Diethylstilbestrol regulates the number of alpha- and beta-adrenergic binding sites in incubated hypothalamus and amygdala

• Published in: Brain research Vol. 248; no. 1; p. 79
• Main Authors: Wilkinson, M, Herdon, H J
• Format: Journal Article
• Language: English
• Published: Netherlands 23.09.1982
• Subjects: Amygdala - drug effects; Animals; Castration; Clomiphene - pharmacology; Culture Techniques; Cyclic AMP - metabolism; Diethylstilbestrol - pharmacology; Dihydroalprenolol - metabolism; Dihydroergotoxine - metabolism; Female; Hypothalamus - drug effects; Male; Rats; Rats, Inbred Strains; Receptors, Adrenergic - drug effects; Receptors, Adrenergic, alpha - drug effects; Receptors, Adrenergic, beta - drug effects; Tamoxifen - pharmacology
• ISSN: 0006-8993
• DOI: 10.1016/0006-8993(82)91149-0

Previous work has identified an effect of circulating estrogens on the number of central adrenergic binding sites. We have further characterized this effect by performing the experiments in vitro and have taken advantage of a well-described hypothalamic preparation in which diethylstilbestrol (DES), is known to elevate cAMP levels through a pathway which involves adrenoreceptors. We show that DES induces a reciprocal change in the numbers of alpha- and beta-adrenergic binding sites in incubated hypothalami obtained from intact immature female rats as well as from ovariectomized adult rats. The alpha-adrenergic binding sites are reduced by 25-30% whereas the beta-adrenergic sites are increased by 60-100%. The effect is maximal at 3 h in vitro (20 microM DES) and largely reversible following a 2 h wash in the absence of DES. Using the change in beta-adrenergic binding sites as a probe, we were further able to show that estradiol (100 microM) and 2-hydroxyestradiol (50 microM) had no effect. Further, the effect of DES was not blocked by the anti-estrogens clomiphene or tamoxifen. Since DES is able to elevate beta-adrenergic binding sites in hypothalamus and amygdala (brain areas known to contain high levels of estrogen receptors) but has no effect in cerebellum, we conclude that we have observed an effect of DES not shared by estradiol but which may be confined to estrogen target areas of the brain.