Sex-related variations in Bovine LH isoforms revealed by chromatofocusing
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Abstract
Luteinizing hormone (LH) is a gonadotropin found in both blood and pituitary tissue, and it plays a critical role in reproductive regulation in ruminants and other species. Distinct isoforms produced by post-translational modifications have been previously reported in the pituitary gland of ovariectomized cows and castrated bulls, treated with progesterone and estradiol, respectively. However, it remains unclear whether variations exist in the molecular forms of this hormone in intact prepubertal cattle. Anterior pituitary extracts of steers and heifers underwent chromatofocusing across a pH gradient (10–3.5), allowing classification of the eluted hormone forms into basic (pH ≥ 7.5), neutral (pH 7.4–6.5), and acidic fractions (pH ≤ 6.4) and on the basis of distinct isoforms (12 peaks of A–K). Radioimmunoassay was used to establish the immunological activity of LH isoforms. Overall, basic LH isoforms were present at higher concentrations than neutral or acidic forms in both steers and heifers. However, in steers the analysis by distinct isoforms of LH exhibited a slightly greater proportion of acidic isoforms J (pH 3.4–5.4) and neutral isoform G (pH 6–6.9) compared to heifers. In contrast, heifers showed slightly higher proportions of basic isoforms B (pH 9.2–9.9) and E (pH 7.8–8.7), neutral isoform F (pH 7.1–7.7), and acidic isoforms I (pH 5.7–6.4) and K (pH 3.3–4.9) than steers. Notably, the overall pituitary LH patterns observed in both groups were consistent with previously reported profiles, suggesting that these patterns are relatively stable despite physiological variation. Nevertheless, the subtle differences identified between sexes suggest that sex may influence the synthesis of LH isoforms at the pituitary level.
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References
Rao CV. Multiple novel roles of luteinizing hormone. Fertility and Sterility. 2001;76(6):1097–1100. doi.org/10.1016/S0015-0282(01)02863-1. DOI: https://doi.org/10.1016/S0015-0282(01)02863-1
Furui K, Suganuma N, Tsukahara S, Asada Y, Kikkawa F, Tanaka M, et al. Identification of two point mutations in the gene coding luteinizing hormone (LH) beta-subunit, associated with immunologically anomalous LH variants. The Journal of Clinical Endocrinology and Metabolism. 1994;78(1):107–113. doi.org/10.1210/jcem.78.1.7904610. DOI: https://doi.org/10.1210/jcem.78.1.7904610
Okuda K, Yamada T, Imoto H, Komatsubara H, Sugimoto O. Antigenic alteration of an anomalous human luteinizing hormone caused by two chorionic gonadotropin-type aminoacid substitutions. Biochemical and Biophysical Research Communications. 1994;200(1):584–590. doi.org/10.1006/bbrc.1994.1488. DOI: https://doi.org/10.1006/bbrc.1994.1488
Suganuma N, Furui K, Furuhashi M, Asada Y, Kikkawa F, Tomoda Y. Screening of the mutations in luteinizing hormone beta-subunit in patients with menstrual disorders. Fertility and Sterility. 1995;63(5):989–995. doi.org/10.1016/S0015-0282(16)57535-9. DOI: https://doi.org/10.1016/S0015-0282(16)57535-9
Ramazi S, Zahiri J. Post-translational modifications in proteins: resources, tools and prediction methods. Database. 2021;2021:baab012. doi.org/10.1093/database/baab012. DOI: https://doi.org/10.1093/database/baab012
Baenziger JU, Green ED. Pituitary glycoprotein hormone oligosaccharides: structure, synthesis and function of the asparagine-like oligosaccharides on lutropin, follitropin and thyrotropin. Biochimica et Biophysica Acta. 1988;947(2):287–306. doi.org/10.1016/0304-4157(88)90012-3. DOI: https://doi.org/10.1016/0304-4157(88)90012-3
Cooke D, Crowe MA, Roche J, Headon D. Gonadotropin heterogeneity and its role in farm animal reproduction. Animal Reproduction Science. 1996;41(2):77–99. doi.org/10.1016/0378-4320(95)01449-7. DOI: https://doi.org/10.1016/0378-4320(95)01449-7
Perera-Marín G, Murcia C, González- Padilla E. Luteinizing hormone (LH) isoforms in ruminants: characterization and physiological relevance. Animal Reproduction Science. 2007;101(3–4):187–207. doi.org/10.1016/j.anireprosci.2007.03.011. DOI: https://doi.org/10.1016/j.anireprosci.2007.03.011
