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Endocrinology, Vol 137, 4730-4737, Copyright © 1996 by Endocrine Society


ARTICLES

How much of the gonadotropin-releasing hormone (GnRH) surge is required for generation of the luteinizing hormone surge in the ewe? Duration of the endogenous GnRH signal

NP Evans, GE Dahl, A Caraty, V Padmanabhan, LA Thrun and FJ Karsch
Department of Physiology, University of Michigan, Ann Arbor 48109, USA.

The preovulatory LH surge in the sheep is accompanied by a massive and sustained surge of GnRH. The objective of this study was to examine the duration of the endogenous GnRH signal required to induce and maintain a LH surge of full amplitude and duration. For this purpose, we assessed the effect of a competitive GnRH receptor antagonist (Nal- Glu), administered at various times relative to the LH surge, on the development and progression of the surge pattern of LH release. All studies were conducted in a physiological model for the follicular phase of the estrous cycle (artificial follicular phase). In this model, as during the natural follicular phase, the onset of the LH surge is coincident with the initiation of a massive and sustained rise in GnRH secretion. The experimental approach was validated in a preliminary study by determination that the GnRH antagonist could block the LH surge without compromising GnRH release, as measured in pituitary portal blood. In the main experiment, 25 ewes were run through five successive artificial follicular phases, during which the antagonist was not given (control) or was administered before the LH surge, during its ascending limb, or during the descending limb. Treatment with antagonist before the expected time of the surge prevented the LH surge. Treatment during the ascending limb of the LH surge interrupted the rise in LH and caused a prompt cessation of the surge. Treatment during the descending limb of the LH surge resulted in a faster decline in circulating LH concentrations than in control cycles and caused premature termination of the LH surge. Our results are consistent with the conclusion that development and progression of the preovulatory LH surge in sheep depend upon GnRH stimulation throughout its entire time course.


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