Acute Effect of <i>▵</i>¹–Tetrahydrocannabinol on the Hypothalamo-Pituitary-Ovarian Axis in the Rat

Abstract

Administration of △¹-tetrahydrocannabinol (△¹-THC), the principal psycho-active ingredient of cannabis, to proestrous rats (2 mg/rat, i.p., between 12.00 and 16.00 h) suppressed the proestrous rise in the plasma levels of LH, FSH and prolactin (Prl) and caused a 24 h delay in ovulation. Furthermore, the increased accumulation of prostaglandins of the E-type (PGE) in the ovaries, normally seen on the evening of proestrus, was prevented. Earlier (08.00–10.30 h) or later (18.00 h) administration of the drug on the day of proestrus was only partially effective in inhibiting ovulation. The suppressive effects of △¹-THC on ovulation and gonadotropin secretion were prevented by administration of gonadotropin releasing hormone (GnRH, 0.2 µg/rat) 1 h after the drug, indicating that the central action of △¹-THC was exerted on the hypothalamus and not on the pituitary gland. Administration of ovine luteinizing hormone (oLH, 2.5 µg/rat) at 16.30 h on the day of proestrus restored ovulation and ovarian PGE accumulation in Nembutal-treated rats, but not in Δ¹-THC-treated rats; higher doses of oLH (5–10 µg/rat) reversed the action of △¹-THC on these two parameters.

Induction of Luteinizing Hormone Release by Electrochemical Stimulation of the Medial Preoptic Area in Δ⁹-Tetrahydrocannabinol-Blocked Proestrous Rats

“…The THC-related blockade of ovulation observed in both unstimulated and sham-stimulated control animals is in accord with the antiovulatory effect of THC previously reported for rats [3], rabbits 11 ], and monkeys [2]. The block ade appears to result predominantly from inhibition of the LH surge and not from effects on the ovary.…”

“…Earlier reports that exogenous LHRH induces an LH surge in THC-blocked proestrous rats [3] and overcomes the THC-induced LH suppression in ovariectomized rats [28], together with similar findings from other species (I, 25). strongly suggest that THC alters LH secretion through cen tral action reducing the release of LHRH into the hypophy sial portal circulation.…”

“…Proestrous ani mals were treated at approximately 13.45 h with THC in a dose of 10 mg/kg BW injected intraperitoneally in a vehicle volume of 0.5 ml/kg BW. That treatment regimen is highly effective in blocking the proestrous LH surge and ovulation [3]. Control animals were injected with the vehicle alone.…”

“…These results are consistent with the hypothesis that THC inhibits gonadotropin secretion by action within the central nervous system, but demonstrate that the central inhibitory effect of THC' does not prevent the release of LH-releasing hormone (LHRH) when the LHRH neurosecretory units are activated by brain stimulation. Thus, the antiovulatory effect of THC appears to result from .an inhibition of LH secretion which does not involve the direct blockade of LHRH release.Inhibition of luteinizing hormone (LH) secretion by AMetrahydrocannabinol (THC), the predominant psy choactive constituent of marijuana [20j, occurs under a var iety of physiological circumstances in man and experimental animals [3,6,8,18,28,29]. In sexually mature cycling females, THC inhibits the preovulatory surge of LH secre tion through action at a site and by a mechanism which remains unclear [1,2,22].…”

“…In sexually mature cycling females, THC inhibits the preovulatory surge of LH secre tion through action at a site and by a mechanism which remains unclear [1,2,22]. However, since THC does not directly inhibit basal or stimulated LH release from pituitary cells in vitro [7,24], and since the administration of exoge nous LH-releasing hormone (LHRH) readily provokes an LH surge during THC-induced suppression of LH secretion [1,3,25,28], asuprapituitary locus forTHC action is indicat ed. Consistent with that indication are reports that the THCinduced inhibition of LH release is associated with changes in the uptake and turnover of hypothalamic neurotransmit ters which may be involved in the release of LHRH [4,15,26] and that the hypothalamic concentration of L.HRII is in creased following acute THC treatment [19].…”