Development and regulation of the prostaglandin F2α receptor in the rat ovary

1981 ◽  
Vol 98 (3) ◽  
pp. 441-445 ◽  
Author(s):  
Ulrich Müller ◽  
Th. Bauknecht ◽  
Jan Willem Siebers
Keyword(s):  
Binding Sites ◽  
Specific Binding ◽  
Prostaglandin F2α ◽  
Cell Type ◽  
Adult Rats ◽  
Endogenous Prostaglandin ◽  
Prostaglandin F ◽  
Inhibition Of Prostaglandin Synthesis ◽  
Specific Receptors ◽  
Rat Ovary

Abstract. Ovaries of adult rats specifically bind PGF2α while those of immature animals do not. Induction of luteinization by hCG in juvenile animals, however, results in specific binding of PGF2α It is suggested that luteal cells are the only cell type of the ovary, which is endowed with specific receptors for PGF2α The number of PGF2α binding sites varies during the ovarian cycle. Most free receptors are detectable in early pro-oestrus, least in the oestrus stage. The oscillation of receptors disappears after inhibition of prostaglandin synthesis by indomethacin. Therefore the apparent cyclic variation of prostaglandin receptors must be ascribed to occupancy of the receptors by varying amounts of endogenous prostaglandin F2α.

THE SERUM LEVELS OF PROGESTERONE AND 20α-DIHYDROPROGESTERONE, AND THE OVARIAN LH, FSH AND PRL BINDING DURING LUTEOLYSIS OF THE SUPERLUTEINIZED RAT OVARY

1977 ◽  
Vol 86 (1) ◽  
pp. 162-172 ◽  
Author(s):  
Peter A. Torjesen ◽  
Asbjørn Aakvaag
Keyword(s):  
Binding Sites ◽  
Ovarian Tissue ◽  
Serum Levels ◽  
Plasma Progesterone ◽  
Luteal Function ◽  
Prostaglandin Analogues ◽  
Prostaglandin F ◽  
Serum Gonadotropin ◽  
Rat Ovary

ABSTRACT The process of luteolysis has been studied in immature rats in which superluteinization had been induced with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotrophin (HCG). Following prostaglandin F2α and the prostaglandin analogues, and at the end of the pseudopregnancy, the plasma levels of progesterone and 20α-dihydroprogesterone were measured and used as parameters of luteal function in relation to the capacity of the ovarian tissue to bind LH, FSH and prolactin (PRL) in vitro. On day 19 after HCG a marked decrease in the progesterone level from the day 8 level was observed concomitant with a marked increase in 20α-dihydroprogesterone. The capacity of the ovarian tissue to bind LH in vitro was markedly reduced on day 19 compared to day 8. Identical changes were observed 21 h after 1 mg prostaglandin F2α or prostaglandin analogues. Progesterone decreased from about 600 ng/ml to about 50 ng/ml, whereas the increase in 20α-dihydroprogesterone was from about 200 ng/ml to 500–1000 ng/ml and the reduction in LH binding sites was from 1.7 × 10−12 to 0.5 × 10−12 mol/mg protein. Nanogram amounts of the analogues were as effective as 1 mg of prostaglandin F2α. The number of FSH or PRL binding sites was not affected by spontaneous luteolysis or the treatment given. By the use of graded doses of the prostaglandin analogues a negative correlation (r=−0.81) was found between plasma progesterone and 20α-dihydroprogesterone levels, and a positive correlation (r = 0.84) between LH binding sites and plasma progesterone levels. The luteolysis induced by prostaglandin F2α or prostaglandin analogues was indistinguishable from the spontaneous luteolysis using these parameters.

scholarly journals Binding kinetics of PAF-acether (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) to intact human platelets

1984 ◽  
Vol 223 (3) ◽  
pp. 901-909 ◽  
Author(s):  
E Kloprogge ◽  
J W N Akkerman
Keyword(s):  
Binding Sites ◽  
Specific Binding ◽  
Human Platelets ◽  
Equilibrium Analysis ◽  
Binding Studies ◽  
Prolonged Incubation ◽  
Fibrinogen Receptor ◽  
Receptor Aggregation ◽  
Specific Receptors ◽  
High Doses

The binding of [3H]PAF-acether (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) to intact human gel-filtered platelets was measured at 22 degrees C. Specific binding reached saturation within 15 min at high doses of [3H]PAF-acether (0.5-0.9 nM), whereas about 90 min were required when low doses (0.02-0.5 nM) were used. Above 1 nM, [3H]PAF-acether non-specific binding increased progressively, which together with the demonstration of a 3H-labelled metabolite suggested uptake and metabolism of [3H]PAF-acether. Equilibrium analysis revealed one class of specific receptors with a Ka of 18.86 +/- 4.82×10(9) M-1 and 242 +/- 64 binding sites per platelet. Non-equilibrium binding revealed a similar Ka (16.87×10(9) M-1). Specific binding became irreversible after prolonged incubation, a process that was enhanced at increasing concentrations of [3H]PAF-acether. Platelets made desensitized to PAF-acether by prior incubation with unlabelled PAF-acether failed to bind a second dose of PAF-acether (3H-labelled), suggesting that desensitization resulted from loss of available binding sites. Under the conditions of the binding studies, PAF-acether induced exposure of the fibrinogen receptor, aggregation (in a stirred suspension) and alterations in (poly)-phosphatidylinositides. These results suggest that PAF-acether initiates platelet responses via receptor-mediated processes.

