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Follicle Stimulating Hormone

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121. Population Pharmacokinetic Modelling of FE 999049, a Recombinant Human Follicle-Stimulating Hormone, in Healthy Women After Single Ascending Doses Full Text available with Trip Pro

Population Pharmacokinetic Modelling of FE 999049, a Recombinant Human Follicle-Stimulating Hormone, in Healthy Women After Single Ascending Doses The purpose of this analysis was to develop a population pharmacokinetic model for a novel recombinant human follicle-stimulating hormone (FSH) (FE 999049) expressed from a human cell line of foetal retinal origin (PER.C6(®)) developed for controlled ovarian stimulation prior to assisted reproductive technologies.Serum FSH levels were measured

2016 Drugs in R&D Controlled trial quality: uncertain

122. Extracellular Signal-regulated Kinase (ERK)-dependent Phosphorylation of Y-Box-binding Protein 1 (YB-1) Enhances Gene Expression in Granulosa Cells in Response to Follicle-stimulating Hormone (FSH) Full Text available with Trip Pro

Extracellular Signal-regulated Kinase (ERK)-dependent Phosphorylation of Y-Box-binding Protein 1 (YB-1) Enhances Gene Expression in Granulosa Cells in Response to Follicle-stimulating Hormone (FSH) Within the ovarian follicle, immature oocytes are surrounded and supported by granulosa cells (GCs). Stimulation of GCs by FSH leads to their proliferation and differentiation, events that are necessary for fertility. FSH activates multiple signaling pathways to regulate genes necessary (...) for follicular maturation. Herein, we investigated the role of Y-box-binding protein-1 (YB-1) within GCs. YB-1 is a nucleic acid binding protein that regulates transcription and translation. Our results show that FSH promotes an increase in the phosphorylation of YB-1 on Ser(102) within 15 min that is maintained at significantly increased levels until ∼8 h post treatment. FSH-stimulated phosphorylation of YB-1(Ser(102)) is prevented by pretreatment of GCs with the PKA-selective inhibitor PKA inhibitor (PKI

2016 The Journal of biological chemistry

123. Delineating the effects of 5-fluorouracil and follicle-stimulating hormone on mouse bone marrow stem/progenitor cells Full Text available with Trip Pro

Delineating the effects of 5-fluorouracil and follicle-stimulating hormone on mouse bone marrow stem/progenitor cells Pluripotent, Lin(-)/CD45(-)/Sca-1(+) very small embryonic-like stem cells (VSELs) in mouse bone marrow (BM) are resistant to total body radiation because of their quiescent nature, whereas Lin(-)/CD45(+)/Sca-1(+) hematopoietic stem cells (HSCs) get eliminated. In the present study, we provide further evidence for the existence of VSELs in mouse BM and have also examined (...) the effects of a chemotherapeutic agent (5-fluorouracil (5-FU)) and gonadotropin hormone (follicle-stimulating hormone (FSH)) on BM stem/progenitor cells.VSELs and HSCs were characterized in intact BM. Swiss mice were injected with 5-FU (150 mg/kg) and sacrificed on 2, 4, and 10 days (D2, D4, and D10) post treatment to examine changes in BM histology and effects on VSELs and HSCs by a multiparametric approach. The effect of FSH (5 IU) administered 48 h after 5-FU treatment was also studied

2016 Stem cell research & therapy

124. Forkhead Box O member FOXO1 Regulates the Majority of Follicle-Stimulating Hormone Responsive Genes in Ovarian Granulosa Cells Full Text available with Trip Pro

Forkhead Box O member FOXO1 Regulates the Majority of Follicle-Stimulating Hormone Responsive Genes in Ovarian Granulosa Cells FSH promotes maturation of ovarian follicles. One pathway activated by FSH in granulosa cells (GCs) is phosphatidylinositol-3 kinase/AKT. The AKT target FOXO1 is reported to function primarily as a repressor of FSH genes, including Ccnd2 and Inha. Based on its broad functions in other tissues, we hypothesized that FOXO1 may regulate many more GC genes. We transduced GCs

2016 Molecular and cellular endocrinology

125. SMAD3 Regulates Follicle-stimulating Hormone Synthesis by Pituitary Gonadotrope Cells in Vivo Full Text available with Trip Pro

