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.