Abstract
Previous research from our laboratory has shown that tumor necrosis factor (TNF)-α, administered either intravenously (iv) or intracerebroventricularly (icv), suppressed the electrical activity of hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator in the rat. The present study was conducted to elucidate the possible roles of prostaglandins (PGs) and corticotropin-releasing hormone (CRH) in mediating the effect of TNF-α. Ovariectomized rats were fitted with chronically implanted electrode arrays in the mediobasal hypothalamus, and multiunit activity (MUA) was recorded under an unrestrained condition. Blood samples were withdrawn every 6 min through an indwelling atrial catheter for the determination of serum luteinizing hormone (LH) concentrations. During a pretreatment control period, characteristic increases (volleys) in MUA coincident with the initiation of each LH pulse were recorded. Indomethacin (1 mg/100 g BW, iv), a cyclooxygenase inhibitor, blocked the decrease in the frequency of MUA volleys induced by iv (1 μg) or icv (50 ng) injection of TNF-α. In contrast, icv injection of the CRH receptor antagonist (α-helical CRH, 100 μg) failed to block the suppressive effect of TNF-α on volley frequency. Neither indomethacin nor α-helical CRH alone affected the recurrence of MUA volleys. These results suggest that TNF-α suppresses GnRH pulse generator activity at least partially through PG-, but not CRH-, dependent mechanisms.
