Concerning Ethnic Differences of Testosterone in Men

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If you live in a diverse country, then you have probably noticed the variations in the body structure between ethnic groups. While individuals within an ethnic group can vary widely in terms of body composition, you can probably still pick out some commonalities among each ethnic group. I’ll state my observations bluntly: African Americans on average seem to be more muscular than the norm, while those of Asian descent on average seem to be less muscular than the norm (I’m not advocating racism; it is a fact of life that people of the same ethnic group are more genetically similar than those of different ethnic groups).  This observation is in fact reinforced by findings of researchers.  Asian Indian adults were found to have more fat and less skeletal muscle than Europeans and Polynesians [1]. Another study focused on the Fat-free mass index, a measurement of Fat-free mass in relation to fat mass and height, of Caucasians, African Americans,  Hispanics, and Asians. Fat-free mass includes everything in your body that is not fat mass and is thus correlated with skeletal muscle mass. The study found that the FFMI was greatest in African Americans and the least in Asians [2].
ffmi

 

One of the most important factors in regulating muscle mass, is the hormone that we relate to all things masculine, testosterone. It is the reason why men are men. In fact, those that are genetically male (carry a Y chromosome) and display complete androgen receptor insensitivity (meaning they can’t respond to testosterone) develop as women [3].  However, if we were to look at our supposed culprit, we would find that there is no statistical difference in free testosterone levels between ethnic groups [4]. It should be noted that this study is limited by its small sample size for Asians.
TestEthnicity

 

One study even showed Asian men to have slightly higher testosterone levels than whites and African-Americans [5].

 

Although plasma testosterone levels are an important factor in sex hormone-dependent features, they obviously cannot explain the ethnic differences in these features. These differences seem to be mediated instead by differential enzyme and androgen receptor activity [6].  Specifically,  5a-reductase, the enzyme that converts testosterone into DHT, activity seems to vary among ethnic groups.  DHT is an androgenic hormone whose affinity to the androgen receptor is multitudes times greater than testosterone. A study recorded the DHT:testosterone ratio, an indicator of 5a-reductase activity[7], among ethnic groups and found levels to be highest in African-Americans, intermediate in Caucasians, and lowest in Asian-Americans [5]. Tissue-specific coactivators of the androgen receptor also play a role in differences in tissue-specific androgenicity. Different levels of these coactivators are found in different tissues(heart, skeletal muscle, and liver), and help determine the responsiveness of these receptors by binding to the androgen-androgen receptor complex [8-12].

 

The genetic differences in the gene encoding the androgen receptor itself contributes greatly to its ability to respond to testosterone and other androgens [13-15].  One of the most distinctive and important genetic differences found is called the CAG repeat polymorphism. This refers to the glutamine-tag attached to the androgen receptor becomes the sequence CAG is translated into the amino acid glutamine. The number of CAG repeats an individual has in his or her androgen receptor gene determines how effective his or her androgen receptor is at binding testosterone; those with less repeats are more sensitive to testosterone and those with a greater amount of repeats are less sensitive [16-21].  It has been found that those with short CAG repeats have the same symptoms of men with high testosterone levels, increased skeletal muscle mass, lower good cholesterol (HDL), and have an earlier onset of prostate cancer [21]. Those born with too many repeats (>38) may be at risk for certain genetic disorders [22].
The inverse association between the number of CAG repeats in the AR gene and functionality of the AR protein. Longer CAG tracts result in lower transcription of target genes and, thus, lower androgenicity. Expansion of the encoded polyglutamine stretch to beyond probably 38 leads to the neuromuscular disorder X-linked spinal bulbar muscular atrophy (XSBMA), a condition in which defective spermatogenesis and undervirilization are observed. Conversely, low numbers of CAG repeats are associated with increased androgenicity of susceptible tissues.

The inverse association between the number of CAG repeats in the AR gene and functionality of the AR protein. Longer CAG tracts result in lower transcription of target genes and, thus, lower androgenicity. Expansion of the encoded polyglutamine stretch to beyond probably 38 leads to the neuromuscular disorder X-linked spinal bulbar muscular atrophy (XSBMA), a condition in which defective spermatogenesis and undervirilization are observed. Conversely, low numbers of CAG repeats are associated with increased androgenicity of susceptible tissues.