SMAD3 Regulates Follicle-stimulating Hormone Synthesis by Pituitary Gonadotrope Cells in Vivo Pituitary follicle-stimulating hormone (FSH) is an essential regulator of fertility in females and of quantitatively normal spermatogenesis in males. Pituitary-derived activins are thought to act as major stimulators of FSH synthesis by gonadotrope cells. In vitro, activins signal via SMAD3, SMAD4, and forkhead box L2 (FOXL2) to regulate transcription of the FSHβ subunit gene (Fshb). Consistent (...) knock-out females were hypogonadal, acyclic, and sterile and had thread-like uteri; their ovaries lacked antral follicles and corpora lutea. Knock-out males were fertile but had reduced testis weights and epididymal sperm counts. These phenotypes were consistent with those of Fshb knock-out mice. Indeed, pituitary Fshb mRNA levels were nearly undetectable in both male and female knock-outs. In contrast, gonadotropin-releasing hormone receptor mRNA levels were significantly elevated in knock-outs

2016 The Journal of biological chemistry

126. Revisiting the expression and function of follicle-stimulation hormone receptor in human umbilical vein endothelial cells Full Text available with Trip Pro

Revisiting the expression and function of follicle-stimulation hormone receptor in human umbilical vein endothelial cells Expression of follicle-stimulation hormone receptor (FSHR) is confined to gonads and at low levels to some extragonadal tissues like human umbilical vein endothelial cells (HUVEC). FSH-FSHR signaling was shown to promote HUVEC angiogenesis and thereafter suggested to have an influential role in pregnancy. We revisited hereby the expression and functionality of FSHR in HUVECs

2016 Scientific reports

127. Featured Article: Transcriptional landscape analysis identifies differently expressed genes involved in follicle-stimulating hormone induced postmenopausal osteoporosis Full Text available with Trip Pro

Featured Article: Transcriptional landscape analysis identifies differently expressed genes involved in follicle-stimulating hormone induced postmenopausal osteoporosis Osteoporosis is a disorder associated with bone tissue reorganization, bone mass, and mineral density. Osteoporosis can severely affect postmenopausal women, causing bone fragility and osteoporotic fractures. The aim of the current study was to compare blood mRNA profiles of postmenopausal women with and without osteoporosis (...) in a follicle-stimulating hormone activated network of increased osteoclast activity and hypogonadal bone loss. The differentially expressed genes identified in this study may contribute to future research of postmenopausal osteoporosis blood biomarkers.

2016 Experimental Biology and Medicine

128. c-JUN Dimerization Protein 2 (JDP2) Is a Transcriptional Repressor of Follicle-stimulating Hormone β (FSHβ) and Is Required for Preventing Premature Reproductive Senescence in Female Mice Full Text available with Trip Pro

c-JUN Dimerization Protein 2 (JDP2) Is a Transcriptional Repressor of Follicle-stimulating Hormone β (FSHβ) and Is Required for Preventing Premature Reproductive Senescence in Female Mice Follicle-stimulating hormone (FSH) regulates follicular growth and stimulates estrogen synthesis in the ovaries. FSH is a heterodimer consisting of an α subunit, also present in luteinizing hormone, and a unique β subunit, which is transcriptionally regulated by gonadotropin-releasing hormone 1 (GNRH (...) in a complex with c-JUN. GNRH treatment induced c-FOS to replace JDP2 as a c-JUN binding partner, forming transcriptionally active AP-1. Subsequently, rapid c-FOS degradation enabled reformation of the JDP2 complex. In vivo studies revealed that JDP2 null male mice have normal reproductive function, as expected from a negative regulator of the FSH hormone. Female JDP2 null mice, however, exhibited early puberty, observed as early vaginal opening, larger litters, and early reproductive senescence. JDP2 null

2016 The Journal of biological chemistry

129. Follicle-Stimulating Hormone (FSH)-dependent Regulation of Extracellular Regulated Kinase (ERK) Phosphorylation by the Mitogen-activated Protein (MAP) Kinase Phosphatase MKP3 Full Text available with Trip Pro

