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Bielohuby, Maximilian (2007): The mouse adrenal gland: age- and gender- dependent alterations of growth and function. Dissertation, LMU München: Tierärztliche Fakultät



The adrenal gland is a complex endocrine organ and its secreted hormones affect a multitude of essential systems, including stress response, immune function, cardio vascular regulation and anabolic or catabolic processes. In order to define age-dependent changes within the adrenal gland in the mouse, a systematic analysis of functional and growth-related parameters was performed by investigating the adrenal glands of male and female mice from weaning to adulthood (weeks 3, 5, 7, 9 and 11) at the organ, compartment, and cellular level. Therefore, an adrenal weight analysis was performed and the absolute volume of every adrenal zone was determined using unbiased stereological methods. At the cellular level, zona fasciculata (ZF) mean cell volume and total cell number were analysed at five distinct points in time. Furthermore, the amount of stored lipids and the expression of two enzymes involved in steroidogenesis, side-chain-cleavage enzyme (SCC) and 11-beta-hydroxylase, were explored in the adrenal glands at selected points in time. Serum aldosterone and corticosterone concentrations were monitored throughout the investigation period as functional readouts of the zona glomerulosa and the ZF, respectively. Results: Increasing weights of the adrenal glands were observed until week 7. Of note is a significant adrenal weight reduction by 25 % exclusively in male mice, between weeks 7 and 9. Adrenal glands in female mice principally displayed higher weights. At an age of 9 weeks, this weight difference reached a maximum, with female mice characterized by two-fold higher adrenal gland weights than male mice. The weight dimorphism was in particular due to an enlarged ZF in female mice. Also the X-Zone and the medulla, showed increased volumes if compared to male littermates. No gender-dependent volume difference was found in the zona glomerulosa. In addition to the gender-dependent growth effects, time-dependent growth features were observed in each zone, and every zone, with the exception of the X-zone in males, gradually increased in volume between weeks 3 and 7 of age. Time- and gender-dependent effects were also studied at the cellular level in the ZF, where effects of sex and age on the mean cell volumes as well as on the total cell number were present. From week 5 onwards, the ZF of female mice comprised significantly more cells if compared to their male counterparts. In both genders, the number of ZF cells reached a maximum at the age of 7 weeks and decreased significantly until week 9. In male mice, the mean volume of ZF cells increased between 3 and 11 weeks of age. In 3- to 7-week-old female mice ZF mean cell volumes were similar, however, between 7 and 9 weeks of age, a volume increase by approximately 50 % was observed. A positive association of ZF total cell number with the estimated total amounts of corticosterone in the circulation (ETAC) could be established, in contrast, no association of ZF mean cell volume and the ETAC was found. Serum aldosterone concentrations were similar in both genders, in contrast serum corticosterone levels were higher, at least as a tendency, in female mice. Moreover, dynamic changes of both steroid hormone concentrations were observed in a time-dependent manner. The aldosterone concentrations increased over time, whereas the corticosterone levels decreased significantly between weeks 3 and 11. The amount of stored lipids in the adrenal glands appeared to be higher in female mice if compared to male mice and the adrenal glands of 11-week-old male and female mice seem to store more lipids than 7-week-old mice. Also the expression of the two analysed enzymes, SCC and 11-beta-hydroxylase, increased between 3 and 11 weeks of age in both sexes, indicating that 11-week-old mice might have a higher steroidbiosynthesis capacity than the younger mice. In conclusion, this study demonstrates that, between weaning and adulthood dynamic processes are present on multiple levels of adrenal gland growth. Specific adrenal growth regulation occurs through the influence of age, sex, cell type, cell number and cell size. A particular finding of the study is, that growth is not a unidirectional process by constant increases of cell size and cell number and that decreases of cell number may be compensated by increases of cell volumes. Certainly, these dynamic processes can be assumed to affect also functional parameters, however the final quantity of corticosterone secreted can only be explained in parts as a function of ZF cell size or ZF cell number, respectively. In general, this work supports the systemic approach integrating multiple information from various levels being more and more relevant for future research projects.