The role of cyclic-AMP in the regulation of steroid metabolism in isolated rat hepatocytes.
In vivo experiments have shown that hepatic steroid metabolism is under hormonal control but the intracellular mechanism of action of the hormones has been little studied. One pathway of hormone action known to be active in the liver is the alteration of cyclic-AMP levels. To investigate the role played by cyclic-AMP in the control of hepatic steroid metabolism, we raised intracellular cyclic-AMP by a number of methods and studied the resultant changes in the metabolism of androst-4-ene-3,17-dione after various periods of time. Results indicate that cyclic-AMP levels are raised to their maximal levels (2-20-fold stimulation) 2-20 min following the additions but that the effects on steroid metabolism were seen later and depended on the initial change in cyclic-AMP levels. At lower rises in cyclic-AMP (up to 5-fold stimulation), a marked inhibition of steroid metabolism is seen at 1/2-1 hr post-treatment, whereas at higher stimulations of cyclic-AMP (greater than 10-fold stimulation), a significant stimulation of steroid metabolism is observed at later time periods (after 1 hr), sometimes following a slight inhibition at 1/2 hr. This indicates that acute rises in intracellular cyclic-AMP produced by hormonal stimulation may play a role in regulating steroid metabolism in the rat liver both in an inhibitory and a stimulatory direction.
Berry
L A
LA
Department of Pharmacology, The University, Glasgow, Scotland.
Skett
P
P
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000735:Androstenedione / Q000378:metabolism*; D000818:Animals; D000242:Cyclic AMP / Q000032:analysis / Q000502:physiology*; D004837:Epinephrine / Q000494:pharmacology; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D015124:8-Bromo Cyclic Adenosine Monophosphate; D000735:Androstenedione; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine; D004837:Epinephrine