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Pituitary Responsiveness following Infusion or Repeated Injections of [D-Leu⁶, des Gly-NH₂¹⁰]-LHRH-Ethylamide in Prepubertal Ewes^_1,2,

Washington State University^,5, Pullman 99164

⁴ Send reprint request to J.J. Reeves.

Abstract

Twenty-four prepubertal ewe lambs were assigned in equal numbers to three treatment groups: group I, continuous infusion with .5 µg/hr, [D-Leu⁶, des Gly-NH₂¹⁰]-LHRH-ethylamide (D-Leu⁶-LHRH); group II, repetitive intramuscular (im) injection of 1.0 µg D-Leu⁶-LHRH every 2 hr; group III, saline injection every 2 hr. All treatments were continued for 72 hours. Sera from three lambs in each treatment group were collected every 30 min during the treatment period. Pituitary uptake of ¹²⁵I-D-Leu⁶-LHRH was determined on these same three lambs in each group by im injection of 70 µCi ¹²⁵I-D-Leu⁶-LHRH (1.5 µCi/ng) at the end of the treatment period. Pituitaries from the ¹²⁵I-D-Leu⁶-LHRH-treated lambs were collected to determine luteinizing hormone (LH) concentration. The remaining five lambs in each group were ovariectomized, and the ovaries were weighed. Serum LH in lambs subjected to D-Leu⁶-LHRH treatment regimes reached maximum concentration between 3 to 4.5 hr after the start of treatment. During the initial 12 hr of treatment, infusion of D-Leu⁶-LHRH resulted in higher (P<.01) LH release than injection; thereafter, injection of the analog was able to maintain LH levels above those resulting from infusion. At the end of treatment, pituitary uptake of ¹²⁵I-D-Leu⁶-LHRH of the group I and II lambs was lower (P<.01) than the uptake of ^125/I-D-Leu⁶-LHRH in the control lambs. Pituitary LH concentration after the ¹²⁵I-D-Leu⁶-LHRH injection at the end of treatment was higher (P<.01) in group I lambs than either group II or III lambs. The lower pituitary LH concentration of the control lambs was due to the higher pituitary response in release of LH to the ¹²⁵I-D-Leu⁶-LHRH injection. Neither infusion nor injection of D-Leu⁶-LHRH induced a significant change in ovarian follicular diameter or weight compared to ovaries from saline-treated animals. From this study, it was concluded that the decline in LH release from the pituitary in spite of continuous hormone treatment was associated in part, to the decrease in pituitary uptake of D-Leu⁶-LHRH related to receptor availability and a decrease in pituitary content of LH.

¹ Scientific Paper No. 4892. College of Agriculture Research Center, Washington State University, Pullman. Project 0137.

² The authors would like to thank Dr. D.H. Coy and Dr. A.V. Schally of the Endocrine and Polypeptide Laboratory, V.A. Hospital, New Orleans, LA for providing [D-Leu⁶, des Gly-NH₂¹⁰]-LHRH-ethylamide; Dr. L.E. Reichert of Emory University, GA for purified ovine LH (LER-1056-C-2) for iodination. the Endocrine Study Section of NIH for NIH-LH-S17 used for standards and Dr. R. Bendel for statistical advice.

³ Present address Faculty of Agriculture, Kabul University, Kabul, Afghanistan.

⁵ Department of Animal Sciences.