Hyperprolactinaemia in hypophysectomized or intact male rats and the development of adjuvant arthritis

Abstract

In rats, complete Freund's adjuvant (CFA), injected at the base of the tail, induced a hyperactivation of cellular immune functions and triggered the development of adjuvant arthritis (AA). Before onset of arthritis (Days 9-10 upon CFA), the positive control rats showed significant increases of pituitary prolactin (Prl) mRNA accumulation (Days 3-5). On the other hand, production of pituitary growth hormone (GH) mRNA was significantly reduced from Day 3 onwards. During this early latent period, plasma Prl levels were transiently increased (at least on Day 4), while GH levels were reduced within 8 days (and onwards). Pituitary proopiomelanocortin (POMC) mRNA content progressively decreased with a nadir between Days 6 and 8, accompanied by a loss of the adrenocortical ornithine decarboxylase (ODC) circadian rhythm of activity and a transient reduction of plasma corticosterone (CS) levels (Days 3-6, obvious during the dark phase). At onset of arthritis, the POMC mRNA accumulation and adrenocortical ODC activity increased over their respective baselines. Elevation of plasma CS levels (obvious during the light phase) and important CS-induced thymolysis occurred. Further, hypophysectomized rats did not develop AA. However, hypophysectomized male rats carrying pituitary grafts under the kidney capsule had mild hyperprolactinaemia and developed a worsened arthritic response to CFA, compared to sham-operated controls. On the other hand, intact hyperprolactinaemic male rats showed a delay in the onset and a reduction in the severity of AA. This difference might be due to stimulation of the adrenal cortex in intact pituitary-grafted rats. Such rats showed increased baselines of pituitary POMC mRNA production, adrenocortical ODC activity and plasma CS levels. In addition, during the latent period after CFA, POMC mRNA accumulation, adrenocortical ODC activity and plasma CS levels were only partially suppressed, less than in sham-operated rats. Extensive thymolysis occurred after CFA in these animals--as in the sham-operated rats--but not in the hypophysectomized pituitary-implanted rats. This suggested that in the presence of adrenocortical deficiency, Prl released by the pituitary graft can freely act on the immune system, without being counter-regulated by CS.