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Home / Equine Research Bank / J Neuroendocrinol / Melatonin receptors and thyroid stimulating hormone in the e...
Journal of neuroendocrinology2025; e70077; doi: 10.1111/jne.70077

Melatonin receptors and thyroid stimulating hormone in the equine pars tuberalis: Potential modulators of seasonal reproduction in the mare.

Abstract: The mechanism by which photoperiod influences the hypothalamic-pituitary-gonadal (HPG) axis and regulates seasonal reproduction in horses has yet to be fully elucidated. The hypophyseal pars tuberalis (PT) has been indicated as a critical site for the transduction of melatonin signals through melatonin-responsive, PT-specific cells that produce thyroid-stimulating hormone (TSH) in many mammalian species. However, this has yet to be investigated in horses. The objective of this study was to explore the interaction of melatonin and thyroid-stimulating hormone in the equine HPG axis. Pituitaries from mares of light-horse breeds (Quarter Horse, Thoroughbred, etc.) categorized as either breeding season or non-breeding season based on season, gross examination of ovarian structures, and plasma progesterone concentrations were collected post-mortem. In situ hybridization revealed melatonin receptor (MT1r) mRNA abundantly expressed in glandular cells of the PT in both breeding and non-breeding season mares. Immunofluorescent analysis revealed a higher abundance of TSH-ir cells (p = .0043) in PT obtained during the breeding season compared to the non-breeding season. In cycling mares, MT1r mRNA co-localized with TSH-producing cells in the PT, suggesting a role for TSH as a modulator of seasonal reproduction in the mare. These findings support a role for melatonin and TSH in modulating seasonal reproduction in the mare, further evidenced by the increased TSH immunosignal observed during the breeding season. Altogether, this study endorses the PT as the key site for integrating multiple cues to regulate seasonal reproduction in the horse, as this study marks the first investigation of the relationship between melatonin and PT-specific TSH cells and release in an equine model.
© 2025 British Society for Neuroendocrinology.
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Publication Date: 2025-08-10 PubMed ID: 40785101DOI: 10.1111/jne.70077Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article investigates the role of melatonin and thyroid-stimulating hormone (TSH) in regulating seasonal reproduction in horses. It provides first-time evidence on the relationship between melatonin, TSH, and the hypothalamic-pituitary-gonadal (HPG) axis in controlling the reproductive cycle in light-horse breeds.

Introduction

  • The study seeks to explain the mechanism by which light exposure (photoperiod) influences the HPG axis, thereby regulating seasonal reproduction in horses. The focus is on the role of the pars tuberalis (PT), a part of the pituitary gland, in this process.
  • Previous reports have suggested the PT, responsive to melatonin signals, and TSH production – a process yet to be explored in horses – might play crucial roles in photoperiodic modulation of mammalian reproduction.

Methods and Materials

  • The researchers collected pituitary glands from deceased mares of light-horse breeds in both breeding and non-breeding seasons based on the season, examination of ovarian structures, and plasma progesterone concentrations.
  • The study applied ‘in situ hybridization’ to examine mRNA expression of melatonin receptor (MT1r) in glandular cells of the PT. This helped to identify the cell types containing this receptor and their distribution.
  • Immunofluorescent analysis was used to quantify TSH-producing cells (TSH-ir) in the PT tissues collected during both seasons.

Results and Discussion

  • MT1r mRNA was found to be abundantly expressed in the PT of both breeding and non-breeding mares, indicating melatonin’s role in this gland regardless of the reproductive season.
  • A higher abundance of TSH-ir cells was discovered in the PT during the breeding season in comparison to the non-breeding season, implying a correlation between TSH levels and breeding season.
  • The researchers found co-localization of MT1r mRNA with TSH-producing cells. This provides evidence for the potential role of TSH as a modulator of seasonal reproduction in mares, possibly acting under the influence of melatonin.

Conclusion

  • The study strengthens the idea that melatonin, in conjunction with TSH, may regulate seasonal reproduction in horses. This regulation is likely undertaken through alterations in TSH levels in the PT during the breeding season.
  • The researchers highlight the PT as a crucial zone integrating several signals to regulate seasonal reproduction in horses. The findings add substantial weight to the understanding of reproductive processes in equine models, marking a first in the investigation of interactions between melatonin and PT-specific TSH cells.

