Adrenocortical hormones and lactation: metabolism of 3H-corticosterone and 3H-aldosterone by rat mammary gland minces and by the nuclear fraction of the homogenates.

3H-Corticosterone undergoes extensive metabolism on incubation with mammary acini and minced mammary glands from lactating rats; 3H-corticosterone-21-oleate was the major radiometabolite formed. In a similar study with 3H-aldosterone, 3H-aldosterone-21-oleate was one of the two major radiometabolites formed. In the present study, an enzyme system highly active in the biosynthesis of 21-acyl-3H-corticosterone was demonstrated to be present chiefly in the nuclear fraction of mammary gland homogenates. The enzyme system comprises: a fatty acid thiokinase (or fatty acyl-CoA synthetase); a fatty acyl transferase. The methods entailed incubation of 3H-corticosterone with the nuclear fraction in the presence and absence of: the cofactors, CoA, ATP, and Mg2+; oleoyl-CoA and other fatty acyl-CoA donors. The results of the present investigation support the view that the major cellular site for the acylation of adrenocortical hormones is the nucleus. It has been suggested that the acylation serves to modulate the biological action of the hormones on the mammary glands by interaction with the glucocorticoid receptor.