The long-term objective of this project is to elucidate the extent and nature of gonadotroph adenomas of the pituitary gland. The work proposed has two specific aims: 1) To determine by in vivo criteria the prevalence of gonadotroph adenomas among pituitary macroadenomas now thought to be """"""""nonsecreting"""""""". Three distinctive characteristics of gonadotroph adenomas recognized in men who have supranormal serum FSH concentrations will be used as criteria to attempt to recognize gonadotroph adenomas in patients now thought to have """"""""nonsecreting"""""""" adenomas: a) supranormal basal serum concentrations of intact FSH but not intact LH in women; b) supranormal basal serum concentrations of alpha and FSHbeta subunits; and c) increases in serum concentrations of intact FSH and LHbeta subunit following TRH administration. These criteria will be applied to 120 patients with """"""""nonsecreting"""""""" pituitary macroadenomas. Blood will be sampled every 15 minutes for 90 min before and 90 min after TRH administration, and the concentrations of gonadotropins and their subunits will be measured. The results will be compared to those of control subjects, as well as to the immunohistologic detection of gonadotropins and their subunits in excised adenoma tissue and the secretion of intact gonadotropins and their subunits in excised adenoma tissue and the secretion of intact gonadotropins and subunits by the excised adenomas in dispersed cell culture. 2) To study the pharmacologic inhibition of gonadotroph adenoma secretion as a preliminary step in finding a pharmacologic treatment of gonadotroph adenomas. The GnRH antagonist, """"""""NalGlu GnRH"""""""", will be administered repetitively for one week to men with documented gonadotroph adenomas. Those patients who exhibit a fall to normal in serum FSH concentration during this week of treatment will be treated for six months, to determine if the adenoma size, as quantitatively measure, decreases. Gonadotroph adenoma tissue from other patients whose adenomas are excised surgically will be cultured and incubated with NalGlu GnRH and with gonadal peptides from porcine follicular fluid.
