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)

Some aspects of prostaglandin (PG) functions are reviewed including: 1) the role of PGs in the hypothalamic and pituitary control of gonadotropin secretions; and 2) their roles in ovulation, 3) in luteinization, and 4) in corpus luteum regression. PGE1 is known for its role in stimulation of increased cyclic adenosine 3',5' monophosphate (cAMP) and hormone secretion in the anterior pituitary. Direct effects of PGs on the secretion of luteinizing hormone, follicle stimulating hormone, and adrenal cortex hormones are not clearly known, but surmised. Such actions may not be the direct effects of PGs on pituitary action. Instead, more studies on receptor functions for PGs in pituitary cells are needed. Systemic administration of PGs has been shown to increase circulating levels of gonadotropins, adrenal cortex hormones, prolactin, follicle stimulating hormone, and luteinizing hormone; and in general, PGs of the E series are more potent than those of the F series. This response to systemic administration seems to be caused by an hypothalamic site of action, a conclusion based on several observations, including the observation that direct application of PGs to brain tissue causes a mimicking of endogenous PG effects of gonadotropin secretion. PGs also play a role in ovulation. Elevated PG levels in follicular tissues are induced by gonadotropins; cyclic nucleotides may be involved in mediating the action of gonadotropins on follicular PG production; a recognized time lag after exposure of the follicle to gonadotropin or cyclic nucleotides indicates that macromolecular synthesis may be involved in follicular PG production; and plasminogen activator may play a role in the process of follicular rupture that leads ot ovulation. The role of PGs in luteinization has been suggested by experiments which showed that granulosa cells cultured with PGE1 and PGE2 luteinized. PGs, particularly PGF2 alpha, cause luteal regression in many species, except perhaps in humans. And PGF2 alpha may be an antagonist of gonadotropin action in the corpus luteum. A proposed mechanism of PGF2 alpha-induced luteolysis in rats is also presented.
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PMID:Prostaglandins in hypothalamo-pituitary and ovarian function. 37 5

We have analyzed the plasminogen activator (PA) content of normal rodent mammary glands at different stages of the mammary life cycle and after exposing the animals to various hormones; we have also assessed the PA response of mammary explants to a variety of hormonal environments. Similar studies were performed on a limited number of primary mammary tumors. Plasminogen activator production was clearly correlated with mammary involution. A large but transient increase in enzyme content followed the initiation of involution in all glands, and the enzyme was produced by mammary cells, not by macrophages or granulocytes. Oxytocin, prolactin and hydrocortisone, which slowed or blocked involution, produced parallel effects on gland regression and PA synthesis. PA synthesis by explants in organ culture was induced by hormonal environments that fostered involution and repressed by those that promoted lactation. Mammary tumors produced much more PA than normal tissue both in vivo and in vitro, and distinct differences were found in the response of enzyme synthesis to hormones. The results reinforce the association of PA with tissue remodeling; show that the enzyme can be used as an indicator of cellular response to a wide range of hormones in both normal and malignant tissue; and suggest that observations of this type in organ culture may be of some value in predicting physiological responses in vivo.
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PMID:Mammary plasminogen activator: correlation with involution, hormonal modulation and comparison between normal and neoplastic tissue. 45 56

Hormonal regulation of plasminogen activator (PA) in rat mammary tumor induced by 7,12-dimethylbenz (a) anthracene (DMBA) was studied both in vivo and in vitro. PA activity in DMBA-tumor was markedly decreased by ovariectomy, and recovered in a dose-dependent fashion upon estradiol administration. This estrogen-stimulated production of the enzyme was prevented by actinomycin D, cycloheximide and tamoxifen. Furthermore DMBA-tumor cells in primary culture displayed similar estrogen-dependency toward the production of the enzyme without any cell proliferation. This indicates that estrogen might regulate de novo synthesis of PA at a transcriptional level via an estrogen receptor system, and that this hormone might support the growth of DMBA-tumor into adjacent tissues by inducing PA in a direct manner via a route distinct from a prolactin pathway. To examine whether PA reflects the functional state of estrogen receptors in human breast cancer, the enzyme activities were determined in extracts prepared from 160 breast cancer specimens and compared on qualitative and quantitative bases with the levels of steroid receptors. The results strongly suggest that PA can be used as an effective functional marker for hormone dependence in human breast cancer.
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PMID:[Estrogen dependent plasminogen activator in breast cancer cells; experimental and clinical studies]. 251 43

