Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

To know the secretory potential of Sertoli cells in pubertal testes of males who underwent orchiopexy at a prepubertal age, the plasminogen activator (PA) activity of 12 patients was measured in vitro and compared with that of pubertal testes of patients with varicocele. The assay system for PA activity was based on the solubilization of 125I-fibrin in the presence of plasminogen, and the PA activity in each patient was obtained as the maximum increment with stimulation by ovine FSH in the culture medium of testicular cells. The mean value of PA activity in patients after orchiopexy was remarkably lower than that in varicocele patients (p less than 0.005), which corresponded with histological differences in spermatogenesis between the two groups. These results suggest that in comparison to those patients with varicocele, the patients with prepubertal undescended testis showed impaired potential for protein biosynthesis despite successful orchiopexy.
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PMID:Plasminogen activator in cultured cells of human undescended testis. 168 7

Using a suspension of seminiferous tubule cells, we had previously shown that equine FSH is superactive in the male rat, i.e. that it exhibits a higher biological potency than expected from its binding activity. In this work we investigated equine FSH superactivity in rat, pig and sheep, by comparing in each species the equine FSH with the homologous FSH, both for their binding activities (in a radioreceptor assay using a testicular membrane fraction) and for their in vitro biological potencies (in a plasminogen activator assay using a Sertoli cell-enriched population cultured on plastic). In the rat, the binding activity of equine FSH was identical to that of rat FSH, and the biological potency of equine FSH was 47 times higher than that of rat FSH. Hence, superactivity of equine FSH was confirmed in the rat. In the pig, equine FSH was not superactive, since it exhibited binding activity and biological potency identical to those of porcine FSH. In the sheep, the binding activity of equine FSH was 6 times higher than that of ovine FSH, and its biological potency was also higher (14 times). Therefore, equine FSH cannot be considered superactive in this species. In conclusion, equine FSH superactivity is closely related to the species from which Sertoli cells are isolated.
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PMID:Equine follicle-stimulating hormone action in cultured Sertoli cells from rat, sheep and pig. 190 69

Tissue-type plasminogen activator (tPA) is secreted by rat granulosa cells in response to treatment with activators of protein kinase A (follitropin, FSH), protein kinase C (gonadotropin-releasing hormone, GnRH) and tyrosine kinase (epidermal growth factor, EGF). Because steroid hormones have been shown to enhance the gonadotropin stimulation of ovarian differentiation, we investigated the effects of steroid hormones, alone or together with various kinase activators, on tPA activities and mRNA levels in cultured rat granulosa cells. Treatment of cells with dexamethasone (DEX; a glucocorticoid agonist) or R1881 (an androgen agonist) caused an increase in tPA secretion and mRNA levels. In addition, the stimulation of tPA activity and mRNA levels by FSH (50 ng/ml) was synergistically enhanced by cotreatment with DEX or R1881 in a time-dependent manner with 2.8- and 1.6-fold increase at 9 h after incubation as compared to cells treated with FSH alone. In contrast, treatment with diethylstilbestrol had no effect on tPA levels. Furthermore, tPA activity and mRNA levels induced by GnRH and EGF were also increased by cotreatment with DEX or R1881 as compared with cells treated with GnRH or EGF alone. Likewise, the stimulation of tPA mRNA levels by dibutyryl cAMP, a protein kinase A activator, and phorbol myristate acetate (PMA), a protein kinase C activator, was enhanced by cotreatment with DEX or R1881. These results demonstrate that glucocorticoid and androgen enhance tPA secretion and mRNA levels stimulated by FSH, GnRH and EGF in granulosa cells. The rat granulosa cells provide a useful model for studying the mechanism of regulation of tPA gene expression by steroid hormones.
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PMID:Synergistic effect of glucocorticoids and androgens on the hormonal induction of tissue plasminogen activator activity and messenger ribonucleic acid levels in granulosa cells. 210 7

A previously described in-vitro rat granulosa cell plasminogen activator bioassay for FSH has been modified and applied in the assay of human serum. This modified method consists of exposing the diethylstilboestrol-stimulated granulosa cells from 25- to 26-day-old rats to FSH or test substance for 3.5 h in wells coated with 125I-labelled fibrinogen and treated with thrombin. Following stimulation with FSH, the dose-related production of plasminogen activator was measured as the degree of 125I-labelled fibrinolysis in the presence of added plasminogen. Using the urinary FSH/LH bioassay reference preparation as the assay standard, the useful range of the assay was 0.3-15 IU/l, with an assay sensitivity of 0.3 IU/l. As determined using purified glycoprotein hormone preparations, the assay was highly specific for FSH. The minor degree of FSH bioactivity measured in some of the hormone preparations was accounted for by the amount of FSH contamination in these preparations. To abolish interference caused by unknown serum factors, we heat-treated the serum samples for 15 min at 56 degrees C before the assay. The results indicated that neither immunoreactivity nor bioactivity was affected by this treatment. Furthermore, heat-treated human sera gave responses parallel to the standard curve at the three dose levels (2, 4 and 8 microliters) studied. We used this bioassay to estimate the FSH-like bioactivity in 15 human serum samples. The estimates of immunoreactive FSH in these samples correlated well with the corresponding FSH bioactivity (r = 0.745, n = 15 and P less than 0.05). The results indicate that with this sensitive and rapid (completed within 24 h) bioassay, it should be possible to measure FSH bioactivity in heat-treated human serum samples.
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PMID:A rat granulosa cell plasminogen activator bioassay for FSH in human serum. 211 93

