Long-term effects of a gonadotrophin-releasing hormone agonist ([D-Ser(But)6]GnRH(1-9)nonapeptide-ethylamide) on gonadotrophin secretion from human pituitary gonadotroph cell adenomas in vitro.
We have studied the effects of TRH and native gonadotrophin-releasing hormone (GnRH), and of a GnRH agonist (Buserelin; [D-Ser(But )6]GnRH(1-9) nonapeptide-ethylamide), on LH, FSH, alpha subunit and LH-beta subunit secretion from three human gonadotrophin-secreting pituitary adenomas in dispersed cell culture. During a 24 h study, treatment with 276 nmol TRH/l resulted in a significant (P less than 0.05) stimulated release of FSH and alpha subunit from all three adenomas, and LH from the two adenomas secreting detectable concentrations of this glycoprotein; treatment with 85 nmol GnRH/l significantly (P less than 0.05) stimulated the release of alpha subunit from all three, but FSH from only two and LH from only one adenoma. During a long-term 28-day study, basal FSH and alpha subunit concentrations were maintained, but secretion of LH, and LH-beta (detectable from one tumour only), declined with time from two of the three adenomas. Addition of Buserelin to the cultures resulted in the continuous (P less than 0.05) stimulation of alpha subunit secretion from all three adenomas, and of LH and FSH from two, whilst a transient stimulatory effect on LH and FSH secretion was seen from a third adenoma, with subsequent secretion rates declining towards control values. These data show that human gonadotrophin-secreting adenomas demonstrate variable stimulatory responses to hypothalamic TRH and GnRH, and that during chronic treatment with a GnRH agonist the anticipated desensitizing effect of the drug was not observed in two out of the three adenomas studied. The mechanisms for this is not clear, but such drugs are unlikely to be of therapeutic value in the management of gonadotrophin-secreting tumours. The data also suggest that GnRH and GnRH agonists have a differential effect on the in-vitro release of intact gonadotrophins and the common alpha subunit.
Daniels
M
M
Department of Medicine, Medical School, University of Newcastle upon Tyne.
Newland
P
P
Dunn
J
J
Kendall-Taylor
P
P
White
M C
MC
D000236:Adenoma / Q000378:metabolism*; D000328:Adult; D000368:Aged; D002064:Buserelin / Q000494:pharmacology*; D002478:Cells, Cultured; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism*; D015292:Glycoprotein Hormones, alpha Subunit / Q000378:metabolism; D006801:Humans; D007986:Luteinizing Hormone / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010906:Pituitary Hormone-Releasing Hormones / Q000494:pharmacology; D010911:Pituitary Neoplasms / Q000378:metabolism*; D013997:Time Factors
D015292:Glycoprotein Hormones, alpha Subunit; D010906:Pituitary Hormone-Releasing Hormones; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D002064:Buserelin