Cite This Article

APA
Bailey VN, Gilbert BM, Vetter M, Oberhaus EL. (2025). Melatonin receptors and thyroid stimulating hormone in the equine pars tuberalis: Potential modulators of seasonal reproduction in the mare. J Neuroendocrinol, e70077. https://doi.org/10.1111/jne.70077

Publication

Journal of neuroendocrinology
ISSN: 1365-2826
NlmUniqueID: 8913461
Country: United States
Language: English
Pages: e70077

Researcher Affiliations

Bailey, Victoria N
  • School of Animal Sciences, Louisiana Agricultural Experiment Station, Louisiana State University Agricultural Center, Baton Rouge, Louisiana, USA.
Gilbert, Bryce M
  • School of Animal Sciences, Louisiana Agricultural Experiment Station, Louisiana State University Agricultural Center, Baton Rouge, Louisiana, USA.
Vetter, Michelle
  • School of Animal Sciences, Louisiana Agricultural Experiment Station, Louisiana State University Agricultural Center, Baton Rouge, Louisiana, USA.
Oberhaus, Erin L
  • School of Animal Sciences, Louisiana Agricultural Experiment Station, Louisiana State University Agricultural Center, Baton Rouge, Louisiana, USA.

References

This article includes 50 references
  1. Nagy P, Guillaume D, Daels P. Seasonality in mares. Anim Reprod Sci 2000;60:245‐262.
    doi: 10.1016/s0378-4320(00)00133-0google scholar: lookup
  2. Malpaux B, Migaud M, Tricoire H, Chemineau P. Biology of mammalian photoperiodism and the critical role of the pineal gland and melatonin. J Biol Rhythms 2001;16(4):336‐347.
    doi: 10.1177/074873001129002051google scholar: lookup
  3. Lewis JE, Ebling FJP. Tanycytes as regulators of seasonal cycles in neuroendocrine function. Front Neurol 2017;8:79.
    doi: 10.3389/fneur.2017.00079google scholar: lookup
  4. Wood S, Loudon A. The pars tuberalis: the site of the circannual clock in mammals?. Gen Comp Endocrinol 2018;258:222‐235.
    doi: 10.1016/j.ygcen.2017.06.029google scholar: lookup
  5. Stankov B, Cozzi B, Lucini V, Fumagalli P, Scaglione F, Fraschini F. Characterization and mapping of melatonin receptors in the brain of three mammalian species: rabbit, horse and sheep. A comparative in vitro binding study. Neuroendocrinology 1991;53(3):214‐221.
    doi: 10.1159/000125721google scholar: lookup
  6. Nonno R, Capsoni S, Lucini V, Moller M, Fraschini F, Stankov B. Distribution and characterization of the melatonin receptors in the hypothalamus and pituitary gland of three domestic ungulates. J Pineal Res 1995;18(4):207‐216.
    doi: 10.1111/j.1600-079x.1995.tb00161.xgoogle scholar: lookup
  7. Morgan PJ, Barrett P, Howell HE, Helliwell R. Melatonin receptors: localization, molecular pharmacology and physiological significance. Neurochem Int 1994;24(2):101‐146.
    doi: 10.1016/0197-0186(94)90100-7google scholar: lookup
  8. Klosen P, Bienvenu C, Demarteau O. The mt1 melatonin receptor and RORβ receptor are co‐localized in specific TSH‐immunoreactive cells in the pars tuberalis of the rat pituitary. J Histochem Cytochem 2002;50(12):1647‐1657.
  9. Yasuo S, Yoshimura T, Ebihara S, Korf HW. Melatonin transmits photoperiodic signals through the MT1 melatonin receptor. J Neurosci 2009;29(9):2885‐2889.
    doi: 10.1523/jneurosci.0145-09.2009google scholar: lookup
  10. Ono H, Hoshino Y, Yasuo S. Involvement of thyrotropin in photoperiodic signal transduction in mice. Proc Natl Acad Sci USA 2008;105(47):18238‐18242.
