The effect of opiates on the activity of human placental aromatase/CYP19

Olga L. Zharikova, Sujal V. Deshmukh, Meena Kumar, Ricardo Vargas, Tatiana Nanovskaya, Gary Hankins, Mahmoud Ahmed

Research output: Contribution to journalArticle

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Abstract

Aromatase, cytochrome P450 19, is a key enzyme in the biosynthesis of estrogens by the human placenta. It is also the major placental enzyme that metabolizes the opiates l-acetylmethadol (LAAM), methadone, and buprenorphine (BUP). Methadone and BUP are used in treatment of the opiate addict and are competitive inhibitors of testosterone conversion to estradiol (E2) and 16α-hydroxytestosterone (16-OHT) to estriol (E3) by aromatase. The aim of this investigation is to determine the effect of 20 opiates, which can be administered to pregnant patients for therapeutic indications or abused, on E2 and E3 formation by placental aromatase. Data obtained indicated that the opiates increased, inhibited, or had no effect on aromatase activity. Their effect on E3 formation was more pronounced than that on E2 due to the lower affinity of 16-OHT than testosterone to aromatase. The Ki values for the opiates that inhibited E3 formation were sufentanil, 7 ± 1 μM; LAAM, 13 ± 8 μM; fentanyl, 25 ± 5 μM; oxycodone, 92 ± 22 μM; codeine, 218 ± 69 μM; (+)-pentazocine, 225 ± 73 μM. The agonists morphine, heroin, hydromorphone, oxymorphone, hydrocodone, propoxyphene, meperidine, levorphanol, dextrorphan, and (-)-pentazocine and the antagonists naloxone and naltrexone caused an increase in E3 formation by 124-160% of control but had no effect on E2 formation. Moreover, oxycodone and codeine did not inhibit E2 formation and the IC50 values for fentanyl, sufentanil, and (+)-pentazocine were >1000 μM. It is unlikely that the acute administration of the opiates that inhibit estrogen formation would affect maternal and/or neonatal outcome. However, the effects of abusing any of them during the entire pregnancy are unclear at this time.

Original languageEnglish (US)
Pages (from-to)279-286
Number of pages8
JournalBiochemical Pharmacology
Volume73
Issue number2
DOIs
StatePublished - Jan 15 2007

Fingerprint

Opiate Alkaloids
Aromatase
Human Activities
Methadyl Acetate
Pentazocine
Oxycodone
Sufentanil
Codeine
Buprenorphine
Methadone
Fentanyl
Testosterone
Estrogens
Oxymorphone
Levorphanol
Hydrocodone
Dextrorphan
Hydromorphone
Dextropropoxyphene
Estriol

Keywords

  • Aromatase/CYP19
  • Estrogen formation
  • Human placenta
  • Opiates
  • Pregnancy

ASJC Scopus subject areas

  • Pharmacology

Cite this

The effect of opiates on the activity of human placental aromatase/CYP19. / Zharikova, Olga L.; Deshmukh, Sujal V.; Kumar, Meena; Vargas, Ricardo; Nanovskaya, Tatiana; Hankins, Gary; Ahmed, Mahmoud.

In: Biochemical Pharmacology, Vol. 73, No. 2, 15.01.2007, p. 279-286.

Research output: Contribution to journalArticle

Zharikova, Olga L. ; Deshmukh, Sujal V. ; Kumar, Meena ; Vargas, Ricardo ; Nanovskaya, Tatiana ; Hankins, Gary ; Ahmed, Mahmoud. / The effect of opiates on the activity of human placental aromatase/CYP19. In: Biochemical Pharmacology. 2007 ; Vol. 73, No. 2. pp. 279-286.
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