Follicle-Stimulating Hormone (FSH)-dependent Regulation of Extracellular Regulated Kinase (ERK) Phosphorylation by the Mitogen-activated Protein (MAP) Kinase Phosphatase MKP3 Within the ovarian follicle, granulosa cells (GCs) surround and support immature oocytes. FSH promotes the differentiation and proliferation of GCs and is essential for fertility. We recently reported that ERK activation is necessary for FSH to induce key genes that define the preovulatory GC. This research focused (...) on the phosphoregulation by FSH of ERK within GCs. FSH-stimulated ERK phosphorylation on Thr(202)/Tyr(204) was PKA-dependent, but MEK(Ser(217)/Ser(221)) phosphorylation was not regulated; rather, MEK was already active. However, treatment of GCs with the EGF receptor inhibitor AG1478, a dominant-negative RAS, an Src homology 2 domain-containing Tyr phosphatase inhibitor (NSC 87877), or the MEK inhibitor PD98059 blocked FSH-dependent ERK(Thr(202)/Tyr(204)) phosphorylation, demonstrating the requirement for upstream

2016 The Journal of biological chemistry

130. Role of Cysteine Residues in the Carboxyl-Terminus of the Follicle-Stimulating Hormone Receptor in Intracellular Traffic and Postendocytic Processing Full Text available with Trip Pro

Role of Cysteine Residues in the Carboxyl-Terminus of the Follicle-Stimulating Hormone Receptor in Intracellular Traffic and Postendocytic Processing Posttranslational modifications occurring during the biosynthesis of G protein-coupled receptors include glycosylation and palmitoylation at conserved cysteine residues located in the carboxyl-terminus of the receptor. In a number of these receptors, these modifications play an important role in receptor function and particularly, in intracellular (...) trafficking. In the present study, the three cysteine residues present in the carboxyl-terminus of the human FSHR were replaced with glycine by site-directed mutagenesis. Wild-type and mutant (Cys627/629/655Gly) FSHRs were then transiently expressed in HEK-293 cells and analyzed for cell-surface plasma membrane expression, agonist-stimulated signaling and internalization, and postendocytic processing in the absence and presence of lysosome and/or proteasome inhibitors. Compared with the wild-type FSHR

2016 Frontiers in Cell and Developmental Biology

131. Characterization of Gonadotrope Secretoproteome Identifies Neurosecretory Protein VGF-derived Peptide Suppression of Follicle-stimulating Hormone Gene Expression Full Text available with Trip Pro

Characterization of Gonadotrope Secretoproteome Identifies Neurosecretory Protein VGF-derived Peptide Suppression of Follicle-stimulating Hormone Gene Expression Reproductive function is controlled by the pulsatile release of hypothalamic gonadotropin-releasing hormone (GnRH), which regulates the expression of the gonadotropins luteinizing hormone and FSH in pituitary gonadotropes. Paradoxically, Fshb gene expression is maximally induced at lower frequency GnRH pulses, which provide a very low (...) average concentration of GnRH stimulation. We studied the role of secreted factors in modulating gonadotropin gene expression. Inhibition of secretion specifically disrupted gonadotropin subunit gene regulation but left early gene induction intact. We characterized the gonadotrope secretoproteome and global mRNA expression at baseline and after Gαs knockdown, which has been found to increase Fshb gene expression (1). We identified 1077 secreted proteins or peptides, 19 of which showed mRNA regulation

2016 The Journal of biological chemistry

132. Characterisation of Population Pharmacokinetics and Endogenous Follicle-Stimulating Hormone (FSH) Levels After Multiple Dosing of a Recombinant Human FSH (FE 999049) in Healthy Women Full Text available with Trip Pro

Characterisation of Population Pharmacokinetics and Endogenous Follicle-Stimulating Hormone (FSH) Levels After Multiple Dosing of a Recombinant Human FSH (FE 999049) in Healthy Women The aim of this study was to characterise the population pharmacokinetics of FE 999049, a novel recombinant human follicle-stimulating hormone (FSH), after multiple dosing in healthy women, taking into account endogenous FSH levels and the reproductive hormone dynamics.Longitudinal measurements of FSH, luteinising (...) hormone, progesterone, estradiol, and inhibin B levels were collected after repeated subcutaneous dosing with 225 IU of FE 999049 in 24 gonadotropin downregulated healthy women. The FSH data were described using nonlinear mixed-effects modelling.The measured FSH levels were modelled as a sum of endogenous FSH and FE 999049. The FE 999049 population pharmacokinetics were best described using a one-compartment model with first-order absorption and elimination, and a transit model for delayed absorption