The mechanism behind the weaker transactivation of androgen receptors with longer CAG repeats was found in a study done in 1999. A coactivator of the androgen receptor, ARA24, was discovered which bound differentially with the polyglutamine region of the androgen receptor. ARA24 was found to bind more weakly to androgen receptors with longer repeats and thus allowed for weaker signalling for the transcription of androgen-related genes [11].

 

Small but significant differences in the average CAG repeat length were found between different ethnic groups. Men of African descent were found to have the lowest number of repeats at 18-20, caucasians at 21-22, and east asians at 22-23[21]. Not only does this information reinforce our observations about body composition and androgenicity among different ethnic groups, but it also offers us some clinical value. The differences in enzyme, coactivator and androgen receptor activity may explain why certain individuals respond to testosterone therapy more strongly than others. It seems, however, that there is no clear winner in the roulette of testosterone sensitivity; one group may see greater strength in the earlier years of life, while the other gains vitality in the later years.

 

Contact me @ andrew.kang@emory.edu

 

Sources:
1. Rush EC, Freitas I, Plank LD. Body size, body composition and fat distribution: comparative analysis of European, Maori, Pacific Island and Asian Indian adults. Br J Nutr. 2009;102(4):632-641.
2. Hull HR, Thornton J, Wang J, et al. Fat-free mass index: changes and race/ethnic differences in adulthood. Int J Obes (Lond). 2011;35(1):121-7.
3. Oakes MB, Eyvazzadeh AD, et al. Complete androgen insensitivity syndrome–a review. J Pediatr Adolesc Gynecol, 2008 Dec;21(6):305-10.
4. Ellis L, Nyborg H. Racial/ethnic variations in male testosterone levels: a probable contributor to group differences in health. Steroids. 1992;57(2):72-5.
5. Wu AH, Whittemore AS, Kolonel LN, John EM, Gallagher RP,West DW et al. Serum androgens and sex hormone-binding globulins in relation to lifestyle factors in older African- American, white and Asian men in the United States and Canada. Cancer Epidemiology Biomarkers and Prevention 1995 4 735±741.
6. Zitzmann M, Nieschlag E. Testosterone levels in healthy men and the relation to behavioural and physical characteristics: facts and constructs. Eur J Endocrinol. 2001;144(3):183-97.
7. Horton, R. Dihydrotestosterone is a peripheral paracrine hormone. J. Androl., 13: 23-27, 1992.
8. Needham M, Raines S, Mcpheat J, et al. Differential interaction of steroid hormone receptors with LXXLL motifs in SRC-1a depends on residues flanking the motif. J Steroid Biochem Mol Biol. 2000;72(1-2):35-46.
9. Müller JM, Isele U, Metzger E, et al. FHL2, a novel tissue-specific coactivator of the androgen receptor. EMBO J. 2000;19(3):359-69.
10. Lee DK, Duan HO, Chang C. From androgen receptor to the general transcription factor TFIIH. Identification of cdk activating kinase (CAK) as an androgen receptor NH(2)-terminal associated coactivator. J Biol Chem. 2000;275(13):9308-13.
11. Hsiao PW, Lin DL, Nakao R, Chang C. The linkage of Kennedy’s neuron disease to ARA24, the first identified androgen receptor polyglutamine region-associated coactivator. J Biol Chem. 1999;274(29):20229-34.
12. Tan JA, Hall SH, Petrusz P, French FS. Thyroid receptor activator molecule, TRAM-1, is an androgen receptor coactivator. Endocrinology. 2000;141(9):3440-50.
13. Wang Q, Ghadessy FJ & Yong EL. Analysis of the transactivation domain of the androgen receptor in patients with male infertility. Clinical Genetics 1998 54 185±192.
14. Robins DM. Androgen receptor and molecular mechanisms of male-specific gene expression. Novartis Found Symp, 2005;268:42-52;discussion 53-6,96-9.
15. Centenera MM, Harris JM, et al. The contribution of different androgen receptor domains to receptor dimerization and signaling. Mol Endocrinol, 2008 Nov;22(11):2373-82.
16. Palazzolo I, Gliozzi A, et al. The role of the polyglutamine tract in androgen receptor. J Steroid Biochem Mol Biol, 2008 Feb;108(3-5):245-53.
17. Robins DM. Androgen receptor and molecular mechanisms of male-specific gene expression. Novartis Found Symp, 2005;268:42-52;discussion 53-6,96-9.
18. Zitzmann M, Gromoll J, et al. The androgen receptor CAG repeat polymorphism. Andrologia, 2005 Dec;37(6):216.
19. Zitzmann M, Nieschlag E. Androgen receptor gene CAG repeat length and body mass index modulate the safety of long-term intramuscular testosterone undecanoate therapy in hypogonadal men. J Clin Endocrinol Metab, 2007 Oct;92(10):3844-53.
20. Zitzmann M. The role of the CAG repeat androgen receptor polymorphism in andrology. Front Horm Res, 2009;37:52-61.
21. Zitzmann M, Nieschlag E. The CAG repeat polymorphism within the androgen receptor gene and maleness. Int J Androl, 2003;26:76-83.
22. Smyth CM, Bremner WJ. Klinefelter syndrome. Arch Intern Med, 1998 Jun 22;158(12):1309-14.

