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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="research-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Membrane and Cell Biology</journal-id><journal-title-group><journal-title xml:lang="en">Membrane and Cell Biology</journal-title><trans-title-group xml:lang="ru"><trans-title>Биологические мембраны</trans-title></trans-title-group></journal-title-group><issn publication-format="print">0233-4755</issn><issn publication-format="electronic">3034-5219</issn><publisher><publisher-name xml:lang="en">The Russian Academy of Sciences</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">405978</article-id><article-id pub-id-type="doi">10.7868/S3034521926010058</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>Articles</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>СТАТЬИ</subject></subj-group><subj-group subj-group-type="article-type"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">GHR Gene Expression in Hen Hierarchical Follicles Is Dependent on Age, Reproductive Senescence, and the Sensitivity to the Preovulatory Surge of Reproductive Hormones</article-title><trans-title-group xml:lang="ru"><trans-title>Экспрессия гена GHR в иерархических фолликулах курицы зависит от возраста, репродуктивного старения и чувствительности к преовуляторной волне репродуктивных гормонов</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Smekalova</surname><given-names>A. A</given-names></name><name xml:lang="ru"><surname>Смекалова</surname><given-names>А. А</given-names></name></name-alternatives><email>irledv@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Kostyunina</surname><given-names>O. V</given-names></name><name xml:lang="ru"><surname>Костюнина</surname><given-names>О. В</given-names></name></name-alternatives><email>-</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Lebedeva</surname><given-names>I. Yu</given-names></name><name xml:lang="ru"><surname>Лебедева</surname><given-names>И. Ю</given-names></name></name-alternatives><email>-</email><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Ernst Federal Research Center for Animal Husbandry</institution></aff><aff><institution xml:lang="ru">Федеральный исследовательский центр животноводства – ВИЖ имени академика Л.К. Эрнста</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2026-02-15" publication-format="electronic"><day>15</day><month>02</month><year>2026</year></pub-date><volume>43</volume><issue>1</issue><issue-title xml:lang="en">VOL 43, NO1 ()</issue-title><issue-title xml:lang="ru">ТОМ 43, №1 ()</issue-title><fpage>49</fpage><lpage>57</lpage><history><date date-type="received" iso-8601-date="2026-04-03"><day>03</day><month>04</month><year>2026</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2026, Russian Academy of Sciences</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2026, Российская академия наук</copyright-statement><copyright-year>2026</copyright-year><copyright-holder xml:lang="en">Russian Academy of Sciences</copyright-holder><copyright-holder xml:lang="ru">Российская академия наук</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/" start_date="2027-02-15"/></permissions><self-uri xlink:href="https://journals.rcsi.science/0233-4755/article/view/405978">https://journals.rcsi.science/0233-4755/article/view/405978</self-uri><abstract xml:lang="en"><p>The expression of growth hormone (GH) receptors depends on numerous factors, including ontogenetic and endocrine ones. In domestic hens (Gallus domesticus), a short-term increase in the blood levels of reproductive hormones observed in each ovulatory cycle causes a rise in the concentration of GH receptors in the granulosa layer of hierarchical follicles. However, it remains