Reproductive Sciences

, Volume 19, Issue 3, pp 290–297 | Cite as

Metabolism of 17-Alpha-Hydroxyprogesterone Caproate by Human Placental Mitochondria

  • Valentina M. Fokina
  • Olga L. Zharikova
  • Gary D. V. Hankins
  • Mahmoud S. Ahmed
  • Tatiana N. NanovskayaEmail author
Original Articles


Perfusion of 17-alpha-hydroxyprogesterone caproate (17HPC) via the maternal circuit of a dually perfused human placental lobule resulted in the extensive formation of 2 metabolites. On the other hand, human placental microsomes biotransformed 17HPC into 5 monohydroxylated metabolites, which did not correspond to those formed during perfusion. The goal of this investigation was to determine the subcellular localization of the enzymes responsible for the biotransformation of 17HPC during its perfusion in human placenta. Crude subcellular fractions of the human placental tissue were utilized. Six 17HPC metabolites were formed by the placental mitochondrial fraction, of which 4 were identical to those formed by the microsomes; whereas the other 2, namely MM and M19, were formed by the mitochondrial fraction only. The latter metabolites were identical to those formed during 17HPC perfusion, as determined by liquid chromatography–mass spectrometry (LC-MS) analysis. Therefore, these data strongly suggest that the enzymes responsible for the biotransformation of 17HPC during its perfusion are predominantly localized in human placental mitochondria.


17-alpha-hydroxyprogesterone caproate metabolism placenta mitochondria LC-MS 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Meis PJ, Klebanoff M, Thom E, et al, and National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Prevention of recurrent preterm delivery by 19 alpha-hydroxyprogesterone caproate. N Engl J med. 2003; 348(24):2379–2385.CrossRefGoogle Scholar
  2. 2.
    Yan R, Fokina V, Hankins GDV, Ahmed MS, Nanovskaya TN. The effect of esterases on 17alpha-hydroxyprogesterone caproate. Am J Obstet Gynecol. 2008;198(2):229.e1–229.e5.CrossRefGoogle Scholar
  3. 3.
    Hemauer SJ, Yan R, Patrikeeva SL, et al. Transplacental transfer and metabolism of 17-α-hydroxyprogesterone caproate. Am J Obstet Gynecol. 2008;199(2):169.e1–169.e5.CrossRefGoogle Scholar
  4. 4.
    Yan R, Nanovskaya TN, Zharikova OL, Mattison DR, Hankins GDV, Ahmed MS. Metabolism of 17alpha-hydroxyprogesterone caproate by hepatic and placental microsomes of human and baboon. Biochem pharmacol. 2008;75(9): 1848–1857.CrossRefGoogle Scholar
  5. 5.
    Deshmukh SV, Nanovskaya TN, Ahmed MS. Aromatase is the major enzyme metabolizing Buprenorphine in human placenta. J Pharmacol Exp Ther. 2003;306(3): 1099–1105.CrossRefGoogle Scholar
  6. 6.
    Onsrud M, Paus E, Haug E, Kjorstad K. Intramuscular administration of hydroxyprogesterone caproate in patients with endometrial carcinoma: pharmacokinetics and effects on adrenal function. Acta Obstet Gynecol Scand. 1985;64(6):519–523.CrossRefGoogle Scholar
  7. 7.
    Clement B, Mau S, Debers S, Havemeyer A. Hepatic, extrahepatic, microsomal, and mitochondrial activation of the N-hydroxylated prodrugs benzamidoxime, guanoxabenz, and RO 48-3656 ([[1-[(2S)-2-[[4-[(hydroxyamino)iminomethyl]benzoyl]amino]-1-oxopropyl]-4-piperidinyl]oxy]-actic acid). Drug Metab Dispos. 2005; 33(11):1740–1747.CrossRefGoogle Scholar
  8. 8.
    da Fonseca EB, Bittar RE, Carvalho MH, Zugaib M. Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk: a randomized placebo-controlled double-blind study. Am J Obstet Gynecol. 2003;188(2):419–424.CrossRefGoogle Scholar
  9. 9.
    Ruddock NK, Shi SQ, Jain S, et al. Progesterone, but not 17-alpha-hydroxyprogesterone caproate, inhibits human myometrial contractions. Am J Obstet Gynecol. 2008;199(4):391.e1–391.e7.CrossRefGoogle Scholar
  10. 10.
    Sexton DJ, O’Reilly MW, Friel AM, Morrison JJ. Functional effects of 17alpha hydroxyprogesterone caproate (17P) on human myometrial contractility in vitro. Reprod Biol Endocrinol. 2004; 2:80.Google Scholar

Copyright information

© Society for Reproductive Investigation 2012

Authors and Affiliations

  • Valentina M. Fokina
    • 1
  • Olga L. Zharikova
    • 1
  • Gary D. V. Hankins
    • 1
  • Mahmoud S. Ahmed
    • 1
  • Tatiana N. Nanovskaya
    • 1
    Email author
  1. 1.Department of Obstetrics and GynecologyUniversity of Texas Medical BranchGalvestonUSA

Personalised recommendations