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7 Responses

  1. Stu says:

    I would like to see a similar study that focuses on native Africans. Slave-decendant Africans are likely to have gone through some selective breeding, or at least been selected for their physical traits when brought to e.g. America.

    • Jim says:

      Niggers are still enslaving niggers in Africa. Niggers are niggers no matter where they are located. The first person in America to own a slave for life was a nigger named Anthony Johnson, prior to this nigger suing for that right both whites and blacks could only be indentured servants for a limited number of years.

  2. Richi Rich says:

    The testosterone levels of Indians in Trinidad were found to be higher than the Afro Trinidadians there

  3. David Irving says:

    You see in “Complete androgen insensitivity syndrome” in conception it’s actually male genetically (Y chromosome). And in fact while it’s politically correct to call the adults with CAIS “women”. They technically are not women.

    They lack ovaries but instead have testes that are only partially formed. They don’t have womb’s. They don’t have fallopian tubes etc.

    Sometimes in puberty their testes will finally come down and protrude as bulges either side of their public bone.

    But what you are really looking at, at the end of the day is a male who failed to sexually differentiate who actually because the testosterone produced by the testes cannot be used, the body aromatizes it into estrogen which will femininzes the body.

    But while the body becomes feminized it isn’t a true woman. As is said there are no ovaries or womb or falopian tubes and the opening of what seems like a high positioned small vagina is usually only half as deep as a normal women and the labia etc are all underformed.

    Essentially calling them “women” is insulting to real woman. They are not women by any means of the definition. Sorry.

  4. Which fool wrote this article? says:

    This study is a joke. “Indian” is not, was not, and will never be an ethnic group. There are more than 2000 different ethnic groups in India, and all major races are represented as well. The “Indians” in this study could just as well have been the NE Indians who live in Assam and are no different in genetic makeup from other East Asians/Chinese. They could also just as easily have been the lower caste Indians who have a completely different genetic makeup from the higher caste Indians and a completely different phenotype as well. Any study that generalizes a subcontinent like India or a diverse region like South Asia is pure trash. An analogous study would randomly sample “American men” as if they were an ethnic group, when they are not even a race, but a nationality with all races and thousands of ethnic groups being represented. It would make no sense whatsoever to sample “American men” and come to a conclusion about all American men, all of whom would be very different based on the ethnic group being sampled. I can’t believe that the author of this article is unaware of this fact. Shameful.

  1. August 4, 2015

    […] Guess what? There is no clear evidence that testosterone is different among racial groups! One report even found that Asians had higher testosterone level than white or […]

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