Roles of progesterone receptor membrane component 1 and membrane progestin receptor alpha in regulation of zebrafish oocyte maturation

Joseph Aizen, Yefei Pang, Caleb Harris, Aubrey Converse, Yong Zhu, Meagan A. Aguirre, Peter Thomas*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Although previous studies suggest membrane progesterone receptor alpha (mPRα/Paqr7) mediates 17, 20β-dihydroxy-4-pregnen-3-one (DHP) induction of oocyte maturation (OM) in zebrafish, critical information needed to establish mPRα as the receptor mediating OM is lacking. The relative potencies of progestins and specific mPRα agonists in inducing OM matched their relative binding affinities for zebrafish mPRα supporting its role in OM. Microinjection of pertussis toxin blocked DHP induction of OM and the progestin-induced decrease in cyclic AMP levels, suggesting mPRα activates an inhibitory G protein (Gi). Microinjection of morpholino antisense oligonucleotides to zebrafish pgrmc1 blocked induction of OM by DHP which was accompanied by decreased levels of Pgrmc1 and mPRα on the oocyte plasma membranes. Similarly, treatment of denuded oocytes with a PGRMC1 inhibitor, AG205, blocked the gonadotropin-induced increase in plasma membrane mPRα levels and attenuated DHP induction of OM. Co-incubation with two inhibitors of epidermal growth factor Erbb2, ErbB2 inhibitor II and AG 879, prevented induction of OM by DHP, indicating the likely involvement of Erbb2 in mPRα-mediated signaling. Treatment with AG205 reversed the inhibitory effects of the Erbb2 inhibitors on OM and also inhibited insulin-like growth factor-1 induction of OM. Close associations between Pgrmc1 and mPRα and between Pgrmc1 and Erbb2 were detected in zebrafish oocytes with in situ proximity ligation assays. The results suggest progestin induction of OM in zebrafish is mediated through an mPRα/Gi/Erbb2 signaling pathway that requires Pgrmc1 for expression of mPRα on oocyte membranes and that Pgrmc1 also is required for induction of OM through Erbb2.

Original languageEnglish (US)
Pages (from-to)51-61
Number of pages11
JournalGeneral and Comparative Endocrinology
Volume263
DOIs
StatePublished - Jul 1 2018

Funding

This research was supported by BARD, the United States – Israel Binational Agricultural Research and Development Fund, Vaadia-BARD Postdoctoral Fellowship Award No. FI-448-11(J.A), by the H.E.B. Endowed Chair in Marine Science Institute at the University of Texas at Austin (P.T) and NIH GM100461 (Y.Z.).

Keywords

  • AG205
  • Adaptor protein
  • Erbb2
  • IGF-1
  • Oocyte maturation
  • Pgrmc1
  • Zebrafish
  • mPRα

ASJC Scopus subject areas

  • Endocrinology
  • Animal Science and Zoology

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