Cortisone-induced growth failure in neonatal rats.

Abstract

Extract: Growth failure in two-day-old rats following a single injection of cortisone has been ascribed to thymic destruction. Specific early degeneration of thymus gland, however, has not been demonstrated. Moreover, the cellular changes in other organs accompanying this induced growth failure are unknown. Within 33 hours of injection of cortisone there is marked destruction of thymic and splenic cells, as indicated by a 50-fold reduction in DNA content of these organs. On about the third day following injection, DNA, RNA, and protein content were proportionally reduced in seven other organs studied, and protein: DNA and RNA: DNA ratios remained normal. All organs, therefore, contained fewer cells of normal size. By three weeks of age, the thymus and the spleen were partially regenerated and showed reductions in DNA, RNA, and protein content in proportion to the amount present in other organs. These data demonstrate that the initial event after injection of 1 mg of cortisone in two-day-old rats is the destruction of thymic and splenic cells. This is followed by partial regeneration of these organs. Later, cell division is slowed in other organs, resulting in a stunted animal whose organs contain fewer cells of normal size.Speculation: Injection of a large dose of steroids into young animals will result in selective destruction of lymphoid tissue, subsequent immunologic tolerance, and growth failure. The stunted animal shows a continually reduced number of cells in certain organs. These data reinforce the concept that growth failure after steroid injection is secondary to massive destruction of lymphoid tissue and further support the hypothesis that the thymus may play a role in the regulation of growth during the neonatal period.