From 2200 h of Day 8 through 2200 h of Day 11, PSP rabbits were injected at 12 h intervals with 0.1 ml sesame oil alone (control), or with oil containing either 1.5 µg E (E-1.5) or 15 µg E (E-15). Several animals from each group were killed between 1000-1100 h the following morning (Day 12). The remaining animals were either switched from E-15 or E-1.5 to oil (E-withdrawal), were switched from E-15 to E-1.5, or were maintained on their original E regiments. The final injections were at 0800 h on Day 14 and the animals were killed 2-3 h later. Adenylyl cyclase activities and serum and luteal progesterone levels were determined.

We found that: 1) Withdrawal of E-15 did not reverse the E-15-induced inactivation of the LH-responsive adenylyl cyclase, nor did it alter the isoproterenol-responsive adenylyl cyclase. 2) Withdrawal of E-1.5 had no effect on the degree of hormonal responsiveness of the adenylyl cyclase when compared with control values. 3) E-15 withdrawal but not E-1.5 withdrawal, resulted in a significant decrease in serum and luteal progesterone content, but 4) did not result in a decrease in the weight of the CL within the 48-h time period tested. 5) Switching from E-15 to E-1.5 treatment did not cause a drop in serum progesterone concentrations, but 6) resulted in LH-stimulated cyclase activity, which although somewhat elevated over that found in animals treated with E-15 throughout, was still markedly decreased compared with controls or rabbits treated with E-1.5.

These results suggest that 1) a high dose of estradiol is required to establish a "dependency" on exogenous E in CL of PSP in rabbits; 2) low levels of exogenous E are sufficient to fulfill the requirements imposed by this E "dependent" state; and 3) the establishment of "dependency" on E is associated with the decrease in the LH-responsive adenylyl cyclase, an unphysiological situation. These data provide evidence that while a partial reversal of the suppression of cyclase activity by high levels of estradiol is possible, it proceeds only slowly taking several days to become effective.