Recent research has suggested a significant interaction between sex and contaminant type in adult teleost fishes [1]. Both polychlorinated biphenyls (PCBs) and mercury (Hg) have been touted as tracers of food consumption by fish, because the predominant pathway of entry of these contaminants into the bodies of fish is via consumption of food. Thus, in theory, the ratio of whole-fish PCB concentration in males to whole-fish PCB concentration in females should equal the ratio of whole-fish Hg concentration in males to whole-fish Hg concentration in females. However, this expected outcome is not observed in nature (Table 1). Rather, the abovementioned PCB ratio is consistently greater than the abovementioned Hg ratio, and this interaction between sex and contaminant type (PCBs or Hg) has been demonstrated to be statistically significant [1,2]. These researchers proposed that the interaction is attributable to adult males eliminating Hg from their bodies at a substantially faster rate than adult females, and that testosterone and 11-

ketotestosterone are the agents facilitating enhanced Hg- elimination rate in males. In contrast, long-term elimination of PCBs by most teleost fishes is essentially negligible for both sexes [3]. In addition, these researchers further proposed that the variation in the differences between the PCB ratio and the Hg ratio across species, as shown in Table 1, is attributable, at least in part, to variation in levels of certain androgens, such as testosterone and 11-ketotestosterone, in males across species. Relatively high amounts of these androgens in males are expected to induce relatively high Hg-elimination rates in males. In turn, the difference between the PCB ratio and the Hg ratio is expected to increase with increasing Hg-elimination rate of males. Thus, burbot males probably have substantially higher levels of these androgens than either lake trout males or white sucker males, as burbot exhibit the greatest discrepancy between the PCB ratio and the Hg ratio of the species presented in Table 1.

Table 1: Polychlorinated biphenyl (PCB) ratios and mercury (Hg) ratios for adult teleost fishes.

^aPCB ratio = ratio of mean whole-fish PCB concentration in adult males to mean whole-fish PCB concentration in adult females.

Ratios were taken from Madenjian [1,2].

^bHg ratio = ratio of mean whole-fish Hg concentration in adult males to mean whole-fish Hg concentration in adult females. Ratios were taken from Madenjian [1,2].

Testosterone has been shown to enhance Hg-elimination rate in laboratory mice (Mus musculus). When laboratory mice are immature, Hg-elimination rate does not vary between the sexes [4]. However, as the mice approach maturity, Hg-elimination rate of the males substantially increases such that Hg-elimination rate of males exceeds Hg-elimination rate of females by roughly a factor of 3 in the C57BL/6N strain of laboratory mice. Results from follow-up experimentation has revealed that testosterone is linked to the enhanced Hg-elimination rate in males. When male mice approaching maturity were castrated, their Hg-elimination rate declined to the level observed in female mice approaching maturity [5]. Moreover, when female mice were injected with testosterone, their Hg-elimination rate increased to the level observed in adult male mice. Taken together, these findings on laboratory mice provide compelling evidence that testosterone boosts Hg-elimination rate [6]. The testosterone found in laboratory mice has the same chemical structure as that found in teleost fishes and other vertebrates. In addition, 11- ketotestosterone is an androgen found in all teleost fishes, and this androgen is very similar to testosterone in molecular structure [1]. Thus, 11-ketotestosterone may also expedite Hg-elimination rate in male teleost fishes. Because the production of testosterone by males is a conserved trait among the vast majority of vertebrate species, most of these vertebrate species likely share the characteristic of males eliminating Hg from their bodies at a faster rate than females [1].

I have recently discovered additional evidence to further support the hypotheses advanced by Madenjian et al. [1] regarding the abovementioned sex – contaminant type interaction. Kostyniak

[7] reported that the Hg-elimination rate for the CFW strain is 2.5 times greater than that for the CBA/J strain of laboratory mice. Thus, this degree of variability in Hg-elimination rates just between different strains of the same species suggests that Hg- elimination rates could substantially vary across vertebrate species. In addition, Kemp and Drinkwater [8] determined the testosterone levels in the blood serum of adult males of the

following 6 strains of laboratory mice: SWR/J, C57BL/6J, C57BR/cdJ, P/J, CBA/J, and SM/J. Testosterone levels of adult males varied more than 4-fold among the strains. Of the 6 strains, the CBA/J strain exhibited the second lowest testosterone level. The combined results of the Kostyniak [7], Hirayama and Yasutake [4], and Kemp and Drinkwater [8] studies indicate that Hg-elimination rate of adult males of a strain tends to increase with increasing testosterone level of adult males. Adult males of the CBA/J strain have a relatively low Hg-elimination rate, and coincidentally these males have relatively low testosterone levels. Moreover, Hirayama and Yasutake [4] characterized the Hg- elimination rate of adult males from the C57BL strains as a relatively high rate compared with that of other strains. In accord with this relatively high Hg-elimination rate, adult males of the C57BL/6J strain have the second highest testosterone level of the 6 strains examined by Kemp and Drinkwater [8].

Synthesizing all of the abovementioned pieces of evidence, the observed interaction between sex and contaminant type (PCBs or Hg) in adult teleost fishes is most likely due to adult males having a substantially higher Hg-elimination rate than adult females. In addition, the variation in the differences between the PCB ratio and Hg ratio across species is probably attributable, at least in part, to variation in Hg-elimination rates of adult males across species. Further, the variation in Hg-elimination rates of adult males across species is explained, at least in part, by levels of certain androgens in the males. In mammals, the key androgen enhancing Hg-elimination rate in males is testosterone. Hg- elimination rate increases with increasing testosterone levels, both among individuals within a certain strain or species and across strains and species. In teleost fishes, testosterone and 11- ketotestosterone are the agents likely responsible for enhanced Hg-elimination rate in adult males.

2. Madenjian CP, Rediske RR, Krabbenhoft DP, Stapanian MA,
3. Chernyak SM. Sex  differences in contaminant concentrations of fish: a synthesis. Biol Sex Differ. 2016; 7: 42.
4. Madenjian CP, Stevens AL, Stapanian MA, Krabbenhoft DP, DeWild JF, et Ratio of mercury concentration to PCB concentration varies with sex of white sucker (Catostomus commersonii). Environments. 2018; 5: 94.
5. Madenjian CP, Hesselberg RJ, DeSorcie TJ, Schmidt LJ, Stedman RM, et al. Estimate of net trophic transfer efficiency of PCBs to Lake Michigan lake trout from their prey. Environ Sci Technol. 1998; 32: 886-891.
6. Hirayama K, Yasutake Sex and age differences in mercury distribution and excretion in methylmercury-administered mice. J Toxicol Environ Health. 1986; 18: 49-60.
7. 
   Tanaka T, Naganuma A, Miura N, Imura N. Role of testosterone in γ-glutamyltranspeptidase-dependent renal methylmercury uptake in Toxicol Appl Pharmacol. 1992; 112: 58-63.
8. National Academy of Toxicological effects of methylmercury. National Academy Press, Washington, DC; 2000.
9. Kostyniak PJ. Differences in elimination rates of methylmercury between two genetic variant strains of mice. Toxicol Lett. 1980; 6: 405-410.
10. Kemp CJ, Drinkwater Genetic variation in liver tumor susceptibility, plasma testosterone levels, and androgen receptor binding in six inbred strains of mice. Cancer Res. 1989; 49: 5044- 5047.