title: The regulated expression of the pregnancy-associated plasma protein-A in the rodent ovary: a proposed role in the development of dominant follicles and of corpora lutea.
abstract: Compelling evidence exists displaying that the intrafollicular IGF-I system constitutes an obligatory mediator of FSH action in the murine ovary. Within this system, the ovarian IGF binding protein-4-directed protease (IGFBP-4ase) may have a critical role. Human IGFBP-4ase has been proved identical to the previously well-characterized pregnancy-associated plasma protein-A (PAPP-A). This communication reports the cloning and sequencing of the mouse PAPP-A cDNA as well as its expression and cellular localization in the mouse ovary. PAPP-A mRNA was undetectable in ovaries of untreated immature 25-d-old mice. Treatment with PMSG led to a marked time-dependent increase in PAPP-A expression in well-defined subsets of granulosa cells and follicles. Specifically, PAPP-A expression was detectable exclusively in centrifugally residing membrana granulosa cells of antral follicles during a 3- to 36-h period post PMSG. PAPP-A expression then fell to nondetectable levels in dominant preovulatory follicles at 48 h post PMSG. Treatment of PMSG-primed mice with human CG caused a rapid reinduction of PAPP-A expression in granulosa cells of dominant follicles and was sustained at relatively high levels throughout the ovulation and luteinization. These results suggest a role for gonadotropin-stimulated PAPP-A gene expression in the physiologic processes of dominant follicle development, ovulation, and luteogenesis in the mammalian ovary. The early onset and extended duration of gonadotropin-dependent PAPP-A expression in granulosa cells may serve to degrade the antigonadotropin IGFBP-4. Accordingly, successful antral follicle development, ovulation, and corpus luteum formation may be contingent on an IGFBP-4-deplete/PAPP-A-replete circumstance, hence resulting in an IGF-I-replete intrafollicular microenvironment.
authors.affiliation: Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Utah Health Sciences Center, Huntsman Cancer Institute, 2000 Circle of Hope, Rm 5221, Salt Lake City, UT 84112, USA.
authors.forename: Ariel
authors.initials: A
authors.lastname: Hourvitz
authors.forename: Akira
authors.initials: A
authors.lastname: Kuwahara
authors.forename: Jon D
authors.initials: JD
authors.lastname: Hennebold
authors.forename: Adriano B
authors.initials: AB
authors.lastname: Tavares
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Negishi
authors.forename: Taek Hoo
authors.initials: TH
authors.lastname: Lee
authors.forename: Gregory F
authors.initials: GF
authors.lastname: Erickson
authors.forename: Eli Y
authors.initials: EY
authors.lastname: Adashi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015152:Blotting, Northern; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D003001:Cloning, Molecular; D003338:Corpus Luteum / Q000502:physiology*; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006801:Humans; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D006080:Ovarian Follicle / Q000502:physiology*; D010053:Ovary / Q000166:cytology / Q000378:metabolism*; D010060:Ovulation / Q000502:physiology; D011247:Pregnancy; D011266:Pregnancy-Associated Plasma Protein-A / Q000096:biosynthesis* / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid
chemical_list: D006063:Chorionic Gonadotropin; D018076:DNA, Complementary; D012333:RNA, Messenger; D011266:Pregnancy-Associated Plasma Protein-A