Therefore, adrenals from mice and other rodents are devoid of the secretion of adrenal androgens ( 19). In contrast to other mammals, mice and rats do not have a functionally distinct zona reticularis because of the lack of 17α-hydroxylase expression in the adrenal gland. These zones play distinct roles in steroid hormone production ( 19). The cortex contains three histologically distinct zones, outmost the “zona glomerulosa”, followed by the “zona fasciculata”, and the “zona reticularis” directly surrounding the medulla ( 1). The mammalian adrenal gland is composed of two distinct functional compartments, i.e., the cortex and the medulla. However, a prerequisite for this approach is detailed knowledge of physiological growth of the adrenal glands in non-transgenic mice ( 34). Genetic engineering ( 9, 16, 35, 36) and random mutagenesis projects ( 17, 26) in the mouse provide novel models for dissecting the roles of growth factor systems and their individual components for adrenal growth processes.

Growth and function of the adrenal glands are regulated by pituitary proopiomelanocortin-derived ACTH, neurotransmitters, neuropeptides, cytokines, and growth factor networks ( 6, 13, 18). The adrenal glands are complex endocrine organs regulating multiple physiological processes, such as metabolism, stress response, immune functions, and the cardiovascular system ( 5, 6, 22).

These factors require careful consideration in studies aiming at the functional dissection of genetic and environmental factors affecting adrenal growth and function. In conclusion, our results demonstrate that growth and function of the adrenal glands are markedly influenced by gender and age. In the zona glomerulosa and in the X-zone, time- and gender-dependent growth effects were observed. Furthermore, total circulating corticosterone was higher in females than in males at an age of 5 and 11 wk. However, the estimated total amounts of corticosterone in the circulation were similar in 3- and 11-wk-old mice. Serum corticosterone concentrations decreased from 3 to 11 wk of age both in male and female mice. In both genders, the number of zona fasciculata cells reached a maximum at the age of 7 wk and decreased significantly until week 9. The volume of the zona fasciculata was consistently higher in female vs. Female adrenal glands displayed a higher weight at any stage investigated. Adrenal weights increased from week 3 to week 7 in male and female mice, remained at this level in females, but decreased by 25% between week 7 and week 9 in males. We performed the first systematic analysis of adrenal gland growth using unbiased stereological methods in male and female mice from weaning to adulthood ( weeks 3, 5, 7, 9, and 11) at the organ, compartment, and cellular levels. The adrenal gland is of critical importance for a plethora of biological processes.

Adrenal cortex adrenal medulla