Smith T J, Drummond G S, Kappas A
Pharmacology. 1987;34(1):9-16. doi: 10.1159/000138242.
Treatment of rats with Co-protoporphyrin, a synthetic metalloporphyrin which produces a marked and sustained induction of hepatic heme oxygenase and decline in cellular cytochrome P-450 content, caused a significant reduction in serum testosterone, serum thyroxine (T4) and 3,5,3'-triiodothyronine (T3) levels. These endocrine changes were not accompanied by reciprocal elevations in either serum luteinizing hormone (LH) or thyroid-stimulating hormone (TSH) concentrations. Seminal vesicles from Co-protoporphyrin-treated animals were atrophic. The pituitary response to luteinizing hormone-releasing hormone (LHRH) in Co-protoporphyrin-treated animals was moderately attenuated (approximately equal to 50%) but the response to thyrotropin-releasing hormone (TRH) was normal. These findings suggest that at least part of the effects of the metalloporphyrin are mediated at the level of the hypothalamus, such that suppression of serum levels of testosterone, T4 and T3 fails to elicit compensatory pituitary outputs of the respective trophic hormones. It is not known whether these effects are due to direct actions of Co-protoporphyrin on the endocrine system or whether they are secondary consequences of other metabolic derangements, such as those related to the pronounced cellular depletion of heme and cytochrome P-450 caused by the synthetic metalloporphyrin.
用合成金属卟啉辅原卟啉治疗大鼠，该物质可显著且持续地诱导肝血红素加氧酶，并使细胞色素P-450含量下降，结果导致血清睾酮、血清甲状腺素（T4）和3,5,3'-三碘甲状腺原氨酸（T3）水平显著降低。这些内分泌变化并未伴随血清促黄体生成素（LH）或促甲状腺激素（TSH）浓度的相应升高。接受辅原卟啉治疗的动物的精囊萎缩。接受辅原卟啉治疗的动物垂体对促黄体生成素释放激素（LHRH）的反应中度减弱（约50%），但对促甲状腺激素释放激素（TRH）的反应正常。这些发现表明，金属卟啉的至少部分作用是在下丘脑水平介导的，因此血清睾酮、T4和T3水平的抑制未能引发相应促激素的代偿性垂体输出。尚不清楚这些作用是由于辅原卟啉对内分泌系统的直接作用，还是其他代谢紊乱的继发后果，例如与合成金属卟啉导致的血红素和细胞色素P-450明显细胞耗竭相关的那些后果。