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

The addition of androgens (testosterone or dihydrotestosterone) resulted in decreased levels of detectable plasminogen activator activity in the medium when Sertoli cells were maintained in culture in a serum-free chemically defined medium in a two-chambered assembly. This occurred in the presence or absence of extracellular matrix or peritubular cells in the system. In the complete two-chambered assembly, addition of androgens simultaneously resulted in a small but significant increase in the integrity of the Sertoli cell barrier separating the two chambers, as indicated by slower rates of equilibration of [3H]methoxyinulin between inner and outer chambers. These responses to steroids appeared to be androgen specific, since other steroids examined (17 beta-estradiol, progesterone, and dexamethasone) had no detectable effects on levels of plasminogen activator activities or on barrier function. We confirmed that when FSH or (Bu)2cAMP is added to stimulate plasminogen activator secretion by Sertoli cells, the integrity of the barrier is decreased, provided no antiproteases are present in the serum-free medium. Simultaneous addition of androgens inhibited these effects of (Bu)2cAMP on Sertoli cells, but did not influence the responses of Sertoli cells to FSH. We compare actions of androgens on Sertoli cells in culture under various conditions and discuss the possible physiological significance of the inhibition of plasminogen activator activity.
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PMID:Androgens inhibit plasminogen activator activity secreted by Sertoli cells in culture in a two-chambered assembly. 215 4

The hormonal regulation of the human urokinase type plasminogen activator (uPA) gene has been studied by introducing into mouse and rat Sertoli cell primary cultures a recombinant plasmid, in which the transcription regulatory elements of the cloned human uPA gene drive the expression of the bacterial chloramphenicol-acetyl-transferase gene. It was found to be expressed and regulated by FSH and (Bu)2cAMP in the mouse cells only, in agreement with data on the expression of the endogenous gene in rat and mouse gonads. The stimulation of transcription by FSH was evident in cultures from 13-day-old but not from 18-day-old mice, even though (Bu)2cAMP induction could be observed at both ages. Phorbol-myristate acetate was found to activate the human uPA promoter in Sertoli cell cultures from mice of both ages, even though the effect was less evident in cultures of 18-day-old animals. Deletion analysis of the human uPA 5'-flanking region showed that the distal enhancer element is not needed for (Bu)2cAMP induction, and that at least two promoter regions are involved in (Bu)2cAMP induced transcription. One of these cAMP responsive regions lies between nucleotides -72 and -29 from the CAP site. The sequence of this region would suggest the binding of transcription factor AP-2, a cell-specific mediator of both cAMP and phorbol esters action on gene expression. However, these sequences do not mediate phorbol ester activation of human uPA promoter in mouse Sertoli cells.
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PMID:Follicle-stimulating hormone and cyclic AMP induce transcription from the human urokinase promoter in primary cultures of mouse Sertoli cells. 217 96

Sertoli cells (SC), plated onto an extracellular matrix-coated membrane mounted in a two-chambered assembly, secrete both transferrin and plasminogen activator (PA) into each chamber. Although transferrin concentrations are greatest in the inner chamber, concentrations of PA activities in the outer chamber are equal to or higher than those in the inner chamber. These data indicate that transferrin and PA are preferentially secreted in different directions. The addition of FSH or cAMP derivatives stimulates the formation and secretion of tissue-type PA. Addition of FSH enhances the polarized secretion of PA into the outer chamber, as measured by elevated ratios of outer to inner compartment PA concentrations. Ratios of PA to transferrin concentrations in the outer compartment are also increased in FSH-treated preparations, demonstrating that the differential secretion of the two products is enhanced by FSH. We interpret these data to indicate that polarized SC preferentially secrete transferrin apically while preferentially secreting PA basally, and that FSH augments this polarity of SC maintained in the two-chamber assembly. The addition of peritubular cells to the system results in decreased levels of total PA activity, with greatest diminution evident in the outer compartment. Data are consistent with previous observations that peritubular cells decrease PA activity by secreting a specific inhibitor of PA. Measurements of relative amounts of transferrin and PA secreted into inner and outer chambers, respectively, provide a means to evaluate the tightness of the seminiferous tubule barrier in the model system and the extent of polarized secretion by SC in the two-chambered assembly.
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PMID:Control of levels of plasminogen activator activity secreted by Sertoli cells maintained in a two-chamber assembly. 245 45

Factors have been identified that influence the integrity of the barrier generated by Sertoli cells (SC) in culture in a two-chambered assembly. The permeability of the barrier was assessed by determining rates of equilibration of [3H]methoxyinulin or [86Rb]Cl across the Sertoli cell monolayer. The complete system consisted of a confluent monolayer of SC maintained on an extracellular matrix (Matrigel)-coated filter together with peritubular cells on the opposite side of the filter. In confirmation of previous results, levels of plasminogen activator (PA) activity secreted were increased by treatment of SC with FSH or with cAMP derivatives [(Bu)2cAMP (dbcAMP)]. PA levels in the culture medium were inversely related to times required for 50% equilibration of [3H]methoxyinulin across the SC monolayer. Thus, elevated PA levels, elicited by stimulation with FSH or dbcAMP, were associated with a decreased integrity of the barrier generated by SC preparations maintained in serum-free medium in the complete system. The increase in permeability of the barrier in SC elicited by FSH dbcAMP could be prevented, however, by the addition of various antiproteases. FSH actions on barrier function were complex. Effects of FSH that favored barrier integrity were most readily detected when proteolytic activity was inhibited. The addition of intact serum increased the integrity of the barrier, but acid-treated serum depleted of antiproteases had no such effect. We advance the hypothesis that proteases are implicated in modulation of the formation and maintenance of the seminiferous tubule barrier by SC.
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PMID:Influences of follicle-stimulating hormone, proteases, and antiproteases on permeability of the barrier generated by Sertoli cells in a two-chambered assembly. 246 39


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