Daily administration of long-acting adrenocorticotropic hormone (ACTH) alters the developmental pattern of plasma fibrinogen in juvenile rats.

Background We previously reported that adrenocorticotropic hormone (ACTH) therapy for infantile epileptic spasm syndrome (IESS) decreases plasma fibrinogen (Fbg) levels. However, the underlying mechanism(s) has not been elucidated. An animal model approximating early childhood in humans uses juvenile rats at postnatal days (P)21-P35, but its applicability to this question has not been examined. Aim To determine the effects of the daily long-acting ACTH administration on plasma Fbg levels in juvenile rats. Methods Wistar rats were intramuscularly injected daily with normal saline (NS), low-dose ACTH (LD), or high-dose ACTH (HD) daily from P21 to P35. Blood samples were collected before administration (P21), 7 days (P28) and 14 days (P35) after treatment initiation. Body weight and plasma corticosterone and Fbg levels were assessed. Results ACTH administration increased plasma corticosterone levels and suppressed weight gain. Fbg levels showed a transient increase at P28 in the HD group, but this was not sustained at P35. In the LD group, Fbg levels did not show developmental increases as observed in controls. No significant decrease in absolute plasma Fbg levels was detected. Repeated-measures correlation analysis revealed no association between corticosterone and Fbg levels. Conclusion Daily ACTH administration in juvenile rats did not reduce absolute plasma Fbg levels but altered the developmental trajectory of Fbg levels. These findings suggest that the decrease in Fbg levels observed during ACTH therapy in human infants may reflect the developmental regulation of fibrinogen production rather than a direct glucocorticoid-mediated effect.