Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eighteen postmenopausal women with severe hot flashes had continuous recordings of finger temperature and skin resistance as objective indexes of flushing episodes, and serial measurements of anterior pituitary hormones as indirect indexes of hypothalamic neurotransmitter activity. Significant increases of growth hormone, adrenocorticotropic hormone (ACTH), and luteinizing hormone (LH) occurred with maximal concentrations at 30, five, and 15 minutes, respectively, after the onset of the skin temperature rises. No significant fluctuations of prolactin (PRL), thyroid-stimulating hormone (TSH), or follicle-stimulating hormone (FSH) were observed. The mean serum cortisol concentration increased 15 minutes after the hot flash, presumably consequent to the preceding elevation of ACTH. Pituitary ACTH release may be secondary to hypothalamic cooling, whereas increased growth hormone and LH output and the thermoregulatory adjustments comprising the flushing episodes are all consistent with cyclic episodes of increased hypothalamic norepinephrine activity.
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PMID:Pituitary hormones during the menopausal hot flash. 609 54

Hypothalamic GHRH is secreted into the portal system, binds to specific surface receptors of the somatotroph cell and elicits intracellular signals that modulate pituitary GH synthesis and/or secretion. Moreover, GHRH is synthesized and expressed in multiple extrapituitary tissues. Excessive peripheral production of GHRH by a tumor source would therefore be expected to cause somatotroph cell hyperstimulation, increased GH secretion and eventually pituitary acromegaly. Immunoreactive GHRH is present in several tumors, including carcinoid tumors, pancreatic cell tumors, small cell lung cancers, endometrial tumors, adrenal adenomas, and pheochromocytomas which have been reported to secrete GHRH. Acromegaly in these patients, however, is uncommon. The distinction of pituitary vs. extrapituitary acromegaly is extremely important in planning effective management. Regardless of the cause, GH and IGF-1 are invariably elevated and GH levels fail to suppress (<1 microg/l) after an oral glucose load in all forms of acromegaly. Dynamic pituitary tests are not helpful in distinguishing acromegalic patients with pituitary tumors from those harbouring extrapituitary tumors. Plasma GHRH levels are usually elevated in patients with peripheral GHRH-secreting tumors, and are normal or low in patients with pituitary acromegaly. Unique and unexpected clinical features in an acromegalic patient, including respiratory wheezing or dyspnea, facial flushing, peptic ulcers, or renal stones sometimes are helpful in alerting the physician to diagnosing non pituitary endocrine tumors. If no facility to measure plasma GHRH is available, and in the absence of MRI evidence of pituitary adenoma, a CT scan of the thorax and abdominal ultrasound could be performed to exclude with good approximation the possibility of an ectopic GHRH syndrome. Surgical resection of the tumor secreting ectopic GHRH should be the logical approach to a patient with ectopic GHRH syndrome. Standard chemotherapy directed at GHRH-producing carcinoid tumors is generally unsuccessful in controlling the activated GH axis. Somatostatin analogs provide an effective option for medical management of carcinoid patients, especially those with recurrent disease. In fact, long-acting somatostatin analogs may be able to control not only the ectopic hormonal secretion syndrome, but also, in some instances, tumor growth. Therefore, although cytotoxic chemotherapy, pituitary surgery, or irradiation still remain available therapeutic options, long-acting somatostatin analogs are now preferred as a second-line therapy in patients with carcinoid tumors and ectopic GHRH-syndrome.
Pituitary 2006
PMID:Neuroendocrine tumors secreting growth hormone-releasing hormone: Pathophysiological and clinical aspects. 1703 95

Infusion of pituitary adenylate cyclase activating peptide-38 (PACAP-38) provokes migraine attacks in migraineurs and headache in non-migraineurs. Adverse events like long-lasting flushing and heat sensation can be terminated with oral antihistamine treatment, indicating the involvement of mast cell activation after PACAP-infusion. Degranulation of rat peritoneal mast cells was provoked by several isoforms of PACAP via previously unknown receptor pharmacology. The effect might thus be mediated either via specific splice variants of the PAC1-receptor or via an unknown receptor for PACAP-38. In the present study, we characterize degranulation of rat meningeal mast cells in response to PACAP-receptor ligands. Furthermore, we investigate if PACAP-38-induced mast cell degranulation is mediated via PAC1-receptor splice variants and/or via the orphan Mas-related G-protein coupled member B3 (MrgB3)-receptor. To address this, the pharmacological effect of different PACAP isoforms on meningeal mast cell degranulation was investigated in the hemisected skull model after toluidine blue staining followed by microscopic quantification. Presence of mRNA encoding PAC1-receptor splice variants and the MrgB3-receptor in rat mast cells was investigated by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) analysis. The effect of PACAP isoforms on PAC1- and MrgB3-receptor-expressing Xenopus laevis oocytes were performed by two-electrode voltage-clamp (TEVC) electrophysiology. PACAP-38 is a more potent mast cell degranulating agent than Pituitary Adenylate Cyclase Activating Peptide-27 (PACAP-27) in the meninges. Presence of mRNA encoding the PAC1-receptor and its different splice variants could not be detected in peritoneal mast cells by RT-PCR, whereas the orphan MrgB3-receptor, recently suggested to be a mediator of basic secretagogues-induced mast cell degranulation, was widely present. In PAC1-receptor-expressing Xenopus laevis oocytes both PACAP-38, PACAP-27 and the specific PAC1-receptor agonist maxadilan were equipotent, however, only PACAP-38 showed a significant degranulatory effect on mast cells. We confirmed Pituitary Adenylate Cyclase Activating Peptide(6-38) [PACAP(6-38)] to be a PAC1-receptor antagonist, and we demonstrated that it is a potent mast cell degranulator and have an agonistic effect on MrgB3-receptors expressed in oocytes. The present study provides evidence that PACAP-induced mast cell degranulation in rat is mediated through a putative new PACAP-receptor with the order of potency being: PACAP-38 = PACAP(6-38) > > PACAP-27 = maxadilan. The results suggest that the observed responses are mediated via the orphan MrgB3-receptor.
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PMID:PACAP-38 and PACAP(6-38) Degranulate Rat Meningeal Mast Cells via the Orphan MrgB3-Receptor. 3098 73