Nuclear effects of the cAMP pathway activation in somatotrophs.
Activation of the cAMP pathway from the cell surface to the nucleus plays a major role in somatotroph differentiation and growth. This pathway is regulated mainly by the antagonistic hypothalamic hormones GHRH and somatostatin. Several pituitary-specific, as well as ubiquitous, expressed genes are regulated by cAMP in GH-secreting cells. Among them are the GH, GHF-1/Pit-1, c-fos and GHRH-receptor genes. Protein kinase A phosphorylation of Ser 133 of the transcription factor cAMP-responsive element binding protein (CREB), seems to play a pivotal role in the activation of the cAMP pathway in normal and tumoral somatotrophs. The oncogenic activating mutations of the G-protein as subunit stimulate transcription and CREB phosphorylation in somatotroph cells. The implications of the nuclear targets of cAMP in the differentiation and growth of somatotrophs are discussed in this review.
Bertherat
J
J
Clinique des Maladies Endocriniennes et Métaboliques, Hôpital Cochin, Paris, France. bertherat@icgm.cochin.inserm.fr
D002467:Cell Nucleus / Q000378:metabolism*; D000242:Cyclic AMP / Q000494:pharmacology*; D017362:Cyclic AMP Response Element-Binding Protein; D019204:GTP-Binding Proteins / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D013007:Growth Hormone-Releasing Hormone / Q000502:physiology; D019382:Human Growth Hormone / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D010902:Pituitary Gland / Q000378:metabolism / Q000648:ultrastructure*; D018013:Receptors, Neuropeptide / Q000502:physiology; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000502:physiology
D017362:Cyclic AMP Response Element-Binding Protein; D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D019382:Human Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; C048250:somatotropin releasing hormone receptor