Down-regulation of estrogen receptor immunoreactivity by 17 beta-estradiol in the guinea pig forebrain.
Low amplitude pulses of estradiol-17 beta (E2-17 beta) are more effective than large single bolus injections or constant exposure to E2-17 beta in inducing progesterone-facilitated sex behavior in female rats and guinea pigs. The present study examined whether the increased responsiveness to E2-17 beta is due to an increase in the number of estrogen receptors in the estrogen receptor rich areas of the hypothalamus and amygdala. Initial studies examined the rapid effects (20 min) of a high dose of E2-17 beta (50 micrograms) on estrogen receptor immunostaining using either the H222 antibody or the ER 21 antiserum. ER 21 immunostaining was not affected by the E2-17 beta treatment suggesting that it binds to both occupied and unoccupied estrogen receptors. Therefore the ER 21 antiserum was used to characterize the regulation of estrogen receptor immunoreactivity (ER-IR) by E2-17 beta. ER-IR was examined for 48 h and serum E2-17 beta for 24 h following a 2 micrograms s.c. injection of E2-17 beta (a dose similar to that used in multiple pulse paradigms). Serum E2-17 beta peaked 15 to 30 min following the injection and returned to baseline values by 1 h. In all but one area maximal suppression of ER-IR occurred at 12 h. In summary, 1) decreases in estrogen receptor immunoreactivity following E2-17 beta are consistent with studies in which estrogen receptors were assayed by binding assays and estrogen receptor mRNA was determined by in situ hybridization; 2) the ER 21 antiserum is able to detect both occupied and unoccupied estrogen receptors and 3) H222 immunoreactivity is influenced by the presence of E2-17 beta, so that the level of H222-IR is a reflection of ligand/receptor binding dynamics. The data suggest that up-regulation of estrogen receptors does not account for the increase in behavioral sensitivity which is observed following multiple pulses of E2-17 beta.
Meredith
J M
JM
Psychology Department, University of Massachusetts, Amherst 01003-7710.
Auger
C J
CJ
Blaustein
J D
JD
D000679:Amygdala / Q000378:metabolism; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism; D015536:Down-Regulation; D004958:Estradiol / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D007031:Hypothalamus / Q000378:metabolism; D007700:Kinetics; D010052:Ovariectomy; D011301:Preoptic Area / Q000378:metabolism; D016548:Prosencephalon / Q000378:metabolism*; D051381:Rats; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism*
D011960:Receptors, Estrogen; D004958:Estradiol