TY - JOUR

T1 - Growth hormone receptor expression and function in pituitary adenomas

AU - Clausen, Lene R

AU - Kristiansen, Mikkel T

AU - Rasmussen, Lars M

AU - Billestrup, Nils

AU - Blaabjerg, Ole

AU - Ledet, Thomas

AU - Jørgensen, Jens O L

PY - 2004/5

Y1 - 2004/5

N2 - OBJECTIVE AND DESIGN: Hypopituitarism, in particular GH deficiency, is prevalent in patients with clinically nonfunctioning pituitary adenomas (NFPAs) both before and after surgery. The factors regulating the growth of pituitary adenomas in general and residual tumour tissue in particular are not fully characterized, and the effect of GH and IGF-I on human pituitary cell proliferation has not previously been reported. In NFPA tissue from 14 patients we evaluated GH receptor (GHR) expression and signal transduction, and the effect of GH and IGF-I exposure on cell proliferation and hormone secretion in vitro.MEASUREMENTS: Tissue samples from 14 NFPAs were investigated. Expression of GHR in tissue samples was assessed by reverse transcription polymerase chain reaction (RT-PCR). Six tumours were immunostained with a GHR antibody. In the cell cultures, STAT5 (signal transducer and activator of transcription 5) phosphorylation was measured by Western blot analysis as an index of GHR signalling; cell proliferation was evaluated by [H3]-thymidine incorporation and glycoprotein hormone production analysed by radioimmunoassay (RIA).RESULTS: All adenomas investigated expressed the GHR, but there was no detection of STAT5 phosphorylation. Overall, GH and IGF-I administration did not significantly stimulate cell proliferation in vitro, although some individual adenomas exhibited a proliferative response to various extents. GH also did not significantly influence glycoprotein hormone secretion in vitro.CONCLUSION: GH receptors are expressed in human pituitary adenoma cells but their functional role is uncertain. GH and IGF-I do not consistently influence the proliferation of cultured pituitary adenoma cells.

AB - OBJECTIVE AND DESIGN: Hypopituitarism, in particular GH deficiency, is prevalent in patients with clinically nonfunctioning pituitary adenomas (NFPAs) both before and after surgery. The factors regulating the growth of pituitary adenomas in general and residual tumour tissue in particular are not fully characterized, and the effect of GH and IGF-I on human pituitary cell proliferation has not previously been reported. In NFPA tissue from 14 patients we evaluated GH receptor (GHR) expression and signal transduction, and the effect of GH and IGF-I exposure on cell proliferation and hormone secretion in vitro.MEASUREMENTS: Tissue samples from 14 NFPAs were investigated. Expression of GHR in tissue samples was assessed by reverse transcription polymerase chain reaction (RT-PCR). Six tumours were immunostained with a GHR antibody. In the cell cultures, STAT5 (signal transducer and activator of transcription 5) phosphorylation was measured by Western blot analysis as an index of GHR signalling; cell proliferation was evaluated by [H3]-thymidine incorporation and glycoprotein hormone production analysed by radioimmunoassay (RIA).RESULTS: All adenomas investigated expressed the GHR, but there was no detection of STAT5 phosphorylation. Overall, GH and IGF-I administration did not significantly stimulate cell proliferation in vitro, although some individual adenomas exhibited a proliferative response to various extents. GH also did not significantly influence glycoprotein hormone secretion in vitro.CONCLUSION: GH receptors are expressed in human pituitary adenoma cells but their functional role is uncertain. GH and IGF-I do not consistently influence the proliferation of cultured pituitary adenoma cells.

KW - Adenoma

KW - Adult

KW - Aged

KW - Analysis of Variance

KW - Cell Culture Techniques

KW - Cell Division

KW - Female

KW - Follicle Stimulating Hormone

KW - Glycoprotein Hormones, alpha Subunit

KW - Human Growth Hormone

KW - Humans

KW - Immunohistochemistry

KW - Insulin-Like Growth Factor I

KW - Luteinizing Hormone

KW - Male

KW - Middle Aged

KW - Pituitary Neoplasms

KW - RNA, Messenger

KW - Receptors, Somatotropin

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Signal Transduction

KW - Tumor Cells, Cultured

U2 - 10.1111/j.1365-2265.2004.02022.x

DO - 10.1111/j.1365-2265.2004.02022.x

M3 - Journal article

C2 - 15104560

VL - 60

SP - 576

EP - 583

JO - Clinical Endocrinology

JF - Clinical Endocrinology

SN - 0300-0664

IS - 5

ER -