The Endocrine Basis of the Synergistic Suppression of Luteinizing Hormone by Estradiol and Progesterone*

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Abstract
The basis of the synergism between estradiol and progesterone in suppressing tonic (pulsatile) LH secretion was examined in the ewe, making use of the observation that progesterone exerts its inhibition selectively on LH pulse frequency, while estradiol decreases only pulse amplitude. To accomplish this, we analyzed changes in LH pulse patterns produced by a low level of progesterone in ovariectomized ewes treated with Silastic estradiol implants from the time of gonadectomy. A. serum progesterone level of about 1 ng/dml was chosen because it inhibits LH only in the presence of estradiol. Under these circumstances, a decrease in LH pulse amplitude during progesterone treatment would suggest that progesterone increased the response to the existing level of estradiol; a decrease in pulse frequency would suggest that estradiol increases the effectiveness of progesterone. It was found that the low level of progesterone produced a decrease in LH pulse frequency in estradioltreated ovariectomized ewes without altering pulse amplitude. These reults are consistent with the hypothesis that the synergism of these two steroids reflects, at least in part, an estradiolinduced increase in the sensitivity of the central nervous system to the negative feedback action of progesterone.