Porcine hypothalamic aromatase cytochrome P450: Isoform characterization, sex-dependent activity, regional expression, and regulation by enzyme inhibition in neonatal boars

C. J. Corbin, T. Berger, J. J. Ford, Charles Roselli, W. Sienkiewicz, B. C. Trainor, J. F. Roser, J. D. Vidal, N. Harada, A. J. Conley

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Domestic pigs have three CYP19 genes encoding functional paralogues of the enzyme aromatase cytochrome P450 (P450arom) that are expressed in the gonads, placenta, and preimplantation blastocyst. All catalyze estrogen synthesis, but the gonadal-type enzyme is unique in also synthesizing a nonaromatizable biopotent testosterone metabolite, 1OH-testosterone (1OH-T). P450arom is expressed in the vertebrate brain, is higher in males than females, but has not been investigated in pigs, to our knowledge. Therefore, these studies defined which of the porcine CYP19 genes was expressed, and at what level, in adult male and female hypothalamus. Regional expression was examined in mature boars, and regulation of P450arom expression in neonatal boars was investigated by inhibition of P450arom with letrozole, which is known to reprogram testicular expression. Pig hypothalami expressed the gonadal form of P450arom (redesignated the "gonadal/hypothalamic" porcine CYP19 gene and paralogue) based on functional analysis confirmed by cloning and sequencing transcripts. Hypothalamic tissue synthesized 1OH-T and was sensitive to the selective P450arom inhibitor etomidate. Levels were 4-fold higher in male than female hypothalami, with expression in the medial preoptic area and lateral borders of the ventromedial hypothalamus of boars. In vivo, letrozoletreated neonates had increased aromatase activity in hypothalami but decreased activity in testes. Therefore, although the same CYP19 gene is expressed in both tissues, expression is regulated differently in the hypothalamus than testis. These investigations, the first such studies in pig brain to our knowledge, demonstrate unusual aspects of P450arom expression and regulation in the hypothalamus, offering promise of gaining better insight into roles of P450arom in reproductive function.

Original languageEnglish (US)
Pages (from-to)388-395
Number of pages8
JournalBiology of Reproduction
Volume81
Issue number2
DOIs
StatePublished - Aug 2009

Fingerprint

Aromatase
Cytochrome P-450 Enzyme System
Hypothalamus
Protein Isoforms
Swine
Enzymes
Testosterone
letrozole
Genes
Testis
Etomidate
Sus scrofa
Preoptic Area
Brain
Gonads
Blastocyst
Placenta
Vertebrates
Organism Cloning
Estrogens

Keywords

  • Aromatase
  • Brain
  • Brain sexual differentiation
  • Hypothalamus
  • Isoform
  • Neuroendocrinology
  • Porcine
  • Regional expression
  • Regulation
  • Sexual dimorphism
  • Steroid hormones
  • Testis

ASJC Scopus subject areas

  • Cell Biology

Cite this

Porcine hypothalamic aromatase cytochrome P450 : Isoform characterization, sex-dependent activity, regional expression, and regulation by enzyme inhibition in neonatal boars. / Corbin, C. J.; Berger, T.; Ford, J. J.; Roselli, Charles; Sienkiewicz, W.; Trainor, B. C.; Roser, J. F.; Vidal, J. D.; Harada, N.; Conley, A. J.

In: Biology of Reproduction, Vol. 81, No. 2, 08.2009, p. 388-395.

Research output: Contribution to journalArticle

Corbin, C. J. ; Berger, T. ; Ford, J. J. ; Roselli, Charles ; Sienkiewicz, W. ; Trainor, B. C. ; Roser, J. F. ; Vidal, J. D. ; Harada, N. ; Conley, A. J. / Porcine hypothalamic aromatase cytochrome P450 : Isoform characterization, sex-dependent activity, regional expression, and regulation by enzyme inhibition in neonatal boars. In: Biology of Reproduction. 2009 ; Vol. 81, No. 2. pp. 388-395.
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