Placental Expression and Molecular Characterization of Aromatase Cytochrome P450 in the Spotted Hyena (Crocuta crocuta)

Alan J Conley, C. J. Corbin, P. Browne, S. M. Mapes, N. J. Place, A. L. Hughes, S. E. Glickman

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

At birth, the external genitalia of female spotted hyenas (Crocuta crocuta) are the most masculinized of any known mammal, but are still sexually differentiated. Placental aromatase cytochrome P450 (P450arom) is an important route of androgen metabolism protecting human female fetuses from virilization in utero. Therefore, placental P450arom expression was examined in spotted hyenas to determine levels during genital differentiation, and to compare molecular characteristics between the hyena and human placental enzymes. Hyena placental P450arom activity was determined at gestational days (GD) 31, 35, 45, 65 and 95 (term, 110), and the relative sensitivity of hyena and human placental enzyme to inhibition by the specific inhibitor, Letrozole, was also examined. Expression of hyena P450arom in placenta was localized by immuno-histochemistry, and a full-length cDNA was cloned for phylogenetic analysis. Aromatase activity increased from GD31 to a peak at 45 and 65, apparently decreasing later in gestation. This activity was more sensitive to inhibition by Letrozole than was human placental aromatase activity. Expression of P450arom was localized to syncytiotrophoblast and giant cells of mid-gestation placentas. The coding sequence of hyena P450arom was 94% and 86% identical to the canine and human enzymes respectively, as reflected by phylogenetic analyses. These data demonstrate for the first time that hyena placental aromatase activity is comparable to that of human placentas when genital differentiation is in progress. This suggests that even in female spotted hyenas clitoral differentiation is likely protected from virilization by placental androgen metabolism. Decreased placental aromatase activity in late gestation may be equally important in allowing androgen to program behaviors at birth. Although hyena P450arom is closely related to the canine enzyme, both placental anatomy and P450arom expression differ. Other hyaenids and carnivores must be investigated to determine the morphological and functional ancestral state of their placentas, as it relates to evolutionary relationships among species in this important taxonomic group.

Original languageEnglish (US)
Pages (from-to)668-675
Number of pages8
JournalPlacenta
Volume28
Issue number7
DOIs
StatePublished - Jul 2007

Fingerprint

Hyaenidae
Aromatase
Cytochrome P-450 Enzyme System
letrozole
Placenta
Androgens
Virilism
Enzymes
Pregnancy
Canidae
Parturition
Female Genitalia
Trophoblasts
Giant Cells
Mammals
Anatomy

Keywords

  • Androgen metabolism
  • Aromatase
  • Cloned sequence
  • Hyena
  • Letrozole
  • Placenta
  • Sexual differentiation
  • Trophoblast

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Placental Expression and Molecular Characterization of Aromatase Cytochrome P450 in the Spotted Hyena (Crocuta crocuta). / Conley, Alan J; Corbin, C. J.; Browne, P.; Mapes, S. M.; Place, N. J.; Hughes, A. L.; Glickman, S. E.

In: Placenta, Vol. 28, No. 7, 07.2007, p. 668-675.

Research output: Contribution to journalArticle

Conley, Alan J ; Corbin, C. J. ; Browne, P. ; Mapes, S. M. ; Place, N. J. ; Hughes, A. L. ; Glickman, S. E. / Placental Expression and Molecular Characterization of Aromatase Cytochrome P450 in the Spotted Hyena (Crocuta crocuta). In: Placenta. 2007 ; Vol. 28, No. 7. pp. 668-675.
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