Effect of Induced Hypoglycemia on Postnatal Development of The Adrenal Gland in Albino Rats

BACKGROUND: Hypoglycemia is a life threatening stressor that is usually encountered in the neonatal period due to congenital hyperinsulinism, inborn error of carbohydrate metabolism or intensive insulin therapy for juvenile onset diabetes mellitus. Recurrent hypoglycemia usually affects the function of the adrenal gland. This evoked a question in this study; does this disaster stressor also affect the postnatal development of this gland? OBJECTIVES: This study was designated to elucidate the effect of experimentally-induced recurrent episodes of hypoglycemia on the postnatal development of the adrenal gland in the albino rat. MATERIAL AND METHODS: Offspring rats of two weeks age were randomly divided into three equal groups, of 24 each. Group 1 (Negative control group): the offspring were not given any medication. Group 2 (Positive control group) were injected with 0.3ml normal saline subcutaneously (SC) three times weekly. Group 3 (Hypoglycemic group) were exposed to hypoglycemic episodes via SC injection with 3 IU/kg of human regular insulin three times weekly. Each of the above-mentioned groups was further subdivided (according to the week of sacrification) into four equal subgroups. 3 weeks (Neonatal), 7 weeks (Pubertal), 11 weeks (Young adult) and 16 weeks (Adult) subgroups. Adrenal gland specimens were processed for light and electron microscopic studies and morphometric measurements including the thickness and cell count of each zone of the gland were performed. Also, body weight and serum cortisol level were measured. RESULTS: In both control groups, the adrenal gland of 3 weeks old rats revealed ill-demarcation between the cortex and medulla. With a stepwise age progress, at the 7 th week there was an apparent differentiation of the cortex into three zones; zona glomerulosa (ZG), zona fasiculata (ZF) and zona reticularis (ZR). At the 11 th week, a differentiation of ZG into outer small and inner large cells was noticed. Ultrastructurally, at 3,7 and 11 weeks, the cortical cells exhibited the normal steroid synthesis criteria of euchromatic nuclei, many mitochondria, smooth endoplasmic reticulum (sER) and many lipid droplets. Also, the chromaffin cells of the medulla displayed their characteristic secretory granules with nerve fibers inbetween. Interestingly, at the 16 th week; nearly similar histological features like those of the previous age subgroup were encountered together with further differentiation of ZF into outer large and inner small cells. On the other hand, hypoglycemia led to detrimental effects on the normal histological architecture of the adrenal gland, where at the 3 rd week, focal hyperplastic areas in the cortex and mild congestion in the medulla were noticed, while at the 7 th week, the cortical zones exhibited more hyperplasia with foci of lipid depletion. Moreover, at 11 th week, partial degenerative changes were displayed, especially in the ZG in the form of irregular small pyknotic nuclei and distorted mitochondria. At 16 th week, the sings of degeneration became prominent in all zones together with marked congestion, cellular infiltration and a decrease in the secretory granules of the medulla. Compared to the both control groups, the hypoglycemic rats exhibited a mild change in the thickness and the cell count of the cortical zones and the medulla. Also, hypoglycemia led to a relative decrease in the body weight and the serum cortisol level at the 16 th week subgroup. CONCLUSION: It could be concluded that hypoglycemia had age-dependent detrimental drawbacks on the postnatal development of the adrenal gland in a zone-specific manner.