scholarly journals Essential Role of the Oocyte in Estrogen Amplification of Follicle-Stimulating Hormone Signaling in Granulosa Cells

Endocrinology ◽  
2005 ◽  
Vol 146 (8) ◽  
pp. 3362-3367 ◽  
Author(s):  
Fumio Otsuka ◽  
R. Kelly Moore ◽  
Xia Wang ◽  
Shweta Sharma ◽  
Tomoko Miyoshi ◽  
...  

Abstract The establishment of dominant ovarian follicles that are capable of ovulating fertilizable oocytes is a fundamental determinant of female fertility. This process is governed by pituitary gonadotropins as well as local ovarian factors. Within the follicle, estrogen acts in an autocrine/paracrine manner to enhance FSH action in the granulosa cells. These effects include the augmentation of P450aromatase expression and estradiol production. This feed-forward effect of estrogen is believed to play a key role in follicle dominance. Here we found the essential role of the oocyte in this physiological process using primary cultures of rat granulosa cells. In the presence, but not absence, of oocytes, estrogen amplified FSH-stimulated increases in mRNA expression of P450aromatase, FSH receptor, LH receptor, and inhibin α-, βA-, and βB-subunits as well as cAMP production. Thus, oocytes mediate the estrogen enhancement of FSH action in the granulosa cells. In comparison with FSH, cotreatment with estrogen and oocytes failed to amplify the stimulatory effects of forskolin or 8-bromoadenosine-cAMP on granulosa cell responses including P450aromatase mRNA expression and cAMP production, indicating that estrogen/oocytes amplify FSH action at a site upstream of adenylate cyclase. These findings support the novel conclusion that communication between the oocyte and granulosa cells plays a crucial role in mediating estrogen action during FSH-dependent folliculogenesis.

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
T Okubo ◽  
H Teruaki ◽  
O Noriyuki ◽  
O Kenji ◽  
S Tomoya

Abstract Study question Do different follicle sizes influence gonadotropins (LH, FSH) and sex steroid (estradiol) in follicular fluids and LH receptor expression (LHCGR) in cumulus oocyte complexes (COCs)? Summary answer It was found that differences in levels of FSH, estradiol values and LHCGR mRNA expression level in COCs between small and large follicles. What is known already The maturity rate in oocytes of small follicle is significantly lower compared to that of large follicles. Study design, size, duration After obtaining written consents from 78 infertile patients, we aspirated the large (>15 mm) and small (<5 mm) follicles, and collected follicular fluids at oocyte retrieval. Participants/materials, setting, methods We measured levels of LH, FSH and estradiol by enzyme immunoassay from large and small follicular fluids after oocytes retrievals. All collected oocytes were distinguished from large and small follicles, we confirmed the maturity of retrieved oocytes by the presence of first polar body. Then we extracted total RNA from granulosa cells and measured mRNA expression of LHCGR, encoding the human LH receptor, by quantitative real-time PCR. Each value was normalized to ACTB mRNA levels. Main results and the role of chance LH levels were nearly equal between small and large follicles (P = 0.8356). Whereas FSH and estradiol levels were significantly lower in small follicles (P < 0.0001). The expression levels of LHCGR mRNA were significantly lower in small follicles than in large follicles during natural cycles. The maturity rate in oocytes of small follicle was significantly lower compared to that of large follicles (96.0% vs. 21.7%, P < 0001). Limitations, reasons for caution The main limitation of the present study was collected by 42 natural cycles and 36 mild stimulation cycles with letrozole following low-dose clomiphene. Wider implications of the findings: In spite of almost the same LH levels between two groups, the reason why the significantly lower maturation rates of oocytes collected from small follicles is poor LHCGR mRNA expression due to insufficient granulosa cells glowth because of low FSH and estradiol levels. Trial registration number Not applicable


Author(s):  
Larisa Botnari

Although very famous, some key moments of the novel In Search of Lost Time, such as those of the madeleine or the uneven pavement, often remain enigmatic for the reader. Our article attempts to formulate a possible philosophical interpretation of the narrator's experiences during these scenes, through a confrontation of the Proustian text with the ideas found in the System of Transcendental Idealism (1800) of the German philosopher F. W. J. Schelling. We thus try to highlight the essential role of the self in Marcel Proust's aesthetic thinking, by showing that the mysterious happiness felt by the narrator, and from which the project of creating a work of art is ultimately born, is similar to the experiences of pure self-consciousness evoked and analyzed by Schellingian philosophy of art.