    doi: 10.1073/pnas.0808952105google scholar: lookup
  11. Wittkowski W, Bergmann M, Hoffmann K, Pera F. Photoperiod‐dependent changes in Tsh‐like Immunoreactivity of cells in the Hypophyseal pars Tuberalis of the Djungarian hamster, Phodopus‐Sungorus. Cell Tissue Res 1988;251(1):183‐187.
    doi: 10.1007/bf00215463google scholar: lookup
  12. Nakao N, Ono H, Yamamura T. Thyrotrophin in the pars tuberalis triggers photoperiodic response. Nature 2008;452(7185):317‐322.
    doi: 10.1038/nature06738google scholar: lookup
  13. Nakao N, Ono H, Yoshimura T. Thyroid hormones and seasonal reproductive neuroendocrine interactions. Reproduction 2008;136(1):1‐8.
    doi: 10.1530/rep-08-0041google scholar: lookup
  14. Bolborea M, Helfer G, Ebling FJ, Barrett P. Dual signal transduction pathways activated by TSH receptors in rat primary tanycyte cultures. J Mol Endocrinol 2015;54(3):241‐250.
    doi: 10.1530/jme-14-0298google scholar: lookup
  15. Yoshimura T, Yasuo S, Watanabe M. Light‐induced hormone conversion of T‐4 to T‐3 regulates photoperiodic response of gonads in birds. Nature 2003;426(6963):178‐181.
    doi: 10.1038/nature02117google scholar: lookup
  16. Klosen P, Sebert ME, Rasri K, Laran-Chich MP, Simonneaux V. TSH restores a summer phenotype in photoinhibited mammals via the RF‐amides RFRP3 and kisspeptin. FASEB J 2013;27(7):2677‐2686.
    doi: 10.1096/fj.13-229559google scholar: lookup
  17. Hanon EA, Lincoln GA, Fustin JM. Ancestral TSH mechanism signals summer in a photoperiodic mammal. Curr Biol 2008;18(15):1147‐1152.
    doi: 10.1016/j.cub.2008.06.076google scholar: lookup
  18. Henson JR, Carter SN, Freeman DA. Exogenous T(3) elicits long day‐like alterations in testis size and the RFamides Kisspeptin and gonadotropin‐inhibitory hormone in short‐day Siberian hamsters. J Biol Rhythms 2013;28(3):193‐200.
    doi: 10.1177/0748730413487974google scholar: lookup
  19. Quignon C, Beymer M, Gauthier K, Gauer F, Simonneaux V. Thyroid hormone receptors are required for the melatonin‐dependent control of Rfrp gene expression in mice. FASEB J 2020;34(9):12072‐12082.
    doi: 10.1096/fj.202000961rgoogle scholar: lookup
  20. Buff PR, Messer NT, Cogswell AM, Johnson PJ, Keisler DH, Ganjam VK. Seasonal and pulsatile dynamics of thyrotropin and leptin in mares maintained under a constant energy balance. Domest Anim Endocrinol 2007;33(4):430‐436.
    doi: 10.1016/j.domaniend.2006.08.007google scholar: lookup
  21. Henneke DR, Potter GD, Kreider JL, Yeates BF. Relationship between condition score, physical measurements and body fat percentage in mares. Equine Vet J 1983;15(4):371‐372.
    doi: 10.1111/j.2042-3306.1983.tb01826.xgoogle scholar: lookup
  22. Nagy P, Solti L, Kulcsar M. Progesterone determination in equine plasma using different immunoassays. Acta Vet Hung 1998;46(4):501‐513.
  23. Decourt C, Tillet Y, Caraty A, Franceschini I, Briant C. Kisspeptin immunoreactive neurons in the equine hypothalamus interactions with GnRH neuronal system. J Chem Neuroanat 2008;36(3–4):131‐137.
    doi: 10.1016/j.jchemneu.2008.07.008google scholar: lookup
  24. Eagle RC, Tortonese DJ. Characterization and distribution of gonadotrophs in the pars distalis and pars tuberalis of the equine pituitary gland during the estrous cycle and seasonal anestrus. Biol Reprod 2000;63(3):826‐832.
