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Identification of ovarian granulosa cells as a novel site of expression for bone morphogenetic protein-3 (BMP-3/osteogenin) and regulation of BMP-3 messenger ribonucleic acids by chorionic gonadotropin in cultured human granulosa-luteal cells.
- Source :
-
The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 1996 Nov; Vol. 81 (11), pp. 3877-82. - Publication Year :
- 1996
-
Abstract
- Bone morphogenetic proteins (BMP) belong structurally to the transforming growth factor-beta superfamily comprising several growth and differentiation factors such as inhibin, activin, and Müllerian inhibitory factor that regulate ovarian function. We studied here the potential expression of BMP-2, -3, and -4 messenger RNAs (mRNAs) in isolated human granulosa cells obtained at oocyte retrieval for in vitro fertilization. Freshly isolated granulosa cells were found to express BMP-3 (also known as osteogenin) mRNAs but not those of BMP-2 or -4. The BMP-3 transcripts were detected with RT-PCR amplification followed by Southern blot hybridization, as well as by Northern and dot blot hybridization analyses. To investigate whether BMP-3 mRNAs are hormonally regulated, cultures of human granulosa-luteal (GL) cells were treated with different concentrations of purified human chorionic gonadotropin (hCG) at varying stages of culture. hCG decreased BMP-3 mRNA levels from the first day of the culture up to day 5. Time-dependence studies showed that a clear decrease in BMP-3 mRNA levels was evident at 24 h after hCG treatment, and that the effect of hCG was concentration dependent with 3 ng/mL hCG decreasing significantly (P < 0.05) BMP-3 mRNA levels. Furthermore, the cAMP analog, 8-bromo-cAMP (8-Br-cAMP), which activates protein kinase-A, and 12-0-tetradecanoylphorbol 13-acetate, an activator of protein kinase-C, both markedly decreased BMP-3 mRNA levels in an 8-h treatment. We conclude that: 1) BMP-3 mRNAs are expressed in human granulosa cells; 2) their steady state levels are hormonally regulated in cultured human GL cells as evidenced by the ability of hCG to markedly decrease BMP-3 transcript levels; and (3) that activation of both protein kinase-A-and protein kinase-C-mediated signaling pathways also results in a decrease in BMP-3 mRNA levels in GL cells. We suggest that BMP-3, like several other members of the transforming growth factor-beta superfamily, is a potential local regulator of female gonadal function.
- Subjects :
- 8-Bromo Cyclic Adenosine Monophosphate pharmacology
Base Sequence
Bone Morphogenetic Protein 3
Cells, Cultured
Chorionic Gonadotropin administration & dosage
DNA Primers genetics
Female
Gene Expression Regulation drug effects
Humans
In Vitro Techniques
Kinetics
Luteal Cells metabolism
Ovary cytology
Ovary metabolism
Polymerase Chain Reaction
Tetradecanoylphorbol Acetate pharmacology
Transforming Growth Factor beta metabolism
Bone Morphogenetic Proteins genetics
Bone Morphogenetic Proteins metabolism
Chorionic Gonadotropin pharmacology
Granulosa Cells metabolism
RNA, Messenger genetics
RNA, Messenger metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0021-972X
- Volume :
- 81
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- The Journal of clinical endocrinology and metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 8923832
- Full Text :
- https://doi.org/10.1210/jcem.81.11.8923832