A critical period for thyroid hormone action on seasonal changes in reproductive neuroendocrine function in the ewe

Thyroid hormones are obligatory for the annually recurring termination of reproductive activity in a spectrum of seasonal breeders, including sheep. Previous studies involving thyroidectomy and T4 replacement have led to the hypothesis that, in the ewe, thyroid hormones are necessary only during a limited interval late in the breeding season for the neuroendocrine processes that cause the transition to anestrus. The present series of experiments tested this hypothesis by assessing the influence of thyroidectomy, with or without T4 replacement for specific durations and at different times of the year, on the transition to anestrus. Seasonal alterations in reproductive neuroendocrine activity were monitored by changes in serum LH concentration in ovariectomized ewes bearing s.c. SILASTIC brand silicon tubing implants containing estradiol. Thyroidectomy in mid-December, just before the putative period of thyroid hormone action, prevented the development of the neuroendocrine anestrous season (fall in LH in this animal model). T4 replacement for 90 days beginning in late December (i.e., during the postulated period of thyroid hormone action) overcame the blockade of anestrus, causing LH to fall in ewes thyroidectomized several months previously. The minimal effective duration of exposure to thyroid hormones required for the transition to anestrus was estimated to be 60-90 days. Further, exposure to T4 for 60-90 days beginning in late December was found to be the only time of the year that thyroid hormones were required to maintain seasonal changes in reproductive neuroendocrine activity. Finally, replacement of T4 for 90 days at a different time of year (beginning in August) failed to provoke development of neuroendocrine anestrus in thyroidectomized ewes. These results support the hypothesis that thyroid hormones are necessary only during a limited interval late in the breeding season to promote seasonal reproductive suppression in the ewe. Further, the reproductive neuroendocrine axis is not equally responsive to thyroid hormone at all times of the year. This suggests there is a critical period of responsiveness during which thyroid hormones must be present for anestrus to develop.