Follicle-stimulating hormone (FSH) activates extracellular signal-regulated kinase phosphorylation independently of beta-arrestin- and dynamin-mediated FSH receptor internalization

Piketty, Vincent; Kara, Elodie; Guillou, Florian; Reiter, Eric; Crépieux, Pascale

doi:10.1186/1477-7827-4-33

Cited by 23 publications

(11 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…β-arrestin recruitment to GRK-phosphorylated FSHR is a well-recognized process leading to receptor internalization ( 153 , 167 , 169 ). In the case of the LHCGR this effect is rather mediated by the interaction with ADP ribosylation factor nucleotide-binding site opener (ARNO), which is an exchange factor for ADP ribosylation factor 6 (ARF6) that recruits β-arrestins when bound to GTP ( 170 , 171 ).…”

Section: Fshr Domains Involved In Internalization and Post-endocytic mentioning

confidence: 99%

Structure-Function Relationships of the Follicle-Stimulating Hormone Receptor

et al. 2018

View full text Add to dashboard Cite

The follicle-stimulating hormone receptor (FSHR) plays a crucial role in reproduction. This structurally complex receptor is a member of the G-protein coupled receptor (GPCR) superfamily of membrane receptors. As with the other structurally similar glycoprotein hormone receptors (the thyroid-stimulating hormone and luteinizing hormone-chorionic gonadotropin hormone receptors), the FSHR is characterized by an extensive extracellular domain, where binding to FSH occurs, linked to the signal specificity subdomain or hinge region. This region is involved in ligand-stimulated receptor activation whereas the seven transmembrane domain is associated with receptor activation and transmission of the activation process to the intracellular loops comprised of amino acid sequences, which predicate coupling to effectors, interaction with adapter proteins, and triggering of downstream intracellular signaling. In this review, we describe the most important structural features of the FSHR intimately involved in regulation of FSHR function, including trafficking, dimerization, and oligomerization, ligand binding, agonist-stimulated activation, and signal transduction.

show abstract

Section: Fshr Domains Involved In Internalization and Post-endocytic mentioning

confidence: 99%

Structure-Function Relationships of the Follicle-Stimulating Hormone Receptor

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Low-molecular weight hormones as adrenaline or dopamine and peptides like melanocortin receptor agonists, which bind fast to their receptors, reveal a stable cAMP signal within 10 minutes after addition of the ligand 22 25 . Relatively slow kinetics of gonadotropin hormones’ binding to their receptors have also been shown with 125 I-labelled radioligand binding experiments to cell membrane preparations 26 27 28 29 and have been explained by hindrance due to steric factors and ligand binding interaction at the binding sites.…”

Section: Resultsmentioning

confidence: 83%

Determination of biological activity of gonadotropins hCG and FSH by Förster resonance energy transfer based biosensors

Mazina

Allikalt

Tapanainen

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Determination of biological activity of gonadotropin hormones is essential in reproductive medicine and pharmaceutical manufacturing of the hormonal preparations. The aim of the study was to adopt a G-protein coupled receptor (GPCR)-mediated signal transduction pathway based assay for quantification of biological activity of gonadotropins. We focussed on studying human chorionic gonadotropin (hCG) and follicle-stimulating hormone (FSH), as these hormones are widely used in clinical practice. Receptor-specific changes in cellular cyclic adenosine monophosphate (cAMP, second messenger in GPCR signalling) were monitored by a Förster resonance energy transfer (FRET) biosensor protein T Epac VV in living cells upon activation of the relevant gonadotropin receptor. The BacMam gene delivery system was used for biosensor protein expression in target cells. In the developed assay only biologically active hormones initiated GPCR-mediated cellular signalling. High assay sensitivities were achieved for detection of hCG (limit of detection, LOD: 5 pM) and FSH (LOD: 100 pM). Even the smallscale conformational changes caused by thermal inactivation and reducing the biological activity of the hormones were registered. In conclusion, the proposed assay is suitable for quantification of biological activity of gonadotropins and is a good alternative to antibody-and animal-testing-based assays used in pharmaceutical industry and clinical research.Gonadotropin medications are widely used in controlled ovarian stimulation and induction of ovulation as key components of infertility treatment. A number of gonadotropin preparations are available, based on the naturally occurring gonadotropins: follicle-stimulating hormone (FSH), luteinizing hormone (LH), and human chorionic gonadotropin (hCG).Gonadotropins are glycoprotein hormones that regulate normal growth, sexual development, and reproductive function. These are large, up to 40 kDa proteins, which are synthesized and secreted by the gonadotropic cells of the anterior pituitary gland (LH and FSH) and by the syncytiotrophoblasts in the placenta (hCG). These hormones may vary in the level of glycosylation depending on myriad of physiological co-factors. Upon binding to FSH receptor (FSHR), a G-protein coupled receptor (GPCR), FSH regulates the development, growth, pubertal maturation, and reproductive processes, like maturation of germ cells in both women and men. LH and hCG bind to a shared GPCR (LH/CG receptor, LHCGR) and regulate mechanisms involved in ovulation, early pregnancy and placental function, respectively, in females, while in men, LH is involved in spermatogenesis and testosterone production 1 . FSH, LH and hCG are heterodimeric proteins that consist of non-covalently linked α -and β -subunits. The gonadotropins share the α -subunit structure, but are each bound to a unique β -subunit resulting in differences in their physiological roles and signalling 1 . Upon binding to their receptor, gonadotropins activate the Gs-coupled signalling pathway resulting in stimulation of ...

