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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cultured blastocysts homozygous for the t6 mutation lose their inner cell mass within a few days of attachment to the culture dish. At about the same time it becomes apparent that putative t6-mutant trophoblast cells and their nuclei fail to enlarge to the degree of their normal counterparts. These abnormalities in mutant embryos are reflected by an abrupt drop on the seventh equivalent gestation day in the rate of increase of beta-glucuronidase activity. The failure of t6/t6 trophoblast nuclei to enlarge normally appears to be due partially to endoreduplication at a slower rate than normal trophoblast nuclei and partially to premature cessation of DNA synthesis. Analyses indicate that this abnormality is not reversed when mutant embryos are placed in chimeric association with normal ones. Trophoblast outgrowths from mutant and normal trophectodermal vesicles are similarly distinguishable by differences in outgrowth and nuclear size as well as DNA content and synthesis. Despite the fact that t6/t6 embryos and trophectodermal vesicles are phenotypically different from normals from early times in culture, the trophoblast cells in the mutant structures acquire and continue to produce two enzymes characteristic of trophoblast differentiation, delta 5, 3 beta-hydroxysteroid dehydrogenase and plasminogen activator. On the basis of these and previous observations, we propose that the primary effect of the t6 mutation is to cause a metabolic lesion which kills inner cell mass cells relatively quickly but which has a more gradual effect upon trophoblast cells. The fact that phenotypically recognizable t6/t6 trophoblast cells can survive for several days before dying makes this a potentially useful system in which to search for the t6 gene product(s).
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PMID:In vitro studies of mouse embryos bearing mutations in the T complex: t6. 74 44

Gonadotropin-releasing hormone (GnRH), in addition to its classical releasing action at the pituitary level, acts on multiple extrapituitary sites to regulate various reproductive functions. In the rat ovary, specific high affinity GnRH receptors have been identified in granulosa and theca cells. These binding sites mediate the inhibitory effects of GnRH and its agonists on gonadotropin-stimulated estrogen, progestin and androgen biosynthesis. At the granulose cell level, GnRH treatment decreases aromatase activity as well as the biosynthesis of pregnenolone and progesterone via inhibition of cholesterol side-chain cleavage and 3 beta-hydroxysteroid dehydrogenase enzymes. High concentrations of GnRH also stimulate low but significant levels of various steroids. In addition, treatment with high concentrations of GnRH induces ovulation and oocyte maturation in hypophysectomized rats. This is associated with the ability of GnRH to stimulate plasminogen activator activity in cultured granulosa cells. In the rat testis, GnRH receptors have been identified in Leydig but not Sertoli cells. Treatment with GnRH inhibits gonadotropin-stimulated androgen biosynthesis by the cultured Leydig cells. The inhibitory effect of GnRH on testicular androgen production occurs at sites distal to the formation of cyclic AMP and pregnenolone and may be due to decreases in the activity of the enzyme 17 alpha-hydroxylase and 17-20 desmolase. Since hypothalamic GnRH is unlikely to act at the gonadal level, several laboratories have attempted to isolate gonadal GnRH-like peptide which may serve as the ligand for specific gonadal GnRH receptors. Although the presence of ovarian GnRH-like substance still remains elusive, testicular GnRH-like substance has been identified. This gonadal peptide(s) may be an important local paracrine hormone. In addition to its action at the gonadal level, GnRH or GnRH-like peptides may play an important role as a neurotransmitter in the central nervous system. Exogenous administration of GnRH in selected brain areas has been shown to modulate sexual behavior in experimental animals, while neural pathways containing GnRH-like immunoreactive substances have been identified in several brain areas. We have recently synthesized a bioluminescent GnRH analog capable of serving as a specific GnRH ligand for a bioluminescent ligand receptor assay which is more sensitive than classical 125I-ligand assays. We have identified GnRH receptors in small, discrete brain regions. Thus, GnRH and GnRH-like peptides may play important paracrine and neurotransmitter roles in the regulation of various reproductive functions in extra-pituitary sites.
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PMID:Gonadotropin-releasing hormone as a paracrine hormone and neurotransmitter in extra-pituitary sites. 286 49

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

The viability of the placental villi in organ culture was investigated both from the morphological and functional points of view. Morphological viability was judged on the appearance of the villi with special emphasis on the trophoblastic cells and the morphological integrity of the placental villi could be maintained for at least 96 h in organ culture. Functional viability was judged by analyses of delta 5-3 beta-hydroxysteroid dehydrogenase; delta 5,4-isomerase (3 beta-HSD) activity with 14C-pregnenolone as the substrate and by the suppressive effect of the cultivated villi on the secretion of plasminogen activator (PA) obtained from mouse peritoneal macrophages stimulated by OK-432. It was found that the 3 beta-HSD activity and suppressive effect on PA secretion could be preserved for at least 120 h in organ culture.
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PMID:Viability of the human placental villi in organ culture. 659 63

The method and technique of organ culture of human chorionic villi was elaborated in our laboratory. In this report, placental specimens obtained at 15 to 18 weeks of gestation were studied in organ culture for 7 days in terms of the maintenance of morphological integrity and the preservation of functions. The morphological aspect of the viability of the various villous elements with special emphasis on the trophoblast cells was described histologically and ultrastructurally. The functional aspect of the viability was discussed by analysis of the suppressive effect of the cultivated villi on plasminogen activator (PA) secretion by OK-432 elicited mouse peritoneal macrophages, by analyses of the activity of delta 5-3 beta-hydroxysteroid dehydrogenase coupled with delta 5-delta 4-isomerase (HSD) and of the radioactivity of [125I]-Iododeoxyuridine ( [125I]-IUdR) retained in the DNA of the trophoblast cells. Specimens of normal placenta were obtained at the time of induced abortion. The gestational ages were 15, 16 and 18 weeks. Specimens for organ culture were prepared under sterile conditions within one hour after expulsion of the placenta. Through gross dissection, the villi were isolated and minced into fragments of approximately 1 to 2 mm3. Incubation was carried out at 37 degrees C in a conventional static chamber with a gas mixture of 95% air, 5% CO2. The culture dishes and culture media were renewed every day. Data are the mean values of the duplicate incubations. In the first series of organ culture, placental fragments were removed at the end of each day of incubation, washed thoroughly and transferred to the new dishes with a culture medium freed from fetal bovine serum, where further incubation was performed for 24 hours. After this, placental fragments were fixed in 4% neutral buffered formalin, processed through paraffin embedding, serially sectioned at 5 micron and stained by periodic-acid Schiff (PAS) procedure. Culture medium obtained in this series at each end of incubation was put into a "macrophage plate" with the addition of plasminogen in the concentration of 2 IU/m1, in which OK-432 elicited mouse peritoneal macrophages with the capacity to secrete PA were cultured. Reaction was terminated at 24 hours unless otherwise indicated. Ten microliters of the medium in the "macrophage plate" was applied to the fibrin plate, and reaction was performed for 18 hours. PA activity was expressed by plasmin activity converted from plasminogen measured by the single radial immuno-diffusion method.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Viability of human chorionic villi in organ culture]. 666 42