    doi: 10.1095/biolreprod63.3.826google scholar: lookup
  25. Sticker LS, Thompson DL, Gentry LR. Pituitary hormone and insulin responses to infusion of amino acids and N‐methyl‐D,L‐aspartate in horses. J Anim Sci 2001;79(3):735‐744.
  26. Bankhead P, Loughrey MB, Fernandez JA. QuPath: open source software for digital pathology image analysis. Sci Rep 2017;7(1):16878.
    doi: 10.1038/s41598-017-17204-5google scholar: lookup
  27. Reppert SM. Melatonin receptors: molecular biology of a new family of G protein‐coupled receptors. J Biol Rhythms 1997;12(6):528‐531.
    doi: 10.1177/074873049701200606google scholar: lookup
  28. Malpaux B, Tricoire H, Mailliet F. Melatonin and seasonal reproduction: understanding the neuroendocrine mechanisms using the sheep as a model. Reprod Suppl 2002;59:167‐179.
  29. de Reviers MM, Ravault JP, Tillet Y, Pelletier J. Melatonin binding sites in the sheep pars tuberalis. Neurosci Lett 1989;100(1–3):89‐93.
    doi: 10.1016/0304-3940(89)90665-4google scholar: lookup
  30. Morgan PJ, Williams LM, Davidson G, Lawson W, Howell E. Melatonin receptors on ovine pars tuberalis: characterization and autoradiographicai localization. J Neuroendocrinol 1989;1(1):1‐4.
    doi: 10.1111/j.1365-2826.1989.tb00068.xgoogle scholar: lookup
  31. Dardente H, Klosen P, Pevet P, Masson-Pevet M. MT1 melatonin receptor mRNA expressing cells in the pars tuberalis of the European hamster: effect of photoperiod. J Neuroendocrinol 2003;15(8):778‐786.
    doi: 10.1046/j.1365-2826.2003.01060.xgoogle scholar: lookup
  32. Skene DJ, Masson-Pevet M, Pevet P. Seasonal changes in melatonin binding sites in the pars tuberalis of male European hamsters and the effect of testosterone manipulation. Endocrinology 1993;132(4):1682‐1686.
    doi: 10.1210/endo.132.4.8462468google scholar: lookup
  33. Gauer F, Masson-Pevet M, Saboureau M, George D, Pevet P. Differential seasonal regulation of melatonin receptor density in the pars tuberalis and the suprachiasmatic nuclei: a study in the hedgehog (Erinaceus europaeus, L.). J Neuroendocrinol 1993;5(6):685‐690.
    doi: 10.1111/j.1365-2826.1993.tb00540.xgoogle scholar: lookup
  34. Bittman EL, Weaver DR. The distribution of melatonin binding sites in neuroendocrine tissues of the ewe. Biol Reprod 1990;43(6):986‐993.
    doi: 10.1095/biolreprod43.6.986google scholar: lookup
  35. Saenz de Miera C, Monecke S, Bartzen-Sprauer J. A circannual clock drives expression of genes central for seasonal reproduction. Curr Biol 2014;24(13):1500‐1506.
    doi: 10.1016/j.cub.2014.05.024google scholar: lookup
  36. Wood SH, Christian HC, Miedzinska K. Binary switching of calendar cells in the pituitary defines the phase of the circannual cycle in mammals. Curr Biol 2015;25(20):2651‐2662.
    doi: 10.1016/j.cub.2015.09.014google scholar: lookup
  37. Guerra MM, Rodriguez EM. Expression of tuberalin II, alpha‐subunit of glycoprotein hormones and beta‐thyrotropin hormone in the pars tuberalis of the rat: immunocytochemical evidence for pars tuberalis‐specific cell types. Neuroendocrinology 2009;90(3):269‐282.
    doi: 10.1159/000244373google scholar: lookup
  38. Stirland JA, Johnston JD, Cagampang FR. Photoperiodic regulation of prolactin gene expression in the Syrian hamster by a pars tuberalis‐derived factor. J Neuroendocrinol 2001;13(2):147‐157.
