Δ-9-Tetrahydrocannabinol Suppression of Episodic Luteinizing Hormone Secretion in the Ovariectomized Rat*

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Abstract
The effect of .DELTA.-tetrahydrocannabinol (THC), the major active principle in marihuana, on episodic LH [luteinizing hormone] release in the long term ovariectomized rat was investigated. Alert, unrestrained animals with indwelling atrial cannulae were treated with THC in doses of 0.5-8.0 mg/kg BW [body weight] injected i.v. Serum LH concentrations in serial blood samples obtained via the cannulae were determined by RIA [radioimmuno assay]. Single injections of THC at all dose levels tested abolished the pulsatile fluctuation in serum LH typical of the ovariectomized rat and evident in all animals before drug treatment. LH concentrations were significantly reduced within 20 min of drug injection, declining at a rate suggestive of profound, perhaps complete suppression of episodic LH secretion. On the average, the suppressive effect dissipated within 1 h after treatment with the lowest dose of THC (0.5 mg/kg BW), but continued for 1-2 h when the dose was increased to 4 mg/kg BW. During the period of suppressed LH secretion, the release of LH was readily evoked by injection of LHRH [luteinizing hormone releasing hormone] (50 ng/kg BW). THC reduces serum LH concentrations in the ovariectomized rat consequent to the suppression of pulsatile LH release. The suppression has a duration which appears dose dependent and, while transient, may for a time be essentially complete. Retention of pituitary responsiveness to LHRH stimulation during the period of induced LH suppression suggests that the inhibitory action of THC primarily involves central neuroendocrine mechanisms.