Biphasic Effect of Estradiol Benzoate on the Pituitary Responsiveness to LH-RH1

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Abstract
Pituitary responses to LH-releasing hormone (LH-RH) was studied in normal diestrous rats 2, 4, 6, 9, 14, 24, and 48 hr after injection of estradiol benzoate (EB). A dose of 0.4 µg LH-RH always raised serum LH in the oil-treated rats. The magnitude of the increase varied according to the stage of the estrous cycle, being greatest in proestrus, and smallest between the evening of the day of diestrus I and the morning of the day of diestrus II. Two to 6 hr after pretreatment with EB, injection of this dose of LH-RH failed to induce a significant rise of serum LH. At 9 hr, the same dose of LH-RH did increase serum LH, the magnitude of the response being the same as that found in the oil-treated control rats. By 14–24 hr, EB had augmented the pituitary response to LH-RH. At 48 hr, the magnitude of the rise of serum LH after LH-RH in EB-treated rats was like that found at 24 hr, but this high responsiveness to LH-RH apparently can not be attributed to the EB since a similar responsiveness was seen in the respective oiltreated group. The basal levels of LH in the oil-treated rats were lowest at the evening of diestrus I and in the morning of diestrus II. On the other hand, pretreatment with EB lowered the basal LH levels 2–24 hr later. From these results, it is evident that in rats EB, at the dose used, exhibited a biphasic effect of the pituitary response to LH-RH, the early effect being inhibitory and the later effect being stimulatory. (Endocrinology94: 1300, 1974)