The Site of the Positive Feedback Action of Estradiol in the Rat*

Abstract

The bilateral stereotaxic implantation of estradiol into the brain of acutely ovariectomized rats was used to determine the hypothalamic sites of the positive feedback action of this steroid. Estradiol transport from the site of implantation to the adenohypophysis was assessed by monitoring pituitary estradiol concentrations by radioimmunoassay. These concentrations were compared with the pituitary estradiol levels associated with LH (luteinizing hormone] release in the intact and estrogen-treated ovariectomized rat. The estradiol concentration in the pituitary increased gradually from 0.2 to 1.0 pg/mg during diestrus day 1 and day 2 of the estrous cycle and then showed a rapid rise to a plateau of 2.8 pg/mg on the morning of diestrus day 3. The pituitary estradiol concentration was maintained at this level until the initiation of the proestrous LH surge and then fell rapidly to diestrous levels. A similar concentration of estradiol in the pituitary (2.9-3.4 pg/mg) was associated with LH release in ovariectomized animals given Silastic capsules containing estradiol s.c. Estradiol implanted in the preoptic area elicited an LH discharge in 56% of the animals, although pituitary estradiol concentrations were only elevated to 1.0 .+-. 0.2 pg/mg (n = 48). A similar frequency of response (64%) was observed in control animals implanted s.c. with Silastic capsules containing estradiol that produced high serum estradiol concentrations (100 pg/ml). Estradiol implants in the anterior hypothalamic area initiated LH release in 36% of the animals and produced pituitary estradiol concentrations of 1.5 .+-. 0.5 pg/mg (n = 22). The implantation of estradiol into the medial basal hypothalamus (MBH) produced pituitary estradiol levels (11.5 .+-. 1.9 pg/mg, n = 34), much greater than the concentration normally associated with LH release but elicited an LH surge in only 6% of the animals. These positive responses could be attributed to the elevation in serum estradiol produced by the MBH implants. Unlike estradiol, estradiol benzoate failed to elicit LH release when implanted into the preoptic area. The difference between the actions of estradiol and estradiol benzoate is a low esterase activity in neural tissue (20% that of blood). This finding provides an explanation for the inability of previous workers to advance ovulation by the implantation of estradiol benzoate into the preoptic area. In the rat high pituitary estradiol concentrations alone cannot stimulate LH surges. The MBH is not the site of the positive feedback action of estradiol. Estradiol can act at the level of the preoptic area to induce LH release.