The mouse adrenal gland

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.