BIOLOGY OF REPRODUCTION 52, 690-696 (1995) Thyroxine Is Permissive to Seasonal Transitions in Reproductive Neuroendocrine Activity in the Ewe' G.E. DAHL , N.P. EVANS, L.A. THRUN, and F.J. KARSCH 2 Reproductive Sciences Program and Departments of Physiology and Biology, University of Michigan Ann Arbor, Michigan 48109-0404 ABSTRACT The observation that circulating thyroxine concentration increases during the breeding season of the ewe, coupled with the finding that thyroid hormones are required for the transition from the breeding season to anestrus in this species, led us to test the hypothesis that the transition to anestrus is driven by a rise in circulating thyroxine. Suffolk ewes were thyroidectomized (THX) late in the anestrous season. Thyroxine was then either not replaced or provided at doses that produced nadir, incremental (simulating the seasonal rise), or mildly hyperthyroid concentrations in serum. Additional ewes remained thyroid-intact. To mon- itor seasonal changes in reproductive neuroendocrine activity, the ewes were ovariectomized and received implants of constant- release Silastic capsules containing estradiol. Serum concentrations of LH and thyroxine were determined in samples collected twice weekly. In all groups, LH increased in mid-September, signifying that manipulation of thyroid status did not influence onset of the neuroendocrine breeding season. In thyroid-intact controls, LH decreased to low concentrations in mid-January, marking the neuroendocrine transition to anestrus. As expected, LH remained elevated through the end of the study (April) in THX controls not receiving thyroxine, confirming that the neuroendocrine transition to anestrus is dependent on thyroid hormones. The seasonal decrease in LH was seen in all ewes treated with thyroxine. This decrease in LH was neither advanced in mildly hyperthyroid ewes nor delayed in ewes exposed to low serum concentrations of thyroxine. These results lead to the conclusion that the seasonal increase in circulating thyroid hormone in the ewe does not drive the transition from the breeding season to anestrus. This supports the view that thyroid hormones act permissively to allow the neuroendocrine changes that lead to the seasonal cessation of reproductive activity. INTRODUCTION Seasonal reproduction has evolved in the vast majority of vertebrates to ensure that the birth of young occurs at a time when environmental conditions favor neonatal sur- vival. A recent development of widespread importance in the area of seasonality is a role for thyroid hormones in the generation of seasonal cycles of reproductive activity in a broad spectrum of species including both birds and mam- mals [1-5]. In the ewe, for example, thyroidectomy blocks neuroendocrine changes that lead to the transition from the breeding season to anestrus, whether the transition is induced by exposure to inhibitory photoperiod or driven by the endogenous rhythm that underlies the seasonal changes of reproductive activity in this species [4-6]. The finding that this effect of thyroidectomy is mediated by the GnRH neurosecretory system [7], in conjunction with the demonstration that thyroxine replacement can prevent this Accepted November 11, 1994. Received August 22, 1994. 'A preliminary report appears in the abstracts of the Annual Meeting of the So- ciety for the Study of Reproduction, 1993. Supported by NIH HD-18337, 07048, 18258 (Sheep Research, Assays and Reagents, Data Analysis and Administrative P30 Core Facilities), and the Office of the Vice President for Research at the University of Mich- igan. 'Correspondence: to FJ. Karsch, Reproductive Sciences Program, University of Michigan, 300 N Ingalls Bldg., Rm. 1101 SW, Ann Arbor, Ml 48109-0404. FAX: (313) 936-8620. response [6], supports the concept that thyroid hormones are necessary for expression of the changes in neuroen- docrine activity that lead to the seasonal cessation of es- trous cyclicity in the ewe. The present study was conducted to determine whether a change in the amount of circulating thyroid hormones actively drives the neuroendocrine processes that lead to anestrus or whether thyroid hormones play a permissive role in this transition. Several observations suggest that an increase in thyroid hormones may drive anestrus in the ewe. First, we have observed that ewes exhibit a seasonal fluc- tuation in circulating thyroxine, rising gradually from a na- dir just prior to onset of the breeding season to peak con- centrations shortly before the transition to anestrus [6]. Second, injection of large doses of thyroxine into thyroid- intact ewes can cause a premature transition to anestrus [8]. Third, a reduction of thyroxine secretion, by treatment with methyl-thiouracil, can extend the breeding season, albeit marginally [9]. None of these previous studies, however, tested the hypothesis that the increase in circulating thy- roxine, which occurs during the course of the breeding season, is necessary for the transition to anestrus. Our ap- proach for testing this hypothesis was to manipulate the pattern of serum thyroxine systematically in thyroidectom- ized (THX) ewes and to monitor the timing of the transi- tion from the breeding season to anestrus. 690 Downloaded from https://academic.oup.com/biolreprod/article-abstract/52/3/690/2761547 by guest on 06 June 2020