Bone morphogenetic protein 7 (BMP-7) increases the expression of follicle-stimulating hormone (FSH) receptor in human granulosa cells.
ABSTRACT To examine the effect of bone morphogenetic protein 7 (BMP-7) on FSH receptor (FSHR) expression in human granulosa cells.
Laboratory study using human samples.
Human granulosa cells were obtained from 60 women undergoing oocyte retrieval for IVF.
Human granulosa cells (GCs) were cultured with recombinant BMP-7, followed by RNA extraction.
mRNA levels of GCs were measured by real-time reverse-transcription polymerase chain reaction.
Bone morphogenetic protein 7 increased FSHR gene expression in human luteinized granulosa cells, whereas it decreased LH receptor gene expression. Bone morphogenetic protein 7 also increased FSH-induced cyclic adenosine monophosphate production in GCs, indicating up-regulation of the cellular response to FSH. Although BMP-7 increased gene expression of activin-betaA and -betaB in GCs, inhibition of activin function did not affect the BMP-7-induced FSHR gene expression.
These findings provide new insight into the biologic function of BMP-7 in the human ovary and demonstrate its unique mechanism of regulating FSHR action.
SourceAvailable from: Junko Nio-Kobayashi[Show abstract] [Hide abstract]
ABSTRACT: Bone morphogenetic proteins (BMPs), members of the tumor growth factor β superfamily, play important roles in folliculogenesis in various species, however, little is known about their role in luteal function. In this study, we investigated the expression, regulation, and effects of BMP2, BMP4, and BMP6 in carefully-dated human corpora lutea and cultured human luteinized granulosa cells. The mRNA abundance of BMPs was increased in the regressing corpus luteum in vivo (P<0.01-0.001). Human chorionic gonadotropin (hCG) down-regulated BMP2, BMP4, and BMP6 transcripts both in vivo (P=0.05-0.001) and in vitro (P<0.001), and decreased the mRNA abundance of BMP receptors (BMPR1A, BMPR1B, BMPR2; P<0.05-0.01) in vitro. Three BMPs were regulated by differential signaling pathways. H89, a protein kinase A inhibitor, increased the expression of both BMP2 (P<0.05) and BMP4 (P<0.05) while decreasing BMP6 (P<0.01). PMA, a protein kinase C activator, decreased both BMP4 and BMP6 expression (P<0.0001) while enhancing the mRNA abundance of BMP2 (P<0.01). BMPs significantly down-regulated transcripts for LH/choriogonadotropin receptor (LHCGR; P<0.001) and steroidogenic acute regulatory protein (STAR; P<0.001), while up-regulating those of follicular stimulating hormone receptor (FSHR; P<0.01) and aromatase (CYP19A1; P<0.05-0.01) in vitro, possessing an effect opposite to hCG but similar to Activin A. Like Activin A, BMP4 and BMP6 stimulated the expression of Inhibin/Activin subunits with a marked effect on INHBB expression (P<0.05-0.01). These data confirm that BMPs are increased during luteal regression and negatively regulated by hCG via differential mechanisms, suggesting that BMPs are one of the mediators of luteolysis in women.Endocrinology 01/2015; DOI:10.1210/en.2014-1704 · 4.64 Impact Factor
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ABSTRACT: Summary The bone morphogenetic protein (BMP) family consists of several growth factor proteins that belong to the transforming growth factor-β (TGF-β) superfamily. BMPs bind to type I and type II serine-threonine kinase receptors, and transduce signals through the Smad signalling pathway. BMPs have been identified in mammalian ovaries, and functional studies have shown that they are involved in the regulation of oogenesis and folliculogenesis. This review summarizes the role of the BMP system during formation, growth and maturation of ovarian follicles in mammals.Zygote 01/2015; DOI:10.1017/S096719941400077X · 1.32 Impact Factor
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ABSTRACT: Bone morphogenetic protein (BMP) cytokine is known to regulate ovulation, as BMP-6 null mice exhibit a decrease in the number of ovulatory follicles without effect on either the morphology or the dynamics of follicular development. In the present study, the role of BMP-6 in ovulatory process was investigated using human granulosa-lutein cells (GCs). Granulosa-lutein cells, obtained from in vitro fertilization patients, were cultured with BMP-6 followed by RNA extraction. The neutrophil-chemotactic activity of the supernatant of cultured GC was investigated. Bone morphogenetic protein 6 significantly increased growth-regulated oncogene α (GRO-α) messenger RNA (mRNA) and protein expression in GC. In the neutrophil-chemotaxis assay, the GC supernatant cultured with BMP-6 attracted more neutrophils than control samples, which was negated with anti-GRO-α neutralizing antibody. Bone morphogenetic protein 6 also suppressed the relative expression of the protease inhibitors, secretory leukocyte peptidase inhibitor, and whey acid protein 14 mRNA in GC. Bone morphogenetic protein 6 might play a role in ovulation by increasing the accumulation of neutrophils in the ovulatory follicle and suppressing the effect of protease inhibitors.Reproductive sciences (Thousand Oaks, Calif.) 01/2014; 21(6). DOI:10.1177/1933719113518988 · 2.18 Impact Factor