Spironolactonum also

Spironolactonum also co-operates with and receptors, no less than with Aldosteronum receptors, and can render and antiandrogenic influences, in that number-occurrence of a gynecomastia and loss . Nonsteroid antagonists of androgens concerns which does not possess hormonal activity, and on the antiandrogenic properties it is similar to tsiproteron-acetate. Like Progestinums, in target tissues oppresses absorption and a delay in kernels order generic ultram of androgens, competing for linkage with their cytosolic receptors. Antagonists of glucocorticoids Present time would not exist clinically applicable antagonist of glucocorticoid effects as augmentation of secretion quickly overcomes action of blockade of these effects at the expense of rising of secretion of a hydrocortisone by adrenals. However some steroids show partial or ability to competitive inhibition of action of a hydrocortisone and related glucocorticoids. The majority of glucocorticoids possesses axial 11 ?-hydroxylic group which can play the important role in linkage and receptor activation [92]. Such steroids as Cortisonum and (11-dezoksikortizol or bond S) and progesterone derivatives, contact glucocorticoid receptors, but practically do not possess own glucocorticoid biological activity. These bonds can operate as partial agonists or antagonists, especially in vitro when they are not metabolized further in glucocorticoids. In vivo last process can interfere with implication of full antiglucocorticoid action of such steroids, except for not metabolized bonds, such, as a tsiproteron-acetate and later the received antagonists [93]. Antagonists of mineralocorticoids Such bonds as Spironolactonum, operate as antagonists of Aldosteronum, inhibiting linkage of the last with receptors and forming the antagonist-receptor a complex which is not exposed to a translocation and linkage in a kernel.
These the antagonist-receptor complexes on to properties differ from complex Aldosteronum-receptor that can reflect an inactive condition of a receptor or the change of conformstion caused by linkage of the antagonist [94]. Besides the described effects, Spironolactonum in high doses oppresses Aldosteronum biosynthesis, rendering to that additional action. To other bonds co-operating with by receptors, nonsteroid agents, such, as resolvents (for example, Phenylbutazonum) and acid concern. These agents compete for linkage to renal receptors and cause a delay of sodium and other steroid effects. Thus, interaction of such bonds-agonists with receptors can lead to development of reaction of cells-targets presumably at the expense of the same nuclear mechanism which mediates effects of endogenous pyridium mineralocorticoids on transport of electrolytes. Linkage of steroid receptors in kernels For implication of biological effects of steroid hormones interaction activated cytoplasmatic complexes with kernels of cells-targets is necessary. Activated the complex gets ability to contact a chromatin, no less than from DNA and others , and to collect in a kernel. Data about presence at a kernel just as in a cytoplasma cells free receptors, testify that they can be distributed on all cell-target, despite dependence of their accumulation in a kernel from transformation in activated the form with balance shift between distribution in a kernel and out of it [81]. In a kernel the activated complexes contact acceptor sites of a chromatin and initiate synthesis specific and fibers [95]. The exact nature of nuclear acceptor sites is not known, but ability testifies to value of DNA in reaction to interfere with linkage complexes with kernels and to liberate from a kernel earlier bound complexes. The chromatin from kernels of cells-targets of androgens and progesterone binds more complexes, than a chromatin from the tissues which are not reacting to these steroids. Like it, the receptors allocated from cells some refractory to glucocorticoids , possess the lowered affinity to kernels and DNA. Linkage of complexes from DNA is defined, apparently, by ionic interactions between positively charged site of a molecule of a receptor and negatively charged phosphatic groups of DNA, and also not ionic forces. Consider, that DNA-binding contains a site of a receptor molecule , and the rests and changes under the influence of the agents operating on sulfhydryl groups. At least one of kinds of receptor molecules (for progesterone) consists of two : one (), possessing nonspecific binding affinity to DNA, and the second (), having specific affinity to a chromatin of cells . Selective. Linkage progesterone-receptor of complexes is defined by interaction V-subedinitsy with special fraction fibers of a chromatin which can cause fabric specificity of action of progesterone. Such double process of linkage could raise matrix activity of a chromatin, providing availability of places synthesis and others , coding fibers [84]. Despite these data about value of linkage with DNA and a chromatin for nuclear effects of steroid hormones, nevertheless there are doubts concerning the nature of acceptor sites and a role of the majority of processes of the linkage observed in a kernel. a complex it is possible from uterus kernels in a combination with a ribonucleoprotein, and activated complexes are strongly bound to nuclear histones and the basic fibers of a kernel.