The Effects of High Peripubertal Caffeine Exposure on the Adrenal Gland in Immature Male and Female Rats

Abstract

The consumption of high levels of dietary caffeine has increased in children and adolescents. Human and animal studies have shown that chronic intake of high doses of caffeine affects serum glucocorticoid levels. Given that glucocorticoids play a role in peripubertal organ growth and development, chronic high doses of caffeine during puberty might impair maturation of the adrenal glands. To evaluate any effects of caffeine exposure on growing adrenal glands, 22-day-old male (n = 30) and female Sprague Dawley rats (n = 30) were divided into three groups (n = 10/group); group 1 received tap water (control) and groups 2 and 3 received water containing 120 and 180 mg/kg/day caffeine, respectively, via gavage for 4 weeks. At the end of the experiment, adrenal glands were weighed and processed for histological analysis. Relative adrenal weights increased in both groups of caffeine-fed males and females, whereas absolute weights were decreased in the females. In the female caffeine-fed groups the adrenal cortical areas resembled irregularly arranged cords and the medullary area was significantly increased, whereas no such effects were seen in the male rats. Our results indicate that the harmful effects of caffeine on the adrenal glands of immature rats differ between females and males. Although female rats seemed to be more susceptible to damage based on the changes in the microarchitecture of the adrenal glands, caffeine affected corticosterone production in both female and male rats. In addition, increased basal adrenocorticotropic hormone levels in caffeine-fed groups may reflect decreased cortical function. Therefore, caffeine may induce an endocrine imbalance that disturbs the establishment of the hypothalamo–pituitary adrenal axis during puberty, thereby leading to abnormal stress responses.

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“…It initiates the release of ACTH that can excite the adrenal medulla and cortex ensuing in the excess release of adrenaline and corticosterone, respectively. The adrenal hypertrophy (increase in adrenal gland weight) takes place in response to the secretion of ACTH from the pituitary for increased corticosterone from cortical cells to contest stress [30] and also continues stress could alter the endocrine balance that disrupts the establishment of the HPA axis, thus it leading to inappropriate stress responses [31] and also adrenal medulla is alarmed due to rapid-onset responses to stress challenges, consisting of an early release of previously stored catecholamines which is directly neurally mediated. By contrast, the adrenocortical response to stress is delayed and consists of a neuroendocrine cascade of humoral mediated processes.…”