Bone morphogenetic protein 7 (BMP-7) increases the expression of follicle-stimulating hormone (FSH) receptor in human granulosa cells.

Department of Obstetrics and Gynecology, University of Tokyo, Tokyo 113-8655, Japan.
Fertility and sterility (Impact Factor: 3.97). 01/2009; 93(4):1273-9. DOI: 10.1016/j.fertnstert.2008.11.014
Source: PubMed

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.
University hospital.
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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: The Bone Morphogenetic Proteins (BMPs) are growth factors involved in the folliculogenesis. Alteration in their expression may compromise the reproductive process in disease such as the polycystic ovary syndrome (PCOS). The present study investigated the expression and role of granulosa cell BMP from normal cycling and PCOS women. METHODS AND RESULTS: This prospective study was performed in granulosa cells obtained from 14 patients undergoing IVF : (i) 6 women with normal ovulatory cycles and tubal or male infertility and (ii) 8 women with PCOS. BMP-2, BMP-4, BMP-5, BMP-6, BMP-7 and BMP-8A, and their receptors BMPR-IA, BMPR-IB and BMPR-II were identified by RT-PCR in granulosa cells from normally cycling and PCOS women. BMP-4, 6 and 7 expression were confirmed by immunohistochemistry, Quantitative transcript analysis showed the predominant expression of BMP-6. In granulosa cells from PCOS women, an over-expression of BMP-6 (p<0.01) and BMPR-IA mRNA (p<0.05) were observed. Granulosa cell culture experiments demonstrated that basal estradiol (E2) production was 3-fold higher but FSH-induced E2 increment 2-fold lower in PCOS compared to controls. In PCOS, BMP-6 and 7 exerted a stimulatory effect on basal E2 production while BMP-4 and 6 inhibited FSH-induced E2 production. FSH receptor and aromatase expression were not different between both groups. CONCLUSION: The BMP system is expressed in human granulosa cells from normal cycling and PCOS women. The BMP may be involved in reproductive abnormalities found in PCOS.
    European Journal of Endocrinology 12/2012; · 3.14 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: PROBLEM: The aim of this study is to evaluate the expression and regulation of proprotein convertase subtilisin/kexin (PCSK) 6, which is known to be an important factor in the production of bone morphogenetic protein (BMP) cytokines in human ovary. METHOD OF STUDY: The localization of PCSK 6 protein in normal human ovaries was examined by immunohistochemistry. Human granulosa cells (GC), obtained from 34 patients undergoing ovarian stimulation for in vitro fertilization, were cultured with BMP-2, BMP-6, BMP-7, BMP-15, growth differentiation factor (GDF)-9, and activin-A with or without FSH. PCSK 6 mRNA expression level was evaluated by quantitative real-time reverse transcription and polymerase chain reaction (RT-PCR). RESULTS: An immunohistochemistry study revealed that GC expressed PCSK 6 throughout follicular development, beginning in the primary follicle stage, while oocytes expressed PCSK 6 from the primordial follicle stage onwards. An in vitro study demonstrated that BMP-2, BMP-6, BMP-7, and BMP-15, not activin-A and GDF-9, decreased PCSK 6 gene expression in human GC. FSH induced PCSK 6 mRNA in the presence of activin-A or GDF-9. GDF-3, which is an inhibitor of BMP cytokines, also induced PCSK 6 mRNA expression. CONCLUSIONS: PCSK 6, which is a critical factor to produce BMP cytokines, was suppressed with BMP stimulation in human GC, suggesting the presence of a negative feedback system in the follicular development process.
    American Journal Of Reproductive Immunology 08/2012; · 3.32 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Brown adipocytes constitute a metabolically active tissue responsible for non-shivering thermogenesis and the depletion of excess calories. Differentiation of brown fat adipocytes de novo or stimulation of pre-existing brown adipocytes within white adipose depots could provide a novel method for reducing the obesity and alleviating the consequences of type II diabetes worldwide. In this review, we addressed several molecular mechanisms involved in the control of brown fat activity, namely, the β(3)-adrenergic stimulation of thermogenesis during exposure to cold or by catecholamines; the augmentation of thyroid function; the modulation of peroxisome proliferator-activated receptor gamma (PPARγ), transcription factors of the C/EBP family, and the PPARγ co-activator PRDM16; the COX-2-driven expression of UCP1; the stimulation of the vanilloid subfamily receptor TRPV1 by capsaicin and monoacylglycerols; the effects of BMP7 or its analogs; the cannabinoid receptor antagonists and melanogenesis modulating agents. Manipulating one or more of these pathways may provide a solution to the problem of harnessing brown fat's thermogenic potential. However, a better understanding of their interplay and other homeostatic mechanisms is required for the development of novel therapies for millions of obese and/or diabetic individuals.
    Progress in lipid research 08/2012; 52(1):51-61. · 10.67 Impact Factor