Disease relevance of FSHR

• Furthermore, when the FSHR phages were used as peptidic vaccines, they induced a reversible inhibition of ovulation rate in ewes, and impaired fertility in female mice [1].
• Daily administration of 6 microg DHT kg(-1) body weight to gilts from day 13 of the oestrous cycle to the following oestrus (Expt 3) did not affect the relative amounts of androgen receptor mRNA, but increased (P < 0.05) the amounts of FSH receptor mRNA in preovulatory follicles as determined by RT-PCR [2].

High impact information on FSHR

• When Western European women with this phenotype were examined for FSHR mutations the result was negative, suggesting that other etiologies corresponding to this clinical pattern are markedly more frequent [3].
• Activation of extracellular-regulated kinase pathways in ovarian granulosa cells by the novel growth factor type 1 follicle-stimulating hormone receptor. Role in hormone signaling and cell proliferation [4].
• The present study was undertaken to analyze how a cytokine, the tumor necrosis factor alpha (TNF alpha), antagonizes the stimulatory action of insulin-like growth factor-I (IGF-I) on FSH receptor levels in testicular Sertoli cells [5].
• These results indicate that exposure to FSH in culture results in down-regulation of the FSH receptor [6].
• Moreover, substantial declines in both FSH receptor and LH receptor mRNAs were found in atretic follicles, consistent with previous reports of their decreased responsiveness to gonadotropins [7].

Biological context of FSHR

• Relative amounts of AR protein in granulosa cells and mRNA in walls of late developing follicles did not significantly change from day 13 to 19; however, amounts of FSHR mRNA decreased in preovulatory follicles by day 19 of the estrous cycle [8].
• Follicle-stimulating hormone (FSH) regulates folliculogenesis in the ovary and spermatogenesis in the testis via specific, high affinity membrane-bound receptors (FSHR) [9].
• This was probably due to upregulation of mRNA synthesis resulting from inhibition of porcine FSHR protein translation [10].
• In contrast, transient transfection studies showed that despite successful transcription, the exon-lacking FSHR variants were unable to bind rhFSH either in intact or in solubilized HEK 293 cells, or to elicit cAMP or progesterone responses in KK-1 cells [11].
• Optimization of superovulation induction by human menopausal gonadotropin in guinea pigs based on follicular waves and FSH-receptor homologies [12].

Anatomical context of FSHR

• Follicle-stimulating hormone (FSH) receptors (FSHR) are critically involved in mediating the responses of granulosa cells and Sertoli cells to FSH [13].
• A full-length porcine FSHR cDNA was cloned and sequenced and recombinant pFSHR protein was stably expressed in a clonal cell line of Chinese hamster ovary cells (pFSHR-CHO) [13].
• Coculture of Sertoli and Leydig cells in the presence of hCG, resulted in a significant increase in FSH receptor number and in FSH-induced plasminogen activator activity [14].
• In this study, we investigated the availability of ovarian oocytes during the estrous cycle, and the follicle stimulating hormone (FSH) receptor (FSH-R) homologies between guinea pigs and other species, in order to identify an effective gonadotropin and optimal time-of-application for the induction of superovulation in the guinea pig [12].
• Polyclonal antibodies were generated against fractions of porcine follicular fluid containing FSH receptor binding inhibitory activity, FSH agonist activity in vitro, and a 58,000 Mr protein recognized by human FSH antiserum [15].

Associations of FSHR with chemical compounds

• It appears, instead, that FSH regulates FSH responsiveness by regulating the interaction of the FSH receptor with stimulatory guanine nucleotide regulatory protein [16].
• Cyclic and maturation-dependent regulation of follicle-stimulating hormone receptor and luteinizing hormone receptor messenger ribonucleic acid expression in the porcine ovary [17].
• Androgen receptor and follicle-stimulating hormone receptor in the pig ovary during the follicular phase of the estrous cycle [8].
• In conclusion, effects of mycotoxins on FSH receptor-dependent and receptor-independent pathways indicate that adenylate cyclase activity and/or regulatory pathways further downstream are targets of mycotoxin actions [18].

Regulatory relationships of FSHR

• In addition, purified recombinant alpha-inhibin proteins were partial in vitro FSH antagonists in a bioassay in which cAMP generation from 293 cells expressing the recombinant FSH receptor is used as an index of FSH biological activity [19].

Other interactions of FSHR

• The relative amounts of AR mRNA in tissue from the largest follicles on days 13, 15, 17, and 19 did not differ; however, amounts of FSHR mRNA in the same follicles were not different between days 13, 15, and 17, but decreased (P < 0.05) by day 19 [8].
• The transient refractoriness to FSH appears to be due to a process that alters the interaction between the FSH receptor and the guanine nucleotide regulatory component of cyclase [20].
• We conclude that downregulation of FSH receptor mRNA in luteinized granulosa cells is mediated by both homologous and heterologous ligands which employ cAMP, and that growth factors that activate the PKC pathway reduce FSH receptor and P450scc mRNA abundance [21].

Analytical, diagnostic and therapeutic context of FSHR

• Samples of surface wall from the largest follicles (4-5 per gilt) were dissected from the other ovary, pooled and processed for determination of AR and FSHR mRNAs using reverse transcription-polymerase chain reaction (RT-PCR) [8].
• Cultures were treated with 0, 40, or 200 ng/ml porcine FSH or medium and terminated at 24 hr intervals for Northern analysis of FSH receptor and cytochrome P450 side chain cleavage (P450scc) mRNA, and for radioimmunoassay of progesterone [21].
• Quantification of porcine follicle-stimulating hormone receptor messenger ribonucleic acid by reverse transcription-competitive polymerase chain reaction [22].

References