Prenatally administered delta-9-tetrahydrocannabinol temporarily inhibits the developing hypothalamo-pituitary system...

We have reported earlier that delta 9-tetrahydrocannabinol (THC) if injected over the 3rd week of pregnancy with a daily dose of 1 micrograms/kg b.wt., caused a significant prolongation of pregnancy and 42% of stillbirths, although no teratological effects were observed. In the present study, we investigated the postnatal development of hypothalamo-hypophyseal-gonadal axis of the above mentioned rats' living litters. The rats were killed every 5th day between the delivery (D0) and the 20th postnatal day (D20). The weight of the body and the gonads was measured and hormonal parameters were registered by RIAs. The body weight was lower in treated animals, with a higher degree in males. The weight of the gonads also decreased. Serum testosterone levels were lower in rats from D0 till D10, while at D15 and D20 no differences were recorded between controls and treated rats. No significant differences were observed in serum estrogen levels during the investigated period. Serum progesterone decreased up to D10. Pituitary luteinizing hormone (LH) diminished postpartum in both sexes up to D5. From D0 till D5, serum LH increased in males while it decreased in females. Hypothalamic luteinizing hormone releasing hormone decreased up to D15 in both sexes, less markedly in females than in males. The neuropeptide Y content of the hypothalamus was also decreased in early postnatal age. We concluded that a very low dose of prenatally administered THC caused transitory inhibition of the developing hypothalamo-pituitary-gonadal axis, i.e., postnatal changes were evoked in the neuroendocrine system. By the 20th postnatal day this effect of THC seemed to be eliminated.