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Üremede Leptinlerin Etkisi

Yıl 2024, Cilt: 9 Sayı: 1, 98 - 114, 30.04.2024

Oya Korkmaz , Ömer Faruk Karaşör , Ali Soleimanzadeh , Mustafa Numan Bucak , Sadık Küçükgünay , Mustafa Kul

https://doi.org/10.51754/cusbed.1459267

Öz

Adipoz doku hem enerji deposu hem de adipokinler olarak adlandırılan biyolojik olarak önemli çok sayıda molekülü salgılayan aktif bir endokrin organ olarak işlev görmektedir. Adipokinlerin üreme fonksiyonlarının düzenlenmesinde yer aldığı kanıtlanmıştır ve tanımlanan ilk adipokin leptindir. Son yıllarda yapılan araştırmalar, leptinin beyine giden enerji depolarının miktarının yalnızca yağ dokusundan türetilen bir habercisi olmadığını, aynı zamanda iltihaplanma, anjiyogenez, hematopoez, bağışıklık fonksiyonu ve üreme gibi bir dizi farklı fizyolojik süreç için çok önemli bir hormon/sitokin olduğunu göstermektedir. Adiposit kaynaklı bir hormon olan leptin, özellikle ergenlik ve üreme döneminde vücutta çok sayıda fizyolojik ve metabolik fonksiyonda önemli rol oynamaktadır. Leptin, merkezi hipotalamik etkilerinin yanı sıra, testisler de dahil olmak üzere birçok periferik organda (mide, iskelet kası, hipofiz hücreleri, plasenta) etki göstermektedir ve hem erkek üreme hem de dişi üreme işlevinde düzenleyici bir role sahiptir. Leptin normal üreme işlevi için gereklidir, ancak fazla miktarda bulunduğunda üreme sistemi üzerinde zararlı etkileri olabilir. Non-obstrüktif azoospermi, oligozoospermi ve oligo-asteno-teratozoospermi dahil olmak üzere testiküler parankimi etkileyen bozuklukları olan infertil erkeklerin yüksek leptin konsantrasyonlarına sahip olduğu bilinmektedir. Literatürde yapılan son çalışmalar, hipotalamik-hipofizeal-gonadal (HPG) ekseni, androjen regülasyonu ve sperm üretimi ile leptin ve infertilite arasında güçlü bir ilişki olduğunu öne sürmektedir. Yapılan bu çalışmalardan yola çıkarak, leptin fazlalığı, eksikliği veya direnci durumlarının anormal üreme işlevi ile ilişkili olabileceğini söylemek mümkündür. Ayrıca, yüksek leptinin neden olduğu bu anormallikler artan oksidatif stres ile de ilişkilendirilmiştir. Eğer ki leptin ve üreme arasındaki ilişki tam olarak anlaşılabilirse, hem erkek hem de kadın infertilitesi için gelecekte hedeflenen tedavilere ışık tutabilecektir. Bu derleme leptin ile fertilite arasındaki ilişkiye odaklanmaktadır.

Anahtar Kelimeler

Üreme Hipotalamik-Hipofizeal-gonadal eksen İnfertilite Leptin

Etik Beyan

Bu çalışma için etik kurul onayı gerekli değildir.

Destekleyen Kurum

Çalışma için herhangi bir finansal destek alınmamıştır.

Kaynakça

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Effect of Leptins in Reproduction

Yıl 2024, Cilt: 9 Sayı: 1, 98 - 114, 30.04.2024

Oya Korkmaz , Ömer Faruk Karaşör , Ali Soleimanzadeh , Mustafa Numan Bucak , Sadık Küçükgünay , Mustafa Kul

