[The study of interaction of different forms of human recombinant anti-mullerian hormone with a chimeric analogue of the AMH type II]. / Issledovanie vzaimodeistviia razlichnykh form rekombinantnogo antimiullerova gormona cheloveka s khimernym analogom ego retseptora II tipa.

The homodimeric glycoprotein, anti-mullerian hormone (AMH), described over 70 years ago by A. Jost, is the least studied member of the transforming growth factor beta superfamily. Despite the antitumor activity of AMH discovered at the end of the last century, the creation of effective drugs based on AMH is hindered primarily by the lack of information on the mechanism of various AMH forms interaction with a specific type II receptor (MISRII). Previously, we have shown that not only the full-length activated hormone but also its C-terminal fragment (C-rAMH) could bind to MISRII. In this work, using the surface plasmon resonance technique, we compared the interaction of three forms of recombinant AMH (rAMH) with the MISRII analogue - the chimeric protein MISRII-Fc containing AMH type II receptor and a Fc-fragment of the human IgG1 heavy chain. Comparison of the binding of MISRII-Fc, immobilized on a chip with group specificity for human immunoglobulins, to C-rAMH, to intact rAMH (pro-rAMH), and to rAMH containing one uncleaved monomer (hc-rAMH), showed that the KD of the complexes increased: 1.7 nM, 88 nM and 110 nM, respectively. Thus, we have shown that C-terminal fragment of AMH has the maximum affinity for the recombinant MISRII analogue, which indicates the prospects for the development of drugs based on this hormone derivative.

[Mullerian inhibiting substance type II receptor as a potential target for antineoplastic therapy]. / Retseptor antimiullerova gormona II tipa kak potentsial'naia mishen' dlia protivoopukholevoi terapii.

The review considers properties of the type II anti-Mullerian hormone receptor (mullerian inhibiting substance receptor type II, MISRII), a transmembrane sensor with its own serine/threonine protein kinase activity, triggering apoptosis of the Mullerian ducts in mammalian embryogenesis and providing formation of the male type reproductive system. According to recent data, MISRII overexpression in the postnatal period is found in cells of a number of ovarian, mammary gland, and prostate tumors, and anti-Mullerian hormone (AMH) has a pro-apoptotic effect on MISRII-positive tumor cells. This fact makes MISRII a potential target for targeted anti-cancer therapy. Treatment based on targeting MISRII seems to be a much more effective alternative to the traditional one and will significantly reduce the drug dose. However, the mechanism of MISRII-AMH interaction is still poorly understood, so the development of new anticancer drugs is complicated. The review analyzes MISRII molecular structure and expression levels in various tissues and cell lines, as well as current understanding of the AMH binding mechanisms and data on the possibility of using MISRII as a target for the action of AMH-based antineoplastic drugs.

[The dynamics of human total and activated anti-mullerian hormone serum levels in different life periods.]

Here, changes in the serum level of total anti-mullerian hormone (AMH) and its activated form in children of both sexes and women with different reproductive status are investigated. This TGFß superfamily cytokine is known to provide the formation of the male-type reproductive system in mammalian embryogenesis, and regulate folliculogenesis, spermatogenesis and the balance of sex hormones after birth. The biologically active form of the hormone (aAMH) is formed as a result of limited proteolysis of the AMH molecule; it is not reliably known in which tissues and under the action of which enzyme it occurs. The serum level of aAMH seems to be a more informative clinical indicator than the content of total AMH (tAMH), but there are no ELISA systems at the world market that provide direct quantitative detection of aAMH. In this work, quantitative detection of total hormone (tAMH) and its biologically active form (aAMH) in serum was performed using specially developed enzyme immunoassay systems. We showed that in girls, the total serum AMH level, as well as the concentration ratio aAMH / tAMH, practically does not change with age, whereas in boys, there is not only a significant decrease in the total serum AMH level previously described in the literature (Pearson correlation coefficient R = - 0.86, p <0.001), but also in the ratios of the aAMH / tAMH level (R = -0.531, p <0.001). It was also found that in pregnant women, the amount of total AMH and the proportion of aAMH in serum was significantly higher (p <0.01 and p <0.001, respectively) than in the control group women. The obtained results are in good agreement with the available data on the total and activated AMH content in the blood serum of people of different sex and age and indicate a change in the ratio of aAMH / tAMH serum levels in pregnancy. These data may be important both for deepening the understanding of AMH biology and for interpreting the results obtained using AMH detection based diagnostics.