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Modulation of adrenal steroidogenesis by c‐AMP specific phosphodiesterase 8
Author(s) -
Tsai LiChun Lisa,
ShimizuAlbergine Masami,
Beavo Joseph A
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.828.2
Subject(s) - phosphodiesterase , medicine , endocrinology , corticosterone , adrenal gland , steroid hormone , biology , adenylyl cyclase , stimulation , hormone , knockout mouse , chemistry , enzyme , receptor , biochemistry
Corticosterone is secreted by mouse adrenal zona fasciculata cells in response to the pituitary hormone adrenocorticotropin (ACTH) in a cAMP/PKA dependent manner. The cAMP/PKA signaling pathway dynamically promotes steroidogenesis by increasing substrate availability, phosphorylation of key enzymes, and transcription of steroidogenic enzymes. Intracellular levels of cAMP are controlled through its synthesis by adenylyl cyclases and its degradation by phosphodiesterases (PDEs). We now show that one of the most recently discovered phosphodiesterase, PDE8B, is highly enriched in adrenal fasiculata cells. Interestingly, PDE8's physiological functions remain largely unexplored due to the lack of specific pharmacological inhibitors. Our laboratory has previously shown that PDE8A is a main modulator of testosterone production in the testes. Here we report that PDE8B modulates adrenal steroid production. We observe that cultures of primary adrenocortical cells isolated from PDE8B knockout mice show elevated levels of basal adrenal steroids, and respond more promptly to ACTH stimulation than wild‐type cells. We also find elevated corticosterone levels in the urine of PDE8B knockout mice, presumably due to adrenal hypersensitivity in vivo . These findings suggest that PDE8B plays an important role in the regulation of adrenal steroidogenesis. Supported by NIH grant DK21723.