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The gonadotrophic response to a single injection of oestradiol benzoate (OB) was studied in acutely ovariectomized adult rats during the different stages of a 4-day ovarian cycle. The results showed a sudden decline of the sensitivity to the gonadotrophin-inhibiting effect of OB between metoestrus and dioestrus. This desensitization to the negative oestrogen feedback was probably caused by an oestrogen action on the medial preoptic area (MPOA). In rats ovariectomized and implanted with OB in the MPOA in metoestrus, an s.c. injection of OB on the presumptive day of pro-oestrus did not lower the circulating LH and FSH levels, whereas a clear suppression of gonadotrophin secretion was seen in females implanted with cholesterol in the MPOA or implanted with OB in the hypothalamic ventromedial–arcuate region. Similar findings were obtained in rats which had been ovariectomized 3–4 weeks before implantation. A final experiment demonstrated that bilateral lesioning of the MPOA also reduced the sensitivity to the negative feedback action of oestrogen in long-term ovariectomized rats. In all experiments performed, diminution of the oestrogen-induced inhibition of LH secretion was more marked than that of suppression of FSH secretion. It is proposed that desensitization to the negative oestrogen feedback, probably resulting from an inhibitory oestrogen action on medial preoptic neurones, is a prerequisite for adequate gonadotrophic support of preovulatory follicle maturation in the presence of a continuously rising oestrogen concentration in the blood.

J. Endocr. (1984) 102, 287–294