Difference of in vivo and in vitro antimineralocorticoid potency of progesterone.
Progesterone (P) given intramuscularly increases renal sodium excretion. We tested the in vitro capacity of P to bind to the human mineralocorticoid receptor (MR) with a reticulocyte lysate system and Ps transactivation potency in transfected CV-1 cells. Progesterone binds with higher affinity to the MR than aldosterone, but shows only low transactivation activity. This results in a very strong anti-mineralocorticoid (MC) potency of P in vitro. To test the in vivo anti-MC potency of P we infused aldosterone intravenously to hypo-MC Addison's patients, followed by increasing P infusions. During the study we measured normal aldosterone plasma concentrations and high P concentrations similar to the third trimester of pregnancy. Despite the 1000-fold higher plasma P concentrations, the in vivo anti-MC effect of P (increase of urinary sodium/potassium ratio) was rather small. We suggest that this may be due to effective MR protection mechanisms, such as conversion of P to inactive metabolites.
Quinkler
M
M
Dept. of Endocrinology, Diabetes and Nutrition, Klinikum Benjamin Franklin, Freie Universität Berlin, 12200 Berlin, Germany. m.o.quinkler@bham.ac.uk
Diederich
S
S
D000224:Addison Disease / Q000097:blood; D000450:Aldosterone / Q000008:administration & dosage / Q000097:blood; D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists; D008901:Mineralocorticoids / Q000037:antagonists & inhibitors*; D011188:Potassium / Q000652:urine; D011374:Progesterone / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D011817:Rabbits; D018161:Receptors, Mineralocorticoid / Q000378:metabolism; D012964:Sodium / Q000652:urine
D000451:Mineralocorticoid Receptor Antagonists; D008901:Mineralocorticoids; D018161:Receptors, Mineralocorticoid; D000450:Aldosterone; D011374:Progesterone; D012964:Sodium; D011188:Potassium