Synergistic induction of aromatase activity in the rat brain by estradiol and 5α-dihydrotestosterone

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67 Scopus citations

Abstract

Estrogens are produced locally from androgen precursors by cells within the hypothalamus and preoptic area (POA). The activity of the aromatase enzyme complex responsible for this intracellular conversion is controlled by gonadal steroids. The purpose of this study was to determine: (1) whether estrogen acts together with androgen to regulate aromatase activity (AA) and (2) whether nuclear androgen receptor levels are increased after exposure to combined treatment with estradiol benzoate (EB) and dihydrotestosterone (DHT). Thus, adult male rats were castrated and treated for 1 week with either vehicle (0.1 ml sesame oil, s.c.), EB (2 μg/day), testosterone (3-cm Silastic implant), DHT (3-cm Silastic implant) or EB + DHT. These treatments produced hormone levels in the physiologic range. We found that both testosterone and DHT significantly stimulated AA (p < 0.05 vs. castrated rats). However, testosterone induced AA significantly more than DHT in the POA (p < 0.05; castrated + testosterone vs. castrated + DHT). EB alone did not affect AA but synergized with DHT to stimulate AA in the POA to levels equivalent with the testosterone-treated group. By comparison, EB alone did not enhance the induction of AA by DHT in the hypothalamus. Combined treatment with EB and DHT had no effect on the concentrations of nuclear androgen receptors in either tissue suggesting that the effect of EB was not mediated through an androgen receptor mechanism. These results suggest that both androgens and estrogens play a physiologic role in the control of estrogen formation in the rat brain. Furthermore, the anatomical specificity that we observed indicates that critical differences in enzyme responsiveness are present in different areas of the brain.

Original languageEnglish (US)
Pages (from-to)79-84
Number of pages6
JournalNeuroendocrinology
Volume53
Issue number1
DOIs
StatePublished - Jan 1 1991

Keywords

  • 5α-dihydrotestosterone
  • androgen receptor
  • aromatase
  • estradiol
  • estrogen synthesis
  • hypothalamus
  • preoptic area

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

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