Ramanujam LN, Liao WX, Roy AC, Loganath A, Goh HH, Ng SC. Association of molecular variants of luteinizing hormone with menstrual disorders. Clinical Endocrinology. 1999(Dec);51:243–246. doi.org/10.1046/j.1365-2265.1999.00791.x. DOI: https://doi.org/10.1046/j.1365-2265.1999.00791.x
Pau CT, Mosbruger T, Saxena R, Welt CK. Phenotype and tissue expression as a function of genetic risk in polycystic ovary syndrome. PloS One. 2017;12(1):e0168870. doi.org/10.1371/journal.pone.0168870. DOI: https://doi.org/10.1371/journal.pone.0168870
Ramanujam N. Fluorescence spectroscopy of neoplastic and non-neoplastic tissues. Neoplasia. 2000;2(1–2):89–117. doi.org/10.1038/sj.neo.7900077. DOI: https://doi.org/10.1038/sj.neo.7900077
Manzella SM, Hooper LV, Baenziger JU. Oligosaccharides containing beta 1,4-linked N-acetylgalactosamine, a paradigm for protein-specific glycosylation. The Journal Biological Chemestry. 1996;271(21):12117–12120. doi.org/10.1074/jbc.271.21.12117. DOI: https://doi.org/10.1074/jbc.271.21.12117
Lambert A, Talbot JA, Anobile CJ, Robertson WR. Gonadotropin heterogeneity and biopotency: implications for assisted reproduction. Molecular Human Reproduction. 1998;4(7):619–629. doi.org/10.1093/molehr/4.7.619. DOI: https://doi.org/10.1093/molehr/4.7.619
Stumpf TT, Roberson MS, Wolfe MW, Zalesky DD, Cupp AS, Werth LA, et al. A similar distribution of gonadotropin isohormones is maintained in the pituitary throughout sexual maturation in the heifers. Biology of Reproduction. 1992;46(3):442–450. doi.org/10.1095/biolreprod46.3.442. DOI: https://doi.org/10.1095/biolreprod46.3.442
Kojima FN, Cupp AS, Stumpf TT, Zalesky DD, Roberson MS, Werth LA, et.al. Effects of 17 beta-estradiol on distribution of pituitary isoforms of luteinizing hormone and follicle- timulating hormone during the follicular phase of the bovine estrous cycle. Biology of Reproduction. 1995;52(2):297–304. doi.org/10.1095/biolreprod52.2.297. DOI: https://doi.org/10.1095/biolreprod52.2.297
Arrieta E, Porras A, González-Padilla E, Murcia C, Rojas S, Perera-Marín G. Ovine serum and pituitary isoforms of luteinising hormone during the luteal phase. Reproduction, Fertility and Development. 2006;18(4):485–95. doi.org/10.1071/RD05094. DOI: https://doi.org/10.1071/RD05094
Perera-Marín G, Gutiérrez CG, Murcia C, León H, González-Padilla E. Progesterone and the distribution of pituitary gonadotropin isoforms in cattle. Animal Reproduction Science. 2008;104(2–4):164–176. doi.org/ 10.1016/j.anireprosci.2007.02.015. DOI: https://doi.org/10.1016/j.anireprosci.2007.02.015
Perera-Marín G, Murcia C, Rojas S, Hernández-Cerón J, González-Padilla E. Pattern of circulating luteinizing hormone isoforms during the estrous and luteal phase in Holstein heifers. Animal Reproduction Science. 2005;86(1–2):53–69. doi.org/10.1016/j.anireprosci.2004.07.001. DOI: https://doi.org/10.1016/j.anireprosci.2004.07.001
Rojas-Maya S, González-Padilla E, Murcia-Mejía C, Olivares-Segura A, Hernández-Cerón J, Perera-Marín G. Caprine luteinizing hormone isoforms during the follicular phase and anestrus. Animal Reproduction Science. 2007;100(3–4):280–290. doi.org/10.1016/j.anireprosci.2006.07.010. DOI: https://doi.org/10.1016/j.anireprosci.2006.07.010
Perera Marín G, Ortiz Rodríguez F, Gamboa Velázquez JJ, Reynoso Mantilla W, Falcón Alcántara A, Salas Valdés A. Obtención, purificación y caracterización de dos formas de hormona luteinizante de la adenohipófisis caprina (gLH). Veterinaria México. 1996;27(1):1–9.
Dias JA. Is there any physiological role for gonadotrophin oligosaccharide heterogeneity in humans? A biochemical point of view. Human Reproduction. 2001;16(5):825–830. doi.org/10.1093/humrep/16.5.825. DOI: https://doi.org/10.1093/humrep/16.5.825
Perera Marín G, Falcón Alcántara A, Murcia Mejía C, Hernández Cerón J, González Padilla E. Purificación de cinco isoformas de la hormona luteinizante bovina (bLH). Caracterización fisicoquímica, biológica e inmunológica. Veterinaria México. 2004;35(2):129–145.
