Resistance to steroid hormones presents a serious problem with respect to their mass use in therapy. It may be caused genetically by mutation of genes involved in hormonal signaling, not only steroid receptors, but also other players in the signaling cascade as co-regulators and other nuclear factors, mediating the hormone-born signal. Another possibility is acquired resistance which may develop under long-term steroid treatment, of which a particular case is down regulation of the receptors. In the review recent knowledge is summarized on the mechanism of main steroid hormone action, pointing to already proven or potential sites causing steroid resistance. We have attempted to address following questions: 1) What does stay behind differences among patients as to their response to the (anti)steroid treatment? 2) Why do various tissues/cells respond differently to the same steroid hormone though they contain the same receptors? 3) Are such differences genetically dependent? The main attention was devoted to glucocorticoids as the most frequently used steroid therapeutics. Further, androgen insensitivity is discussed with a particular attention to acquired resistance to androgen deprivation therapy of prostate cancer. Finally the potential causes are outlined of breast and related cancer(s) resistance to antiestrogen therapy., R. Hampl, K. Vondra., and Obsahuje bibliografii
Maternal hyperandrogenism during pregnancy might have metabolic and endocrine consequences on the offspring as shown for the polycystic ovary syndrome. Despite numerous experiments, the impact of prenatal hyperandrogenic environment on postnatal sex steroid milieu is not yet clear. In this study, we investigated the effect of prenatal testosterone excess on postnatal concentrations of luteinizing hormone, corticosterone and steroid hormones including testosterone, pregnenolone, progesterone, estradiol and 7β-hydroxyepiandrosterone in the offspring of both sexes. Pregnant rats were injected daily with either testosterone propionate or vehicle from gestational day 14 until parturition. The hormones were evaluated in plasma of the adult offspring. As expected, females had lower testosterone and higher pregnenolone, progesterone and estradiol in comparison to males. In addition, corticosterone was higher in females than in males, and it was further elevated by prenatal testosterone treatment. In males, prenatal testosterone exposure resulted in higher 7β-hydroxyepiandrosterone in comparison to control group. None of the other analyzed hormones were affected by prenatal testosterone. In conclusion, our results did not show major effects on sex hormone production or luteinizing hormone release in adult rats resulting from testosterone excess during their fetal development. However, maternal hyperandrogenism seems to partially affect steroid biosynthesis in sex-specific manner., E. Domonkos, V. Borbélyová, L. Kolátorová, T. Chlupáčová, D. Ostatníková, J. Hodosy, L. Stárka, P. Celec., and Obsahuje bibliografii
Sex and gender matter in all aspects of life. Humans exhibit sexual dimorphism in anatomy, physiology, but also pathology. Many of the differences are due to sex chromosomes and, thus, genetics, other due to endocrine factors such as sex hormones, some are of social origin. Over the past decades, huge number of scientific studies have revealed striking sex differences of the human brain with remarkable behavioral and cognitive consequences. Prenatal and postnatal testosterone influence brain structures and functions, respectively. Cognitive sex differences include especially certain spatial and language tasks, but they also affect many other aspects of the neurotypical brain. Sex differences of the brain are also relevant for the pathogenesis of neuropsychiatric disorders such as autism spectrum disorders, which are much more prevalent in the male population. Structural dimorphism in the human brain was welldescribed, but recent controversies now question its importance. On the other hand, solid evidence exists regarding gender differences in several brain functions. This review tries to summarize the current understanding of the complexity of the effects of testosterone on brain with special focus on their role in the known sex differences in healthy individuals and people in the autism spectrum.