2016 Drugs in R&D Controlled trial quality: uncertain

133. Targeting the Follicle Stimulating Hormone Receptor (FSHR) To Treat Fertility Disorders Full Text available with Trip Pro

Targeting the Follicle Stimulating Hormone Receptor (FSHR) To Treat Fertility Disorders 27096038 2016 04 20 2018 11 13 1948-5875 7 4 2016 Apr 14 ACS medicinal chemistry letters ACS Med Chem Lett Targeting the Follicle Stimulating Hormone Receptor (FSHR) To Treat Fertility Disorders. 345-7 10.1021/acsmedchemlett.6b00082 Abdel-Magid Ahmed F AF Therachem Research Medilab (India) Pvt. Ltd. , Jaipur, India. eng Journal Article 2016 03 04 United States ACS Med Chem Lett 101521073 1948-5875 2016 02 25

2016 ACS medicinal chemistry letters

134. Lack of Specificity of Plasma Concentrations of Inhibin B and Follicle-Stimulating Hormone for Identification of Azoospermic Survivors of Childhood Cancer: A Report From the St Jude Lifetime Cohort Study Full Text available with Trip Pro

Lack of Specificity of Plasma Concentrations of Inhibin B and Follicle-Stimulating Hormone for Identification of Azoospermic Survivors of Childhood Cancer: A Report From the St Jude Lifetime Cohort Study Many male survivors of childhood cancer are at risk for azoospermia. Although both the levels of follicle-stimulating hormone (FSH) and inhibin B are correlated with sperm concentration, their ability to predict azoospermia in survivors of childhood cancer remains uncertain.Semen analysis

2013 EvidenceUpdates

135. Basal Follicle-Stimulating Hormone or Inhibin B Combined with Age as Predictors of Pregnancy After Treatment by Donor Sperm Insemination. (Abstract)

Basal Follicle-Stimulating Hormone or Inhibin B Combined with Age as Predictors of Pregnancy After Treatment by Donor Sperm Insemination. To evaluate the clinical significance of basal reproductive hormones and basal inhibin B (INHB) combined with age on predicting the outcomes of artificial insemination with donor sperm (AID).A retrospective analysis was performed in 1,772 patients who underwent AID at the Department of Assisted Re- production, Tongji Medical College, from 2009-2011. We (...) compared the age and The levels of basal menstrual cycle day 3 reproductive hormones and INHB regarding the pregnancy rates after AID treatment.There was a low clinical pregnancy rate in women with a basal follicle-stimulating hormone (FSH) ≥ 15 IU/L or a basal INHB < 25 ng/mL. An age-related decrease in the pregnancy rate was found also. Moreover, the pregnancy rate dropped remarkably when the FSH x age value was > 500, and it rose to 70.6% when the INHB ÷ age value was > 10.Basal FSH and basal INHB

2015 Journal of Reproductive Medicine

136. Follicle-stimulating hormone induces postmenopausal dyslipidemia through inhibiting hepatic cholesterol metabolism. Full Text available with Trip Pro

Follicle-stimulating hormone induces postmenopausal dyslipidemia through inhibiting hepatic cholesterol metabolism. The elevated low-density-lipoprotein cholesterol (LDL-C) in menopausal women is associated with higher risks of cardiovascular diseases.The aim of this study is to investigate the influence and mechanism by which high postmenopausal FSH levels affect lipid profiles.The serum FSH and lipid levels were examined in 400 Chinese postmenopausal women. The FSH receptor (FSHR) expression (...) with FSH levels of 40-78.3 IU/L (P < .01). The improvements of total cholesterol and LDL-C levels were more significant in higher FSH women group after treatment with hormone replacement therapy. It was only in the women whose FSH levels were reduced more than 30% after hormone replacement therapy who showed significant improvement of lipid levels. Ovariectomized mice had high serum FSH and lipids levels and reduced hepatic LDLR expression. In HepG2 cells, FSH inhibited the LDLR in a dose- and time

