Luteinizing hormone-secreting pituitary tumor: biosynthetic characterization and clinical studies

Although gonadotropin-secreting pituitary adenomas are increasingly recognized, tumors secreting only LH are rare. Since gonadotropin production by pituitary adenomas may reflect imbalanced glycoprotein biosynthesis, we studied tumor LH and subunit biosynthesis and secretion in a patient with a LH- and alpha-subunit-producing pituitary tumor. Northern blot analysis of RNA from the tumor revealed the presence of mRNAs encoding both alpha- and beta-subunits of LH with a marked excess of the mRNA encoding LH beta. Analysis of tumor extracts by gel filtration chromatography confirmed an excess of free LH beta relative to free alpha-subunit. Clinical studies demonstrated that the secretion of LH and alpha-subunit by the tumor increased in response to the acute administration of LHRH (100 micrograms, iv) and decreased during a 4-h dopamine infusion (4 micrograms/kg X min). During a 4-week course of LHRH analog (D-Trp6-Pro9-NEt-LHRH) administration, given as a daily sc dose (8 micrograms/kg X day), serum LH and alpha-subunit concentrations increased 7- and 3-fold, respectively, consistent with a chronic agonist effect. Chronic administration of bromocriptine resulted in reduction of serum LH and alpha-subunit levels to normal.