Regulation of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of MMP, and progesterone secretion in luteinized granulosa cells from normally ovulating women with polycystic ovary disease

Izhar Ben-Shlomo, Izhar Ben‐Shlomo, Shlomit Goldman, Eliezer Shalev
Fertility and sterility · 2003 · vol. 79 , pp. 694–701 · doi:10.1016/s0015-0282(02)04814-8 · PMID:12620479 · W2038455452
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This study investigated how polycystic ovary disease affects MMP-9, its inhibitor, and progesterone secretion in luteinized granulosa cells from normally ovulating women.

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Abstract

OBJECTIVE: To investigate the regulation of MMP-9, TIMP-1, and progesterone via three signal transduction pathways in luteinized granulosa cells from normal ovulatory and PCOD women. DESIGN: In vitro study. SETTING: Laboratory for Research in Reproductive Sciences, Department of Obstetrics and Gynecology, Ha'Emek Hospital, Afula, Israel. PATIENT(S): Ten normal ovulatory and 10 women with polycystic ovary disease (PCOD) treated in an assisted reproduction program. INTERVENTION(S): Cultured cells were exposed to phorbol 12-myristate 13-acetate (TPA), acting via protein kinase C (PKC), to epidermal growth factor (EGF), acting via protein tyrosine kinase (PTK), and to forskolin, acting via protein kinase A (PKA). MAIN OUTCOME MEASURE(S): Secretion of MMP-9, TIMP-1, and progesterone. RESULT(S): Phorbol 12-myristate 13-acetate elicited an increase in MMP-9 and TIMP-1 secretion in both groups and apparently did not affect progesterone secretion. Epidermal growth factor did not change significantly neither MMP-9 nor TIMP-1 secretion but dose dependently decreased MMP-9-TIMP-1 ratio and increased progesterone secretion in the PCOD group. Forskolin inhibited MMP-9 activity and increased TIMP-1 and progesterone secretion in both groups. Progesterone production was inversely related to the ratio of MMP-9-TIMP-1 regardless of cell origin. CONCLUSION(S): In this preliminary study, similar and divergent patterns have emerged in the regulation of MMP-9 and TIMP-1 in human luteinized granulosa cells. Repressing MMP-9-TIMP-1 ratio may have an important modulatory effect on progesterone secretion.

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MeSH descriptors

Granulosa Cells Luteinization Matrix Metalloproteinase 9 Polycystic Ovary Syndrome Progesterone Tissue Inhibitor of Metalloproteinase-1 Adult Blotting, Western Colforsin Colforsin Cyclic AMP-Dependent Protein Kinases Cyclic AMP-Dependent Protein Kinases Epidermal Growth Factor Epidermal Growth Factor Female Granulosa Cells Granulosa Cells Humans Luteinization Matrix Metalloproteinase 9

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