Montero-Pardo A, Diaz D, Olivares A, González-Padilla E, Murcia C, Gómez- Chavarín M, et al. Effect of ovine luteinizing hormone (oLH) charge isoforms on VEGF and cAMP production. Animal Reproduction Science. 2015;163:35–47. doi.org/10.1016/j.anireprosci.2015.09.015. DOI: https://doi.org/10.1016/j.anireprosci.2015.09.015
Ortega A, Olivares A, Murcia C, Díaz D, González-Padilla E, Montero A, et al. Biological and immunological activity in bovine luteinizing hormone charge isoforms. Revista Mexicana de Ciencias Pecuarias. 2016;7(1):29–51. doi.org/10.22319/rmcp.v7i1.4148. DOI: https://doi.org/10.22319/rmcp.v7i1.4148
Wakabayashi K. Heterogeneity of rat luteinizing hormone revealed by radioimmunoassay and electrofocusing studies. Endocrinologia Japonica. 1977;24(5):473–485. doi.org/10.1507/endocrj1954.24.473. DOI: https://doi.org/10.1507/endocrj1954.24.473
Keel BA, Grotjan HE Jr. Characterization of rat pituitary luteinizing hormone charge microheterogeneity in male and female rats using chromatofocusing: effects of castration. Endocrinology. 1985;117(1):354–360. doi.org/10.1210/endo-117-1-354. DOI: https://doi.org/10.1210/endo-117-1-354
Zalesky DD, Grotjan HE. Comparison of intracellular and secreted isoforms of bovine and ovine luteinizing hormone. Biology of Reproduction.1991;44(6):1016–1024. doi.org/10.1095/biolreprod44.6.1016. DOI: https://doi.org/10.1095/biolreprod44.6.1016
Christianson SL, Zalesky DD, Grotjan HE. Ovine luteinizing hormone heterogeneity: androgens increase the percentage of less basic isohormones. Domestic Animal Endocrinology.1998;15(2):87–92. doi.org/10.1016/s0739-7240(97)00082-9. DOI: https://doi.org/10.1016/S0739-7240(97)00082-9
Keel BA, Schanbacher BD, Grotjan HE Jr. Ovine luteinizing hormone I: effects of castration and steroid administration on the charge heterogeneity of pituitary luteinizing hormone. Biology of Reproduction.1987;36(5):1102–1113 doi.org/10.1095/biolreprod36.5.1102. DOI: https://doi.org/10.1095/biolreprod36.5.1102
Keel BA, Schanbacher BD. Charge heterogeneity of ovine follicle-stimulating hormone in rams and steroid-treated wethers. Biology of Reproduction. 1987;37(4):786–796. doi.org/10.1095/biolreprod37.4.786. DOI: https://doi.org/10.1095/biolreprod37.4.786
Keel BA, Zalensky DD, Sohaili I, Schanbacher BD, Grotjan HE. Heterogeneity of gonadotropins and levels of uncombined luteinizing hormone subunits in pituitaries of cryptorchid rams. Journal of Andrology. 1994;15(1):29–35. doi.org/10.1002/j.1939-4640.1994.tb01678.x. DOI: https://doi.org/10.1002/j.1939-4640.1994.tb01678.x
Perera, M, Falcon, A, Salas, V, editores. Estandarización de la técnica de radiomarcaje con Iodo-gen. In: Memorias del XXXIX Congreso Nacional de Ciencias Fisiológicas; 1996. Puebla, Mexico.
Bollag DM, Edelstein SJ. Protein Methods. New York, US: Wiley-Liss; 1991.
Matteri RL, Papkoff H, Swedlow JR, Chang YS. Isolation and characterization of three forms of luteinizing hormone from the pituitary gland of the horse. Biology of Reproduction. 1986;34(3):571–578. doi.org/10.1095/biolreprod34.3.571. DOI: https://doi.org/10.1095/biolreprod34.3.571
Arey BJ, López FJ. Are circulating gonadotropin isoforms naturally occurring biased agonists? Basic and therapeutic implications. Reviews in Endocrine and Metabolic Disorders. 2011;12(4) 275–288. doi.org/10.1007/s11154-011-9188-y. DOI: https://doi.org/10.1007/s11154-011-9188-y
Hattori M, Ozawa K, Wakabayashi K. Sialic acid moiety is responsible for the charge heterogeneity and the biological potency of rat lutropin. Biochemical and Biophysical Research Communications. 1985;127(2):501–508. doi.org/10.1016/S0006-291X(85)80188-1. DOI: https://doi.org/10.1016/S0006-291X(85)80188-1
Hortin G, Natowicz M, Pierce J, Baenziger J, Parsons T, Boime I. Metabolic labeling of lutropin with [35S] sulfate. Proceedings of the National Academy of Sciences of the United States of America. 1981;78(12):7468–7472. doi.org/10.1073/pnas.78.12.7468. DOI: https://doi.org/10.1073/pnas.78.12.7468
Green ED, van Halbeek H, Boime I, Baenziger JU. Structural elucidation of the disulfated oligosaccharide from bovine lutropin. The Journal of Biological Chemistry. 1985;260(29):15623–15630. doi.org/10.1016/S0021-9258(17)36304-4. DOI: https://doi.org/10.1016/S0021-9258(17)36304-4
Stanton PG, Burgon PG, Hearn MT, Robertson DM. Structural and functional characterisation of hFSH and hLH isoforms. Molecular and Cellular Endocrinology. 1996;125(1–2):133–141. doi.org/10.1016/S0303-7207(96)03958-5. DOI: https://doi.org/10.1016/S0303-7207(96)03958-5
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