Non-genomic actions of steroid hormones in pregnant and non-pregnant uterine tissues: in vivo and vitro studies

It is known that the results of the non-genomic action can be the same as or even different from the effects mediated through the genomic pathway. For example, in the cardiovascular system and diabetes mellitus, the outcome of both signaling pathways is the same 27–30, but in breast cancer cell lines, their actions can be the opposite 26. Since the prompt actions of steroids on uterine contractility are not fully explored yet, we aimed to investigate the fast, non-genomic action of sex steroids (E2, progesterone (P4), T) and corticosteroids (MC fludrocortisone (FLD) and GC (DEX)) on uterine contractions and signaling pathways both late (22-day) pregnant and non-pregnant rats in vitro and in vivo as well

Non-genomic actions of steroid hormones on the contractility of non-vascular smooth muscles

Steroid hormones play an important role in physiological processes. The classical pathway of steroid actions is mediated by nuclear receptors, which regulate genes to modify biological processes. Non-genomic pathways of steroid actions are also known, mediated by cell membrane-located seven transmembrane domain receptors. Sex steroids and glucocorticoids have several membrane receptors already identified to mediate their rapid actions. However, mineralocorticoids have no identified membrane receptors, although their rapid actions are also measurable. In non-vascular smooth muscles (bronchial, uterine, gastrointestinal, and urinary), the rapid actions of steroids are mediated through the modification of the intracellular Ca2+ level by various Ca-channels and the cAMP and IP3 system. The non-genomic action can be converted into a genomic one, suggesting that these distinct pathways may interconnect, resulting in convergence between them. Sex steroids mostly relax all the non-vascular smooth muscles, except androgens and progesterone, which contract colonic and urinary bladder smooth muscles, respectively. Corticosteroids also induce relaxation in bronchial and uterine tissues, but their actions on gastrointestinal and urinary bladder smooth muscles have not been investigated yet. Bile acids also contribute to the smooth muscle contractility. Although the therapeutic application of the rapid effects of steroid hormones and their analogues for smooth muscle contractility disorders seems remote, the actions and mechanism discovered so far are promising. Further research is needed to expand our knowledge in this field by using existing experience. One of the greatest challenges is to separate genomic and non-genomic effects, but model molecules are available to start this line of research

Phenotypic plasticity of melanocytes derived from human adult skin

We previously described a novel in vitro culture technique for dedifferentiated human adult skin melanocytes. Melanocytes cultured in a defined, cholera toxin and PMA free medium became bipolar, unpigmented, and highly proliferative. Furthermore, TRP-1 and c-Kit expression disappeared and EGFR receptor and nestin expression were induced in the cells. Here, we further characterized the phenotype of these dedifferentiated cells and by comparing them to mature pigmented melanocytes we detected crucial steps in their phenotype change. Our data suggest that normal adult melanocytes easily dedifferentiate into pluripotent stem cells given the right environment. This dedifferentiation process described here for normal melanocyte is very similar to what has been described for melanoma cells, indicating that phenotype switching driven by environmental factors is a general characteristic of melanocytes that can occur independent of malignant transformation