Wc. Engeland et al., DIFFERENTIAL GENE-EXPRESSION OF CYTOCHROME-P450 11-BETA-HYDROXYLASE IN RAT ADRENAL-CORTEX AFTER IN-VIVO ACTIVATION, Endocrinology, 138(6), 1997, pp. 2338-2346
In situ hybridization histochemistry was used to monitor the expressio
n of 3 beta-hydroxysteroid dehydrogenase, delta(4)-isomerase (3 beta H
SD) and cytochrome P450 11 beta-hydroxylase (P45011 beta) messenger RN
A (mRNA) in adult rat adrenals after stimulation in vivo. In Exp I, ad
renals were collected from rats injected with saline or ACTH for I, 2,
3, or 4 days. Adrenal sections from saline-treated rats showed unifor
m expression of 3 beta HSD mRNA that extended fr om the adrenal capsul
e to the medullary border. In contrast, P45011 beta mRNA showed high l
evels in the outer fasciculata and low levels in the inner fasciculata
/reticularis. In response to ACTH, the integrated density of 3 beta HS
D hybridizatian did not increase until 4 days. The integrated density
of P45011 beta hybridization increased in ACTH-treated rats between 1-
4 days due to increased hybridization in the inner fasciculata/reticul
aris. In Exp 2, rats were treated with ACTH or saline, and adrenals we
re harvested at 4, 8, or 24 h. The hybridization density of 3 beta HSD
did not change after ACTH or saline injection. Increased expression o
f P45011 beta mRNA was observed at 4 and 8 h, but not 24 h post-ACTH.
In Exp 3, to determine the response to acute stress, adrenals were col
lected from rats 24 h after surgical laparotomy. The integrated densit
y of 3 beta HSD labeling did not change, whereas both hybridization ar
ea and mean density of P45011 beta increased. Increased expression of
P45011 beta mRNA was observed in the inner fasciculata similar to that
observed after ACTH injection. In addition, adrenal cells were more r
esponsive to ACTH tn ultra after surgical stress. These results sugges
t that the rat adrenal cortex can respond to acute stress by up-regula
tion of the expression of steroidogenic enzyme genes and that this occ
urs in part by increasing the number of cells actively expressing P450
11 beta mRNA. The adrenal response after stress most likely results at
least in part from stimulation by ACTH. These findings suggest that c
hanges in adrenal steroidogenesis in response to ACTH may result from
recruitment of steroidogenic cells to synthesize and secrete corticost
eroids.