2020 ◽  
pp. 81-104
Author(s):  
Neil C. Renic

This chapter locates the role of reciprocal risk within the Just War Tradition. This begins with the ‘conventionalist’ account of the moral right to kill. The chapter then considers the most recent challenge to this position in the form of Just War ‘revisionism’. Following this, it will examine the more consequentialist approach of ‘contractarianism’. The chapter will demonstrate that within all three of these approaches, an assumption of war as a site of reciprocal structural risk plays an essential role in the permissiveness of inter-combatant violence. The chapter then explores the tension between the coherence of these justifications and conditions of radical asymmetry.


2007 ◽  
Vol 88 (11) ◽  
pp. 3187-3197 ◽  
Author(s):  
Fleur Roberts ◽  
Gwen E. Allison ◽  
Naresh K. Verma

The temperate phage SfV encodes the genes responsible for the serotype conversion of Shigella flexneri strains from serotype Y to 5a. Bacteriophages often encode proteins that prevent subsequent infection by homologous phages; the mechanism by which this is accomplished is referred to as superinfection immunity. The serotype conversion mediated following lysogenization of SfV is one such mechanism. Another mechanism is the putative λ-like CI protein within SfV. This study reports the characterization of a third superinfection mechanism, transcription termination, in SfV. The presence of a small immunity-mediating RNA molecule, called CI RNA, and its essential role in the establishment of immunity, is shown. The novel role of the gene orf77, located immediately downstream from the transcription termination region, in inhibiting the establishment of CI RNA-mediated immunity is also presented.


Endocrinology ◽  
2015 ◽  
Vol 156 (9) ◽  
pp. 3192-3202 ◽  
Author(s):  
Kohshiro Nakao ◽  
Hiroshi Kishi ◽  
Fumiharu Imai ◽  
Hiroto Suwa ◽  
Takashi Hirakawa ◽  
...  

Several inflammatory cytokines regulate ovarian function. TNF-α is produced in granulosa cells under physiological conditions and has a reciprocal action on follicle development. In contrast, in pelvic inflammatory diseases, TNF-α is excessively produced in the pelvic cavity and has an adverse effect on reproductive functions. The objective of this study was to elucidate the mechanism of action of TNF-α on the expression of LH receptor (LHR) in immature rat granulosa cells. TNF-α suppressed FSH-induced LHR mRNA and protein expression and was not associated with cAMP accumulation. By using a luciferase assay, the construct containing base pairs −1389 to −1 of the rat Lhcgr promoter revealed that TNF-α decreased FSH-induced promoter activity. In response to TNF-α, nuclear factor (NF)-κB p65 was translocated to the nucleus, and the suppressive effect of TNF-α on LHR mRNA expression was abrogated by an NF-κB inhibitor. In a chromatin immunoprecipitation assay, TNF-α induced the association of NF-κB p65 with the rat Lhcgr transcriptional promoter region. NF-κB p65 and histone deacetylase (HDAC) interact to mediate expression of several genes at a transcriptional level. HDAC activity is thought to induce tight connections within local chromatin structures and repress gene transcription. Furthermore, the TNF-α–induced suppression of LHR mRNA expression was blocked by an HDAC inhibitor. Taken together, these results suggest that the interaction of NF-κB p65 with HDAC in the promoter region of rat Lhcgr might be responsible for TNF-α action on the regulation of LHR.


2014 ◽  
Vol 25 (22) ◽  
pp. 3569-3580 ◽  
Author(s):  
Kyoko Chiba ◽  
Masahiko Araseki ◽  
Keisuke Nozawa ◽  
Keiko Furukori ◽  
Yoichi Araki ◽  
...  

Alzheimer's β-amyloid precursor protein (APP) associates with kinesin-1 via JNK-interacting protein 1 (JIP1); however, the role of JIP1 in APP transport by kinesin-1 in neurons remains unclear. We performed a quantitative analysis to understand the role of JIP1 in APP axonal transport. In JIP1-deficient neurons, we find that both the fast velocity (∼2.7 μm/s) and high frequency (66%) of anterograde transport of APP cargo are impaired to a reduced velocity (∼1.83 μm/s) and a lower frequency (45%). We identified two novel elements linked to JIP1 function, located in the central region of JIP1b, that interact with the coiled-coil domain of kinesin light chain 1 (KLC1), in addition to the conventional interaction of the JIP1b 11–amino acid C-terminal (C11) region with the tetratricopeptide repeat of KLC1. High frequency of APP anterograde transport is dependent on one of the novel elements in JIP1b. Fast velocity of APP cargo transport requires the C11 domain, which is regulated by the second novel region of JIP1b. Furthermore, efficient APP axonal transport is not influenced by phosphorylation of APP at Thr-668, a site known to be phosphorylated by JNK. Our quantitative analysis indicates that enhanced fast-velocity and efficient high-frequency APP anterograde transport observed in neurons are mediated by novel roles of JIP1b.


