Localization of the Inhibitory Actions of Ovulation-Blocking Drugs on Release of Luteinizing Hormone in Ovariectomized Rats1

Plasma LH concentrations were meas-ured by radioimmunoassay in blood withdrawn through atrial cannulas at 10-min intervals in longterm ovariectomized rats. Urethane (1.5 g/kg body wt) or phenobarbital (75 mg/kg body wt) injected ip inhibited the pulsatile discharge of the hormone and depressed plasma LH concentration for over 2 hr. Partial or total deafferentation of the medial basal hypothalamus 4–6 weeks prior to ovariectomy did not interfere with the pulsatile rhythm in high plasma LH concentration after ovariectomy and injection of urethane or phenobarbital inhibited LH release in these deafferented rats as effectively as in nondeafferented animals. An ip injection of pen-tobarbital (32 mg/kg body wt) caused a marked but temporary depression in plasma LH concentration. Within 1 hr after administration of pentobarbital, the pulsatile fluctuations in plasma LH had re-sumed. Continuous deep ether anesthesia sup-pressed the pulsatile rhythm in plasma LH but levels remained steady in the low range of pretreatment values. Injection of 0.6 ml of 95‰ ethanol through the atrial cannula had no observable effect on the fluctuating patterns in plasma LH concentration. None of the treatments significantly inhibited pituitary LH release in response to injection of synthetic LHRH. Of these five different treatments, all of which are highly effective in inhibiting pituitary LH release on the afternoon of proestrus. only two caused a marked, prolonged depression in plasma LH concentration in ovariectomized animals. The results suggest that the inhibitory effects of urethane and phenobarbital on LH release are exerted via blockade of LHRH synthesis and⁄o release from the medial basal hypothalamus anc that pentobarbital, ether and ethanol are not a.1 effective as urethane and phenobarbital in inhibit ing LH release in ovariectomized rats. (Endocrinology95: 999, 1974)