{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T01:01:26Z","timestamp":1783645286563,"version":"3.55.0"},"reference-count":0,"publisher":"Oxford University Press (OUP)","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2004,8,1]]},"abstract":"<jats:p>OBJECTIVES: Ghrelin is a brain-gut peptide with GH-releasing and appetite-inducing activities and a widespread tissue distribution. Ghrelin is the endogenous ligand of the GH secretagogue receptor type 1a (GHS-R1a), and both ghrelin and the GHS-R1a are expressed in the pituitary. There are conflicting data regarding the effects of ghrelin on cell proliferation. A positive effect on proliferation and activation of the mitogen-activated protein kinase (MAPK) pathway has been found in hepatoma, adipose, cardiomyocyte and prostate cell lines. However, ghrelin has also been shown to have anti-proliferative effects on breast, lung and thyroid cell lines. We therefore examined the effect of ghrelin on the rat pituitary cell line GH3. METHODS: RT-PCR was used for the detection of GHS-R1a and pre-proghrelin mRNA expression in GH3 cells. The effect of ghrelin on cell proliferation was studied using [(3)H]thymidine incorporation; cell counting and the activation of the MAPK pathway were studied using immunoblotting and inhibitors of the extracellular signal-regulated kinase 1 and 2 (ERK 1\/2), protein kinase C (PKC) and tyrosine phosphatase pathways. RESULTS: GHS-R1a and ghrelin mRNA expression were detected in GH3 cells. Ghrelin, at 10(-10) to 10(-6) M concentrations, significantly increased [(3)H]thymidine incorporation (at 10(-9) M, 183+\/-13% (means+\/-s.e.m.) compared with untreated controls), while 12-phorbol 13-myristate acetate (PMA) at 10(-7) M (used as a positive control) caused a 212+\/-14% increase. A reproducible stimulatory effect of desoctanoyl ghrelin was also observed on [(3)H]thymidine incorporation (135+\/-5%; P&lt;0.01 at 10(-9) M compared with control), as well as on the cell count (control 6.8 x 10(4)+\/-8.7 x 10(3) cells\/ml vs desoctanoyl ghrelin (10(-9) M) 1.04 x 10(5)+\/-7.5 x 10(3) cells\/ml; P&lt;0.01). Ghrelin caused a significant increase in phosphorylated ERK 1\/2 in immunoblotting, while desoctanoyl ghrelin showed a smaller but also significant stimulatory effect. The positive effect of ghrelin and desoctanoyl ghrelin on [(3)H]thymidine incorporation was abolished by the MAPK kinase inhibitor U0126, the PKC inhibitor GF109203X and the tyrosine kinase inhibitor tyrphostin 23, suggesting that the ghrelin-induced cell proliferation of GH3 cells is mediated both via a PKC-MAPK-dependent pathway and via a tyrosine kinase-dependent pathway. This could also be clearly demonstrated by Western blot analysis, where a transient increase in ERK 1\/2 phosphorylation by ghrelin was attenuated by all three inhibitors. CONCLUSION: We have shown a novel role for ghrelin in stimulating the proliferation of a somatotroph pituitary tumour cell line, suggesting that ERK activation is involved in mediating the effects of ghrelin on cell proliferation. Desoctanoyl ghrelin showed a similar effect. As ghrelin has been shown to be expressed in both normal and adenomatous pituitary tissue, locally produced ghrelin may play a role in pituitary tumorigenesis via an autocrine\/paracrine pathway.<\/jats:p>","DOI":"10.1530\/eje.0.1510233","type":"journal-article","created":{"date-parts":[[2005,1,24]],"date-time":"2005-01-24T21:34:41Z","timestamp":1106602481000},"page":"233-240","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":105,"title":["Ghrelin exerts a proliferative effect on a rat pituitary somatotroph cell line via the mitogen-activated protein kinase pathway"],"prefix":"10.1093","author":[{"given":"AM","family":"Nanzer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Khalaf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"AM","family":"Mozid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"RC","family":"Fowkes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MV","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JM","family":"Burrin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"AB","family":"Grossman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Korbonits","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","container-title":["European Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/151\/2\/233.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/151\/2\/233.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T16:33:51Z","timestamp":1676392431000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/151\/2\/233\/6694407"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,8,1]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1530\/eje.0.1510233","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,8,1]]}}}