Different mechanisms mediate the in vivo aldosterone and corticosterone responses to 5-bromo-2′-deoxyuridine in rats

Summary

The subcutaneous injection of 5'-bromo-2'deox-yuridine (BrdU) was found to raise the plasma concentrations of ACTH, aldosterone and corticosterone in rats. The aldosterone response was observed at a lower dose of BrdU and lasted for a longer period than those of ACTH and corticosterone (1.25 versus 2.50 mg/100 g body weight; 48 versus 24 h). Corticosterone response to BrdU was partially reversed by the ACTH-receptor antagonist corticotropin-inhibiting peptide (CIP), and aldosterone response by the arginine vasopressin (AVP) VI-receptor antagonist [am- ino-Pen¹,Val⁴, D-Arg⁸]-vasopressin (AVP-A). The angiotensin-II (ANG-II)-receptor antagonist [Sar¹,Val⁵, Ala⁸,]-ANG-

II (SAR) was ineffective. CIP, AVP-A and SAR, when administered alone, did not alter basal levels of ACTH, aldosterone and corticosterone. In light of these findings the following conclusions can be drawn: (i) BrdU stimulates the hypothalamo-pituitary-adrenal axis in rats, and this effect may influence the results of cell-kinetics studies carried out with the BrdU-labelling technique, especially in those tissue that are highly responsive to glucocorticoids (e.g. pituitary, adrenal and lymphatic tissues); and (ii) different mechanisms underlie the aldosterone and corticosterone secretagogue effects of BrdU, the former being at least in part de-pendent on the stimulation of AVP release and the latter on the rise in ACTH secretion.

Key words

5-Bromo-2'-deoxyuridine - hypothalamo-pituitary-adrenal axis - steroid secretion - rat