BINDING OF HUMAN CHORIONIC GONADOTROPHIN TO RAT OVARY DURING DEVELOPMENT

1977 ◽  
Vol 73 (3) ◽  
pp. 491-496 ◽  
Author(s):  
J. W. SIEBERS ◽  
F. PETERS ◽  
MARIA TERESA ZENZES ◽  
J. SCHMIDTKE ◽  
W. ENGEL
Keyword(s):  
Specific Binding ◽  
Ovarian Tissue ◽  
Developmental Period ◽  
Chorionic Gonadotrophin ◽  
Human Chorionic Gonadotrophin ◽  
Early Postnatal Development ◽  
Old Rats ◽  
Specific Receptors ◽  
Rat Ovary ◽  
Hcg Receptor

SUMMARY Ovarian tissue of prenatal, newborn, and 5-day-old rats does not specifically bind 125Ilabelled HCG. Specific binding of HCG was first observed in ovaries of 10-day-old animals and binding increased with age. These results indicate that, contrary to rat testis, the HCG receptor in the rat ovary is not present during foetal and early postnatal development. Thus, the insensitivity of the ovary to endogenous and exogenous LH or HCG during this developmental period is due to the lack of specific receptors.

scholarly journals Specific receptors for synthetic GH secretagogues in the human brain and pituitary gland

1998 ◽  
Vol 157 (1) ◽  
pp. 99-106 ◽  
Author(s):  
G Muccioli ◽  
C Ghe ◽  
MC Ghigo ◽  
M Papotti ◽  
E Arvat ◽  
...  
Keyword(s):  
Substance P ◽  
Human Brain ◽  
Pituitary Gland ◽  
Binding Sites ◽  
Specific Binding ◽  
Scatchard Analysis ◽  
Dependent Manner ◽  
Gh Secretagogues ◽  
Specific Binding Sites ◽  
Specific Receptors

In vitro studies have been performed to demonstrate and characterize specific binding sites for synthetic GH secretagogues (sGHS) on membranes from pituitary gland and different human brain regions. A binding assay for sGHS was established using a peptidyl sGHS (Tyr-Ala-hexarelin) which had been radioiodinated to high specific activity at the Tyr residue. Specific binding sites for 125I-labelled Tyr-Ala-hexarelin were detected mainly in membranes isolated from pituitary gland and hypothalamus, but they were also present in other brain areas such as choroid plexus, cerebral cortex, hippocampus and medulla oblongata with no sex-related differences. In contrast, negligible binding was found in the thalamus, striatum, substantia nigra, cerebellum and corpus callosum. The binding of 125I-labelled Tyr-Ala-hexarelin to membrane-binding sites is a saturable and reversible process, depending on incubation time and pH of the buffer. Scatchard analysis of the binding revealed a finite number of binding sites in the hypothalamus and pituitary gland with a dissociation constant (Kd) of (1.5 +/- 0.3) x 10(-9) and (2.1 +/- 0.4) x 10(-9) mol/l respectively. Receptor activity is sensitive to trypsin and phospholipase C digestion, suggesting that protein and phospholipids are essential for the binding of 125I-labelled Tyr-Ala-hexarelin. The binding of 125I-labelled Tyr-Ala-hexarelin to pituitary and hypothalamic membranes was displaced in a dose-dependent manner by different unlabelled synthetic peptidyl (Tyr-Ala-hexarelin, GHRP2, hexarelin, GHRP6) and non-peptidyl (MK 0677) sGHS. An inhibition of the specific binding was also observed when binding was performed in the presence of [D-Arg1-D-Phe5-D-Trp7,9-Leu11]-substance P, a substance P antagonist that has been found to inhibit GH release in response to sGHS. In contrast, no competition was observed in the presence of other neuropeptides (GHRH, somatostatin, galanin or Met-enkephalin) which have a known influence on GH release. In conclusion, the present data demonstrate that sGHS have specific receptors in human brain and pituitary gland and reinforce the hypothesis that these compounds could be the synthetic counterpart of an endogenous GH secretagogue involved in the neuroendocrine control of GH secretion and possibly in other central activities.

