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

Cheryl A Conover, G. F. Faessen, K. E. Ilg, Y. Aladin Chandrasekher, M. Christiansen, M. T. Overgaard, C. Oxvig, L. C. Giudice

Research output: Contribution to journalArticle

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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 androgendominant 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 luteinizing granulosa cells treated with IGF-II (0-200 ng/mL), FSH (0-100 ng/mL) or hCG (0-100 ng/mL), suggesting an alternative source (other than granulosa) for proMBP, compared to PAPP-A. The data demonstrate granulosa cells as a source of PAPP-A in human ovary and suggest that PAPP-A is a marker of ovarian follicle selection and corpus luteum formation. In addition the data suggest complex regulation of this system in human ovary.

Original languageEnglish (US)
Pages (from-to)2155-2158
Number of pages4
JournalEndocrinology
Volume142
Issue number5
DOIs
StatePublished - 2001

Fingerprint

Pregnancy-Associated Plasma Protein-A
Granulosa Cells
Corpus Luteum
Insulin-Like Growth Factor Binding Protein 4
Follicular Fluid
Peptide Hydrolases
Eosinophil Major Basic Protein
Conditioned Culture Medium
Insulin-Like Growth Factor Binding Proteins
Insulin-Like Growth Factor II
Somatomedins
Ovary
Estrogens
Enzyme-Linked Immunosorbent Assay
Ovarian Follicle
Protein Binding
Proteolysis
Monoclonal Antibodies

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

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. / Conover, Cheryl A; Faessen, G. F.; Ilg, K. E.; Chandrasekher, Y. Aladin; Christiansen, M.; Overgaard, M. T.; Oxvig, C.; Giudice, L. C.

In: Endocrinology, Vol. 142, No. 5, 2001, p. 2155-2158.

Research output: Contribution to journalArticle

Conover, Cheryl A ; Faessen, G. F. ; Ilg, K. E. ; Chandrasekher, Y. Aladin ; Christiansen, M. ; Overgaard, M. T. ; Oxvig, C. ; Giudice, L. C. / 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. In: Endocrinology. 2001 ; Vol. 142, No. 5. pp. 2155-2158.
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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 androgendominant 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 luteinizing granulosa cells treated with IGF-II (0-200 ng/mL), FSH (0-100 ng/mL) or hCG (0-100 ng/mL), suggesting an alternative source (other than granulosa) for proMBP, compared to PAPP-A. The data demonstrate granulosa cells as a source of PAPP-A in human ovary and suggest that PAPP-A is a marker of ovarian follicle selection and corpus luteum formation. In addition the data suggest complex regulation of this system in human ovary.",
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AU - Conover, Cheryl A

AU - Faessen, G. F.

AU - Ilg, K. E.

AU - Chandrasekher, Y. Aladin

AU - Christiansen, M.

AU - Overgaard, M. T.

AU - Oxvig, C.

AU - Giudice, L. C.

PY - 2001

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