Role of Estrogen as Initiator of Daily LH Surges in the Ovariectomized Rat¹²

Abstract

The following studies were performed to determine whether the occurrence of daily LH surges in long-term ovariectomized rats requires an increment in circulating estradiol concentrations, and if so, to investigate the nature of the estrogen stimulus. On the 15th day after bilateral ovariectomy (day 0), estradiol benzoate (EB, 50 μg/rat SC in sesame oil), estradiol–17β in Silastic capsules implanted SC, or sesame oil was administered at 7:00 AM. Within 10 hr following EB treatment, circulating estrogen increased to approximately 1800 pg/mland then declined progressively during the next 4 days to 100 pg/ml. Following insertion of estradiolimplants, however, serum estradiol levels attained maxima of approximately 125 pg/ml within 1 hr anddecreased within 14 hr to 75 pg/ml, a level maintained until implant removal. Blood samples were withdrawn from unanesthetized rats by carotid cannula or by cardiac puncture at 6:00 AM on day 0 and at 12:30 and 5:00 PM on days 0–4. Within 5½ hr following administration of EB or estradiol, circulating LH concentrations declined approximately 65% to levels 10- to 20-fold greater than those seen in diestrous rats, and remained low for 5 days insamples obtained at 12:30 PM. This sustained suppression of tonic LH secretion was interrupted by a striking increase in plasma LH levels on each of the next 4 days at 5:00 PM, a time coinciding with the preovulatory LH surge. These observations,coupled with the finding that the daily LH discharge could be blocked by administration of sodium pentobarbital, suggest that the mechanism controlling LH surges in long-term ovariectomized rat functions with 24-hr periodicity and has a neural component. A daily LH discharge was not observed at 5:00 PM in oil-treated ovariectomized controls. Finally, when the increment in serum estradiol was terminated abruptly by removal of the implants after 29½hr, the LH surges persisted for 4 days. These results suggest that an increment in circulating estradiol concentrations is necessary for the initiation, but not continuation, of a daily LH surge in long-term ovariectomized rats. (Endocrinology96: 50, 1975)