scholarly journals Dynamic CTCF binding directly mediates interactions among cis-regulatory elements essential for hematopoiesis

Blood ◽  
2020 ◽  
Author(s):  
Qian Qi ◽  
Li Cheng ◽  
Xing Tang ◽  
Yanghua He ◽  
Yichao Li ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Blood Cell ◽  
Binding Sites ◽  
Specific Binding ◽  
Regulatory Elements ◽  
Cell Development ◽  
Ctcf Binding ◽  
Cell Type ◽  
Dynamic Cell ◽  
Cell Type Specific

While constitutive CTCF-binding sites are needed to maintain relatively invariant chromatin structures, such as topologically associating domains, the precise roles of CTCF to control cell type-specific transcriptional regulation remain poorly explored. We examined CTCF occupancy in different types of primary blood cells derived from the same donor to elucidate a new role for CTCF in gene regulation during blood cell development. We identified dynamic, cell type-specific binding sites for CTCF that colocalize with lineage-specific transcription factors. These dynamic sites are enriched for single nucleotide polymorphisms that are associated with blood cell traits in different linages, and they coincide with the key regulatory elements governing hematopoiesis. CRISPR/Cas9-based perturbation experiments demonstrated that these dynamic CTCF-binding sites play a critical role in red blood cell development. Furthermore, precise deletion of CTCF-binding motifs in dynamic sites abolished interactions of erythroid genes, such as RBM38, with their associated enhancers and led to abnormal erythropoiesis. These results suggest a novel, cell type-specific function for CTCF in which it may serve to facilitate interaction of distal regulatory emblements with target promoters. Our study of the dynamic, cell type-specific binding and function of CTCF provides new insights into transcriptional regulation during hematopoiesis.

EFFECTS OF OESTROGEN AND PROSTAGLANDIN F2α ON LUTEINIZING HORMONE RECEPTORS IN HUMAN CORPORA LUTEA

1981 ◽  
Vol 88 (3) ◽  
pp. 401-408 ◽  
Author(s):  
RYOSUKE NAKANO ◽  
MAREO YAMOTO ◽  
MASAFUMI IWASAKI
Keyword(s):  
Menstrual Cycle ◽  
Binding Sites ◽  
Luteal Phase ◽  
Hormone Receptors ◽  
Specific Binding ◽  
Prostaglandin F2α ◽  
Scatchard Analysis ◽  
Corpora Lutea ◽  
Luteal Tissue ◽  
Number Of Binding Sites

The binding of 125I-labelled human LH (hLH) to the 2000 g subcellular fraction of human corpora lutea of the menstrual cycle was examined. Displacement studies demonstrated that 125I-labelled hLH was specifically bound in the 2000 g fraction of human luteal tissue. Specific binding of 125I-labelled hLH was demonstrated in all the corpora lutea examined except for two aged corpora lutea at an early proliferative phase of the cycle. The number of binding sites for hLH increased between the early to mid-luteal phase and decreased towards the late luteal phase. However, the apparent dissociation constant (Kd) in each corpus luteum did not vary throughout the menstrual cycle. In addition, the effects of treatment with diethylstilboestrol diphosphate (DES) and prostaglandin F2α (PGF2α) on the binding of 125I-labelled hLH to the 2000 g fraction of luteal tissue were investigated and the changes in hLH receptors were estimated by Scatchard analysis. The number of binding sites were 1·59 × 10−14 mol/mg protein in control tissue, 0·86 × 10 −14 mol/mg protein in DES-treated luteal tissue and 2·95 × 10−14 mol/mg protein in PGF2α-treated luteal tissue. Thus, the binding sites for hLH decreased as a result of treatment with DES and increased by treatment with PGF2α. In contrast, the apparent Kd in each luteal tissue revealed almost the same value (4·24 × 10−10 to 6·07 × 10−10 mol/l) after treatment with DES or PGF2α. The results of the present study suggest that oestrogen and prostaglandin might have an important role in modulating hLH receptor in human corpora lutea.

Chick hepatic lectins: An electron microscopic study on isolated hepatocytes during development

1991 ◽  
Vol 11 (5) ◽  
pp. 257-264
Author(s):  
L. Falasca ◽  
P. Mattioli ◽  
L. Dini
Keyword(s):  
Binding Sites ◽  
Specific Binding ◽  
Ultrastructural Level ◽  
Isolated Hepatocytes ◽  
Cell Surfaces ◽  
Electron Microscopic ◽  
Specific Binding Sites ◽  
Neonatal Life ◽  
Specific Receptors ◽  
Recognition Systems

We studied the carbohydrate recognition systems of hepatocytes isolated from 16-day-old embryos, 19-day-old embryos and chicks within 24 h of hatching. We localized and quantified at the ultrastructural level the binding sites for glycoproteins exposing terminal N-acetylglucosamine (GlcNAc), mannose and N-acetylgalactosamine (GalNAc) residues by means of protein-gold complexes. Binding sites specific for GlcNAc and mannose residues are present on hepatocytes from embryos and chicks. On the contrary GalNAc specific binding sites are exclusively observed on cells from 16-day-old embryos. The number and distribution of gold particles on hepatocyte cell surfaces depend on the binding sites and the age considered. We describe a modulation in the number of GlcNAc, and mannose specific receptors present on the cell surface between the embryonal stage and neonatal life.