Since prolactin, like the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate, induces ornithine decarboxylase and plasminogen activator activities, biochemical markers of a trophic response, this hormone might likewise promote neoplasia. To test this theory, rats were initiated with a hepatocarcinogen followed by six weeks of ovine prolactin. This regimen caused hepatomegaly and the development of enzyme-altered foci. Promotion with prolactin for 23 weeks further increased the numbers of enzyme-altered foci. We suggest that prolactin is an endogenous tumor promoter for chemically initiated cells.
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PMID:Prolactin is a tumor promoter in rat liver. 286 49

Ro 15-1788, a selective benzodiazepine (BZD) antagonist, is known to precipitate withdrawal reactions in BZD-pretreated animals. We examined whether a high dose of Ro 15-1788 can precipitate withdrawal reactions relating to behavior and changes in the stress-hormone plasma levels after acute BZD treatment in man. On two consecutive days, 15 min and 24 h respectively after a single treatment with either lormetazepam (0.06 mg/kg: LMZ group), flunitrazepam (0.03 mg/kg: FNZ group) or placebo (PLA group), 18 healthy volunteers received two injections of Ro 15-1788 (0.01 mg/kg). Behavioral responses (mood changes, anxiety), cortisol and prolactin plasma levels, and physiological parameters were examined. In all groups there were only slight changes in the circulation parameters. Minor anxiety reactions were seen after Ro 15-1788, which occurred the 1st day in the PLA group and the 2nd day in the BZD groups. Depression was noted especially in the FNZ group after both injections of Ro 15-1788. The physiological morning decrease in cortisol plasma level was influenced on the 1st day in the LMZ group (2 volunteers showed high plasma levels) and the 2nd day in the FNZ group: a slight increase of cortisol plasma level was measured after the 2nd injection of Ro 15-1788. Prolactin plasma levels arose immediately after LMZ injection and continued to increase after Ro 15-1788 injection. No increase in prolactin plasma levels was found in the other groups or in the LMZ group after the 2nd challenge by Ro 15-1788.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Benzodiazepine antagonism by RO 15-1788: psychometric, hormonal and biophysical parameters]. 290 13

By comparing the 5'-flanking region of the porcine gene for the urokinase form of plasminogen activator with those of other cAMP-regulated genes, we identify a 29-nucleotide sequence that is tentatively proposed as the cAMP-regulatory unit. Homologous sequences are present (i) in the cAMP-regulated rat tyrosine aminotransferase, prolactin, and phosphoenolpyruvate carboxykinase genes and (ii) 5' to the transcription initiation sites of cAMP-regulated Escherichia coli genes. From this we conclude that the expression of cAMP-responsive genes in higher eukaryotes may be controlled, as in E. coli, by proteins that form complexes with cAMP and then show sequence-specific DNA-binding properties. The complex formed by cAMP and the regulatory subunit of the type II mammalian protein kinase might be one candidate for this function. Based on several homologies we suggest that this subunit may have retained both the DNA-binding specificity and transcription-regulating properties in addition to the nucleotide-binding domains of the bacterial cAMP-binding protein. If this were so, dissociation of protein kinase by cAMP would activate two processes: (i) protein phosphorylation by the catalytic subunit and (ii) transcription regulation by the regulatory subunit.
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PMID:Gene expression and cAMP. 299 82

