Perinatal cannabinoid exposure: demasculinization in male mice
Dalterio, S.L.; Michael, S.D.; Thomford, P.J.
Neurobehavioral Toxicology and Teratology 8(4): 391-397
1986
ISSN/ISBN: 0275-1380 PMID: 3762849 Document Number: 279026
Maternal exposure to psychoactive or non-psychoactive cannabinoids produces long-term changes in body weight regulation, pituitary-gonadal feedback, testicular function, and also affects adult sexual behavior in male offspring. Alterations in brain biogenic amine concentration and metabolism have also been observed in adult males perinatally-exposed to cannabinoids. The possibility that these effects are mediated by cannabinoid-induced suppression or interference with fetal and/or neonatal androgen production is discussed. In addition, data are presented showing that exposure to the major psychoactive component of marihuana, .DELTA.9-tetrahydrocannabinol (THC), on day 12 of gestation significantly increased hepatic cytochrome P-450 levels. In contrast, cytochromes P-450 levels were significantly decreased in adult males exposed to these cannabinoids on day 1 post-partum. The response of these animals to the negative feedback effects of exogenous androgen was also influenced by perinatal cannabinoid exposure. One hr after injection of 20 .mu.g testosterone (T), plasma levels of luteinizing hormone (LH), were markedly increased in castrated males exposed to CBD on day 12 of gestation, while the THC and control mice showed no response to T injection. In contrast to the reduced plasma LH levels in the controls, the levels of LH were significantly increased in postnatal THC-exposed males, while the CBN and CBD-exposed mice exhibited no reduction in plasma LH in response to exogenous androgen. Prenatal exposure to THC resulted in a greater suppression of plasma follicle-stimulating hormone (FSH) levels in mice receiving 20 .mu.g T, compared to the effects in the castrated controls. In contrast, plasma FSH levels in the cannabinoid-exposed males were higher than those of the castrated control mice also injected with T. Plasma FSH levels in animals exposed to CBN or CBD on day 1 post-partum showed no evidence of negative feedback response to T. Previous data, together with the present findings, appear consistent with the hypothesis that early exposure to psychoactive components of marihuana exert a long-term "demasculinization" effect in male mice.