To determine if PRL stimulates astrocyte proliferation and cytokine expression in vivo, we examined the effect of PRL on the wound-induced increase in the expression of glial fibrillary acid protein (GFAP) and tumor necrosis factor-alpha (TNF-alpha) in the CNS. Low levels of GFAP detected by Western blot analysis were identified in the non-wounded controls. Five days after the infliction of the wound, the relative abundance of GFAP in the tissue surrounding the wound site was greater than those of intact controls. Injection of PRL into the wound site markedly increased GFAP expression in the hypothalamus. Western blot analysis failed to detect TNF-alpha in the hypothalamus of non-wounded animals. In contrast, TNF-alpha was easily detected in the hypothalamus of wounded rats, and was markedly increased in PRL injected animals. To confirm the PRL-induced increase in TNF-alpha levels, TNF-alpha levels in hypothalamic extracts were measured by bioassay. In non-wounded controls, low but detectable TNF-alpha levels were found in the hypothalamus by bioassay (0.13 +/- 0.02 ng/mg protein). Infliction of a hypothalamic wound markedly increased TNF-alpha levels to 1.4 +/- 0.3 ng/mg protein. Injection of PRL into the wound site resulted in a further increase in TNF-alpha levels to 11.4 +/- 2.6 ng/mg protein. Further, infliction of the hypothalamic wound increased hypothalamic PRL content and PRL mRNA levels.(ABSTRACT TRUNCATED AT 250 WORDS)