Steroid transformations in pregnant mares: metabolism of exogenous progestins and unusual metabolic activity in vivo and in vitro.
Abstract: The mare possesses unique steroid hormone metabolic activity during pregnancy in that peripheral 4-pregnene-3,20-dione (progesterone; P4) is undetectable by 220 days gestation. This study examines in vivo metabolism of progestins by the pregnant mare and in vitro metabolic activity of maternal and fetal tissues. Pregnant mares (n = 3) received intravenous infusions of 3 beta-hydroxy-5-pregnen-20-one (pregnenolone; P5), P4, 5 alpha-pregnane-3,20-dione (5 alpha-DHP), 3 beta-hydroxy-5 alpha-pregnan-20-one (3 beta-5 alpha), deuterium labeled (D4)-P5, D4-3 beta-5 alpha and vehicle. Anestrous mares (n = 2) were infused with P5, P4, and vehicle. Also, placenta, endometrium, fetal gonad, maternal and fetal liver, and adrenal from 4 animals were incubated in D4-P5, D4-5 alpha-DHP, or D4-3 beta-5 alpha. Pregnant mares (in vivo) converted infused P5 predominantly to 5-pregnene-3 beta,20 beta-diol (P5-beta beta), 5 alpha-DHP, 20 alpha-hydroxy-5 alpha-pregnan-3-one (20 alpha-5 alpha), and 3 beta-5 alpha while only minor concentrations of P4 were detected. Infused P4 was converted primarily to 5 alpha-DHP and 20 alpha-hydroxypregnanes and when 5 alpha-DHP served as a substrate, other 5 alpha-pregnanes were formed. Infused 3 beta-5 alpha was either reduced to beta alpha-diol or oxidized to 5 alpha-DHP. Regardless of treatment, anestrous mares were incapable of producing any 20 alpha-hydroxypregnanes but could convert P5 to P5-beta beta and P4 in quantities similar to that of pregnant mares. In vitro, placenta converted D4-P5 to D4-P4 while D4-3 beta-5 alpha was oxidized to D4-5 alpha-DHP. Endometrium converted substrate primarily to D4-20 alpha-hydroxypregnanes. Both maternal and fetal liver produced D4-20 beta-hydroxy compounds regardless of substrate. Maternal and fetal adrenal were capable of conversion of D4-P5 to D4-P4 while fetal gonad did not perform any significant metabolism of substrate, though it produced P5. These data explain the absence of P4 and presence of other progestin metabolites in maternal circulation during mid- and late pregnancy. Pregnenolone can be 5 alpha-reduced to 3 beta-5 alpha, and 3 beta-5 alpha could be 3-oxidized to 5 alpha-DHP. It is 5 alpha-DHP that may serve as substrate for other 5 alpha-pregnanes.
Publication Date: 1996-02-01 PubMed ID: 8750439DOI: 10.1016/0039-128x(95)00199-zGoogle Scholar: Lookup
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- Journal Article
- Research Support
- U.S. Gov't
- Non-P.H.S.
Summary
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The research study analyzes the unique metabolic activity of steroid hormones in pregnant mares. It investigates the in vivo metabolism of progestins and the in vitro metabolic activity of both maternal and fetal tissues.
Research Methodology
- Three pregnant mares were used for in vivo testing. They were intravenously infused with different steroids and progestins to find out how these substances would be metabolized.
- Two anestrous mares were similarly infused for comparison purposes.
- For in vitro testing, tissues like placenta, endometrium, adrenal glands, and liver from both the mother and the fetus were incubated in specific steroids.
Findings
- Results showed that pregnant mares metabolize progestins in a peculiar manner. The infused pregnenolone, a type of progestin, was mainly converted into other progestin metabolites, with only minor amounts of progesterone detected. This explains the earlier assertion about the undetectable levels of peripheral progesterone in pregnant mares after 220 days of gestation.
- On the other hand, anestrous mares did not produce any transformed pregnanes but were able to convert pregnenolone to progesterone and another progestin metabolite in quantities comparable to that of pregnant mares. This function ceased with the capability to produce 20 alpha-hydroxypregnanes.
- In vitro observations revealed diverse metabolic activity in different tissues. The placenta and adrenal glands of both mother and fetus converted pregnenolone into progesterone. Though the fetal gonad did not show significant metabolic activity, it produced pregnenolone.
Implications
- The study provided a better understanding of steroid hormone metabolic activity in pregnant mares, opening avenues for further research on equine pregnancy and related health issues or conditions.
- The distinct metabolism of progestins in pregnant mares, including the absence of measurable peripheral progesterone levels and the presence of other progestin metabolites, is key in understanding and possibly manipulating equine reproductive processes.
- These findings may also provide valuable insight into physiological changes and adaptations during equine pregnancy.
Cite This Article
APA
Schutzer WE, Holtan DW.
(1996).
Steroid transformations in pregnant mares: metabolism of exogenous progestins and unusual metabolic activity in vivo and in vitro.
Steroids, 61(2), 94-99.
https://doi.org/10.1016/0039-128x(95)00199-z Publication
Researcher Affiliations
- Department of Animal Sciences, Oregon State University, Corvallis, USA.
MeSH Terms
- 5-alpha-Dihydroprogesterone
- Animals
- Biotransformation
- Deuterium
- Endometrium / metabolism
- Female
- Horses / metabolism
- In Vitro Techniques
- Infusions, Intravenous
- Liver / embryology
- Liver / metabolism
- Organ Specificity
- Pharmaceutical Vehicles
- Placenta / metabolism
- Pregnancy
- Pregnancy, Animal / metabolism
- Pregnanediones / pharmacokinetics
- Pregnanolone / pharmacokinetics
- Pregnenolone / pharmacokinetics
- Progestins / metabolism
- Progestins / pharmacokinetics
Citations
This article has been cited 1 times.- Wierer M, Schrey AK, Kühne R, Ulbrich SE, Meyer HH. A single glycine-alanine exchange directs ligand specificity of the elephant progestin receptor. PLoS One 2012;7(11):e50350.
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