Mechanisms of Altered Prolactin Secretion due to the Administration of Interleukin-1 β into the Brain Ventricles of the Rat

The ability of the intracerebroventricular (icv) injection of interleukin-1β (IL-1β) to alter plasma prolactin (PRL) levels in rats remains controversial, with reports of increases, decreases, or no changes in secretory rate. These discordant results may reflect, at least in part, the use of different doses of cytokines, as well as a gender specificity in the response of the brain circuits that control PRL release. In a first series of experiments, we investigated the effect of one acute icv injection of IL-1β to alter PRL secretion in intact male and female rats. Using this paradigm, we also determined the potential modulating role of secretagogues reportedly released by IL-1β, such as dopamine, corticosterone and progesterone. A second series of experiments involved the long-term (3-5 days) icv infusion of IL-1β to identify the influence of gender on the pattern of PRL release. The acute icv injection of IL-1β (5-50 ng) to intact adult males or females caused comparable and significant (p < 0.01) decreases in plasma PRL levels 1-5.5 h after treatment. At the 8 h time point PRL secretion started to increase in females exposed to the cytokine, while PRL values of males were comparable in vehicle- and IL-1-injected rats. In intact males, blockade of pituitary dopamine receptors with domperidone (3.5 mg/kg) did not reverse the inhibitory effect of the immune protein. In either gender, blockade of IL-1-induced corticosterone and adrenal progesterone release with CRF antibodies was also without effect on PRL secretion. We then studied the consequences of long-term IL-1β infusion (4 ng/h). Both intact males and females showed significant decreases in PRL release measured between 11:00 and 14:00 h. In the evening (20:00-23:00 h), a marked sex difference became apparent with males still exhibiting decreased PRL levels, but females showing dramatically elevated PRL secretion. As previously reported [Rivier and Erickson, Endocrinology 1993; 133:2431], these females also had markedly increased progesterone concentrations, a finding that suggested the possibility that the ovaries might participate in the gender-specific pattern of PRL secretion. This hypothesis was tested by comparing the effect of chronic IL-1β treatment in intact and ovariectomized (OVX) rats. On the third day of cytokine treatment, the expected decrease (mid-day) and increase (early evening) in PRL release were present in intact females infused with IL-1β. In contrast, OVX rats treated with the cytokine failed to exhibit significant changes in PRL levels at any time. Taken together, our results indicate that in both intact male and female rats, the acute decrease in PRL release caused by the icv injection of IL-1β is not secondary to increases in circulating levels of corticosterone or progesterone, and also appears independent of dopamine influence. During long-term infusion with the cytokine, the dramatic increase in evening concentrations of PRL in females appears at least in part related to increased ovarian activity.