2010 ◽  
Vol 29 (2) ◽  
pp. 327-348 ◽  
Author(s):  
Tim Whitmarsh

Other Greek novels open in poleis, before swiftly shunting their protagonists out of them and into the adventure world. Why does Achilles Tatius' Leucippe and Clitophon open in a house (with no sign of any political apparatus), and stay there for almost one quarter of the novel? This article explores the cultural, psychological, and metaliterary role of the house in Achilles, reading it as a site of conflict between the dominant, patriarchal ideology of the father and the subversive intent of the young lovers. If the house principally embodies the authoritarian will of the father to order and control, it nevertheless provides the lovers with opportunities to re-encode space opportunistically as erotic. The house cannot be reconstructed archaeologically (Clitophon is too flittish a narrator for that), but it is nevertheless clearly divided into different qualitative zones—diningroom, bedrooms, garden—each of which has its own psychosocial and emotional texture, its own challenges, and its own resources. Achilles' modelling of the house may reflect Roman ideas of domestic aristocratic display, and perhaps even the influence of Roman literature (particularly love elegy).


2005 ◽  
Vol 20 (4) ◽  
pp. 813-817
Author(s):  
Subhayan Biswas ◽  
Sandip Chatterjee ◽  
P. Chatterjee ◽  
A.K. Nigam ◽  
S.K. De

The dependence of the novel properties observed in colossal magnetoresistance (CMR) materials, other than average ionic radii 〈rA〉 and Mn valence ratio (Mn3+/Mn4+), was investigated through examination of the transport and magnetic properties of Pr0.65(Ca0.7Sr0.3)0.35MnO3, La0.123Pr0.527(Ca0.8Sr0.2)0.35MnO3, and Pr0.65(Ca0.866Ba0.134)0.35MnO3. The average ionic radii 〈rA〉 and valence ratio of all three samples have been kept equal. The results of this investigation indicate a more intense role of the nature of individual A-site cation and the lattice mismatch. A remarkably large magnetoresistance of the order of 108 at moderate magnetic field has been observed for Ba-doped sample.


Blood ◽  
2000 ◽  
Vol 95 (11) ◽  
pp. 3423-3428 ◽  
Author(s):  
Mirko Pinotti ◽  
Raffaella Toso ◽  
Domenico Girelli ◽  
Debora Bindini ◽  
Paolo Ferraresi ◽  
...  

Abstract Previous studies have established that factor VII gene (F7) polymorphisms (5′F7 and R353Q) contribute about one-third of factor VII (FVII) level variation in plasma. However, F7 genotyping in patients with cardiovascular disease has produced conflicting results. Population and expression studies were used to investigate the role of intron 7 (IVS7 ) polymorphisms, including repeat and sequence variations, in controlling activated FVII (FVIIa) and antigen (FVIIag) levels. Genotype–phenotype studies performed in 438 Italian subjects suggested a positive relation between the IVS7 repeat number and FVII levels. The lowest values were associated with theIVS7 + 7G allele. The screening of 52 patients with mild FVII deficiency showed an 8-fold increase in frequency (8%) of this allele, and among heterozygotes for identical mutations, lower FVII levels were observed in the IVS7 + 7G carriers. This frequent genetic component participates in the phenotypic heterogeneity of FVII deficiency. The evaluation of the individual contribution of polymorphisms was assisted by the expression of each IVS7variant, as a minigene, in eukaryotic cells. The novel quantitative analysis revealed that higher numbers of repeats were associated with higher mRNA expression levels and that the IVS7 + 7Gallele, previously defined as a functionally silent polymorphism, was responsible for the lowest relative mRNA expression. Taken together, these findings indicate that the IVS7 polymorphisms contribute to the plasmatic variance of FVII levels via differential efficiency of mRNA splicing. These studies provide further elements to understand the control of FVII levels, which could be of importance to ensure the hemostatic balance under pathologic conditions.


2002 ◽  
Vol 8 (6) ◽  
pp. 449-452 ◽  
Author(s):  
Kensuke Miyake ◽  
Yoshinori Nagai ◽  
Sachiko Akashi ◽  
Masakazu Nagafuku ◽  
Masato Ogata ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document