Progesterone, thyroid hormone and relaxin in the regulation of the invasive potential of extravillous trophoblast at the early stage of placental development

Manufacturer: Alina Pharma LLC
Active ingredients

• Not indicated. See instructions

Pharmacological action

• Not indicated. See instructions

• Composition of Relaxin
• Indications for use of the drug Relaxin
• Release form of the drug Relaxin
• Use of the drug Relaxin during pregnancy
• Contraindications to the use of the drug Relaxin
• Side effects of the drug Relaxin
• Method of administration and dosage of the drug Relaxin
• Overdose of Relaxin
• Precautions when taking Relaxin
• Storage conditions for the drug Relaxin
• Shelf life of the drug Relaxin

Best before date

24 months

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The description of vitamin Relaxin is intended for informational purposes only. Before starting to use any drug, it is recommended to consult a doctor and read the instructions for use. For more complete information, please refer to the manufacturer's instructions. Do not self-medicate; EUROLAB is not responsible for the consequences caused by the use of information posted on the portal. Any information on the project does not replace consultation with a specialist and cannot be a guarantee of the positive effect of the drug you use. The opinions of EUROLAB portal users may not coincide with the opinions of the site Administration.

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Function [edit]

In people[edit]

In women, relaxin is produced primarily by the corpus luteum in both pregnant and non-pregnant women. [1] Relaxin levels peak around 14 days after ovulation, and then decrease in the absence of pregnancy, leading to menstruation. [7] Relaxin may be involved in the vital process of decidualization, working together with steroid hormones to allow the endometrium to prepare for implantation. [8] During the first trimester of pregnancy, relaxin levels increase and the decidua produces additional relaxin. Relaxin peaks in the first trimester (14 weeks) and during labor. Relaxin mediates the hemodynamic changes that occur during pregnancy, such as increased cardiac output, increased renal blood flow, and increased arterial elasticity. [ citation needed

] It also relaxes other pelvic ligaments.
[9] It is believed to soften the symphysis pubis. [ citation needed
]

In men, relaxin increases sperm motility in seminal fluid. [10]

In the cardiovascular system, relaxin works primarily by activating the nitric oxide pathway. Other mechanisms include activation of NFκB leading to transcription of vascular endothelial growth factor (VEGF) and matrix metalloproteinases. [eleven]

Relaxin has been shown to relax vascular smooth muscle cells and increase nitric oxide production in rat endothelial cells, thereby playing a role in regulating cardiovascular function by dilating systemic resistance arteries. [11] Relaxin increases the speed and strength of heart contractions in rat models. [12] Through activation of VEGF, relaxin plays a key role in blood vessel formation (angiogenesis) during pregnancy, tumor development, or ischemic wounds. [12]

In other animals[edit]

In animals, relaxin expands the pubic bone and facilitates childbirth; it also softens the cervix (cervical ripening) and relaxes the uterine musculature. [ citation needed

] Thus, for a long time, relaxin was considered as a pregnancy hormone.
However, its significance can reach much more. Relaxin can influence collagen metabolism by inhibiting collagen synthesis and increasing its breakdown by increasing matrix metalloproteinases. [13] It also enhances angiogenesis and is a potent renal vasodilator. [ citation needed
]

In a mouse model, relaxin was found to promote cardiomyocyte maturation. [12]

Several animal studies have shown that relaxin has a cardioprotective function against ischemia and reperfusion injury, reducing cell damage through anti-apoptotic and anti-inflammatory effects. [ citation needed

] Relaxin reduces cardiac fibrosis in animal models by inhibiting collagen-secreting cardiac fibroblasts and stimulating matrix metalloproteinase. [12] [11]

In the European rabbit ( Oryctolagus cuniculus

) relaxin is associated with squamous differentiation and is expressed in tracheobronchial epithelial cells rather than being involved in reproduction. [14]

