Cobalt-Protoporphyrin Suppresses Thyroid and Testicular Hormone Concentrations in Rat Serum: A Novel Action of this Synthetic Heme Analogue

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Abstract
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 (≈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.

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