Involution of rat thymus: characterization of cytoplasmic glucocorticoid receptors, evidence of glucocorticoid resistant dexamethasone receptor-positive cells.

Abstract

In rats, thymic relative weight increased after birth reaching maximum values between days 15-30 and then decreased markedly in a similar way in both sexes, while the organ's absolute weight continued to increase until days 80-90 and declined slowly with apparent sex differences from day 30 onward. Scatchard analysis revealed that the [3H] dexamethasone (Dexa) receptor sites concentration showed a pattern comparable to that found in relative thymic weight, with no change in the apparent KD. The reduction of lymphocytes mitotic activity resulting in reduction of immature thymocytes production must be accompanied by a fall of the number of glycocorticoid receptors in ageing thymuses. Despite the profound decrease in the glucocorticoid receptor sites levels, the thymus sensitivity to Dexa remained unchanged during development. Indeed, in prepuberal and adult rats, the steroid administration was followed 4 days after by a transient thymic weight loss of about 70-80% which was mainly linked to the reduction in the cortical area. In contrast, the density of [3H] Dexa binding sites was reduced unexpectedly by 25% only after steroid treatment. These findings provided evidence that Dexa receptor-positive population cells in thymus was formed in a large part by relatively glucocorticoid resistant cells.