2015 Journal of Clinical Endocrinology and Metabolism

137. Development and characterization of a novel long-acting recombinant follicle stimulating hormone agonist by fusing Fc to an FSH-β subunit. Full Text available with Trip Pro

Development and characterization of a novel long-acting recombinant follicle stimulating hormone agonist by fusing Fc to an FSH-β subunit. Does a novel long-acting recombinant human FSH, KN015, a heterodimer composed of FSHα and FSHβ-Fc/Fc, offer a potential FSH alternative?KN015 had in vitro activity and superior in vivo bioactivity than recombinant human FSH (rhFSH), suggesting KN015 could serve as a potential FSH agonist for clinical therapy.rhFSH has very short half-life so that repeat (...) dUDP nick-end labeling (TUNEL), RT-PCR and western blot. In the latter, 26-day-old female SD rats (n = 8/group) were injected with different doses of KN015 or rhFSH, and were sacrificed at 24 h after an injection of hCG (20 IU/rat). Moreover, the molecular responses stimulated by KN015 or rhFSH in the ovary were also analyzed through detecting expression of the FSH target genes (Cyp19a1, Fshr and Lhcgr) and phosphatidylinositide 3-kinase (PI3K) pathway activation.KN015 has a molecular weight of 82

2015 Human Reproduction

138. Ectopic expression of follicle-stimulating hormone receptors in thyroid tumors Full Text available with Trip Pro

Ectopic expression of follicle-stimulating hormone receptors in thyroid tumors In normal conditions follicle-stimulating hormone receptors (FSHR) are expressed in the ovary and the testis. They can also be expressed in gonadal tumors. However, recently we have found FSHR immunostaining in pituitary adenomas, adrenal tumors and neuroendocrine tumors (carcinoids). The aim of this study was to determine whether the same occurs in thyroid tumors.Thirty-six samples of surgically excised thyroids (...) were examined. Follicle-stimulating hormone receptors immunostaining was performed on paraffin sections using the rabbit anti-human FSHR polyclonal antibody raised against a 1-190 amino acid sequence from the human FSHR (sc-13935, Santa Cruz).Normal thyroid follicles do not show immunopositivity for FSHR. The same concerns the majority of benign lesions, diagnosed as hyperplasia nodularis or thyroid adenomas. However, positive FSHR immunostaining in some follicles was observed. In all but one

2015 Archives of medical science : AMS

139. Follicle-stimulating hormone is associated with non-alcoholic fatty liver disease in Chinese women over 55 years old. (Abstract)

Follicle-stimulating hormone is associated with non-alcoholic fatty liver disease in Chinese women over 55 years old. Obesity and diabetes are related to non-alcoholic fatty liver disease (NAFLD). A reduction in follicle-stimulating hormone (FSH) is associated with obesity and diabetes in postmenopausal women. Thus, we aim to investigate whether FSH is associated with NAFLD in women over 55 who were postmenopausal with a high probability.Our data were obtained from the 2014 Survey on Prevalence (...) but persisted in the fully adjusted model (P for trend <0.01).Follicle-stimulating hormone was negatively associated with NAFLD in women over 55 years old. Adiposity and insulin resistance explained most of the association of mild hepatic steatosis and partially explained the association of moderate-severe hepatic steatosis with FSH.© 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

2015 Journal of gastroenterology and hepatology

140. Microdose flare protocol with interrupted follicle stimulating hormone and added androgen for poor responders-an observational pilot study. Full Text available with Trip Pro

Microdose flare protocol with interrupted follicle stimulating hormone and added androgen for poor responders-an observational pilot study. To investigate whether temporarily withholding FSH and adding androgen could improve follicular response during a microdose flare protocol in women with slow follicular growth or asynchronous follicular development.Observational pilot study.University-affiliated private fertility center.Twenty-six women aged 34-47 years with poor response to stimulation (...) or a previous cancelled IVF cycle and with slow or asynchronous follicular growth during a microdose flare cycle.For 13 women, after initiation of ovarian stimulation using the microdose flare protocol, gonadotropin administration was interrupted and transdermal testosterone gel was added for several days (4.4 ± 1.2 d) starting after cycle day 7 (mean cycle day 10 ± 2.6).FSH, E2, follicular growth, and total number of mature oocytes retrieved were determined for all of the patients. Cycle cancellation rate

2015 Fertility and Sterility

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