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The Journal of endocrinology2018; 238(1); 25-32; doi: 10.1530/JOE-18-0215

5α-dihydroprogesterone concentrations and synthesis in non-pregnant mares.

Abstract: and evidence indicates that the bioactive, 5α-reduced progesterone metabolite, 5α-dihydroprogesterone (DHP) is synthesized in the placenta, supporting equine pregnancy, but its appearance in early pregnancy argues for other sites of synthesis also. It remains unknown if DHP circulates at relevant concentrations in cyclic mares and, if so, does synthesis involve the non-pregnant uterus? Jugular blood was drawn daily from cyclic mares ( = 5). Additionally, ovariectomized mares (OVX) and geldings were administered progesterone (300 mg) intramuscularly. Blood was drawn before and after treatment. Incubations of whole equine blood and hepatic microsomes with progesterone were also investigated for evidence of DHP synthesis. Sample analysis for progesterone, DHP and other steroids employed validated liquid chromatography-tandem mass spectrometry methods. Progesterone and DHP appeared a day (d) after ovulation in cyclic mares, was increased significantly by d3, peaking from d5 to 10 and decreased from d13 to 17. DHP was 55.5 ± 3.2% of progesterone concentrations throughout the cycle and was highly correlated with it. DHP was detected immediately after progesterone administration to OVX mares and geldings, maintaining a relatively constant ratio with progesterone (47.2 ± 2.9 and 51.2 ± 2.7%, respectively). DHP was barely detectable in whole blood and hepatic microsome incubations. We conclude that DHP is a physiologically relevant progestogen in cyclic, non-pregnant mares, likely stimulating the uterus, and that it is synthesized peripherally from luteal progesterone but not in the liver or blood. The presence of DHP in pregnant perissodactyla as well as proboscidean species suggests horses may be a valuable model for reproductive endocrinology in other exotic taxa.
Publication Date: 2018-06-02 PubMed ID: 29853526DOI: 10.1530/JOE-18-0215Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research article focuses on the discovery that the hormone, 5α-dihydroprogesterone (DHP), is significantly present and synthesized in non-pregnant, ovulating horses. Findings also suggest that DHP may be synthesized outside the placenta, making horses potential models for studying reproductive hormonal behavior in other exotic species.

Research Methodology

  • The study involved daily drawing of jugular blood from ovulating horses.
  • Further, horses which had their ovaries removed (OVX) and geldings were administered with a dose of progesterone and had blood drawn before and after, to study the synthesis and ratio of DHP to progesterone.
  • To investigate evidence of DHP synthesis, the research team conducted incubations of a horse’s whole blood and hepatic microsomes with progesterone.
  • Sample analysis was completed employing a validated method of liquid chromatography-tandem mass spectrometry to ensure accurate results.

Findings

  • In ovulating horses, progesterone and DHP were detected one day after ovulation, significantly increasing by the 3rd day, peaking at days 5-10, and decreasing from the 13th to 17th day.
  • DHP was 55.5 ± 3.2% of progesterone concentrations throughout the cycle and showed a high correlation with it.
  • Administering progesterone to OVX horses and geldings led to an immediate detection of DHP. The relative ratio was maintained between DHP and progesterone (47.2 ± 2.9 and 51.2 ± 2.7%, respectively).
  • However, DHP was barely detectable in the whole blood and hepatic microsome incubations.

Conclusion

  • The article concludes that DHP is a physiologically relevant progestogen in non-pregnant, ovulating horses, likely stimulating the uterus.
  • It identifies that DHP is synthesized peripherally from luteal progesterone and not in the liver or blood.
  • The presence of DHP in pregnant mammalian species suggests horses could be a valuable model for studying reproductive endocrinology in other exotic species.

Cite This Article

APA
Conley AJ, Scholtz EL, Legacki EL, Corbin CJ, Knych HK, Dujovne GD, Ball BA, Moeller BC, Stanley SD. (2018). 5α-dihydroprogesterone concentrations and synthesis in non-pregnant mares. J Endocrinol, 238(1), 25-32. https://doi.org/10.1530/JOE-18-0215

Publication

ISSN: 1479-6805
NlmUniqueID: 0375363
Country: England
Language: English
Volume: 238
Issue: 1
Pages: 25-32

Researcher Affiliations

Conley, A J
  • Department of Population Health & ReproductionSchool of Veterinary Medicine, University of California, Davis, California, USA ajconley@ucdavis.edu.
Scholtz, E L
  • Department of Population Health & ReproductionSchool of Veterinary Medicine, University of California, Davis, California, USA.
Legacki, E L
  • Department of Population Health & ReproductionSchool of Veterinary Medicine, University of California, Davis, California, USA.
Corbin, C J
  • Department of Population Health & ReproductionSchool of Veterinary Medicine, University of California, Davis, California, USA.
Knych, H K
  • Department of Molecular BiosciencesSchool of Veterinary Medicine, University of California, Davis, California, USA.
Dujovne, G D
  • Department of Population Health & ReproductionSchool of Veterinary Medicine, University of California, Davis, California, USA.
Ball, B A
  • Gluck Equine Research CenterDepartment of Veterinary Science, University of Kentucky, Lexington Kentucky, USA.
Moeller, B C
  • Department of Molecular BiosciencesSchool of Veterinary Medicine, University of California, Davis, California, USA.
Stanley, S D
  • Department of Molecular BiosciencesSchool of Veterinary Medicine, University of California, Davis, California, USA.

MeSH Terms

  • 5-alpha-Dihydroprogesterone / analysis
  • 5-alpha-Dihydroprogesterone / biosynthesis
  • 5-alpha-Dihydroprogesterone / blood
  • Animals
  • Blood Chemical Analysis / veterinary
  • Estrous Cycle / blood
  • Female
  • Horses
  • Liver / metabolism
  • Metabolic Networks and Pathways
  • Pregnancy
  • Progesterone / metabolism

Citations

This article has been cited 2 times.
  1. Lawson EF, Grupen CG, Baker MA, Aitken RJ, Swegen A, Pollard CL, Gibb Z. Conception and early pregnancy in the mare: lipidomics the unexplored frontier. Reprod Fertil 2022 Jan 1;3(1):R1-R18.
    doi: 10.1530/RAF-21-0104pubmed: 35350651google scholar: lookup
  2. Scarlet D, Schuler G, Malama E, Bollwein H, Bocci C, Colleoni S, Lazzari G, Galli C, Kowalewski MP. Endocrine profile and OPU-ICSI outcomes in mares: a comparative study. Reprod Fertil 2025 Jul 1;6(3).
    doi: 10.1530/RAF-25-0027pubmed: 40539920google scholar: lookup