title: Inhibition of follicle-stimulating hormone secretion from gonadotroph adenomas by repetitive administration of a gonadotropin-releasing hormone antagonist.
abstract: As a preliminary step in searching for a pharmacological treatment for gonadotroph adenomas, we administered the GnRH antagonist analog Nal-Glu GnRH to five patients, four men and a woman, with FSH-secreting gonadotroph adenomas in order to determine its effect on FSH secretion. Administration of a single 10-mg dose of Nal-Glu GnRH to four of the patients produced a significant decrease in the serum FSH concentration in two patients and returned the FSH level to normal in only one. Administration of 5 mg Nal-Glu every 12 h for 7 days, however, produced a significant (P less than 0.001) decrease, and to within the normal range, in four of the five patients (mean +/- SEM, 32.7 +/- 5.6 IU/L during the 3 days before treatment and 9.8 +/- 1.4 IU/L during the last 3 days of treatment). Also, in response to the 7-day treatment, LH fell significantly in all five patients, alpha-subunit fell in three, and testosterone fell in all four men. Administration for 6 weeks of the GnRH agonist analog leuprolide did not decrease the serum FSH concentration of one of the patients whose serum FSH did decrease in response to Nal-Glu GnRH. We conclude that repetitive administration of Nal-Glu GnRH may often inhibit FSH secretion by gonadotroph adenomas and that FSH secretion by gonadotroph adenomas may be dependent on endogenous GnRH secretion.
authors.affiliation: Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104.
authors.forename: L
authors.initials: L
authors.lastname: Daneshdoost
authors.forename: S N
authors.initials: SN
authors.lastname: Pavlou
authors.forename: M E
authors.initials: ME
authors.lastname: Molitch
authors.forename: T A
authors.initials: TA
authors.lastname: Gennarelli
authors.forename: P J
authors.initials: PJ
authors.lastname: Savino
authors.forename: R C
authors.initials: RC
authors.lastname: Sergott
authors.forename: T M
authors.initials: TM
authors.lastname: Bosley
authors.forename: J E
authors.initials: JE
authors.lastname: River
authors.forename: W W
authors.initials: WW
authors.lastname: Vale
authors.forename: P J
authors.initials: PJ
authors.lastname: Snyder
mesh_terms: D000236:Adenoma / Q000378:metabolism* / Q000601:surgery; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D004305:Dose-Response Relationship, Drug; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D016729:Leuprolide; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009384:Paraneoplastic Endocrine Syndromes / Q000188:drug therapy*; D010911:Pituitary Neoplasms / Q000378:metabolism* / Q000601:surgery; D013739:Testosterone / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: C057805:LHRH, N-Ac-2-Nal(1)-4-Cl-Phe(2)-3-Pal(3)-Arg(5)-Glu(6)-AlaNH2(10)-; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D016729:Leuprolide