https://doi.org/10.51754/cusbed.1459267

Öz

Adipose tissue functions both as an energy store and as an active endocrine organ secreting a large number of biologically important molecules called adipokines. Adipokines have been shown to be involved in the regulation of reproductive function and the first adipokine identified was leptin. Recent research shows that leptin is not only an adipocyte-derived precursor of the amount of energy stores going to the brain, but also a hormone/cytokine crucial for a number of different physiological processes such as inflammation, angiogenesis, hematopoiesis, immune function and reproduction. Leptin, an adipocyte-derived hormone, plays an important role in numerous physiological and metabolic functions in the body, especially during puberty and reproduction. Besides its central hypothalamic effects, leptin acts in many peripheral organs (stomach, skeletal muscle, pituitary cells, placenta), including the testes, and has a regulatory role in both male reproductive and female reproductive function. Leptin is essential for normal reproductive function, but in excess it can have detrimental effects on the reproductive system. Infertile men with disorders affecting the testicular parenchyma, including non-obstructive azoospermia, oligozoospermia and oligo-astheno-teratozoospermia, are known to have high leptin concentrations. Recent studies in the literature suggest a strong association between the hypothalamic-hypophyseal-gonadal (HPG) axis, androgen regulation and sperm production, leptin and infertility. Based on these studies, it is possible to suggest that leptin excess, deficiency or resistance may be associated with abnormal reproductive function. Furthermore, these abnormalities caused by high leptin have also been associated with increased oxidative stress. If the relationship between leptin and reproduction can be fully understood, it may shed light on future targeted therapies for both male and female infertility. This review focuses on the relationship between leptin and fertility.

