Pregnancy-associated plasma protein-a is the insulin-like growth factor binding protein-4 protease secreted by human ovarian granulosa cells and is a marker of dominant follicle selection and the corpus luteum

Endocrinology
C A ConoverL C Giudice

Abstract

Insulin-like growth factors (IGFs), IGF binding proteins (IGFBPs), and IGFBP proteases are important in ovarian function. IGFs stimulate granulosa steroidogenesis, an effect that is inhibited by IGFBP-4 and augmented by IGFBP-4 proteolysis. We have recently identified the IGFBP-4 protease in human ovarian follicular fluid (FF) as pregnancy-associated plasma protein-A (PAPP-A). In the current study, we identify the IGFBP-4 protease secreted by cultured human ovarian granulosa cells as PAPP-A, based on specific immunoinhibition and immunodepletion of the IGFBP-4 protease activity with PAPP-A polyclonal antibodies and immunorecognition by PAPP-A monoclonal antibodies in ELISA. PAPP-A was barely detectable in conditioned media (CM) from granulosa derived from </=9 mm androgen-dominant follicles, but was secreted by cultured granulosa from estrogen-dominant follicles >/=9 mm, coincident with dominant follicle selection, and by luteinizing granulosa. PAPP-A levels in CM from the latter did not change in response to IGF-II or hCG (100 ng/mL). A naturally occurring inhibitor of PAPP-A, proform of eosinophil major basic protein (proMBP), was detected by ELISA in estrogen-dominant follicular fluid FF, but not in CM from granulosa or lute...Continue Reading

Citations

Jul 19, 2005·Journal of Assisted Reproduction and Genetics·Dorothea M WunderNick A Bersinger
Apr 22, 2008·The Urologic Clinics of North America·Jared C Robins, Sandra A Carson
Jan 27, 2015·Journal of Cell Communication and Signaling·Claus Oxvig
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Oct 26, 2006·Paediatric and Perinatal Epidemiology·Kenneth L Campbell, John C Rockett
Oct 22, 2008·Molecular Reproduction and Development·Zhilin LiuEric Antoniou
Nov 14, 2006·Archives of Biochemistry and Biophysics·Raquel García-CastellanosF Xavier Gomis-Rüth
Dec 31, 2016·Aging Cell·Cheryl A Conover, Claus Oxvig
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Sep 13, 2003·The Journal of Clinical Endocrinology and Metabolism·Bing-Kun ChenCheryl A Conover
Mar 17, 2019·Journal of Assisted Reproduction and Genetics·Jane Alrø BøtkjærClaus Yding Andersen

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