Effect of Bone Morphogenetic Protein-7 on Folliculogenesis and Ovulation in the Rat

We have previously established the presence of a functional bone morphogenetic protein (BMP) system in the ovary by demonstrating the expression of BMP ligands and receptors as well as novel cellular functions. Specifically, BMP-4 and BMP-7 are expressed in theca cells, and their receptors by granul...

Full description

Saved in:
Bibliographic Details
Published in:Biology of reproduction 2001-10, Vol.65 (4), p.994-999
Main Authors: LEE, Woo-Sik, OTSUKA, Fumio, MOORE, R. Kelly, SHIMASAKI, Shunichi
Format: Article
Language:English
Subjects:
Animals
Aromatase - genetics
Biological and medical sciences
Bone Morphogenetic Protein 7
Bone Morphogenetic Proteins - pharmacology
Cells, Cultured
Cholesterol Side-Chain Cleavage Enzyme - genetics
Estradiol - biosynthesis
Female
Follicle Stimulating Hormone - pharmacology
Fundamental and applied biological sciences. Psychology
Granulosa Cells - cytology
Granulosa Cells - drug effects
Granulosa Cells - metabolism
Humans
Mammalian female genital system
Morphology. Physiology
Ovarian Follicle - drug effects
Ovarian Follicle - physiology
Ovulation - drug effects
Phosphoproteins - genetics
Progesterone - biosynthesis
Rats
Rats, Sprague-Dawley
Recombinant Proteins - pharmacology
RNA, Messenger - analysis
Transforming Growth Factor beta
Vertebrates: reproduction
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:We have previously established the presence of a functional bone morphogenetic protein (BMP) system in the ovary by demonstrating the expression of BMP ligands and receptors as well as novel cellular functions. Specifically, BMP-4 and BMP-7 are expressed in theca cells, and their receptors by granulosa cells. These BMPs enhanced and attenuated the stimulatory action of FSH on estradiol and progesterone production, respectively. To investigate the underlying mechanism of the differential regulation, we analyzed mRNA levels for key regulators in the steroid biosynthetic pathways by RNase protection assay. BMP-7 enhanced P450 aromatase (P450 arom ) but suppressed steroidogenic acute regulatory protein (StAR) mRNAs induced by FSH, whereas mRNAs encoding further-downstream steroidogenic enzymes, including P450 side-chain cleavage enzyme and 3β-hydroxysteroid dehydrogenase, were not significantly altered. These findings suggest that BMP-7 stimulation and inhibition of P450 arom and StAR mRNA expression, respectively, may play a role in the mechanisms underlying the differential regulation of estradiol and progesterone production. To establish the physiological relevance of BMP functions, we investigated the in vivo effects of injections of recombinant BMP-7 into the ovarian bursa of rats. Ovaries treated with BMP-7 had decreased numbers of primordial follicles, yet had increased numbers of primary, preantral, and antral follicles, suggesting that BMP-7 may act to facilitate the transition of follicles from the primordial stage to the pool of primary, preantral, and antral follicles. In this regard, we have also found that BMP-7 caused an increase in DNA synthesis and proliferation of granulosa cells from small antral follicles in vitro. In contrast to the stimulatory activity, BMP-7 exhibited pronounced inhibitory effects on ovulation rate and serum progesterone levels. These findings establish important new biological activities of BMP-7 in the context of ovarian physiology, including folliculogenesis and ovulation.
ISSN:0006-3363
1529-7268
DOI:10.1095/biolreprod65.4.994