Anahtar Kelimeler

Reproduction Hypothalamic-hypophyseal-gonadal axis Infertility Leptin

Kaynakça

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  • Sáinz, N., Barrenetxe, J., Moreno-Aliaga, M.J., & Martínez, J.A. (2015). Leptin resistance and diet-induced obesity: central and peripheral actions of leptin. Metabolism, 64, 35-46.
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  • Scaramuzzi, R.J., & Martin, G.B. (2008). The importance of interactions among nutrition, seasonality and socio-sexual factors in the development of hormone-free methods for controlling fertility. Reprod Domest Anim, 43, 129-36.
  • Schinzari, F., Tesauro, M., Rovella, V., Di Daniele, N., Mores, N., Veneziani, A., & Cardillo, C. (2013). Leptin stimulates both endothelin-1 and nitric oxide activity in lean subjects but not in patients with obesity-related metabolic syndrome. J Clin Endocrinol Metab, 98, 1235-41.
  • Schroeter, M.R., Leifheit-Nestler, M., Hubert, A., Schumann, B., Glückermann, R., Eschholz, N., Krüger, N., Lutz, S., Hasenfuss, G., Konstantinides, S., & Schäfer, K. (2013). Leptin promotes neointima formation and smooth muscle cell proliferation via NADPH oxidase activation and signalling in caveolin-rich microdomains. Cardiovasc Res, 99, 555-65.
  • Schubring, C., Englaro, P., Siebler, T., Blum, W.F., Demirakca, T., Kratzsch, J., & Kiess, W. (1998). Longitudinal analysis of maternal serum leptin levels during pregnancy, at birth and up to six weeks after birth: relation to body mass index, skinfolds, sex steroids and umbilical cord blood leptin levels. Horm Res, 50, 276-83.
  • Schubring, C., Prohaska, F., Prohaska, A., Englaro, P., Blum, W., Siebler, T., Kratzsch, J., & Kiess, W. (1999). Leptin concentrations in maternal serum and amniotic fluid during the second trimenon: differential relation to fetal gender and maternal morphometry. Eur J Obstet Gynecol Reprod Biol, 86, 151-7.
  • Sharma, K., & Considine, R.V. (1998). The Ob protein (leptin) and the kidney. Kidney Int, 53, 1483-7.
  • Shimizu, H., Shimomura, Y., Nakanishi, Y., Futawatari, T., Ohtani, K., Sato, N., & Mori, M. (1997). Estrogen increases in vivo leptin production in rats and human subjects. J Endocrinol, 154, 285-92.
  • Shiraishi, K., & Naito, K. (2007). Effects of 4-hydroxy-2-nonenal, a marker of oxidative stress, on spermatogenesis and expression of p53 protein in male infertility. J Urol, 178, 1012-7.
  • Singh, B., Prasad, S., & Gupta, H.P. (2012). Effect of leptin on in-vitro maturation of oocytes and on early embryonic development in buffaloes. Indian J Anim Reprod, 33, 1-6.
  • Singhal, A., Farooqi, I.S., O'Rahilly, S., Cole, T.J., Fewtrell, M., & Lucas, A. (2002). Early nutrition and leptin concentrations in later life. Am J Clin Nutr, 75, 993-9.
  • Slieker, L.J., Sloop, K.W., Surface, P.L., Kriauciunas, A., LaQuier, F., Manetta, J., Bue-Valleskey, J., & Stephens, T.W. (1996). Regulation of expression of ob mRNA and protein by glucocorticoids and cAMP. J Biol Chem, 271, 5301-4.
  • Smith, J.T., & Waddell, B.J. (2003). Leptin distribution and metabolism in the pregnant rat: transplacental leptin passage increases in late gestation but is reduced by excess glucocorticoids. Endocrinology, 144, 3024-30.
  • Smith, J.T., & Waddell, B.J. (2002). Leptin receptor expression in the rat placenta: changes in ob-ra, ob-rb, and ob-re with gestational age and suppression by glucocorticoids. Biol Reprod, 67, 1204-10.
  • Sobhani, I., Bado, A., Vissuzaine, C., Buyse, M., Kermorgant, S., Laigneau, J.P., Attoub, S., Lehy, T., Henin, D., Mignon, M., & Lewin, M.J. (2000). Leptin secretion and leptin receptor in the human stomach. Gut, 47, 178-83.
  • Solinas, G. (2010). Leptin signalling coordinates lipid oxidation with thermogenesis and defence against oxidative stress. Clin Exp Pharmacol Physiol, 37, 953-4.
  • Stone, R.T., Kappes, S.M., & Beattie, C.W. (1996). The bovine homolog of the obese gene maps to chromosome 4. Mamm Genome, 7, 399-400.
  • Strobel, A., Issad, T., Camoin, L., Ozata, M., & Strosberg, A.D. (1998). A leptin missense mutation associated with hypogonadism and morbid obesity. Nat Genet, 18, 213-5.
  • Sullivan, S.D., & Moenter, S.M. (2004). Gamma-aminobutyric acid neurons integrate and rapidly transmit permissive and inhibitory metabolic cues to gonadotropin-releasing hormone neurons. Endocrinology, 145, 1194-202.
  • Swain, J.E., Dunn, R.L., McConnell, D., Gonzalez-Martinez, J., & Smith, G.D. (2004). Direct effects of leptin on mouse reproductive function: regulation of follicular, oocyte, and embryo development. Biol Reprod, 71, 1446-52.
  • Tartaglia, L.A., Dembski, M., Weng, X., Deng, N., Culpepper, J., Devos, R., Richards, G.J., Campfield, L.A., Clark, F.T., Deeds, J., Muir, C., Sanker, S., Moriarty, A., Moore, K.J., Smutko, J.S., Mays, G.G., Wool, E.A., Monroe, C.A., & Tepper, R.I. (1995). Identification and expression cloning of a leptin receptor, OB-R. Cell, 83, 1263-71.
