Sexual dimorphism of hepatic 11 beta-hydroxysteroid dehydrogenase in the rat: the role of growth hormone patterns.
11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD) catalyses the reversible metabolism of corticosterone to inert 11-dehydrocorticosterone. At least two isoforms exist. 11 beta-HSD-1, the first to be characterised and the only isoform for which a cDNA has been isolated, is highly expressed in liver, kidney and hippocampus. The activity of 11 beta-HSD in rat liver is higher in males, due to oestrogen repression of 11 beta-HSD-1 gene transcription in females. Sexual dimorphism in rodent liver proteins is frequently mediated indirectly via sex-specific patterns of GH release (continuous in females, pulsatile in males). We have now investigated whether this applies to 11 beta-HSD, using dwarf rats (congenitally deficient in GH) and hypophysectomised animals. 11 beta-HSD activity and 11 beta-HSD-1 mRNA expression in liver was significantly lower in control female than male rats (50% and 72% of male levels respectively). These sex differences in the liver were attenuated in dwarf rats, with both males and females showing similar levels of 11 beta-HSD activity to control males. Administration of continuous (female pattern) GH to dwarf male rats decreased hepatic 11 beta-HSD activity (30% fall) and mRNA expression (77% fall), whereas the same total daily dose of GH given in the male (pulsatile) pattern had no effect on hepatic 11 beta-HSD in female dwarf rats. Continuous GH also attenuated hepatic 11 beta-HSD activity (25% fall) and 11 beta-HSD-1 mRNA expression (82% fall) in hypophysectomised animals.(ABSTRACT TRUNCATED AT 250 WORDS)
University of Edinburgh, Department of Medicine, Western General Hospital, UK.
S C
SC
Low
K E
KE
Chapman
C R
CR
Edwards
T
T
Wells
I C
IC
Robinson
J R
JR
Seckl
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000818:Animals; D005260:Female; D013006:Growth Hormone / Q000172:deficiency / Q000378:metabolism*; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D007016:Hypophysectomy; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011922:Rats, Mutant Strains; D012727:Sex Characteristics
D012333:RNA, Messenger; D013006:Growth Hormone; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases