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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...
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| Published in: | Biology of reproduction 2001-10, Vol.65 (4), p.994-999 |
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| container_title | Biology of reproduction |
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| creator | LEE, Woo-Sik OTSUKA, Fumio MOORE, R. Kelly SHIMASAKI, Shunichi |
| description | 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. |
| doi_str_mv | 10.1095/biolreprod65.4.994 |
| format | article |
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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.</description><identifier>ISSN: 0006-3363</identifier><identifier>EISSN: 1529-7268</identifier><identifier>DOI: 10.1095/biolreprod65.4.994</identifier><identifier>PMID: 11566718</identifier><identifier>CODEN: BIREBV</identifier><language>eng</language><publisher>Madison, WI: Society for the Study of Reproduction</publisher><subject>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</subject><ispartof>Biology of reproduction, 2001-10, Vol.65 (4), p.994-999</ispartof><rights>2002 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14146196$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11566718$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>LEE, Woo-Sik</creatorcontrib><creatorcontrib>OTSUKA, Fumio</creatorcontrib><creatorcontrib>MOORE, R. Kelly</creatorcontrib><creatorcontrib>SHIMASAKI, Shunichi</creatorcontrib><title>Effect of Bone Morphogenetic Protein-7 on Folliculogenesis and Ovulation in the Rat</title><title>Biology of reproduction</title><addtitle>Biol Reprod</addtitle><description>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.</description><subject>Animals</subject><subject>Aromatase - genetics</subject><subject>Biological and medical sciences</subject><subject>Bone Morphogenetic Protein 7</subject><subject>Bone Morphogenetic Proteins - pharmacology</subject><subject>Cells, Cultured</subject><subject>Cholesterol Side-Chain Cleavage Enzyme - genetics</subject><subject>Estradiol - biosynthesis</subject><subject>Female</subject><subject>Follicle Stimulating Hormone - pharmacology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Granulosa Cells - cytology</subject><subject>Granulosa Cells - drug effects</subject><subject>Granulosa Cells - metabolism</subject><subject>Humans</subject><subject>Mammalian female genital system</subject><subject>Morphology. Physiology</subject><subject>Ovarian Follicle - drug effects</subject><subject>Ovarian Follicle - physiology</subject><subject>Ovulation - drug effects</subject><subject>Phosphoproteins - genetics</subject><subject>Progesterone - biosynthesis</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Recombinant Proteins - pharmacology</subject><subject>RNA, Messenger - analysis</subject><subject>Transforming Growth Factor beta</subject><subject>Vertebrates: reproduction</subject><issn>0006-3363</issn><issn>1529-7268</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><recordid>eNpFkUtLxDAUhYMoOj7-gAvJRncd806zVPEFiuJjXdLk1kYyzdi0Dv57i464OZfD-TiLcxE6pGROiZGndUixh2WfvJJzMTdGbKAZlcwUmqlyE80IIargXPEdtJvzOyFUcMa30Q6lUilNyxl6vmwacANODT5PHeD71C_b9AYdDMHhxz4NELpC49ThqxRjcGP8SXPI2HYeP3yO0Q5hikOHhxbwkx320VZjY4aD9d1Dr1eXLxc3xd3D9e3F2V3RMqWHwhiimdUOpCLMm0YyD5NKaWujSOnL2gkvNRV2cpo5BRR8rUrjtRCGcr6HTn57pwk-RshDtQjZQYy2gzTmSlNaSqbUBB6twbFegK-WfVjY_qv6m2ECjteAzc7GpredC_mfE1QoatQ_14a3dhV6qPLCxjjV8mq1WilZiWp6A_8GGel6bw</recordid><startdate>20011001</startdate><enddate>20011001</enddate><creator>LEE, Woo-Sik</creator><creator>OTSUKA, Fumio</creator><creator>MOORE, R. Kelly</creator><creator>SHIMASAKI, Shunichi</creator><general>Society for the Study of Reproduction</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20011001</creationdate><title>Effect of Bone Morphogenetic Protein-7 on Folliculogenesis and Ovulation in the Rat</title><author>LEE, Woo-Sik ; OTSUKA, Fumio ; MOORE, R. Kelly ; SHIMASAKI, Shunichi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h267t-99072a7ce5602d9f52de9f555ab9608d8bc4d5714a60872c6e1edb689d7449133</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Animals</topic><topic>Aromatase - genetics</topic><topic>Biological and medical sciences</topic><topic>Bone Morphogenetic Protein 7</topic><topic>Bone Morphogenetic Proteins - pharmacology</topic><topic>Cells, Cultured</topic><topic>Cholesterol Side-Chain Cleavage Enzyme - genetics</topic><topic>Estradiol - biosynthesis</topic><topic>Female</topic><topic>Follicle Stimulating Hormone - pharmacology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Granulosa Cells - cytology</topic><topic>Granulosa Cells - drug effects</topic><topic>Granulosa Cells - metabolism</topic><topic>Humans</topic><topic>Mammalian female genital system</topic><topic>Morphology. Physiology</topic><topic>Ovarian Follicle - drug effects</topic><topic>Ovarian Follicle - physiology</topic><topic>Ovulation - drug effects</topic><topic>Phosphoproteins - genetics</topic><topic>Progesterone - biosynthesis</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Recombinant Proteins - pharmacology</topic><topic>RNA, Messenger - analysis</topic><topic>Transforming Growth Factor beta</topic><topic>Vertebrates: reproduction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>LEE, Woo-Sik</creatorcontrib><creatorcontrib>OTSUKA, Fumio</creatorcontrib><creatorcontrib>MOORE, R. Kelly</creatorcontrib><creatorcontrib>SHIMASAKI, Shunichi</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Biology of reproduction</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>LEE, Woo-Sik</au><au>OTSUKA, Fumio</au><au>MOORE, R. Kelly</au><au>SHIMASAKI, Shunichi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of Bone Morphogenetic Protein-7 on Folliculogenesis and Ovulation in the Rat</atitle><jtitle>Biology of reproduction</jtitle><addtitle>Biol Reprod</addtitle><date>2001-10-01</date><risdate>2001</risdate><volume>65</volume><issue>4</issue><spage>994</spage><epage>999</epage><pages>994-999</pages><issn>0006-3363</issn><eissn>1529-7268</eissn><coden>BIREBV</coden><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>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.</abstract><cop>Madison, WI</cop><pub>Society for the Study of Reproduction</pub><pmid>11566718</pmid><doi>10.1095/biolreprod65.4.994</doi><tpages>6</tpages></addata></record> |
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| ispartof | Biology of reproduction, 2001-10, Vol.65 (4), p.994-999 |
| issn | 0006-3363 1529-7268 |
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| source | Oxford Journals - Connect here FIRST to enable access |
| 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 |
| title | Effect of Bone Morphogenetic Protein-7 on Folliculogenesis and Ovulation in the Rat |
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