Follitropin Signal Transduction: Alternative Splicing of the FSH Receptor Gene Produces a Dominant Negative Form of Receptor Which Inhibits Hormone Action

Sairam, M.R.; Jiang, L.G.; Yarney, T.A.; Khan, Haseena

doi:10.1006/bbrc.1996.1419

Cited by 71 publications

(47 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…FSH regulates a large number of genes encoding nuclear, cytoplasmic, membrane associated (1), and secreted proteins (2). The full length FSH receptor (hereafter called FSH-R1) belongs to a super family of Gprotein coupled receptors, which interact with intracellular effector system through seven transmembrane domains (3)(4)(5). This FSH-R1 receptor like LH and TSH (thyroid stimulating hormone-thyrotropin) receptors has a large extracellular (EC) amino terminal domain comprised of more than 300 amino acid residues.…”

Section: Introductionmentioning

confidence: 99%

“…There are many reports on the identification of various alternatively spliced transcripts for most glycoprotein hormone receptors including that of FSH in the ovary and testis, the two exclusive targets of the hormone action (4,5,8,9). In our previous investigations, we have reported the cloning of 5 MAP kinase activation were reported in primary granulosa cell cultures in response to FSH (18)(19)(20) and some of the actions are apparently mediated by cAMP independent pathways (19,20).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Activation of Extracellular-regulated Kinase Pathways in Ovarian Granulosa Cells by the Novel Growth Factor Type 1 Follicle-stimulating Hormone Receptor

Babu¹,

Krishnamurthy²,

Chedrese³

et al. 2000

Journal of Biological Chemistry

104

View full text Add to dashboard Cite

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Activation of Extracellular-regulated Kinase Pathways in Ovarian Granulosa Cells by the Novel Growth Factor Type 1 Follicle-stimulating Hormone Receptor

Babu¹,

Krishnamurthy²,

Chedrese³

et al. 2000

Journal of Biological Chemistry

104

View full text Add to dashboard Cite

show abstract

“…2 Binding of FSH to FSHR results in adenylyl cyclase activation leading to cAMP synthesis, associated with intracellular rise of Ca 2ϩ , activation of protein kinase A (PKA) and other downstream signal transduction pathways. [2][3][4][5][6] It has been reported that FSH treatment stimulates cell proliferation on normal human OSE cells, immortalized OSE cells and OC cell lines. 7,8 However, little has been known on the effects of FSH in the process of tumorigenesis and growth stimulation on human OSE at molecular levels.…”

mentioning

confidence: 99%

Follicle stimulating hormone‐induced growth promotion and gene expression profiles on ovarian surface epithelial cells

Liu

Chen

et al. 2004

Intl Journal of Cancer

View full text Add to dashboard Cite

Ovarian cancer (OC) is one of the leading causes of death in patients with gynecologic malignancies. The vast majority of ovarian cancers have a cell origin of ovarian surface epithelium (OSE), which is derived from Mullerian epithelium covering embryonic gonads. Since the incidence of OC sharply increases after menopause, critical roles of gonadotropins and their receptors in ovarian carcinogenesis are speculated by investigators. 1 Follicle stimulating hormone (FSH), through interaction with its specific receptor, FSHR, plays an essential role in mammalian reproduction and ovarian folliculogenesis. 2 Binding of FSH to FSHR results in adenylyl cyclase activation leading to cAMP synthesis, associated with intracellular rise of Ca 2ϩ , activation of protein kinase A (PKA) and other downstream signal transduction pathways. [2][3][4][5][6] It has been reported that FSH treatment stimulates cell proliferation on normal human OSE cells, immortalized OSE cells and OC cell lines. 7,8 However, little has been known on the effects of FSH in the process of tumorigenesis and growth stimulation on human OSE at molecular levels.In this study, we first determined FSHR expression levels quantitatively in human ovarian normal and neoplastic tissues. Then the effects of FSH treatment on cell proliferation were examined using human OSE cell lines as well as Chinese hamster ovary (CHO) cell lines permanently transfected with human FSHR. Finally, gene expression profiles for FSH treatment were analyzed by cDNA MicroArray using a selected human OSE cell line that has best growth response to FSH treatment from cell proliferation assays. MATERIAL AND METHODS

show abstract

“…Two isoforms of FSHR mRNA exist in the latter species, a full-length (FL-FSHR) and a truncated (Tr-FSHR) transcript missing exon 3 (Genebank AY524543.1, AY521181.1) that contains the signal peptides for a site involved in FSH binding (Heckert et al 1992, Fan & Hendrickson 2005. Although the physiological role of FSHR splice variants remains unclear for most species, truncated or mutated transcripts have been shown to function as dominant negative receptors in the sheep (Sairam et al 1996) or to interfere with the translation and dimerization of wild-type FSHRs in the human .…”

Section: Introductionmentioning

confidence: 99%

Absence of seasonal changes in FSHR gene expression in the cat cumulus–oocyte complex in vivo and in vitro

Hobbs

Howard²,

Wildt³

et al. 2012

Reproduction

View full text Add to dashboard Cite

Domestic cat oocytes are seasonally sensitive to FSH. Compared with those collected during the breeding season, oocytes from the nonbreeding (NB) season require more FSH during in vitro maturation to achieve comparable developmental competence. This study tested the hypothesis that this seasonal variation was due to altered expression of FSH receptors (FSHR) and/or FSH-induced genes. Relative expression levels of FSHR mRNA and FSH-enhanced gene estrogen receptor b (ESR2) were measured by qPCR in whole ovaries and immature cumulus-oocyte complexes (COCs) isolated from cat ovaries during the natural breeding vs NB seasons. Expression levels of FSH-induced genes prostaglandin-endoperoxide synthase 2 (PTGS2), early growth response protein-1 (EGR1), and epidermal growth factor receptor (EGFR) were examined in mature COCs from both seasons that were a) recovered in vivo or b) matured in vitro with conventional (1 mg/ml) or high (10 mg/ml) FSH concentrations. Overall, FSHR mRNA levels were lower in whole ovaries during the NB compared with breeding season but were similar in immature COCs, whereas ESR2 levels did not differ in either group between intervals. We observed changes in PTGS2, EGR1, and EGFR mRNA expression patterns across maturation in COCs within but not between the two seasons. The lack of seasonal differentiation in FSH-related genes was not consistent with the decreased developmental capacity of oocytes fertilized during the NB season. These findings reveal that the seasonal decrease in cat oocyte sensitivity to FSH occurs both in vivo and in vitro. Furthermore, this decline is unrelated to changes in expression of FSHR mRNA or mRNA of FSH-induced genes in COCs from antral follicles.

show abstract

Follitropin Signal Transduction: Alternative Splicing of the FSH Receptor Gene Produces a Dominant Negative Form of Receptor Which Inhibits Hormone Action

Cited by 71 publications

References 0 publications

Activation of Extracellular-regulated Kinase Pathways in Ovarian Granulosa Cells by the Novel Growth Factor Type 1 Follicle-stimulating Hormone Receptor

Activation of Extracellular-regulated Kinase Pathways in Ovarian Granulosa Cells by the Novel Growth Factor Type 1 Follicle-stimulating Hormone Receptor

Follicle stimulating hormone‐induced growth promotion and gene expression profiles on ovarian surface epithelial cells

Absence of seasonal changes in FSHR gene expression in the cat cumulus–oocyte complex in vivo and in vitro

Contact Info

Product

Resources

About