Please use this identifier to cite or link to this item: https://doi.org/10.1210/me.2002-0435
Title: Phosphodiesterase regulation is critical for the differentiation and pattern of gene expression in granulosa cells of the ovarian follicle
Authors: Park, JY
Richard, F
Chun, SY
Park, JH
Law, E 
Horner, K
Jin, SLC
Conti, M
Keywords: Science & Technology
Life Sciences & Biomedicine
Endocrinology & Metabolism
MESSENGER-RIBONUCLEIC-ACID
PROSTAGLANDIN-ENDOPEROXIDE SYNTHASE-2
CAMP-SPECIFIC PHOSPHODIESTERASES
HORMONAL-REGULATION
CYCLIC ADENOSINE-3',5'-MONOPHOSPHATE
STIMULATING-HORMONE
SIGNALING PATHWAYS
OVULATION
INDUCTION
ACTIVATION
Issue Date: 1-Jun-2003
Publisher: OXFORD UNIV PRESS INC
Citation: Park, JY, Richard, F, Chun, SY, Park, JH, Law, E, Horner, K, Jin, SLC, Conti, M (2003-06-01). Phosphodiesterase regulation is critical for the differentiation and pattern of gene expression in granulosa cells of the ovarian follicle. MOLECULAR ENDOCRINOLOGY 17 (6) : 1117-1130. ScholarBank@NUS Repository. https://doi.org/10.1210/me.2002-0435
Abstract: Feedback regulations are integral components of the cAMP signaling required for most cellular processes, including gene expression and cell differentiation. Here, we provide evidence that one of these feedback regulations involving the cyclic nucleotide phosphodiesterase PDE4D plays a critical role in cAMP signaling during the differentiation of granulosa cells of the ovarian follicle. Gonadotropins induce PDE4D mRNA and increase the cAMP hydrolyzing activity in granulosa cells, demonstrating that a feedback regulation of cAMP is operating in granulosa cells in vivo. Inactivation of the PDE4D by homologous recombination is associated with an altered pattern of cAMP accumulation induced by the gonadotropin LH/human chorionic gonadotropin (hCG), impaired female fertility, and a markedly decreased ovulation rate. In spite of a disruption of the cAMP response, LH/hCG induced P450 side chain cleavage expression and steroidogenesis in a manner similar to wild-type controls. Morphological examination of the ovary of PDE4D-/- mice indicated luteinization of antral follicles with entrapped oocytes. Consistent with the morphological finding of unruptured follicles, LH/hCG induction of genes involved in ovulation, including cyclooxygenase-2, progesterone receptor, and the downstream genes, is markedly decreased in the PDE4D-/- ovaries. These data demonstrate that PDE4D regulation plays a critical role in gonadotropin mechanism of action and suggest that the intensity and duration of the cAMP signal defines the pattern of gene expression during the differentiation of granulosa cells.
Source Title: MOLECULAR ENDOCRINOLOGY
URI: https://scholarbank.nus.edu.sg/handle/10635/228814
ISSN: 08888809
19449917
DOI: 10.1210/me.2002-0435
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