GHR Gene Expression in Hen Hierarchical Follicles Is Dependent on Age, Reproductive Senescence, and the Sensitivity to the Preovulatory Surge of Reproductive Hormones

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

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 < 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 < 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 < 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 < 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.

About the authors

A. A Smekalova

Ernst Federal Research Center for Animal Husbandry

Email: irledv@mail.ru
Podolsk, Russia

O. V Kostyunina

Ernst Federal Research Center for Animal Husbandry

Podolsk, Russia

I. Yu Lebedeva

Ernst Federal Research Center for Animal Husbandry

Podolsk, Russia

References

  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. Bartke A. 2022. Somatotropic axis, pace of life and aging. Front. Endocrinol. (Lausanne). 13, 916139. https://www.doi.org/10.3389/fendo.2022.916139
  12. 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
  13. 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
  14. 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
  15. 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
  16. 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
  17. 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
  18. 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
  19. 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
  20. 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
  21. 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
  22. 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
  23. 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
  24. 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
  25. 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
  26. 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
  27. 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
  28. 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
  29. 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
  30. 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
  31. 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
  32. 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
  33. 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
  34. 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

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2026 Russian Academy of Sciences