Differential up- and down-regulation of type I and type II receptors for adrenocorticosteroid hormones in mouse brain.
Adult female mice were adrenalectomized and ovariectomized and the concentration of Type I and Type II receptors in whole brain, kidney, and liver cytosol determined at various time thereafter by incubation with [3H]aldosterone (+ RU 26988 to prevent binding to Type II receptors) or [3H]dexamethasone, respectively. Type I receptor binding in brain was found to undergo a dramatic biphasic up-regulation, with levels six times that of intact levels by 24 h post-surgery and a doubling again by 4-8 days post-surgery. By 16 days, however, Type I specific binding had returned to intact levels. Similar, but less dramatic fluctuations were seen in kidney and liver, whereas much smaller fluctuations were seen for Type II receptors in all three tissues. In a follow-up study with Scatchard analyses we observed a similar transient up- and down-regulation in maximal binding for Type I, and to a lesser extent Type II receptors in all three tissues. As expected, the apparent binding affinity for both receptors increased after surgical removal of competing endogenous steroids. Radioimmunoassays revealed that plasma concentrations of corticosterone were reduced to near undetectable levels by 24 h post-surgery. A direct comparison of male and female mice revealed no sex-related differences in Type I receptor binding capacity fluctuations in brain cytosol after adrenalectomy-gonadectomy. Lastly, treatment with exogenous aldosterone or corticosterone was found to prevent adrenalectomy-gonadectomy-induced up-regulation of Type I and, to a lesser extent, Type II receptors in brain. Somewhat surprisingly, the potency of these two adrenocorticosteroids appeared to be very similar for both receptor types.
Luttge
W G
WG
Department of Neuroscience, University of Florida College of Medicine, Gainesville 32610.
Rupp
M E
ME
D000315:Adrenalectomy; D000450:Aldosterone / Q000502:physiology; D000732:Androstanols / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D010052:Ovariectomy; D018043:Receptors, Corticotropin; D011979:Receptors, Pituitary Hormone / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D013256:Steroids / Q000378:metabolism
D000732:Androstanols; D018043:Receptors, Corticotropin; D011979:Receptors, Pituitary Hormone; D013256:Steroids; D000450:Aldosterone; C038341:RU 26988; D003907:Dexamethasone