The main emphasis of this paper is on the changes in function of granulosa cells as they undergo cytodifferentiation in follicles developing from the preantral to the antral stage, and on the hormones present in the milieu of gonadotrophins and steroids which are essential for these events to proceed normally. We found that FSH alone could induce aromatase activity in cultures of immature granulosa cells and that this effect could be duplicated by dibutyryl cyclic AMP. Incubation of cell sonicates under optimal conditions indicated that FSH acted on granulosa cells to increase the cellular concentration of active aromatase. Prior treatment with androgens augmented the FSH effect. Progesterone synthesis is another differentiated function which can be induced in culture by FSH alone and augmented in the presence of androgens. In assessing the enzymes involved in progesterone synthesis we found that cholesterol side-chain cleavage activity had similar hormonal requirements whereas 3 beta-hydroxysteroid dehydrogenase activity was stimulated by FSH alone. FSH also stimulates cyclic AMP binding activity in cultured granulosa cells during cytodifferentiation. These proteins represent another class of intracellular proteins, quite distinct from the steroidogenic enzymes, which increase as the granulosa cells mature. The ability of FSH to induce the appearance of LH and prolactin receptors, and stimulate the secretion of plasminogen activator and proteoglycans is reviewed. It is concluded that the appearance of steroidogenic enzymes and other intracellular proteins, cell-surface and secreted proteins as well as morphological maturation of granulosa cells require the presence of FSH. In the "turning-on" of some of these differentiated functions androgens play a permissive role. Having established events which occur during normal development of the follicle, we considered ways by which this overall process could be interrupted and fertility controlled. Here we describe the ways by which prolactin and LHRH interfere with the normal process of granulosa cell cytodifferentiation.
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PMID:Hormonal interactions in the control of granulosa cell differentiation. 631 Feb 32

Hormonal regulation of plasminogen activator in rat mammary tumor induced by 7,12-dimethylbenz[a]anthracene (DMBA) was studied both in vivo and in vitro. Plasminogen activator activity in DMBA-induced tumor (DMBA-tumor) was markedly decreased by ovariectomy, and recovered in a dose-dependent fashion upon estradiol administration, reaching a maximal level at 12 hr. This estrogen-stimulated production of the enzyme was prevented by actinomycin D, cycloheximide, and tamoxifen, indicating that in DMBA-tumor, estrogen might regulate de novo synthesis of plasminogen activator at a transcriptional level via an estrogen receptor system. Furthermore, DMBA-tumor cells in primary culture displayed similar estrogen-dependency toward the production of the enzyme without any cell proliferation. This indicates that the action of estrogen is mediated neither by cell division nor by prolactin, another hormone pastulated to be responsible for the development and growth of DMBA-tumor. Taken together, the present results have led to support the view that the primary function of estrogen is to induce plasminogen activator, which is probably essential to maintain the malignant state of DMBA-tumor.
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PMID:Estrogen-dependent plasminogen activator in 7,12-dimethylbenz[a]anthracene-induced rat mammary tumors in vivo and in vitro. 643 30

Administration of ovine prolactin resulted in a rapid and significant induction of plasminogen activator activity within two hours in the rat adrenal gland, heart, aorta and liver. Prolactin exposure reduced baseline proteolytic activity in lung and skeletal muscle at 6-8 hours following hormonal challenge. This was coincident with a return toward baseline levels in enzyme activity demonstrated in other tissues. Pretreatment with actinomycin D or cycloheximide ameliorated the enzymic induction in the liver and adrenal and partially inhibited the aortic response. These data suggest that prolactin exposure leads to increased proteolytic activity through de novo biosynthesis in a variety of solid organs. In addition, pro-enzyme activation may also occur in vascular tissue.
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PMID:Rapid elevation of plasminogen activator activity in rat tissues by prolactin. 654 Oct 40

The production of plasminogen activator (PA) and its regulation by hormones and other effectors were studied in organ cultures of primary rat and mouse mammary tumors. PA was quantitated using the radioiodinated fibrin plate method. The level of PA in tumor tissue was 10- to 100-fold higher than that in normal rat or mouse mammary glands; the rates of PA secretion were 10- to 1000-fold higher in the tumor cultures. PA production was stimulated by prolactin and pituitary extracts in N-nitrosomethylurea- and 7,12-dimethylbenz(a)anthracene-induced rat tumors but not in mammary tumor virus-induced mouse tumors; hydrocortisone inhibited PA production in all three tumor categories. Sex hormones and agents such as cholera toxin and retinoic acid effectively modulated enzyme production by some tumors. Three major points of interest emerge from our findings: (a) the pattern of tumor PA response to hormones differs qualitatively and quantitatively from that previously determined for the normal mammary; (b) the profile of responses of tumor PA and tumor growth to hormones shows numerous correlations suggesting that these two parameters may be coordinately regulated; (c) pituitary extracts contain an apparently novel factor that stimulates rat mammary tumor PA synthesis.
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PMID:Modulation of plasminogen activator in rodent mammary tumors by hormones and other effectors. 668 1


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