unclear whether this change is related to an increase in the content of the corresponding mRNA. We performed a comparative study of the expression of the GH receptor gene (GHR) in granulosa and theca cells of two largest preovulatory follicles F1 and F2 at different stages of the ovulatory cycle depending on the hen age and reproductive aging. Three groups of birds were used in experiments: young hens with long egg clutches (YLC), old hens with long clutches (OLC), and old hens with short clutches (OSC). The expression level of the GHR gene in follicular cells was assessed by the content of the GH receptor mRNA, which was determined by real-time reverse transcription-PCR, followed by the data analysis using the 2–ΔΔCt method. A significant rise (p &lt; 0.05) in the content of the studied mRNA in granulosa cells from the largest hierarchical follicle F1 was found in OLC hens during the preovulatory hormonal surge, compared to the middle of the ovulatory cycle. These birds also showed a higher (p &lt; 0.001–0.01) expression of GHR in the granulosa layer of F1 and F2 follicles at both stages of the ovulatory cycle compared with YLC and OSC groups. In addition, in OLC hens, the hormone preovulatory surge increased (p &lt; 0.01) the relative level of GH receptor mRNA in theca cells of F2 follicles. Concurrently, the highest content of GHR transcripts in the thecal layer of F2 follicles was observed in YLC hens in the middle of the ovulatory cycle and in OLC hens during the preovulatory surge (p &lt; 0.01–0.05). The findings suggest that the increase in the GHR gene expression in granulosa cells of large hierarchical follicles, especially under the influence of the preovulatory surge of reproductive hormones on F1 follicles, may have a compensatory significance for maintaining a high egg laying intensity in aged hens.</p></abstract><trans-abstract xml:lang="ru"><p>Экспрессия рецепторов гормона роста (ГР) зависит от множества факторов, включая онтогенетические и эндокринные. У домашних кур (Gallus domesticus) кратковременное возрастание в крови уровней репродуктивных гормонов, наблюдаемое в каждом овуляторном цикле, обусловливает повышение концентрации рецепторов ГР (ГР-Р) в гранулезном слое иерархических фолликулов. Однако остается неясным, связано ли это изменение с повышением содержания соответствующей мРНК. Нами проведено сравнительное исследование экспрессии гена рецептора ГР (GHR) в клетках гранулезы и теки двух самых больших преовуляторных фолликулов F1 и F2 в разные стадии овуляторного цикла в зависимости от возраста и репродуктивного старения кур. В экспериментах были использованы три группы птиц: молодые с длинными кладками яиц (МДК), постаревшие с длинными кладками (ПДК) и постаревшие с короткими кладками (ПКК). Уровень экспрессии гена GHR в фолликулярных клетках оценивали по содержанию мРНК ГР-Р, которое определяли методом обратной транскрипции и ПЦР в режиме реального времени с последующим анализом данных по методу 2–∆∆Ct. У кур в группе ПДК обнаружено статистически значимое увеличение (p &lt; 0.05) содержания исследуемой мРНК в клетках гранулезы из самого большого иерархического фолликула F1 во время преовуляторной волны гормонов, по сравнению с серединой овуляторного цикла. У этих птиц также была выявлена более высокая (p &lt; 0.001–0.01) экспрессия GHR в гранулезном слое фолликулов F1 и F2 на обеих стадиях овуляторного цикла по сравнению с птицами в группах МДК и ПКК. Кроме того, у ПДК кур преовуляторная волна гормонов повышала (p &lt; 0.01) относительный уровень мРНК ГР-Р в клетках теки фолликулов F2. При этом самое высокое содержание транскриптов GHR в текальном слое фолликулов F2 наблюдалось у МДК кур в середине овуляторного цикла и у ПДК кур во время преовуляторной волны (p &lt; 0.01–0.05). Полученные данные предполагают, что повышение экспрессии гена GHR в клетках гранулезы больших иерархических фолликулов, особенно при воздействии преовуляторной волны репродуктивных гормонов на фолликулы F1, может иметь компенсаторное значение для сохранения высокой интенсивности яйценоскости у постаревших кур.