PROLACTIN AND THE REGULATION OF 20α-DIHYDROPROGESTERONE SECRETION OF THE SUPER-LUTEINIZED RAT OVARY DURING LUTEOLYSIS INDUCED BY A PROSTAGLANDIN F2α ANALOGUE

1978 ◽  
Vol 87 (3) ◽  
pp. 625-631 ◽  
Author(s):  
P. A. Torjesen ◽  
R. Dahlin ◽  
E. Haug ◽  
A. Aakvaag
Keyword(s):  
Prostaglandin F2α ◽  
Serum Levels ◽  
Chorionic Gonadotrophin ◽  
Human Chorionic Gonadotrophin ◽  
Female Rats ◽  
Serum Progesterone ◽  
Prostaglandin F ◽  
Rat Ovary ◽  
Pre Treatment ◽  
Observation Period

ABSTRACT Twenty-five day old female rats were treated with pregnant mare's serum gonadotrophin (PMSG) and human chorionic gonadotrophin (HCG) to achieve a state of luteinization. Eight days after the HCG administration luteolysis was induced by a subcutaneous injection of 5 μg of the prostaglandin F2α analogue cloprostenol (Estrumate®, ICI 80996). In animals treated with 2-Br-α-ergocryptine (BEC), administration of cloprostenol decreased serum progesterone levels from 580 to 20 ng/ml in 5 h and progesterone remained low for the next 18 h. The serum levels of 20α-dihydroprogesterone (20α-DHP) and prolactin (PRL) remained at pre-treatment values (20α-DHP 85 to 170 ng/ml; PRL less than 5 ng/ml) throughout the observation period. When animals treated with both BEC and cloprostenol were given PRL 5 h after the prostaglandin injection, an increased 20α-DHP level (630 ng/ml) was found 23 h after the cloprostenol administration, while the progesterone level was decreased (70 ng/ml). These findings were similar to the observations following cloprostenol treatment alone. The study indicates a causal relationship between the increase in the serum levels of PRL and 20α-DHP observed after PGF2α induced luteolysis in rats with superluteinized ovaries.

scholarly journals Annotations capturing cell type-specific TF binding explain a large fraction of disease heritability

2019 ◽  
Vol 29 (7) ◽  
pp. 1057-1067 ◽  
Author(s):  
Bryce van de Geijn ◽  
Hilary Finucane ◽  
Steven Gazal ◽  
Farhad Hormozdiari ◽  
Tiffany Amariuta ◽  
...  
Keyword(s):  
Binding Sites ◽  
Complex Traits ◽  
Complex Disease ◽  
Specific Binding ◽  
Large Fraction ◽  
Cell Types ◽  
Genome Wide Association ◽  
Cell Type ◽  
Genome Wide ◽  
Cell Type Specific

Abstract Regulatory variation plays a major role in complex disease and that cell type-specific binding of transcription factors (TF) is critical to gene regulation. However, assessing the contribution of genetic variation in TF-binding sites to disease heritability is challenging, as binding is often cell type-specific and annotations from directly measured TF binding are not currently available for most cell type-TF pairs. We investigate approaches to annotate TF binding, including directly measured chromatin data and sequence-based predictions. We find that TF-binding annotations constructed by intersecting sequence-based TF-binding predictions with cell type-specific chromatin data explain a large fraction of heritability across a broad set of diseases and corresponding cell types; this strategy of constructing annotations addresses both the limitation that identical sequences may be bound or unbound depending on surrounding chromatin context and the limitation that sequence-based predictions are generally not cell type-specific. We partitioned the heritability of 49 diseases and complex traits using stratified linkage disequilibrium (LD) score regression with the baseline-LD model (which is not cell type-specific) plus the new annotations. We determined that 100 bp windows around MotifMap sequenced-based TF-binding predictions intersected with a union of six cell type-specific chromatin marks (imputed using ChromImpute) performed best, with an 58% increase in heritability enrichment compared to the chromatin marks alone (11.6× vs. 7.3×, P = 9 × 10−14 for difference) and a 20% increase in cell type-specific signal conditional on annotations from the baseline-LD model (P = 8 × 10−11 for difference). Our results show that TF-binding annotations explain substantial disease heritability and can help refine genome-wide association signals.

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