title: Cortisol 21-mesylate exerts glucocorticoid action on the induction of milk protein synthesis in cultured mammary gland.
abstract: Cortisol 21-mesylate, an alkylating derivatives of cortisol, was previously shown to exert an anti-glucocorticoid action in rat hepatoma cell culture (Simons, Thompson and Johnson 1980). In this study the effect of cortisol 21-mesylate on milk protein synthesis induced in cultured mouse mammary gland by glucocorticoid, insulin, and prolactin was investigated. Addition of cortisol 21-mesylate at concentrations ranging from 10(-8) M to 10(-6) M produced no inhibition of casein synthesis that was induced by glucocorticoid, insulin and prolactin in mammary explants from midpregnant mice. On the other hand, cortisol 21-mesylate in combination with insulin and prolactin stimulated casein synthesis in cultured tissue. The potency of cortisol mesylate was about 1/10 to 1/30th of that of cortisol. Cortisol 21-mesylate, like cortisol, also augmented the accumulation of alpha-lactalbumin in midpregnant rat mammary tissue cultured in the presence of insulin and prolactin. A cell-free competition study of glucocorticoid receptors using cytoplasmic extracts from mouse mammary tissue showed that cortisol 21-mesylate competitively inhibited the binding of dexamethasone on glucocorticoid receptors. The apparent affinity of cortisol 21-mesylate for glucocorticoid receptors is about 1/10th of that of cortisol. These results indicate that cortisol 21-mesylate acts as a glucocorticoid but not as an antiglucocorticoid in the mammary gland.
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002364:Caseins / Q000096:biosynthesis; D003907:Dexamethasone / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D006854:Hydrocortisone / Q000031:analogs & derivatives* / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007768:Lactalbumin / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008894:Milk Proteins / Q000096:biosynthesis*; D009924:Organ Culture Techniques; D011247:Pregnancy; D011388:Prolactin / Q000494:pharmacology; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000378:metabolism
chemical_list: D002364:Caseins; D005938:Glucocorticoids; D007328:Insulin; D008894:Milk Proteins; D011965:Receptors, Glucocorticoid; C027504:cortisol 21-mesylate; D003907:Dexamethasone; D011388:Prolactin; D007768:Lactalbumin; D006854:Hydrocortisone