This Article Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Leal, J. A. Articles by Hodgen, G. D. Search for Related Content PubMed PubMed Citation Articles by Leal, J. A. Articles by Hodgen, G. D.

PROLONGED DURATION OF GONADOTROPIN INHIBITION BY A THIRD GENERATION GNRH ANTAGONIST^*,&

The Jones Institute for Reproductive Medicine, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Medical College of Hampton Roads 855 W. Brambleton Ave, Suite B, Norfolk, Virginia 23510

The dose-response effects of a single administration of Nal-Lys-GnRHant (antagonist) on serum LH and FSH concentrations were compared to the effects of Nal-Glu-GnRHant in monkeys. Twenty ovariectomized monkeys were divided into four sc treatment groups: a) 1.0 mg/kg Nal-Glu-GnRHant; or Nal-Lys-GnRHant at b) 0.3; c) 1.0; d) 3.0 mg/kg. Each monkey received vehicle (propylene glycol/water, 1:1) on day 0, followed by an antagonist preparation on day 11. Serum LH and FSH were measured by RIA; serum LH was also measured by in vitro bioassay. The short-term effects were similar among the four treatment groups. Typically, serum LH declined (p < 0.05) within 4 to 8 h, achieving maximal reduction by 24 h. Serum FSH levels declined more slowly, but were significantly reduced by 24 h (p < 0.05). Recovery during the study interval to pretreatment control values occurred in only two groups: a) Nal-Glu-GnRHant (1.0 mg/kg) by day 4 posttreatment and b) Nal-Lys-GnRHant (0.3 mg/kg) by day 2 post-treatment. Monkeys receiving 1.0 or 3.0 mg/kg Nal-Lys-GnRHant had a prolonged inhibition of serum LH and FSH levels. In all animals, serum FSH and LH returned to control levels within 2 months. The duration of gonadotropin inhibition was also prolonged when the Nal-Lys-GnRHant was administered iv. In contrast, Nal-Glu-GnRHant reduced serum LH and FSH for 3 days or less in all monkeys. The serum bioassayable LH levels paralleled those of immunoassayable LH.

The prolonged inhibition of gonadotropin secretion following Nal-Lys-GnRHant distinguishes its action from those of previous GnRH antagonists and make this compound of great interest for clinical investigations.

^& Supported in part by the CONRAD program, funded by the USAID, Washington, D.C.

^* Portions of this work were presented at the 70th Endocrine Society Meeting, New Orleans, Louisiana, 1988

^# Postdoctoral Research Fellow of the Rockefeller Foundation

⁺ To whom correspondence should be addressed

Received July 29, 1988.

This article has been cited by other articles:

				J. Xu, R.L. Stouffer, R.P. Searles, and J.D. Hennebold Discovery of LH-regulated genes in the primate corpus luteum Mol. Hum. Reprod., March 1, 2005; 11(3): 151 - 159. [Abstract] [Full Text] [PDF]

				K. Gordon, R. T. Scott, R. F. Williams, D. R. Danforth, H. J. J. Loozen, H. J. Kloosterboer, and G. D. Hodgen In Vivo Effects of a Potent GnRH Antagonist ORG 30850: Physiologic Evidence That Down-Regulation of GnRH Receptors Does Not Occur Reproductive Sciences, October 1, 1994; 1(4): 290 - 296. [Abstract] [PDF]