</p></trans-abstract><kwd-group xml:lang="en"><kwd>growth hormone receptors</kwd><kwd>GHR gene</kwd><kwd>hen hierarchical follicles</kwd><kwd>hormonal preovulatory surge</kwd><kwd>reproductive aging</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>рецепторы гормона роста</kwd><kwd>ген GHR</kwd><kwd>иерархические фолликулы кур</kwd><kwd>гормональная преовуляторная волна</kwd><kwd>репродуктивное старение</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Работа выполнена в рамках государственного задания (тема № FGGN-2024-0014).</funding-statement></funding-group></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Caputo M., Pigni S., Agosti E., Daffara T., Ferrero A., Filigheddu N., Prodam F. 2021. Regulation of GH and GH signaling by nutrients. Cells. 10 (6), 1376. https://www.doi.org/10.3390/cells10061376</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>López-Otin C., Blasco M.A., Partridge L., Serrano M., Kroemer G. 2023. Hallmarks of aging: an expanding universe. Cell. 186 (2), 243–278. https://www.doi.org/10.1016/j.cell.2022.11.001</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>Zhang J., Chen Q., Du D., Wu T., Wen J., Wu M., Zhang Y., Yan W., Zhou S., Li Y., Jin Y., Luo A., Wang S. 2019. Can ovarian aging be delayed by pharmacological strategies? Aging (Albany N.Y.). 11 (2), 817–832. https://www.doi.org/10.18632/aging.101784</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>Tesarik J., Galán-Lázaro M., Mendoza-Tesarik R. 2021. Ovarian aging: Molecular mechanisms and medical management. Int. J. Mol. Sci. 22 (3), 1371. https://www.doi.org/10.3390/ijms22031371</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>Tatone C., Amicarelli F., Carbone M.C., Monteleone P., Caserta D., Marci R., Artini P.G., Piomboni P., Focarelli R. 2008. Cellular and molecular aspects of ovarian follicle ageing. Hum. Reprod. Update. 14 (2), 131–142. https://www.doi.org/10.1093/humupd/dmn048</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>Camaioni A., Ucci M.A., Campagnolo L., De Felici M., Klinger F.G. 2022. The process of ovarian aging: It is not just about oocytes and granulosa cells. J. Assist. Reprod. Genet. 39 (4), 783–792. https://www.doi.org/10.1007/s10815-022-02478-0</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>Cavalcante M.B., Sampaio O.G.M., Câmara F.E.A., Schneider A., de Ávila B.M., Proszczek J., Masternak M.M., Campos A.R. 2023. Ovarian aging in humans: Potential strategies for extending reproductive lifespan. Geroscience. 45 (4), 2121–2133. https://www.doi.org/10.1007/s11357-023-00768-8</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>Han L., Tian H., Guo X., Zhang L. 2023. Regulation of ovarian function by growth hormone: Potential intervention of ovarian aging. Front. Endocrinol. (Lausanne). 13, 1072313. https://www.doi.org/10.3389/fendo.2022.1072313</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>Dehkhoda F., Lee C.M.M., Medina J., Brooks A.J. 2018. The growth hormone receptor: Mechanism of receptor activation, cell signaling, and physiological aspects. Front. Endocrinol. (Lausanne). 9, 35. https://www.doi.org/10.3389/fendo.2018.00035</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>Chang C.W., Sung Y.W., Hsueh Y.W. 2022. Growth hormone in fertility and infertility: Mechanisms of action and clinical applications. Front. Endocrinol. (Lausanne). 