Disease relevance of Fshr

• Before injection, heat stress diminished only the amount of FSH receptor on granulosa cells of antral follicles [1].
• Pretreatment with pertussis toxin (1 mg/liter) to dissociate the FSH-receptor interaction from its G-protein-mediated linkage to adenylate cyclase also suppressed the FSH-induced rise in cytosolic calcium (97 +/- 11 vs. 213 +/- 16 nM) [2].
• METHODS: Rat granulosa cells were cultured and transduced with adenovirus carrying FSHR gene [3].
• LH- and FSH-receptor content per testis were unaffected by cryptorchidism at 12, 16 and 20 days of age but were depressed markedly at 30 days of age [4].

High impact information on Fshr

• Pituitary follicle-stimulating hormone (FSH) induces CREM gene expression in Sertoli cells: involvement in long-term desensitization of the FSH receptor [5].
• Induction of the repressor ICER accompanies early down-regulation of the FSH receptor transcript, which leads to long-term desensitization [5].
• Here we show that ICER represses FSH receptor expression by binding to a CRE-like sequence in the regulatory region of the gene [5].
• The rat follitropin receptor (rFSHR) is an unusual G protein-coupled receptor in that agonist-induced activation leads to the phosphorylation of the first and third intracellular loops instead of the C-terminal tail [6].
• This is clearly distinct from the mechanism of BMP-15 action, which causes the suppression of basal FSH receptor (FSH-R) expression, without affecting adenylate cyclase activity [7].

Chemical compound and disease context of Fshr

• Follicle-stimulating hormone receptor-mediated uptake of 45Ca2+ by cultured rat Sertoli cells does not require activation of cholera toxin- or pertussis toxin-sensitive guanine nucleotide binding proteins or adenylate cyclase [8].

Biological context of Fshr

• Identification of the sites of N-linked glycosylation on the follicle-stimulating hormone (FSH) receptor and assessment of their role in FSH receptor function [9].
• The FSHR gene contained 10 exons and nine introns [10].
• Comparison of the FSHR gene to the LH receptor gene revealed a number of striking similarities which clearly indicate that these receptors evolved through gene duplication [10].
• Comparison of the sequences of the extracellular domains (ECD) of the receptors reveals two regions (amino acids 4-56 and 265-319 in FSH-R) that share relatively little amino acid sequence similarity [11].
• Fshr rats, however, exhibited a circadian pattern (P less than 0.02) only with regard to water consumption under an LD 12:12 lighting schedule; they did not exhibit circadian patterns of drinking water (P less than 0.054) in DD or ethanol in LD (P less than 0.24) or in DD (P less than 0.67) conditions [12].

Anatomical context of Fshr

• In immature animals, low levels of FSH receptor mRNA are observed in the granulosa cells of small follicles, while low levels of LH receptor mRNA are found in the thecal cells of these same follicles [13].
• Effects of removal of carboxy-terminal extension from equine luteinizing hormone (LH) beta-subunit on LH and follicle-stimulating hormone receptor-binding activities and LH steroidogenic activity in rat testicular Leydig cells [14].
• In the presence, but not absence, of oocytes, estrogen amplified FSH-stimulated increases in mRNA expression of P450aromatase, FSH receptor, LH receptor, and inhibin alpha-, betaA-, and betaB-subunits as well as cAMP production [15].
• Again, germ-cell number was decreased with the greatest effect in those pups whose mothers were immunized against both FSHR and LHR [16].
• Properties of follitropin-receptor interaction. Characterization of the interaction of follitropin with receptors in purified membranes isolated from mature rat testes tubules [17].

Associations of Fshr with chemical compounds

• The selectivity for FSH is attested by the fact that the related human glycoprotein hormones human CG and human TSH do not stimulate adenylyl cyclase in FSH-R expressing cells even when these hormones are present at high concentrations [18].
• Voluntary drinking responses to an alternating three-bottle, two-choice paradigm to tap water or to 5% ethanol were measured in adult male Fisher (Fshr; N = 14) and spontaneously hypertensive (SP; N = 16) rats for 6-9 days [12].
• Estradiol also enhanced the extent of LH and FSH receptor formation by other cAMP-inducing ligands, including FSH, prostaglandin E2, and forskolin [19].
• Although cortisol and dexamethasone increased choleragen-induced cAMP accumulation, only cortisol elevated LH receptors, and dexamethasone inhibited FSH receptor formation [19].
• However, when eLH was assayed in the eCG-primed cells, it did show stimulating activity with respect to the production of plasminogen activator and progesterone; however, the dose-response curves were not parallel to those of eFSH and eCG. eCG had much less FSH receptor-binding activity (0.29 X NIH FSH-S13) than eLH [20].

Regulatory relationships of Fshr

• FSH receptor mRNA levels show a similar pattern of change, but the FSH receptor mRNA is of lower abundance and is not as highly regulated as the LH receptor mRNA [13].
• In summary, TGF beta up- or down-regulated LHR and FSHR binding coordinately within species.(ABSTRACT TRUNCATED AT 250 WORDS)[21]
• Bone morphogenetic protein-15 inhibits follicle-stimulating hormone (FSH) action by suppressing FSH receptor expression [22].
• Changes in ovarian luteinizing hormone and follicle-stimulating hormone receptor content and in gonadotropin-induced ornithine decarboxylase activity during prepubertal and pubertal development of the female rat [23].
• Since the inhibitory effect of follistatin on activin-induced FSH binding to rat granulosa cells had been investigated, we studied the action of follistatin on the levels of activin-induced FSH receptor mRNA in rat granulosa cell culture.(ABSTRACT TRUNCATED AT 250 WORDS)[24]

Other interactions of Fshr

• At 21 days of age data showed that FSH-R mRNA levels were significantly higher in both hyper- and hypothyroid rat testes compared to controls, but no differences were detected in recovered 50-day-old rats [25].
• These results suggested that androgens regulate granulosa cell aromatase activity not only as substrates, but also by acting at a site before cAMP production (possibly at the level of the FSH receptor) in the control of FSH-induced enzyme activity [26].
• Interestingly, BMP-15 severely reduced the levels of FSH receptor mRNA in both basal and FSH-stimulated cells [22].
• As assumed, BMP-6 did not alter basal FSH-R mRNA levels, whereas it inhibited FSH- and forskolin- but not 8-bromo-cAMP-induced FSH-R mRNA accumulation [7].
• Moreover, TNF-alpha impairs the LH receptor formation induced by forskolin, cholera toxin or 8-Bromo-cAMP, indicating that the cytokine also acts at a step distal to FSH receptor and to cAMP formation [27].

Analytical, diagnostic and therapeutic context of Fshr

• Southern blot analysis indicated that there was only a single gene for the FSHR [10].
• In situ hybridization experiments revealed that both the P-450arom and FSHR hybridization signals were localized to follicles [28].
• In animals immunized against both FSHR and LHR there was also a significant reduction in sperm number although spermatogenesis was never completely ablated [16].
• Northern blot analysis revealed two transcripts for the FSHR, a 2.6-kilobase (kb) transcript, which is the predominant mRNA, and a 4.5-kb transcript [29].
• A DNA probe for the rat FSH receptor (FSHR) was generated by the polymerase chain reaction, and a partial genomic clone was isolated [29].

References