Cellular abnormalities in pituitary tumors.
Pituitary cells appear to be programmed to proliferate in response to cyclic adenosine monophosphate (cAMP), leading to tumorigenesis. Stimulatory neurohormones and inhibitory inputs normally act in opposition to control cAMP levels, but receptor/postreceptor alterations may affect their relative effects. Most growth hormone (GH), corticotropin (ACTH)-, prolactin (PRL)-, and gonadotropin-secreting adenomas and nonfunctioning pituitary adenomas (NFPA) possess specific thyrotropin-releasing hormone (TRH) receptors, normally coupled with cytosolic [Ca2+]i increase and diacyl glycerol production. These cells are also sensitive to other peptides such as vasoactive intestinal peptide (VIP) and pituitary adenylyl cyclase-activating peptide (PACAP), which activate adenylyl cyclase in many hormone-secreting adenomas and in all NFPA. The two main inhibitory agents controlling pituitary function are somatostatin (SS) and dopamine (DA), which have been reported to reduce hormone hypersecretion and tumor growth in a variable percentage of patients. Inhibition of adenylyl cyclase activity and cytosolic [Ca2-]i levels is involved in the transduction of DA signals in normal and tumoral mammotrophs, but in GH-secreting adenomas DA receptors are exclusively and defectively coupled only with [Ca2+]i reduction. The abnormal expression of these receptors can amplify stimulatory signals with both secretory and proliferative potential. The availability of specific G proteins may qualify the cell response to inhibitory agents. For example, in a subset of NFPA, SS alone or DA alone causes an abnormal increase in [Ca2+]i levels due to Ca2+ mobilization from intracellular stores.
Spada
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A
Institute of Endocrine Sciences, Ospedale Maggiore IRCCS, University of Milan, Italy.
Lania
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A
Mantovani
S
S
D000818:Animals; D006801:Humans; D018377:Neurotransmitter Agents / Q000502:physiology; D010902:Pituitary Gland / Q000503:physiopathology; D010911:Pituitary Neoplasms / Q000473:pathology / Q000503:physiopathology*
D018377:Neurotransmitter Agents