EFFECT OF PROLONGED EXPOSURE TO ESTRADIOL ON SUBSEQUENT LH-SECRETION IN EWES

Abnormal follicles can produce oestradiol continuously for up to 20 da ys and this inhibits the hypothalamic-pituitary axis. The present expe rimental series was designed to determine the minimum exposure to high or low follicular phase concentrations of oestradiol that were requir ed to exert inhibitory effects on LH surge secretion induced by additi onal oestradiol administered at the end of continuous exposure to oest radiol. Experiments were also included to establish whether the inhibi tory effects of prolonged oestradiol were mediated at the pituitary, a nd whether the failure of response to the oestradiol challenge could b e corrected by exposure to normal luteal phase patterns of progesteron e. Treatment of ewes between 2 and 12 clays with 1, 2 or 4 oestradiol implants (3 cm) totally blocked the subsequent normal LH surge in resp onse to an oestradiol challenge in 45 of 52 ewes pretreated with oestr adiol. In the seven ewes that did have an increase in LH, the response occurred at the expected time but was greatly reduced (14 versus 40 n g ml(-1)), and occurred only in ewes pretreated with oestradiol implan ts for 2 or 4 days. We were unable to establish a robust linear time-d ose relationship, i.e., when ewes were treated with lower doses of oes tradiol (one or two implants) for a reduced time (2, 4 or 8 days), the re was random distribution of the 7 of 32 animals that had a reduced L H surge after oestradiol challenge (with four implants or 50 mu g inje ction). The present study is the first to show that exposure for only 2-4 days to continuous oestradiol at late follicular phase concentrati ons can disrupt LH surge release. However, in oestradiol-treated ewes, LH secretion was provoked by high or low doses (0.5 mg or 0.5 Pg) of GnRH, although it was reduced by 50%, and a GnRH self-priming effect w as still evident. All of these results suggest that inhibitory effects occur at the pituitary and hypothalamus. It remains to be confirmed w hether the major effect is at the pituitary by reducing GnRH receptor or LH synthesis, or at the hypothalamus via inhibition of GnRH secreti on.