Species-Specificity of Corticosteroid Receptors in Hamster and Rat Brains

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Abstract
In vitro cytosolic receptor binding assays and autoradiographical procedures have shown the localization and properties of two corticoid receptors types in the brain of the rat, a species in which corticosterone (B) is the predominant circulating glucocorticoid. The present study was designed to examine the localization, heterogeneity, and binding specificity of corticosteroid receptors in the brain of the hamster, a species which secretes B and cortisol (F), the latter being the predominantly circulating form. Our results show that two corticoid receptor systems can also be distinguished in the hamster brain. The type I receptor has an almost exclusive localization in the hippocampal region and the amounts measured in hypothalamic or whole brain (without the hippocampus) were negligible. The type II receptor, on the other hand, has a wider distribution in the brain. Scatchard and Woolf analyses of the binding data revealed that the hamster type I receptor has similar affinity to both F and B [dissociation constant (Kd) 0.9 nM]. In contrast the rat type I binds with higher affinity to B (Kd, 0.9 nM) than to F (Kd, 2.2 nM). The hamster type II binds to F with much higher affinity (Kd, 2.9 nM) than does the rat type II to F (Kd, 20.1 nM). This was similarly observed, although less pronounced in the binding of the hamster type II and the rat type II to B (Kd, 0.5 and 3.9 nM, respectively). Analysis of relative binding affinity of each receptor type gave the following results. Hamster type I: F > B .mchgt. aldosterone (ALDO) > dexamethasone (DEX); rat type I: B > F > ALDO > DEX; hamster type II: B > DEX > F .mchgt. ALDO; rat type II: DEX > B .mchgt. F .mchgt. ALDO. Graded doses of F or B given sc to adrenalectomized animals result in differential occupancy of the two receptor systems. In hamster, 1.0 .mu.g F vs. 1.0 mg B/100 g BW is required to occupy 80% of type I site. The rat shows the opposite (1.0 .mu.g B vs. 5.0 to 10.0 mg F/100 g BW to occupy type I to the same extent). The hamster type II is 80-90% occupied by an equal dose of F or B (1.0 mg/100 g BW) whereas in the rat, F at 5-10 mg/100 g BW (doses 5-10 times that of B) is required to achieve this same occupancy. This data demonstrate the existence of two corticoid-receptor systems in the brain of hamster, a species which resembles primates including human in having F as the predominantly circulating glucocorticoid. Moreover, the type I receptor system displays in vivo stringent preference for retention of F in hamsters vs. B in rats and has lost its affinity towards mineralocorticoids as observed in the rat. Finally, the type II system does not show preference for B or F in the hamster but displays low affinity to F in the rat.