756 
PHARMACOLOGY 
Autoradiographs were prepared from thymus 
imprints on gelatin coated slides which were 
fixed in ten percent formalin with phosphate 
buffer. They were dipped in Kodak NTB-3 nu- 
clear track emulsion, exposed for eight weeks at 
4° C and developed with Kodak D-19 developer 
and F-5 fixer at 18° C. For autoradiographic 
studies, the rats were injected with five fxc per 
gram body weight of ^H-deoxycytidine intra- 
peritoneally one hour prior to sacrifice. Routine 
histological sections of the thymus fixed in 
phosphate buffered ten percent formalin and 
stained with hematoxylin and eosin were exam- 
ined at zero and eight hours and at one, two, 
three, four, five, seven, and ten days after dexa- 
methasone injection. 
RESULTS 
The rate of DNA synthesis in the thymus 
reached its minimum one day after dexametha- 
sone while the DNA content of the thymus 
reached its minimum at three days and the rate 
of cell production was reduced to a minimum 
during the entire interval one to three days 
after dexamethasone (Table I). By ten days, 
these three parameters had returned essentially 
to normal. The percentage of cells labeled with 
^H-deoxycji;idine in autoradiographs paralleled 
the changes in DNA turnover. One to three 
days after dexamethasone, the percentage of la- 
belled cells fell to the range of five to ten per- 
cent as compared with twenty percent in 
untreated controls. Five days after dexametha- 
sone, fifty to sixty-five percent of the cells were 
synthesizing DNA and by ten days this had re- 
turned essentially back to normal. 
Histologically there were massive numbers of 
pycnotic thymic lymphocytes in the cortex eight 
hours after dexamethasone. At one day, the cor- 
Table I. — Response of the Adult Rat Thymus to a 
Single Intravenous Injection of Dexamethasone 
Time after DNA-P content DNA turnover Cell production 
dexamethasone (uKm per hour per hour 
0 _ 910 0.040 54 X 10« 
1 day 352 0.0035 1.8 x 10" 
3 days 88 0.056 7.3 x 10« 
5 days 266 0.082 32 x 10' 
10 days _ 798 0.045 53 x 10» 
tex was reduced in width and the numbers of 
these pycnotic nuclei had diminished. At three 
days, the thinned cortex consisted chiefly of epi- 
thelial cells while the medulla contained many 
lymphocytes, a reversal of the cortico-meduUary 
ratio. At five days in the cortex there was a sig- 
nificant return of thymic lymphocytes, many of 
which were undergoing mitosis and by ten days, 
the histological appearance had been nearly re- 
stored to normal. 
DISCUSSION 
The thymus may be divided into three com- 
partments: A replicating cell compartment, a 
differentiating cell compartment, and a residual 
cell compartment. The replicating cell compart- 
ment consists of stem cells that divide repeat- 
edly. Approximately one-half of the daughter 
cells are retained in this compartment as stem 
cells and of the remaining newly formed cells, a 
portion of them migrate from the thymus or are 
destroyed within the thymus soon after mitosis 
is completed. The remaining daughter cells 
enter the second compartment which consists 
chiefly of small thymocytes where they remain 
for a period of time and where differentiation 
of some of the cell membrane determinants oc- 
curs. The third or residual cell compartment 
consists of epithelial and stromal cells and me- 
dullary lymphcytes which are long-lived and un- 
affected by adrenocorticosteroids. 
The size of the replicating compartment can 
be estimated from the percentage of cells la- 
beled at one hour on autoradiographs with 
^H-deoxycytidine to contain about twenty per- 
cent of the thymus cells. The residual cell com- 
partment can be estimated from the fraction of 
cells remaining when the thymus attains its 
minimum size after dexamethasone to contain 
ten percent of the thymus cells. The differen- 
tiating or small thymocjte compartment con- 
tains the balance of thymus cells or seventy 
percent of the thymus. The average generation 
time of cells in the replicating compartment 
was approximately five hours on the basis of the 
hourly fractional turnover rate for the whole 
thymus and the size of the replicating compart- 
ment. The average holding time for cells in the 
small thymocyte compartment can be estimated 
