Identification and In vitro Characterization of Follicle Stimulating Hormone (FSH) Receptor Variants Associated with Abnormal Ovarian Response to FSH

Gerasimova, Tsilya; Thanasoula, Maria N.; Zattas, Dimitrios; Seli, Emre; Sakkas, Denny; Lalioti, Maria D.

doi:10.1210/edrv.31.1.9988

Cited by 14 publications

(26 citation statements)

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“…Several heterogeneous FSHR splice variants have been detected in various animals species (Gromoll et al, 1993;Khan et al, 1993;Rajapaksha et al, 1996;Yarney et al, 1997a;Tena-Sempere et al, 1999;Babu et al, 2001;Neubauer et al, 2006), including humans (Kelton et al, 1992;Song et al, 2002;Gerasimova et al, 2010;Robinson et al, 2010;Zhou et al, 2013;Karakaya et al, 2014). Because many of the detected alternative transcripts are not translated into a protein or translation yields severely misfolded proteins unable to traffic to the cell surface plasma membrane, the function and regulatory role of FSHR transcript variants has been scarcely studied.…”

Section: Fshr Structurementioning

confidence: 99%

The Follitropin Receptor: Matching Structure and Function

Ulloa‐Aguirre¹,

Zariñán²

2016

Mol Pharmacol

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Follitropin, or follicle-stimulating hormone (FSH) receptor (FSHR), is a G protein-coupled receptor belonging to the glycoprotein hormone receptor family that plays an essential role in reproduction. Although its primary location is the gonad, the FSHR has also been reported in extragonadal tissues including bone, placenta, endometrium, liver, and blood vessels from a number of malignant tumors. The recently resolved crystal structure of FSH bound to the entire FSHR ectodomain has been instrumental in more clearly defining the role of this domain in ligand binding and receptor activation. Biochemical, biophysical, and structural data also indicate that the FSHR exists as a higher order structure and that it may heterodimerize with its closely related receptor, the luteinizing hormone receptor; this association may have physiologic implications during ovarian follicle maturation given that both receptors may simultaneously coexist in the same cell. FSHR heterodimerization is unique to the ovary because in the testes, gonadotropin receptors are expressed in separate compartments. FSHR self-association appears to be required for receptor coupling to multiple effectors and adaptors, for the activation of multiple signaling pathways and the transduction of asymmetric signaling, and for negative and positive receptor cooperativity. It also provides a mechanism through which the glycosylation variants of FSH may exert distinct and differential effects at the target cell level. Given its importance in regulating activation of distinct signaling pathways, functional selectivity at the FSHR is briefly discussed, as well as the potential implications of this particular functional feature on the design of new pharmacological therapies in reproduction.

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Section: Fshr Structurementioning

confidence: 99%

The Follitropin Receptor: Matching Structure and Function

Ulloa‐Aguirre¹,

Zariñán²

2016

Mol Pharmacol

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“…Next, the ovarian response to FSH stimulation in all subjects was separated based on the number of oocytes retrieved, as previously reported . A yield of no more than five oocytes was considered to indicate a poor response, whereas all other yields were considered to indicate a good response.…”

Section: Resultsmentioning

confidence: 99%

“…Next, the ovarian response to FSH stimulation in all subjects was separated based on the number of oocytes retrieved, as previously reported. 23 A yield of no more than five oocytes was considered to indicate a poor response, whereas all other yields were considered to indicate a good response. The poor ovarian response group was found to have been treated with higher amounts of exogenous FSH to achieve an adequate amount of eggs in comparison to the good response group (2398 AE 944 IU vs. 2075 AE 556 IU, Fig.…”

Section: Resultsmentioning

confidence: 99%

The Ser680Asn polymorphism in the follicle‐stimulating hormone receptor gene is associated with the ovarian response in controlled ovarian hyperstimulation

Huang

et al. 2014

Clinical Endocrinology

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“…In addition to the SNPs, we have identified a number of splice variants of the FSHR in women undergoing ovarian stimulation that may contribute to the variability in FSH response [77 ]. Our approach was to analyze FSHR mRNA extracted from cumulus cells that enabled us to evaluate the post-transcriptional processing of FSHR mRNA, as well as the genomic sequence of FSHR.…”

Section: Follicle Stimulating Hormone Receptor Variants In Infertilitmentioning

confidence: 99%