DOWN-REGULATION OF ESTROGEN-RECEPTOR IMMUNOREACTIVITY BY 17-BETA-ESTRADIOL IN THE GUINEA-PIG FOREBRAIN

Low amplitude pulses of estradiol-17 beta (E(2)-17 beta) are more effe ctive than large single bolus injections or constant exposure to E(2)- 17 beta in inducing progesterone-facilitated sex behavior in female ra ts and guinea pigs. The present study examined whether the increased r esponsiveness to E(2)-17 beta is due to an increase in the number of e strogen receptors in the estrogen receptor rich areas of the hypothala mus and amygdala. Initial studies examined the rapid effects (20 min) of a high dose of E(2)-17 beta (50 mu g) on estrogen receptor immunost aining using either the H222 antibody or the ER 21 antiserum. ER 21 im munostaining was not affected by the E(2)-17 beta treatment suggesting that it binds to both occupied and unoccupied estrogen receptors. The refore the ER 21 antiserum was used to characterize the regulation of estrogen receptor immunoreactivity (ER-IR) by E(2)-17 beta. ER-IR was examined for 48 h and serum E(2)-17 beta for 24 h following a 2 mu g s .c. injection of E(2)-17 beta (a dose similar to that used in multiple pulse paradigms). Serum E(2)-17 beta peaked 15 to 30 min following th e injection and returned to baseline values by 1 h. In all but one are a maximal suppression of ER-IR occurred at 12 h. In summary, 1) decrea ses in estrogen receptor immunoreactivity following E(2)-17 beta are c onsistent with studies in which estrogen receptors were assayed by bin ding assays and estrogen receptor mRNA was determined by in situ hybri dization; 2) the ER 21 antiserum is able to detect both occupied and u noccupied estrogen receptors and 3) H222 immunoreactivity is influence d by the presence of E(2)-17 beta, so that the level of H222-IR is a r eflection of ligand/receptor binding dynamics. The data suggest that u p-regulation of estrogen receptors does not account for the increase i n behavioral sensitivity which is observed following multiple pulses o f E(2)-17 beta.