PITUITARY-ADRENAL AXIS AND ANTERIOR-PITUITARY PROLACTIN AND GROWTH-HORMONE MESSENGER-RNA RESPONSES OF ADJUVANT-ARTHRITIC RATS TO CYCLOSPORINE-A ARE DEPENDENT UPON THE TIME OF ITS ADMINISTRATION

In the rat, adjuvant arthritis (AA) is an inflammatory joint disease associated with chronic stimulation of the pituitary-adrenal axis and altered regulation of pituitary prolactin and GH mRNA expression. In the present study we have compared the effects of different periods of administration of the immunosuppressant cyclosporine A (CsA) on the activation of the pituitary-adrenal axis and the changes in pituitary prolactin and GH mRNA accumulation that accompany AA. CsA given during any tested time period of 5 d prior to decapitation (on d 14 and 21 following adjuvant injection) induced a reduction in the raised levels of plasma ACTH and corticosterone (B) and anterior pituitary POMC mRNA seen in untreated AA animals. This effect was more prominent when CsA was given in the period immediately prior to sacrifice (d 9-14 and d 14-19, respectively). In animals killed on d 14 following adjuvant injection, CsA given during the period immediately prior to sacrifice induced a decrease in anterior pituitary prolactin and GH mRNA levels in comparison to levels observed in untreated AA animals. On the other hand, GH and prolactin mRNA levels were increased in animals given CsA on d 9-14 and d 14-19 and killed on d 21 post-injection. These data suggest that an active immunological stimulus is an important component of the pituitary-adrenal axis activation seen in AA and is at least in part responsible for the changes in prolactin and GH mRNA expression during the development of this disease.