13, 1040503. https://www.doi.org/10.3389/fendo.2022.1040503</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>Bartke A. 2022. Somatotropic axis, pace of life and aging. Front. Endocrinol. (Lausanne). 13, 916139. https://www.doi.org/10.3389/fendo.2022.916139</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>Hage C., Salvatori R. 2023. Growth hormone and aging. Endocrinol. Metab. Clin. North Am. 52 (2), 245–257. https://www.doi.org/10.1016/j.ecl.2022.10.003</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>Lebedeva I.Y., Singina G.N., Lopukhov A.V., Shedova E.N., Zinovieva N.A. 2015. Prolactin and growth hormone affect metaphase-II chromosomes in aging oocytes via cumulus cells using similar signaling pathways. Front. Genet. 6, 274. https://www.doi.org/10.3389/fgene.2015.00274</mixed-citation></ref><ref id="B14"><label>14.</label><mixed-citation>Frank S.J. 2020. Classical and novel GH receptor signaling pathways. Mol. Cell. Endocrinol. 518, 110999. https://www.doi.org/10.1016/j.mce.2020.110999</mixed-citation></ref><ref id="B15"><label>15.</label><mixed-citation>Lebedeva I.Y., Lebedev V.A., Grossmann R., Kuzmina T.I., Parvizi N. 2004. Characterization of growth hormone binding sites in granulosa and theca layers at different stages of follicular maturation and ovulatory cycle in the domestic hen. Biol. Reprod. 71 (4), 1174–1181. https://www.doi.org/10.1095/biolreprod.104.030056</mixed-citation></ref><ref id="B16"><label>16.</label><mixed-citation>Hrabia A., Paczoska-Eliasiewicz H.E., Berghman L.R., Harvey S., Rzasa J. 2008. Expression and localization of growth hormone and its receptors in the chicken ovary during sexual maturation. Cell Tissue Res. 332 (2), 317–328. https://www.doi.org/10.1007/s00441-008-0595-7</mixed-citation></ref><ref id="B17"><label>17.</label><mixed-citation>Смекалова А.А., Лебедева И.Ю. 2024. Роль соматотропного гормона в эндокринном и локальном контроле репродуктивной функции у домашней курицы (Gallus domesticus L.). Сельскохозяйственная биология. 59 (6), 1076–1090. https://www.doi.org/10.15389/agrobiology.2024.6.1076rus</mixed-citation></ref><ref id="B18"><label>18.</label><mixed-citation>Hrabia A. 2015. Growth hormone production and role in the reproductive system of female chicken. Gen. Comp. Endocrinol. 220, 112–118. https://www.doi.org/10.1016/j.ygcen.2014.12.022</mixed-citation></ref><ref id="B19"><label>19.</label><mixed-citation>Talamantes F., Ortiz R. 2002. Structure and regulation of expression of the mouse GH receptor. J. Endocrinol. 175 (1), 55–59. https://www.doi.org/10.1677/joe.0.1750055</mixed-citation></ref><ref id="B20"><label>20.</label><mixed-citation>Birzniece V., Sata A., Ho K.K. 2009. Growth hormone receptor modulators. Rev. Endocr. Metab. Disord. 10 (2), 145–156. https://www.doi.org/10.1007/s11154-008-9089-x</mixed-citation></ref><ref id="B21"><label>21.</label><mixed-citation>Chen H., Cui Y., Yu S. 2018. Expression and localisation of FSHR, GHR and LHR in different tissues and reproductive organs of female yaks. Folia Morphol. (Warsz.). 77 (2), 301–309. https://www.doi.org/10.5603/FM.a2016.0095</mixed-citation></ref><ref id="B22"><label>22.</label><mixed-citation>Mense K., Meyerholz M., Gil Araujo M., Lietzau M., Knaack H., Wrenzycki C., Hoedemaker M., Piechotta M. 2015. The somatotropic axis during the physiological estrus cycle in dairy heifers – effect on hepatic expression of GHR and SOCS2. J. Dairy Sci. 98 (4), 2409–2418. https://www.doi.org/10.3168/jds.2014-8734</mixed-citation></ref><ref id="B23"><label>23.</label><mixed-citation>Silva P.R.B., Weber W.J., Crooker B.A., Collier R.J., Thatcher W.W., Chebel R.C. 2017. Hepatic mRNA expression for genes related to somatotropic axis, glucose and lipid metabolisms, and inflammatory response of periparturient dairy cows treated with recombinant bovine somatotropin. J. Dairy Sci. 100 (5), 3983–3999. https://www.doi.org/10.3168/jds.2016-12135</mixed-citation></ref><ref id="B24"><label>24.