    doi: 10.1046/j.1365-2826.2001.00611.xgoogle scholar: lookup
  39. Morgan PJ, Williams LM. The pars tuberalis of the pituitary: a gateway for neuroendocrine output. Rev Reprod 1996;1(3):153‐161.
    doi: 10.1530/ror.0.0010153google scholar: lookup
  40. Lincoln GA, Clarke IJ. Photoperiodically‐induced cycles in the secretion of prolactin in hypothalamopituitary disconnected rams—evidence for translation of the melatonin signal in the pituitary‐gland. J Neuroendocrinol 1994;6(3):251‐260.
    doi: 10.1111/j.1365-2826.1994.tb00580.xgoogle scholar: lookup
  41. Lincoln GA, Clarke IJ. Evidence that melatonin acts in the pituitary gland through a dopamine‐independent mechanism to mediate effects of daylength on the secretion of prolactin in the ram. J Neuroendocrinol 1995;7(8):637‐643.
    doi: 10.1111/j.1365-2826.1995.tb00802.xgoogle scholar: lookup
  42. Sakai T, Sakamoto S, Ijima K, Matsubara K, Kato Y, Inoue K. Characterization of TSH‐positive cells in foetal rat pars tuberalis that fail to express Pit‐1 factor and thyroid hormone β2 receptors. J Neuroendocrinol 1999;11(3):187‐193.
  43. Bockmann J, Bockers TM, Winter C. Thyrotropin expression in hypophyseal pars tuberalis‐specific cells is 3,5,3′‐triiodothyronine, thyrotropin‐releasing hormone, and Pit‐1 independent. Endocrinology 1997;138(3):1019‐1028.
    doi: 10.1210/en.138.3.1019google scholar: lookup
  44. Unfried C, Ansari N, Yasuo S, Korf HW, von Gall C. Impact of melatonin and molecular clockwork components on the expression of thyrotropin beta‐chain (Tshb) and the Tsh receptor in the mouse pars tuberalis. Endocrinology 2009;150(10):4653‐4662.
    doi: 10.1210/en.2009-0609google scholar: lookup
  45. Ikegami K, Liao XH, Hoshino Y. Tissue‐specific posttranslational modification allows functional targeting of thyrotropin. Cell Rep 2014;9(3):801‐810.
    doi: 10.1016/j.celrep.2014.10.006google scholar: lookup
  46. Barrett P, Ebling FJ, Schuhler S. Hypothalamic thyroid hormone catabolism acts as a gatekeeper for the seasonal control of body weight and reproduction. Endocrinology 2007;148(8):3608‐3617.
    doi: 10.1210/en.2007-0316google scholar: lookup
  47. Watanabe M, Yasuo S, Watanabe T. Photoperiodic regulation of type 2 deiodinase gene in Djungarian hamster: possible homologies between avian and mammalian photoperiodic regulation of reproduction. Endocrinology 2004;145(4):1546‐1549.
    doi: 10.1210/en.2003-1593google scholar: lookup
  48. Revel FG, Saboureau M, Pevet P, Mikkelsen JD, Simonneaux V. Melatonin regulates type 2 deiodinase gene expression in the Syrian hamster. Endocrinology 2006;147(10):4680‐4687.
    doi: 10.1210/en.2006-0606google scholar: lookup
  49. Yasuo S, Watanabe M, Iigo M. Differential response of type 2 deiodinase gene expression to photoperiod between photoperiodic Fischer 344 and nonphotoperiodic Wistar rats. Am J Physiol Regul Integr Comp Physiol 2007;292(3):R1315‐R1319.
    doi: 10.1152/ajpregu.00396.2006google scholar: lookup
  50. Yasuo S, Yoshimura T, Ebihara S, Korf HW. Temporal dynamics of type 2 deiodinase expression after melatonin injections in Syrian hamsters. Endocrinology 2007;148(9):4385‐4392.
    doi: 10.1210/en.2007-0497google scholar: lookup

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