  • Tena-Sempere, M., Pinilla, L., González, L.C., Diéguez, C., Casanueva, F.F., & Aguilar, E. (1999). Leptin inhibits testosterone secretion from adult rat testis in vitro. J Endocrinol, 161, 211-8.
  • Thomas, M.G., Enns, R.M., Hallford, D.M., Keisler, D.H., Obeidat, B.S., Morrison, C.D., Hernandez, J.A., Bryant, W.D., Flores, R., Lopez, R., & Narro, L. (2002). Relationships of metabolic hormones and serum glucose to growth and reproductive development in performance-tested Angus, Brangus, and Brahman bulls. J Anim Sci, 80, 757-67.
  • Trayhurn, P., Thomas, M.E., Duncan, J.S., & Rayner, D.V. (1995). Effects of fasting and refeeding on ob gene expression in white adipose tissue of lean and obese (oblob) mice. FEBS Lett, 368, 488-90.
  • Wallace, A.M. (2000). Measurement of leptin and leptin binding in the human circulation. Ann Clin Biochem, 37, 244-52.
  • Wang, Y.Y., Wang, Y.L., Li, H.P., Zhu, H.S., Jiang,.Q.D., Zhang, L., Wang, L.F., Han, L.Q., Zhong, K., Guo, Y.J., Lu, W.F., Li, H.J., & Yang, G.Y. (2011). Leptin mRNA expression in the rat mammary gland at different activation stages. Genet Mol Res, 10, 3657-63.
  • Wang, X., Zhang, X., Hu, L., & Li, H. (2018). Exogenous leptin affects sperm parameters and impairs blood testis barrier integrity in adult male mice. Reprod Biol Endocrinol, 16(1), 55.
  • Wannamethee, S.G., Shaper, A.G., Whincup, P.H., Lennon, L., & Sattar, N. (2013). Adiposity, adipokines, and risk of incident stroke in older men. Stroke, 44, 3-8.
  • Weir, C.P., & Robaire, B. (2007). Spermatozoa have decreased antioxidant enzymatic capacity and increased reactive oxygen species production during aging in the Brown Norway rat. J Androl, 28, 229-40.
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  • Wolsk, E., Mygind, H., Grøndahl, T.S., Pedersen, B.K., & van Hall, G. (2012). Human skeletal muscle releases leptin in vivo. Cytokine, 60, 667-73.
  • Yamagishi, S., Amano, S., Inagaki, Y., Okamoto, T., Takeuchi, M., & Inoue, H. (2003). Pigment epithelium-derived factor inhibits leptin-induced angiogenesis by suppressing vascular endothelial growth factor gene expression through anti-oxidative properties. Microvasc Res, 65, 186-90.
  • Yu, W.H., Kimura, M., Walczewska, A., Karanth, S., & McCann, S.M. (1997). Role of leptin in hypothalamic-pituitary function. Proc Natl Acad Sci U S A, 94, 1023-8.
  • Yuan, M., Huang, G., Li, J., Zhang, J., Li, F., Li, K., Gao, B., Zeng, L., Shan, W., Lin, P., & Huang, L. (2014). Hyperleptinemia directly affects testicular maturation at different sexual stages in mice, and suppressor of cytokine signaling 3 is involved in this process. Reprod Biol Endocrinol, 12, 15.
  • Zegers-Hochschild, F., Adamson, G.D., Dyer, S., Racowsky, C., de Mouzon, J., Sokol, R., Rienzi, L., Sunde, A., Schmidt, L., Cooke, I.D., Simpson, J.L., & van der Poel, S. (2017). The International Glossary on Infertility and Fertility Care, 2017. Hum Reprod, 32, 1786-1801.
  • Zembayashi, M., Nishimura, K., Lunt, D.K., & Smith, S.B. (1995). Effect of breed type and sex on the fatty acid composition of subcutaneous and intramuscular lipids of finishing steers and heifers. J Anim Sci, 73, 3325-32.
  • Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., & Friedman, J.M. (1994). Positional cloning of the mouse obese gene and its human homologue. Nature, 372, 425-32.
  • Zieba, D.A., Amstalden, M., Maciel, M.N., Keisler, D.H., Raver, N., Gertler, A., & Williams, G.L. (2003). Divergent effects of leptin on luteinizing hormone and insulin secretion are dose dependent. Exp Biol Med (Maywood), 228, 325-30.
  • Zorn, B., Osredkar, J., Meden-Vrtovec, H., & Majdic, G. (2007). Leptin levels in infertile male patients are correlated with inhibin B, testosterone and SHBG but not with sperm characteristics. Int J Androl, 30, 439-44.
Toplam 230 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Veteriner Bilimleri (Diğer)
Bölüm Derleme
Yazarlar

Oya Korkmaz 0000-0003-2923-5869

Ömer Faruk Karaşör 0000-0002-5090-779X

Ali Soleimanzadeh 0000-0002-1591-2198

Mustafa Numan Bucak 0000-0002-2955-8599

Sadık Küçükgünay 0009-0005-7520-6788

Mustafa Kul 0000-0002-9170-5094

Erken Görünüm Tarihi 29 Nisan 2024
Yayımlanma Tarihi 30 Nisan 2024
Gönderilme Tarihi 27 Mart 2024
Kabul Tarihi 24 Nisan 2024
Yayımlandığı Sayı Yıl 2024Cilt: 9 Sayı: 1

Kaynak Göster

APA Korkmaz, O., Karaşör, Ö. F., Soleimanzadeh, A., Bucak, M. N., vd. (2024). Üremede Leptinlerin Etkisi. Cumhuriyet Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi, 9(1), 98-114. https://doi.org/10.51754/cusbed.1459267
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