Endocrinology, Vol 121, 1405-1411, Copyright © 1987 by Endocrine Society

ARTICLES

Species-specificity of corticosteroid receptors in hamster and rat brains

W Sutanto and ER De Kloet
Rudolf Magnus Institute for Pharmacology, Medical Faculty, University of Utrecht, The Netherlands.

In vitro cytosolic receptor binding assays and autoradiographical procedures have shown the localization and properties of two corticoid receptor 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 greater than B much greater than aldosterone (ALDO) greater than dexamethasone (DEX); rat type I: B greater than F greater than ALDO greater than DEX; hamster type II: B greater than DEX greater than F much greater than ALDO; rat type II: DEX greater than B much greater than F much greater than 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 microgram 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 microgram 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

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