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Inhibition of Follicle-Stimulating Hormone Secretion from Gonadotroph Adenomas by Repetitive Administration of a Gonadotropin-Releasing Hormone Antagonist^*

LEELA DANESHDOOST, SPYROS N. PAVLOU, MARK E. MOLITCH, THOMAS A. GENNARELLI, PETER J. SAVINO, ROBERT C. SERGOTT, THOMAS M. BOSLEY, JEAN E. RIVER, WYLIE W. VALE and PETER J. SNYDER

Endocrinology Section, Department of Medicine (L.D., P.J.Sn.), and Division of Neurologic Surgery (T.A.G.), University of Pennsylvania School of Medicine Philadelphia, Pennsylvania 19104
the Division of Endocrinology, Department of Internal Medicine, Vanderbilt University School of Medicine (S.N.P.) Nashville, Tennessee 37232
Center for Endocrinology, Metabolism, and Nutrition, Northwestern University Medical School (M.E.M.) Chicago, Illinois 60611
Neuroophthalmology Service, Wills Eye Hospital (P.J.Sa., R.C.S., T.M.B.) Philadelphia, Pennsylvania 19107
the Peptide Biology Laboratory, Salk Institute (J.E.R., W. W. V.) La Jolla, California 92138

Address all correspondence and requests for reprints to: Peter J. Snyder, M.D., 627 Clinical Research Building, 422 Curie Boulevard, Philadelphia, Pennsylvania 19104-6049.

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 t o normal in only one. Administration of 5 mg Nal-Glu every 12h for 7 days, however, produced a significant (P < 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, a-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.

^* This work was supported by USPHS Grants RR-0040, RR-0048, DK-42139, and HD-13527. Conducted in part by the Clayton Foundation for Research, California Division.

Clayton Foundation Investigator.

Received January 8, 1990.

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