Journal article
Luteinizing Hormone Causes Phosphorylation and Activation of the cGMP Phosphodiesterase PDE5 in Rat Ovarian Follicles, Contributing, Together with PDE1 Activity, to the Resumption of Meiosis
Biology of reproduction, Vol.94(5), pp.110-110
05/2016
DOI: 10.1095/biolreprod.115.135897
PMCID: PMC4939740
PMID: 27009040
Abstract
The meiotic cell cycle of mammalian oocytes in preovulatory follicles is held in prophase arrest by diffusion of cGMP from the surrounding granulosa cells into the oocyte. Luteinizing hormone (LH) then releases meiotic arrest by lowering cGMP in the granulosa cells. The LH-induced reduction of cGMP is caused in part by a decrease in guanylyl cyclase activity, but the observation that the cGMP phosphodiesterase PDE5 is phosphorylated during LH signaling suggests that an increase in PDE5 activity could also contribute. To investigate this idea, we measured cGMP-hydrolytic activity in rat ovarian follicles. Basal activity was due primarily to PDE1A and PDE5, and LH increased PDE5 activity. The increase in PDE5 activity was accompanied by phosphorylation of PDE5 at serine 92, a protein kinase A/G consensus site. Both the phosphorylation and the increase in activity were promoted by elevating cAMP and opposed by inhibiting protein kinase A, supporting the hypothesis that LH activates PDE5 by stimulating its phosphorylation by protein kinase A. Inhibition of PDE5 activity partially suppressed LH-induced meiotic resumption as indicated by nuclear envelope breakdown, but inhibition of both PDE5 and PDE1 activities was needed to completely inhibit this response. These results show that activities of both PDE5 and PDE1 contribute to the LH-induced resumption of meiosis in rat oocytes, and that phosphorylation and activation of PDE5 is a regulatory mechanism.
Details
- Title: Subtitle
- Luteinizing Hormone Causes Phosphorylation and Activation of the cGMP Phosphodiesterase PDE5 in Rat Ovarian Follicles, Contributing, Together with PDE1 Activity, to the Resumption of Meiosis
- Creators
- Jeremy R Egbert - Department of Cell Biology, University of Connecticut Health Center, Farmington, Connecticut egbert@uchc.eduTracy F Uliasz - Department of Cell Biology, University of Connecticut Health Center, Farmington, ConnecticutLeia C Shuhaibar - Department of Cell Biology, University of Connecticut Health Center, Farmington, ConnecticutAndreas Geerts - Bayer Pharma AG, Pharma Research Center, Wuppertal, GermanyFrank Wunder - Bayer Pharma AG, Pharma Research Center, Wuppertal, GermanyRobin J Kleiman - Translational Neuroscience Center, Boston Children's Hospital, Boston, MassachusettsJohn M Humphrey - Pfizer Worldwide Research & Development, Groton, ConnecticutPaul D Lampe - Translational Research Program, Fred Hutchinson Cancer Research Center, Seattle, WashingtonNikolai O Artemyev - Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IowaSergei D Rybalkin - Department of Pharmacology, University of Washington, Seattle, WashingtonJoseph A Beavo - Department of Pharmacology, University of Washington, Seattle, WashingtonMatthew A Movsesian - Cardiology Section, VA Salt Lake City Health Care System and Division of Cardiovascular Medicine, University of Utah School of Medicine, Salt Lake City, UtahLaurinda A Jaffe - Department of Cell Biology, University of Connecticut Health Center, Farmington, Connecticut ljaffe@uchc.edu
- Resource Type
- Journal article
- Publication Details
- Biology of reproduction, Vol.94(5), pp.110-110
- Publisher
- United States
- DOI
- 10.1095/biolreprod.115.135897
- PMID
- 27009040
- PMCID
- PMC4939740
- ISSN
- 0006-3363
- eISSN
- 1529-7268
- Grant note
- R01 GM083926 / NIGMS NIH HHS R01 GM055632 / NIGMS NIH HHS R37 HD014939 / NICHD NIH HHS
- Language
- English
- Date published
- 05/2016
- Academic Unit
- Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Ophthalmology and Visual Sciences
- Record Identifier
- 9984025363102771
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