STIMULATION OF OVULATION IN IMMATURE FEMALE RATS USING ORTHOSTERIC AND ALLOSTERIC LUTEINIZING HORMONE RECEPTOR AGONISTS

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Human chorionic gonadotropin (hCG) and luteinizing hormone (LH) are widely used for the treatment of reproductive disorders and for controlled ovulation induction, but their use is limited by side effects. Allosteric agonists of the LH/hCG receptor, including thieno[2,3-d]thienopyrimidine TP03 developed by us, can become an alternative. TP03 (50 mg/rat, i.p.) when administered to immature female rats treated 48 hours before with Follimag has been shown to increase progesterone levels (maximum 8 hours post-treatment) and induce ovulation, as indicated by the appearance at 24 hours corpus luteum (8.6 ± 0.5 per ovary). In terms of its activity, TP03 is comparable to hCG, although it acts more moderately. In the ovaries, unlike hCG, TP03 does not lead to an increase in the expression of vascular endothelial growth factor, which can cause ovarian hyperstimulation syndrome. Thus, TP03 is a promising drug as an ovulation inducer and ovarian steroidogenesis stimulator.

作者简介

E. Fokina

Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences

Email: alex_shpakov@list.ru
Russian Federation, St. Petersburg

K. Derkach

Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences

Email: alex_shpakov@list.ru
Russian Federation, St. Petersburg

A. Bakhtuykov

Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences

Email: alex_shpakov@list.ru
Russian Federation, St. Petersburg

V. Sorokoumov

Institute of Chemistry, St. Petersburg State University

Email: alex_shpakov@list.ru
Russian Federation, St. Petersburg

I. Lebedev

Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences

Email: alex_shpakov@list.ru
Russian Federation, St. Petersburg

I. Morina

Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences

Email: alex_shpakov@list.ru
Russian Federation, St. Petersburg

A. Shpakov

Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences

编辑信件的主要联系方式.
Email: alex_shpakov@list.ru
Russian Federation, St. Petersburg

参考

  1. Martinez F., Racca A., Rodríguez I., et al. Ovarian stimulation for oocyte donation: a systematic review and meta-analysis // Hum Reprod Update. 2021. V. 27. P. 673–696.
  2. Riccetti L., Yvinec R., Klett D., et al. Human Luteinizing Hormone and Chorionic Gonadotropin Display Biased Agonism at the LH and LH/CG Receptors // Sci Rep. 2017. V. 7. P. 940.
  3. Casarini L., Simoni M. Recent advances in understanding gonadotropin signaling // Fac Rev. 2021. V. 10. P. 41.
  4. Jiang X., Dias J.A., He X. Structural biology of glycoprotein hormones and their receptors: insights to signaling // Mol Cell Endocrinol. 2014. V. 382. P. 424–451.
  5. van Koppen C.J., Zaman G.J., Timmers C.M., et al. A signaling-selective, nanomolar potent allosteric low molecular weight agonist for the human luteinizing hormone receptor // Naunyn Schmiedebergs Arch Pharmacol. 2008. V. 378. P. 503–514.
  6. Nataraja S.G., Yu H.N., Palmer S.S. Discovery and Development of Small Molecule Allosteric Modulators of Glycoprotein Hormone Receptors // Front Endocrinol (Lausanne). 2015. V. 6. P. 142.
  7. Bakhtyukov A.A., Derkach K.V., Gureev M.A., et al. Comparative Study of the Steroidogenic Effects of Human Chorionic Gonadotropin and Thieno[2,3-D]pyrimidine-Based Allosteric Agonist of Luteinizing Hormone Receptor in Young Adult, Aging and Diabetic Male Rats // Int J Mol Sci. 2020. V. 21. P. 7493.
  8. Bakhtyukov A.A., Derkach K.V., Sorokoumov V.N., et al. The Effects of Separate and Combined Treatment of Male Rats with Type 2 Diabetes with Metformin and Orthosteric and Allosteric Agonists of Luteinizing Hormone Receptor on Steroidogenesis and Spermatogenesis // Int J Mol Sci. 2021. V. 23. P. 198.
  9. van de Lagemaat R., Timmers C.M., Kelder J., et al. Induction of ovulation by a potent, orally active, low molecular weight agonist (Org 43553) of the luteinizing hormone receptor // Hum Reprod. 2009. V. 24. P. 640–648.
  10. Gerrits M., Mannaerts B., Kramer H., et al. First evidence of ovulation induced by oral LH agonists in healthy female volunteers of reproductive age // J Clin Endocrinol Metab. 2013. V. 98. P. 1558–1566.
  11. Fang L., Li Y., Wang S., et al. TGF-β1 induces VEGF expression in human granulosa-lutein cells: a potential mechanism for the pathogenesis of ovarian hyperstimulation syndrome // Exp Mol Med. 2020. V. 52. P. 450–460.
  12. Быков В.Л., Юшканцева С.И. Гистология, цитология и эмбриология. М.: Издательская группа “ГЭОТАР-Медиа”; 2018. [Bykov V.L., Yushkanceva S.I. Gistologiya, citologiya i embriologiya. M.: Izdatel’skaya gruppa “GEOTAR-Media”; 2018. (In Russ.)]
  13. Gao X., Greenbaum L.M., Mahesh V.B., et al. Characterization of the kinin system in the ovary during ovulation in the rat // Biol Reprod. 1992. V. 47. P. 945–951. https://doi.org/10.1095/biolreprod47.6.945
  14. Duggal P.S., Van Der Hoek K.H., Milner C.R., et al. The in vivo and in vitro effects of exogenous leptin on ovulation in the rat // Endocrinology. 2000. V. 141. P. 1971–1976.
  15. Stevenson P.M., Klinken S.P., Boyne P., et al. Identification of the enzymic control point in “de-differentiation” of oestrogen synthesis in superovulated rat ovary // Biochim Biophys Acta. 1982. V. 713. P. 251–259.

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