Pituitary adenomas with high and low basal inositol phospholipid turnover; the stimulatory effect of kinins and an association with interleukin-6 secretion.
OBJECTIVE
We examined basal inositol phospholipid turnover and the response to the kinin, kallidin, in human pituitary adenomas and determined whether or not there was an association between these parameters and interleukin (IL-6) secretion status by the tumours.


METHODS
Pituitary adenoma tissue was dispersed and cells were cultured in monolayer for 96 hours. The medium was then removed and assayed for IL-6 and anterior pituitary hormones. The cells were labelled with 3H-myoinositol for 24 hours and then incubated under basal conditions with kallidin and, in some cases, with TRH and GnRH for 60 minutes. Total inositol phosphate accumulation and pituitary hormone secretion were assessed.


METHODS
Tissue was collected from 29 consecutive patients being treated surgically for pituitary adenomas.


METHODS
Total 3H-inositol phosphates, growth hormone, prolactin, LH, FSH, TSH and immunoreactive IL-6.


RESULTS
Two groups of pituitary adenomas were identified, one with high and one with low basal inositol phospholipid turnover. Kallidin stimulated inositol phosphate accumulation in seven of the 29 adenomas studied. The kallidin-responsive adenomas were associated with high basal phosphoinositide turnover. All seven kallidin-responsive adenomas secreted IL-6. The adenomas studied with high basal inositol phosphate production were also responsive to TRH and in two tumours to GnRH. Kallidin stimulated GH release in one GH-secreting adenoma but had no effect on hormone secretion from any other tumour.


CONCLUSIONS
Two groups of pituitary adenomas have been identified with high and low basal inositol phosphoinositide turnover. Phosphoinositide metabolism is readily stimulated by kallidin and TRH in adenomas with high but not low turnover. Kinin-responsive adenomas secreted IL-6 but IL-6 secretor status does not preclude that they will respond to kallidin.
Jones
T H
TH
University Department of Medicine, Clinical Sciences Centre, Sheffield, UK.
Kennedy
R L
RL
Justice
S K
SK
Price
A
A
D000236:Adenoma / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D013006:Growth Hormone / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D007609:Kallidin / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010716:Phosphatidylinositols / Q000378:metabolism*; D010911:Pituitary Neoplasms / Q000378:metabolism*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D015850:Interleukin-6; D010716:Phosphatidylinositols; D007987:Gonadotropin-Releasing Hormone; D007609:Kallidin; D013973:Thyrotropin-Releasing Hormone; D013006:Growth Hormone