The HORMONAL REGULATION OF HEPATIC MICROSOMAL 11β-Hydroxysteroid DEHYDROGENASE ACTIVITY IN THE RAT

Abstract

Hepatic microsomal 11β-hydroxysteroid dehydrogenase activity is higher in male than in female rat liver. Gonadectomy on day 25 of life only affects the activity in the adult male animal, causing a decrease towards the normal female level. Administration of testosterone to gonadectomized rats of either sex causes the induction of typical male activity levels. On the basis of these experiments, this enzyme activity may be classified as androgen-dependent. However, 11β-hydroxysteroid dehydrogenase differs from other known androgen-dependent activities in that administration of oestradiol to gonadectomized animals of either sex causes a further significant repression of the activity to levels close to the limits of detection. Hypophysectomy on day 50 of life does not affect the activity in 75 day-old male rats, but causes the appearance of typically male activity levels in females. These results indicate that the hypophysis exerts a repressive influence on hepatic 11β-hydroxysteroid dehydrogenase in female rats. The fact that this activity is not influenced by androgen or oestrogen administration once the pituitary has been removed demonstrates the obligatory role of the hypophysis for sex hormone action.

Interactions between oestradiol and glucocorticoid regulatory effects on liver-specific glucocorticoid-inducible genes: possible evidence for a role of hepatic 11beta-hydroxysteroid dehydrogenase type 1

“…E2 administration reduced hepatic 11 -HSD-1 mRNA expression to undetectable levels and markedly decreased 11 -HSD activity, confirming previous studies (Lax et al 1978, Low et al 1993. Residual 11 -HSD-1 activity is likely to be due to low levels of gene transcription not detected by Northern analysis.…”

“…Residual 11 -HSD-1 activity is likely to be due to low levels of gene transcription not detected by Northern analysis. This effect of E2 is relatively specific to the rat liver, since hippocampal 11 -HSD-1 was unaffected, and E2 does not reduce 11 -HSD-2 activity in either kidney or placenta (Lax et al 1978, Baggia et al 1990, Low et al 1993. E2 administration, as opposed to conventional liquorice-related 11 -HSD inhibitors, was employed as a method of hepatic 11 -HSD-1 attenuation for several reasons: (i) 11 -HSD-2 is unaffected; (ii) the effect is relatively selective to the liver; and (iii) the inhibition achieved in vivo is much more marked.…”

“…Reduced 11 -HSD-1-mediated reactivation of 11-dehydrocorticosterone is anticipated to reduce expression of glucocorticoid-sensitive transcripts. Alternatively, 'feminisation' of the male liver may induce 5 -reductase activity (Leblanc & Waxman 1988), thus increasing corticosterone metabolism to inactive products; and (iii) there may be other indirect effects of chronic E2 administration, as seen, for example, with effects of patterns of GH secretion on the liver (Lax et al 1978, Low et al 1994a.…”

“…Indeed, chronic oestradiol (E2) administration almost completely suppresses hepatic 11 -HSD-1 expression in both male and female rats (Lax et al 1978, Low et al 1993. The aim of this study was therefore to examine the contribution which reactivation of glucocorticoids by hepatic 11 -HSD-1 makes to the expression of liver-specific glucocorticoidmodulated genes in the rat by exploiting the selective suppression of hepatic 11 -HSD-1 by E2 in vivo.…”

11 beta-hydroxysteroid dehydrogenase type 1 is a predominant 11 beta-reductase in the intact perfused rat liver

“…The well-documented sexual dimorphism of biochemical activity (Lax et al 1978) was reflected in the ex vivo activity of 11 -reductase in whole liver, with female rats having approximately half the activity of males.…”