Mechanisms of biphasic action of glucocorticoids on alpha-lactalbumin production by rat mammary gland explants.
The highly selective Type II glucocorticoid ligand RU28362 showed a clear biphasic effect on alpha-lactalbumin (alpha-LA) production in rat mammary gland explants, with a peak at 1 nM and a return to basal levels at 30-300 nM; dexamethasone showed a similar profile. Corticosterone, which has a higher affinity for Type I than Type II receptors, produced a variable response. In six out of eleven studies this was biphasic, with a maximum at 300 nM; in five no increase above baseline was seen. Classical Type I receptor ligands--aldosterone and deoxycorticosterone--showed responses parallel to their Type II agonist activity. We interpret these data as follows occupancy of Type I receptors does not increase alpha-LA production the response to selective Type II receptor ligands is truly biphasic and one explanation of this pattern may be the existence of both "turn-on" and "turn-off" acceptor sites in the nucleus.
Quirk
S J
SJ
Gannell
J E
JE
Fullerton
M J
MJ
Funder
J W
JW
D000450:Aldosterone / Q000494:pharmacology; D000732:Androstanols / Q000494:pharmacology; D000818:Animals; D003345:Corticosterone / Q000494:pharmacology; D003900:Desoxycorticosterone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D007768:Lactalbumin / Q000096:biosynthesis*; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000378:metabolism
D000732:Androstanols; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D003900:Desoxycorticosterone; D000450:Aldosterone; C049154:11,17-dihydroxy-6-methyl-17-(1-propynyl)androsta-1,4,6-triene-3-one; D007768:Lactalbumin; D003345:Corticosterone