Participation of mitogen-activated protein kinase in luteinizing hormone-induced differential regulation of steroidogenesis and steroidogenic gene expression in mural and cumulus granulosa cells of mouse preovulatory follicles

Journal:Biology of Reproduction

Place of Publication:UK

Key Words:cumulus cells,granulosa cells,luteinizing hormone,MAPK3/1,ovulation,signal transduction,steroidogenesis,steroidogenic gene expression

Abstract:The LH surge induces the terminal differentiation and onset of luteinization in granulosa cells of preovulatory follicles, a process that involves the differential expression of genes essential for steroidogenesis and appears to be mediated by complex signaling pathways. The objective of this study was to investigate whether these processes that commonly occur in mural granulosa cells (MGCs) also occur in cumulus cells, and whether they are mediated by the mitogen-activated protein kinase (MAPK), specifically MAPK3/1 (also commonly known as extracellular signal-regulated kinase 1&2, ERK1/2). The standard superovulation model for premature female mice was used to obtain MGCs and cumulus-oocyte complexes (COCs), and sensitive real-time RT-PCR was used to simultaneously detect the expression levels of transcripts encoding key steroidogenic enzymes in the same sample. We observed significant downregulation of Cyp19a1 and upregulation of Star and Cyp11a1 mRNA expression in both COCs and MGCs after in vivo administration of hCG or in vitro treatment with gonadotropins or 8-Br-cAMP. This differential pattern of steroidogenic gene expression was correlated with the ultimate changes of circulating estradiol (E2) and progesterone (P4) levels after administration of hCG. In vitro, when MGCs and COCs were treated with U0126—a specific inhibitor of MAPK3/1 activation—gonadotropin-induced P4 production, 8-Br-cAMP-induced P4 production, and expression of Star and Cyp11a1 mRNA were significantly downregulated, whereas the levels of E2 and Cyp19a1 mRNA in the same samples were significantly upregulated. We conclude that the surge of preovulatory LH induces the differential expression of transcripts encoding key steroidogenic enzymes essential for E2 and P4 synthesis in both cumulus and MGCs, and this process is mediated by the MAPK3/1-dependent pathway.

All the Authors:Mette Nyegaard , Michael Toft Overgaard , Jie Qiao

First Author:You-Qiang Su

Indexed by:Journal Article

Correspondence Author:Linda C. Giudice

Document Code:10.1095/biolreprod.106.052613

Volume:75

Issue:6

Page Number:859-867

ISSN No.:0006-3363

Translation or Not:no

Date of Publication:2006-12-01

Date of Publication:2006-12-01