We have examined testicular and pituitary function in inbred CD-F rats and DBA/2J mice with chronic hyperprolactinemia induced by grafting 4 anterior pituitaries from adult females of the same strain under the kidney capsule. Eight rats were given pituitary isografts and 9 were sham-operated; blood samples were collected at 4-7 week intervals, and the animals were killed 6 months later. One month after surgery, PRL levels in grafted rats were elevated (348 +/- 15 vs. 94 +/- 11 ng/ml; P less than 0.001), LH levels were depressed (16 +/- 3 vs. 59 +/- 9 ng/ml; P less than 0.001), but T levels were not affected (1.0 +/- 0.1 vs. 1.1 +/- 0.2 ng/ml). The elevated PRL levels in grafted animals did not decline during the subsequent 5 months, while LH levels increased slightly, and T levels remained indistinguishable from those in the controls. At the time of autopsy, FSH levels were reduced in grafted rats (230 +/- 40 vs. 501 +/- 108 ng/ml; P less than 0.05). Multiple pituitary isografts did not affect the weight of the testes or the ventral prostate, but increased the weight of the seminal vesicles (P less than 0.001). In 11 mice examined 5.5 months after receiving pituitary isografts, plasma PRL levels were dramatically elevated (330 +/- 35 vs. 27 +/- 2 ng/ml; P less than 0.001), but plasma T levels and testicular weight were not different from those observed in 12 sham-operated controls. The weight of the seminal vesicles in grafted mice was increased (P less than 0.01). In both rats and mice, chronic hyperprolactinemia did not affect plasma testosterone levels or testes weight and increased seminal vesicle weight.
Maternal exposure to the major psychoactive delta 9-tetrahydrocannabinol (THC), or to the nonpsychoactive cannabinol (CBN) or cannabidiol (CBD) on day 12 of gestation, or on day 1 postpartum, affected the concentrations of hepatic cytochromes P-450 in adult male offspring. Levels of P-450 were significantly increased in adult males prenatally exposed to cannabinoids, but were reduced after postnatal exposure. The response to exogenous testosterone was also differentially affected by perinatal cannabinoid exposure, with reduced plasma androgen in males prenatally exposed to THC, but increased levels of hormone in mice exposed postnatally to THC or CBN. There was a concomitant decrease in plasma albumin and increased gamma-globulin in adult males postnatally exposed to CBN. Beta-globulin levels were also significantly increased in adult males exposed to cannabichromene (CBC) on day 1 postpartum. Cannabinoid exposure during perinatal periods of development exert effects on hepatic function, plasma androgen levels, and on the immune system. These effects may reflect the ability of perinatal cannabinoid exposure to interfere with androgen-mediated processes of differentiation.
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