Jjr. Hermans et al., COMPARISON OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE IN SPONTANEOUSLY HYPERTENSIVE AND WISTAR-KYOTO RATS, Steroids, 60(11), 1995, pp. 773-779
11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD) modulates glucocort
icoid interactions with mineralocorticoid and glucocorticoid receptors
in vivo, by converting 11 beta-hydroxyglucocorticoids to their inacti
ve 11-ketone derivatives. Defective 11 beta-oxidation of glucocorticoi
ds has been associated with hypertension. The objective of this study
was to investigate whether 11 beta-HSD contributes to the occurrence o
f hypertension in spontaneously hypertensive rats (SHRs). The liver an
d kidney microsomal oxidations of corticosterone (the physiological gl
ucocorticoid in rats) in organs from juvenile (3 weeks old) and adult
(3 months old) SHR and Wistar-Kyoto (WKY) rats, with NAD and NADP, sho
w no differences between rat strains. For cortisol, with NADP, adult S
HRs show (1.3-3 times; P < 0.05) lower kidney microsomal oxidation rat
es. The liver microsomal reduction of cortisone shows remarkable inter
strain differences: with NADH, reduction is conducted only by adult WK
Y rats, whereas with NADPH, juvenile animals show similar reduction ra
tes, but at adulthood, only WKYs reduce cortisone. Using Western blot
analysis with antibodies against 11 beta-HSD1, positive signals are ob
tained only for liver microsomes, appearing somewhat lower in SHRs for
juvenile but not adult animals. Urinary corticosterone/11-dehydrocort
icosterone ratios (measured in adult animals) are not different betwee
n rat strains, but are elevated after administration of corticosterone
in both strains (although significant only in SHRs). The data provide
no indications for exaggerated stimulation of renal corticosteroid re
ceptors, due to modified 11 beta-HSD, in SHRs. However, the experiment
s suggest the existence of multiple 11 beta-HSDs, in addition to 11 be
ta-HSD1 and 11 beta-HSD2, some of which may be modified in SHR, but th
e nature and physiological role of these 11 beta-HSDs is unclear.