A Quantitative Analysis of the Physiological Role of Estradiol and Progesterone in the Control of Tonic and Surge Secretion of Luteinizing Hormone in the Rat*

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Abstract
The implantation of Silastic capsules containing estradiol in oil or crystalline progesterone was used to analyze the physiological role of estradiol and progesterone in the control of tonic and cyclic LH [luteinizing hormone] secretion in the rat. Implants were placed s.c. immediately after ovariectomy and blood samples collected 3 or 4 days later. Concentrations of LH, estradiol and progesterone were measured by specific radioimmunoassays and compared with the levels of these hormones during the estrous cycle. In the absence of any progesterone treatment diestrous concentrations of estradiol (up to 23 pg/ml) were unable to inhibit completely the post-castration rise in serum LH levels. Increasing the serum progesterone concentration to the basal level observed on diestrus day 3 (8 ng/ml) had no effect on tonic LH secretion in the absence of estradiol treatment. In the presence of this concentration of progesterone, diestrus day 2 levels of estradiol (13 pg/ml) were effective in inhibiting tonic LH secretion. Luteal phase concentrations of progesterone further reduced the level of estradiol required to inhibit the post-castration rise in serum LH so that diestrus day 1 estradiol levels (10 pg/ml) were sufficient. The time course of tonic LH secretion throughout the rat estrous cycle can be accounted for by the secretory pattern of both estradiol and progesterone during the cycle. Although progesterone enhanced the negative feedback action of estradiol on tonic LH secretion, it appeared to inhibit the positive feedback effects of estrogen. Increasing serum estradiol concentrations to diestrous levels (12 pg/ml) in the ovariectomized rat resulted in an LH surge. In the presence of diestrus day 3 levels of progesterone (9 ng/ml), proestrous levels of estradiol (32 pg/ml) were required to induce LH release. Basal secretion of progesterone by the ovary increases the serum concentration of estradiol required to trigger the preovulatory LH surge and hence acts to limit this discharge of LH to the day of proestrus. Luteal phase levels of progesterone (30 ng/ml) blocked the ability of proestrous levels of estradiol (32 pg/ml) to induce an LH discharge. This blockade has no physiological significance, since estradiol levels are too low throughout diestrus day 1 and day 2 to initiate LH release in the presence of basal progesterone secretion by the ovary.