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

Alan J Conley, E. L. Scholtz, E. L. Legacki, C. J. Corbin, Heather K Knych, Ghislaine Dujovne, B. A. Ball, Benjamin Moeller, Scott D Stanley

Research output: Contribution to journalArticle

Abstract

In vivo and in vitro 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 (n = 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.

LanguageEnglish (US)
Pages25-32
Number of pages8
JournalJournal of Endocrinology
Volume238
Issue number1
DOIs
StatePublished - Jul 1 2018

Fingerprint

20-alpha-Dihydroprogesterone
Progesterone
Horses
Microsomes
Uterus
Perissodactyla
Liver
Pregnancy
Endocrinology
Corpus Luteum
Progestins
Tandem Mass Spectrometry
Ovulation
Liquid Chromatography
Placenta
Neck

Keywords

  • Equine
  • Female reproduction
  • Novel progestin
  • Progesterone
  • Steroidogenesis

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

5α-dihydroprogesterone concentrations and synthesis in non-pregnant mares. / Conley, Alan J; Scholtz, E. L.; Legacki, E. L.; Corbin, C. J.; Knych, Heather K; Dujovne, Ghislaine; Ball, B. A.; Moeller, Benjamin; Stanley, Scott D.

In: Journal of Endocrinology, Vol. 238, No. 1, 01.07.2018, p. 25-32.

Research output: Contribution to journalArticle

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