In horses ( Equus caballus

) relaxin is also an important hormone involved in pregnancy, however, before pregnancy occurs, relaxin is expressed by ovarian structures during the estrous cycle. [15] Before ovulation, relaxin will be produced by ovarian stromal cells, which will promote the secretion of gelatinases and tissue inhibitors of metalloproteinases. These enzymes will then promote the ovulation process, leading to the release of the developed follicle into the fallopian tube. [15] In addition, granule cells and theca cells in follicles will express relaxin at increasing levels depending on their size. [15] In early pregnancy, the preimplantation conceptus will express relaxin, which will promote angiogenesis in the endometrium through activation of VEGF. [15] [16] This will allow the endometrium to prepare for implantation. Only in horses will the embryo in the uterus express relaxin mRNA at least 8 days after ovulation. Expression will then increase as the conceptus develops, likely to promote embryonic development. [15]

In addition to the production of relaxin by the equine embryo, the maternal placenta is the main source of relaxin production, whereas in most animals the main source of relaxin is the corpus luteum. [15] Placental trophoblast cells produce relaxin, but the size of the placenta does not determine the level of relaxin production. This is seen because different breeds of horses show different levels of relaxin. [17] Beginning at day 80 of gestation, the mare's serum relaxin levels will increase, peaking in late pregnancy. [17] [18] Moreover, the expression pattern of relaxin will correspond to the expression of estrogen. However, the relationship between these two hormones is not yet known. [18] During labor, there is a surge of relaxin 3–4 hours before birth, which is involved in relaxing the myometrium and softening the pelvic ligaments, which helps prepare the birth canal for the birth of the equine fetus. [15] [17] After birth, relaxin levels will gradually decrease if the placenta is also delivered, however, if the placenta is retained by the mare, relaxin levels will remain high. [17] Additionally, if a mare undergoes an abortion, relaxin levels will decrease as the placenta stops functioning. [17]

Diseases[edit]

Women who took relaxin during unrelated clinical trials experienced heavier bleeding during their menstrual cycle, suggesting that relaxin levels may play a role in abnormal uterine bleeding. [20] However, more research is needed to confirm that relaxin is the direct cause. [ citation needed

]

Lower expression of relaxin has been found in women with endometriosis. Research in this area is limited, and a more detailed study of the role of relaxin could greatly contribute to the understanding of endometriosis. [20]

Specific disorders associated with relaxin have not been described in detail, but an association with scleroderma and fibromyalgia has also been suggested. [21]

Pregnancy[edit]

It is possible that relaxin in the placenta may be a contributing factor in inducing labor in humans, and that serum levels of relaxin during pregnancy are therefore associated with preterm birth. [20]

Receptors[edit]

Relaxin interacts with the relaxin receptors LGR7 (RXFP1) and LGR8 (RXFP2), which belong to the G protein-coupled receptor superfamily. [19] They contain a heptal transmembrane domain and a large glycosylated ectodomain remotely associated with glycoproteogormone receptors such as the LH receptor or FSH receptor.

Relaxin receptors have been found in the heart, smooth muscle, connective tissue, and the central and autonomic nervous systems. [ citation needed

]

Evolution [edit]

Relaxin 1 and relaxin 2 arose from duplication of the proto-RLN gene between 44.2 and 29.6 million years ago in the last common ancestor of bluetongue primates. [22] The duplication that led to RLN1 and RLN2 is believed to have been the result of positive selection and convergent evolution at the nucleotide level between the relaxin gene in New World monkeys and the RLN1 gene in monkeys. [22] As a result, Old World monkeys, a group that includes the subfamilies colobines and cercopithecines, lost the RLN1 paralogue, but the monkeys retained the RLN1 and RLN2 genes. [22]

Links[edit]

