Pregnancy-associated plasma protein-A gene expression in human ovaries is restricted to healthy follicles and corpora lutea.
Recently, Pregnancy-Associated Plasma Protein-A (PAPP-A) in human follicular fluid was identified as an insulin-like growth factor binding protein-4 protease (IGFBP-4ase). The ability of IGFBP-4ase to inactivate the FSH antagonist, IGFBP-4, has suggested a possible role for PAPP-A in regulating FSH action. Despite growing interest in this protease, the question of whether the PAPP-A gene is expressed in ovaries of normal cycling women is unknown. To fill this basic gap in our knowledge, we have identified the cellular sites of PAPP-A gene expression in normal human ovaries by in situ hybridization. PAPP-A mRNA was low or undetectable in preantral follicles, small (1-2 mm) healthy and atretic antral follicles, larger atretic antral follicles, surface epithelium, tunica albuginea and connective tissue cells. In contrast, an intense PAPP-A hybridization signal was evident in the healthy antral follicles examined from 5 mm to the preovulatory stage. In these follicles, the signal was restricted to the granulosa cells (GC). An intense signal for PAPP-A mRNA was also present in healthy corpora lutea (CL), being localized to a subset of large luteal cells. Collectively, these results provide the first evidence that the gene encoding PAPP-A is expressed in ovaries of normal cycling women and show that the gene is expressed almost exclusively in healthy GC and CL cells. The restricted pattern of PAPP-A expression in normal human ovaries suggests that PAPP-A may be a functional marker of the dominant follicle and its product, the CL. Although the physiological function of ovarian PAPP-A remains to be identified, we hypothesize it might play a role in controlling survival, growth, and/or differentiation of the dominant follicle and CL by inactivating the gonadotropin antagonist, IGFBP-4.
Hourvitz
A
A
Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Utah Health Science Center, Salt Lake City, Utah.
Widger
A E
AE
Filho
F L
FL
Chang
R J
RJ
Adashi
E Y
EY
Erickson
G F
GF
D000328:Adult; D017209:Apoptosis / Q000502:physiology; D003338:Corpus Luteum / Q000378:metabolism*; D017931:DNA Primers; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D006080:Ovarian Follicle / Q000378:metabolism*; D010053:Ovary / Q000378:metabolism*; D011266:Pregnancy-Associated Plasma Protein-A / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis
D017931:DNA Primers; D012333:RNA, Messenger; D011266:Pregnancy-Associated Plasma Protein-A