Peroxisome proliferation hormonal effects

Figure 29-6. Gene transcription is regulated by retinoic acid.Ah-Zrwm-retinoic acid and 9-cA-retinoic acid are ligands for retinoic acid receptors (RARs) and retinoid X receptors (RXRs), respectively. The RXRs can form heterodimers with RARs and with the thyroid hormone receptors (TRs), the vitamin D receptor (VDR), and the peroxisome proliferator-activated receptors (PPARs) and a number of other hormone- and nutrient-responsive transcription factors to moderate gene transcription. Because of the ability of RXR to form heterodimers with other nuclear receptors, vitamin A has abroad effect on many hormonally and nutrient-responsive genes.

Few experimental carcinogens of the epigenetic type have been associated with cancer in humans, these are mainly hormones or immunosuppressants. Humans have been exposed to many pesticides known to cause cancer in experimental animals, but none has been linked to cancer in humans (38). The absence of effects in humans has been suggested to be due the fact that exposures of humans are below the threshold for the biological effect (e.g. peroxisome proliferation or membrane alteration and consequent promoting action) underlying carcinogenicity (36). Moreover, some of the conditions necessary for tumor Induction in rodents may not be attainable or tolerable to humans. 

In rats ammonium perfluorooctanoate induced hepatomegaly that was more pronounced in the male than in the female. Male rats are thought to be more sensitive to the toxic effects of ammonium perfluorooctanoate because of their slower excretion rate. The rapid excretion by female rats is due to active renal tubular secretion, which is considered to be hormonally controlled by estradiol and testosterone levels. The hepatomegaly was hypertrophic rather than hyperplastic and involved proliferation of peroxisomes. 

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