</label><mixed-citation>Mao J.N., Cogburn L.A., Burnside J. 1997. Growth hormone down-regulates growth hormone receptor mRNA in chickens but developmental increases in growth hormone receptor mRNA occur independently of growth hormone action. Mol. Cell. Endocrinol. 129 (2), 135–143. https://www.doi.org/10.1016/s0303-7207(97)04052-5</mixed-citation></ref><ref id="B25"><label>25.</label><mixed-citation>Lebedeva I.Y., Lebedev V.A., Grossmann R., Parvizi N. 2010. Age-dependent role of steroids in the regulation of growth of the hen follicular wall. Reprod. Biol. Endocrinol. 8, 15. https://www.doi.org/10.1186/1477-7827-8-15</mixed-citation></ref><ref id="B26"><label>26.</label><mixed-citation>He W., Wang H., Tang C., Zhao Q., Zhang J. 2023. Dietary supplementation with astaxanthin alleviates ovarian aging in aged laying hens by enhancing antioxidant capacity and increasing reproductive hormones. Poult. Sci. 102 (1), 102258. https://www.doi.org/10.1016/j.psj.2022.102258</mixed-citation></ref><ref id="B27"><label>27.</label><mixed-citation>Лебедева И.Ю., Митяшова О.С., Алейникова О.В., Монтвила Е.К. 2024. Уровни гормонов гипофизарно-тиреоидной оси и их связь с овариальными гормонами во время овуляторного цикла у молодых кур-несушек (Gallus Domesticus L.). Сельскохозяйственная биология. 59 (6), 1169–1178. https://www.doi.org/10.15389/agrobiology.2024.6.1169rus</mixed-citation></ref><ref id="B28"><label>28.</label><mixed-citation>Gilbert A.B., Evans A.J., Perry M.M., Davidson M.H. 1977. A method for separating the granulosa cells, the basal lamina and the theca of the preovulatory ovarian follicle of the domestic fowl (Gallus domesticus). J. Reprod. Fertil. 50 (1), 179–181. https://www.doi.org/10.1530/jrf.0.0500179</mixed-citation></ref><ref id="B29"><label>29.</label><mixed-citation>Qin N., Shan X., Sun X., Liswaniso S., Chimbaka I.M., Xu R. 2020. Evaluation and validation of the six housekeeping genes for normalizing mRNA expression in the ovarian follicles and several tissues in chicken. Braz. J. Poultry Sci. 22 (3), eRBCA-2019-1256. https://www.doi.org/10.1590/1806-9061-2019-1256</mixed-citation></ref><ref id="B30"><label>30.</label><mixed-citation>Hrabia A., Grzegorzewska A.K., Sechman A. 2013. Expression and localization of growth hormone receptor in the oviduct of the laying hen (Gallus domesticus). Folia Biol. (Krakow). 61 (3–4), 271–276. https://www.doi.org/10.3409/fb61_3-4.271</mixed-citation></ref><ref id="B31"><label>31.</label><mixed-citation>Livak K.J., Schmittgen T.D. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2-(Delta Delta C(T)) method. Methods. 25 (4), 402–408. https://www.doi.org/10.1006/meth.2001.1262</mixed-citation></ref><ref id="B32"><label>32.</label><mixed-citation>Wu J.M., Zelinski M.B., Ingram D.K., Ottinger M.A. 2005. Ovarian aging and menopause: Current theories, hypotheses, and research models. Exp. Biol. Med. (Maywood). 230 (11), 818–828. https://www.doi.org/10.1177/153537020523001106</mixed-citation></ref><ref id="B33"><label>33.</label><mixed-citation>Johnson A.L. Ovarian follicle selection and granulosa cell differentiation. 2015. Poult. Sci. 94 (4), 781–785. https://www.doi.org/10.3382/ps/peu008</mixed-citation></ref><ref id="B34"><label>34.</label><mixed-citation>Juengel J.L., Nett T.M., Anthony R.V., Niswender G.D. 1997. Effects of luteotrophic and luteolytic hormones on expression of mRNA encoding insulin-like growth factor I and growth hormone receptor in the ovine corpus luteum. J. Reprod. Fertil. 110 (2), 291–298. https://www.doi.org/10.1530/jrf.0.1100291</mixed-citation></ref></ref-list></back></article>