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2. “If a gopher can do it...”. Time Magazine. 1944-04-10. Retrieved May 20, 2009.
3. Becker GJ, Hewitson TD (March 2001). "Relaxin and renal fibrosis". Kidney International
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4. Wilkinson TN, Speed ​​TP, Tregear GW, Bathgate RA (February 2005). "Evolution of the relaxin-like peptide family". BMC Evolutionary Biology
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5. MacLennan A H (1991). "The role of the hormone relaxin in human reproduction and relaxation of the pelvic girdle." Scandinavian Journal of Rheumatology. Addition
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6. Hossain MA, Rosengren KJ, Samuel CS, Shabanpoor F, Chan LJ, Bathgate RA, Wade JD (October 2011). "Minimal active structure of human relaxin-2". Journal of Biological Chemistry
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7. Hayes ES (June 2004). "The biology of primate relaxin: a paracrine signal in early pregnancy?" . Reproductive biology and endocrinology
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8. Karp N, Torchinsky A, Fain A, Toder V (December 2001). "Hormones, cytokines and fetal abnormalities in recurrent abortion." Gynecological endocrinology
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9. ↑
   Konrad KP (August 2011).
   "Maternal vasodilation during pregnancy: a new role for relaxin". American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
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10. ↑
    Weiss G (February 1989).
    "Relaxin in masculinity". Biology of Reproduction
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11. ^ abc Roley JM, Toldo S, Das A, Abbot A, Salloum FN (July 2021). "Relaxing the Heart: A New Therapeutic Method." Journal of Cardiovascular Pharmacology and Therapeutics
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12. ^ abcd Feijo-Bandin S, Aragon-Herrera A, Rodríguez-Penas D, Portoles M, Rosello-Lleti E, Rivera M, González-Juanatey Jr., Lago F (2017). "Relaxin-2 in cardiometabolic diseases: mechanisms of action and future prospects". Frontiers of Physiology
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13. Mukherjee I, Solly NR, Royce SG, Tregear GW, Samuel CS, Tang ML (February 2006). "Endogenous relaxin regulates collagen deposition in an animal model of allergic airway disease". Endocrinology
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14. Arroyo JI, Hoffmann FG, Opazo JC (February 2012). "Gene duplication and positive selection explain the unusual physiological role of the relaxin gene in the European rabbit." Journal of Molecular Evolution
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    (1–2): 52–60. DOI: 10.1007/s00239-012-9487-2. PMID 22354201. S2CID 15030230.
15. ^ B s d e g Klein C (July 2016). "The role of relaxin in the reproductive physiology of mares: a comparative review with other species". Theriogenology
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    (1):451–6. DOI: 10.1016/j.theriogenology.2016.04.061. PMID 27158127.
16. Jump up
    ↑ Klein C (July 2016).
    "Early pregnancy in the mare: old concepts revisited." Endocrinology of Companion Animals
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17. ^ abcde Ousey JC (December 2006). "Hormonal profiles and treatments for late pregnant mares." Veterinary clinics in North America. Equestrian practice
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18. ^ a b Pashen R.L. (July 1984). "Maternal and fetal endocrinology in late pregnancy and birth in a mare." Equine Veterinary Journal
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    (4): 233–8. DOI: 10.1111/j.2042-3306.1984.tb01918.x. PMID 6383806.
19. Hsu SY, Nakabayashi K, Nishi S, Kumagai J, Kudo M, Sherwood OD, Xue AJ (January 2002). "Activation of orphan receptors by the hormone relaxin." The science
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20. ^ abcd Marshall SA, Senadheera SN, Parry LJ, Girling JE (March 2021). "The role of relaxin in normal and abnormal uterine function during the menstrual cycle and early pregnancy." Reproductive Sciences
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21. ↑
    Van Der Westhuizen ET, Summers RJ, Halls ML, Bathgate RA, Sexton PM (January 2007).
    “Relaxin receptors are new drug targets for a variety of disease conditions.” Current drug goals
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22. ^ abc Arroyo J. I., Hoffmann F. G., Opazo J. C. (March 2014). "Evolution of the relaxin/insulin-like gene family in anthropoid primates". Genomic biology and evolution
    .
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    (3): 491–9. DOI: 10.1093/GbE/evu023. PMC 3971578. PMID 24493383.