimulated the secretion of tPA activity in a dose- and time-dependent manner (onset, 12 h; maximum, 48 h). Northern blot hybridization of total RNA using a rat cRNA probe for tPA showed the accumulation of a 22S species mRNA in cells treated with EGF or TGF alpha, but not with nerve growth factor, suggesting increased expression of the tPA gene. Furthermore, slot blot hybridization of RNA from these cells confirmed a time-dependent increase in tPA mRNA preceding that in enzyme activity. Cotreatment of a saturating dose of EGF with phorbol myristate acetate (PMA) or GnRH resulted in additive increases in both tPA enzyme activity and mRNA levels. In addition, pretreatment with PMA desensitized the cells to subsequent treatment with PMA or GnRH, but did not diminish EGF-induced tPA mRNA, suggesting that EGF acts through a pathway independent of protein kinase-C. Also, extracellular cAMP levels did not increase with EGF treatment in the presence or absence of a phosphodiesterase inhibitor, suggesting the lack of involvement of the protein kinase-A pathway. Suppression of protein synthesis by cycloheximide inhibited the induction of tPA mRNA by EGF, whereas similar treatment resulted in the superinduction of tPA mRNA in FSH-treated cells, suggesting that EGF and FSH do not share the same pathway. These results suggest that EGF and TGF alpha induce tPA mRNA and activity in granulosa cells through a pathway independent of protein kinases-A (FSH) and -C (GnRH and phorbol ester), providing an interesting model for future elucidation of the molecular mechanism involved in tPA gene expression.
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PMID:Epidermal growth factor stimulates tissue plasminogen activator activity and messenger ribonucleic acid levels in cultured rat granulosa cells: mediation by pathways independent of protein kinases-A and -C. 254 97

The plasma concentrations of tissue plasminogen activator (t-PA) antigen, cortisol, testosterone, dehydroepiandrosterone sulphate, FSH and LH were studied in 33 men undergoing major abdominal surgery. Significant positive correlation was found between the concentrations of t-PA antigen and cortisol, suggesting that the adrenal cortex has a role in the regulation of extrinsic fibrinolysis. These two variables, however, did not distinguish between patients with postoperative deep vein thrombosis (diagnosed by 125I-fibrinogen uptake test) and those without this complication. Such distinction was possible, however, with another steroid hormone of the adrenal cortex, dehydroepiandrosterone sulphate. At present, no explanation in terms of haemostatic mechanisms can be offered for this finding.
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PMID:Relationships between tissue plasminogen activator, steroid hormones and deep vein thrombosis. 293 51


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