show abstract

“…tein-linked signal transduction system working generally through cAMP production. They operate by activating Alternatively Spliced Isoforms of FSHR adenylyl cyclase and phospholipase C. It is worthwhile to discuss regulation of its gene expression, many iso-Although SNPs as mentioned above will give rise to their respective isoforms, potentially functional FSHR forms and pathways of desensitization through uncou 234 BOSE protein isoforms are possible by alternatively spliced ternalization of the FSHR to initiate ERK phosphorylation (46). mRNA transcripts both in the ovary and in the testis with preserved open reading frame (39,40).…”

Section: Role Of Fshmentioning

confidence: 98%

Follicle Stimulating Hormone Receptor in Ovarian Surface Epithelium and Epithelial Ovarian Cancer

Bose

2008

oncol res

View full text Add to dashboard Cite

Epithelial ovarian cancer (EOC) has remained an enigmatic disease, the etiology of which is mostly unknown. Considering the age incidence around menopause, a "gonadotrophin theory" has been proposed, and considering the association with infertility, an "incessant ovulation" theory has been proposed. EOC originates from ovarian surface epithelium (OSE), which not only secretes cytokines/growth factors and steroids but expresses gonadotrophin and steroid hormone receptors as well. The most important gonadotrophin receptor is the follicle stimulating hormone receptor (FSHR), which has definite oncogenic potential and is a probable candidate for oncogenesis. In this article, we review existing knowledge of FSHR in ovary, in OSE, and in epithelial ovarian cancer and try to establish relative importance of this receptor over its ligand. A systematic review through PubMed was done on the subject of FSHR and its metabolism. For the obvious difficulty of meager amounts of tissue available, most of studies so far see it in granulosa cells and cell lines rather than in OSE. Thus, effort was made to deduce workable knowledge that can establish its role and can then be applied in OSE and EOC. There is great deal of information regarding metabolism of FSHR, including regulation of its gene expression, isoforms, and pathways of desensitization and degradation with which ovarian cancer etiology researchers have to be familiar with, and there are a number of steps where manipulation may stop carcinogenesis. Hormone therapy of such cancer has so far been only mildly active, probably because we do not understand the role and mechanism of action of FSH and FSHR in the hypothalamo-pituitary-ovarian axis in development of such cancer.

show abstract

Follicle-stimulating hormone (FSH) activates extracellular signal-regulated kinase phosphorylation independently of beta-arrestin- and dynamin-mediated FSH receptor internalization

Cited by 23 publications

References 43 publications

Structure-Function Relationships of the Follicle-Stimulating Hormone Receptor

Structure-Function Relationships of the Follicle-Stimulating Hormone Receptor

Determination of biological activity of gonadotropins hCG and FSH by Förster resonance energy transfer based biosensors

Follicle Stimulating Hormone Receptor in Ovarian Surface Epithelium and Epithelial Ovarian Cancer

Contact Info

Product

Resources

About