Novel effects of deoxycorticosterone on testicular 11beta-hydroxysteroid dehydrogenase activity and plasma testosterone levels in normal and adrenalectomized rats.
The 11beta-hydroxysteroid dehydrogenase (11beta-HSD) protects the testis from the inhibitory effects of corticosterone on testosterone (T) production. The objectives of the present studies were to determine the effects of deoxycorticosterone (DOC) and its mechanism of actions on testicular 11beta-HSD activity and plasma T levels after 7 days of treatment. The results revealed that at the end of 7 days treatment, DOC significantly increased testicular 11beta-HSD activity and plasma T levels in normal rats. However, the time course showed that high plasma T levels lowered 11beta-HSD activity on day 14 and by 21 days both the levels normalized. In adrenalectomized (ADX) rats, only the enzyme activity increased significantly but not plasma T levels. Spironolactone, a competitive inhibitor of mineralocorticoid receptor (MR), did not change testicular 11beta-HSD activity in both normal and DOC treated rats suggesting that DOC did not act through MR in increasing 11beta-HSD activity. On the other hand, spironolactone significantly decreased plasma T levels in DOC treated rats. Progesterone (P), a competitive inhibitor of glucocorticoid receptors (GR) or corticosterone significantly suppressed testicular enzyme activity and plasma T levels in DOC treated normal rats. Carbenoxolone which is an inhibitor of 11beta-HSD activity significantly depressed testicular 11beta-HSD activity and plasma T levels in DOC treated normal rats. This paper suggests that DOC increased testicular 11beta-HSD activity through GR; whilst increase in plasma T levels required functioning adrenal glands. The testicular 11beta-HSD is one of the regulators of T levels and vice versa.
Nwe
K H
KH
Department of Physiology, Faculty of Medicine, National University of Malaysia. khahhnwe@medic.ukm.my
Morat
P B
PB
Hamid
A
A
Fadzilah
S
S
Khalid
B A
BA
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000311:Adrenal Glands / Q000502:physiology*; D000315:Adrenalectomy; D000818:Animals; D002229:Carbenoxolone / Q000494:pharmacology; D003900:Desoxycorticosterone / Q000494:pharmacology*; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D008297:Male; D011374:Progesterone / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D013148:Spironolactone / Q000494:pharmacology; D013737:Testis / Q000187:drug effects / Q000201:enzymology*; D013739:Testosterone / Q000097:blood*
D013148:Spironolactone; D013739:Testosterone; D003900:Desoxycorticosterone; D011374:Progesterone; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D002229:Carbenoxolone