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  • Boc-D-FMK br Conclusions In summary we report a novel prelim

    2024-06-24


    Conclusions In summary, we report a novel preliminary finding of a potential racial difference in the association of Cd-content and AR expression in prostate cancer that will need to be confirmed in larger studies. Although the association of Cd and AR protein expression is not strong in tumor tissue of adult African American men, it is the first direct evidence of an association between the two to be reported for human prostate tissue and it is unknown whether this association exists in normal prostate tissue (in men without cancer or BPH) or is present and important during development. Future studies should focus on direct measurements of metals and AR in the prostate or development of more accurate surrogate measures for estimating prostate Cd-content and AR expression. The later may be difficult since Minguez-Alarcon et al. [41] have shown that Cd-concentrations in blood and seminal plasma have low correlation with one another. Correlations between blood or urine Cd-concentrations and prostate tissue Cd-content may also be low. Capturing exposures across the life course may help identify windows of opportunity in which Cd exposure has the greatest influence on AR activity and prostate carcinogenesis. If this African American-specific Cd-AR association is real, then further exploration into any role Cd plays in racial differences in tumor aggressiveness or disease recurrence is also warranted.
    Funding National Institute of Environmental Health Sciences (R01 ES011126 to B.A.R., R21 ES024379 to C.N.D.), Wayne State University, President’s Research Enhancement Program (to C.N.D.) and Wayne State University/HenryFordHealth System INPHAASE program (to C.N.D.), National Center for Research Resources (NCRR) (UL1 RR024156 to R.B.M).
    Conflicts of interest
    Introduction The skin has the ability to produce androgens both de novo from cholesterol or using circulating adrenal precursors, such as dehydroepiandrosterone (DHEA), through specific enzymatic activities. Skin is a dynamic tissue that is renewed periodically, and so is the hair follicle, which grows following a strict renewing Boc-D-FMK that is divided into defined phases. Androgens regulate many of these processes and others related to skin embryogenesis.
    Role of androgens in skin physiology Many long terminal hairs e.g. scalp hairs, eyelashes and eyebrows are developed from birth and maintained throughout life and have protective functions. Other hair types are a secondary sexual characteristic and can be divided into two groups, adult axillary and pubic hairs in both sexes and beard and chest hairs in adult men (Randall, 1994, Marshall and Tanner, 1969, Marshall and Tanner, 1970). They begin to grow to terminal hairs during puberty in response to the rise of plasma androgen levels (Winter and Faiman, 1972, Winter and Faiman, 1973). Sebum production by sebaceous glands is also under the control of androgens. A significant rise in sebum production, comparable to that of young adults, was observed in both sexes during the first days after birth, and is maintained until the second month of life, whereupon, a notably reduction is observed (Agache et al., 1980). This increase in sebum production correlates with the appearance of the so called genital crisis characterized by breast swelling, genital edema with hydrocele in boys and genital bleeding in girls that last two to three days. These results indicated that this sebum production rise would be related to androgen stimulation and correlated to the significant rise in plasma level of DHEA that is maintained through the first three month of life (de Peretti and Forest, 1976). After the seventh year of life a new increase in DHEA secretion by the adrenal glands (adrenarche) is observed in both sexes before any sign of puberty (de Peretti and Forest, 1976). In this sense, a positive correlation of pre-pubertal acne, relative sebum secretion and urinary excretion of 17-ketosteroides was observed in both sexes. Even though 17-ketosteroids are weak steroids, the sebaceous glands can respond to their stimulus at this stage of development (Pochi et al., 1977). It was also demonstrated that dihydrotestosterone (DHT) stimulation is sufficient to induce commitment of functional AR-expressive immature sebocytes into the lipogenic differentiation process (Barrault et al., 2015). After puberty, sebum production in men is significantly increased and is greater in men than in age-matched women (Pochi and Strauss, 1974, Strauss, 1963), men suffering complete androgen insensitivity (Imperato-McGinley et al., 1993) or castrated men. In this last study group, the oral administration of methyltestosterone significantly increased sebum production (Pochi et al., 1962).