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. 2001 Mar;109(3):257–264. doi: 10.1289/ehp.01109257

Sexual dimorphism of brain aromatase activity in medaka: induction of a female phenotype by estradiol.

A C Melo 1, J S Ramsdell 1
PMCID: PMC1240244  PMID: 11333187

Abstract

In this study we identified sex-dependent dimorphism of brain aromatase in the teleost medaka and examined its regulation by sex steriods. We first investigated differential distribution of brain aromatase activity in sexually mature male and female medaka in serial coronal sections of the brain and identified the hypothalamic nuclei contained in each section using the brain atlas of medaka. In the brain of male medaka, high levels of activity are localized in sections containing the preoptic (POA) and suprachiasmatic nuclei (SC) (63-75 fmol/hr) and low levels in the nuclei periventricular dorsalis (HD), ventralis (HV), and caudalis (Hc), nuclei diffusus of lobulus inferiores (NDIL), and nuclei tuberi anteriores (TA) and posteriores (TP) (< 25 fmol/hr). In the brain of female medaka high aromatase activity is localized in sections containing the HD, HV, Hc, NDIL, TA, and TP (85-80 fmol/hr) and highly variable levels in the POA and SC (23-70 fmol/hr). The concentration and time dependency of the exposure of male medaka to estradiol on the total brain aromatase activity and morphologic sex characteristics were determined next. Estradiol increased the activity of brain aromatase in a concentration-dependent manner at 2.5 and 25 microg/L, but the increase was lower at higher concentrations of the hormone. The effect was time dependent, gradually increasing up to the fifth day of exposure, after which it reached a plateau. Estradiol induction of brain aromatase analyzed using Lineweaver-Burke plots of saturation assays revealed a non-first-order reaction. The results indicate that a positive feedback mechanism regulates brain aromatase and imply that the sexual dimorphic distribution of aromatase may be highly sensitive to physiologic cues and environmental perturbations in fish.

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Selected References

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  1. Balthazart J., Ball G. F. New insights into the regulation and function of brain estrogen synthase (aromatase). Trends Neurosci. 1998 Jun;21(6):243–249. doi: 10.1016/s0166-2236(97)01221-6. [DOI] [PubMed] [Google Scholar]
  2. Balthazart J., Foidart A. Brain aromatase and the control of male sexual behavior. J Steroid Biochem Mol Biol. 1993 Mar;44(4-6):521–540. doi: 10.1016/0960-0760(93)90256-v. [DOI] [PubMed] [Google Scholar]
  3. Callard G. V., Petro Z., Ryan K. J. Estrogen synthesis in vitro and in vivo in the brain of a marine teleost (Myoxocephalus). Gen Comp Endocrinol. 1981 Feb;43(2):243–255. doi: 10.1016/0016-6480(81)90318-x. [DOI] [PubMed] [Google Scholar]
  4. Callard G. V., Petro Z., Ryan K. J. Phylogenetic distribution of aromatase and other androgen-converting enzymes in the central nervous system. Endocrinology. 1978 Dec;103(6):2283–2290. doi: 10.1210/endo-103-6-2283. [DOI] [PubMed] [Google Scholar]
  5. Callard G., Schlinger B., Pasmanik M., Corina K. Aromatization and estrogen action in brain. Prog Clin Biol Res. 1990;342:105–111. [PubMed] [Google Scholar]
  6. Choi I., Troyer D. L., Cornwell D. L., Kirby-Dobbels K. R., Collante W. R., Simmen F. A. Closely related genes encode developmental and tissue isoforms of porcine cytochrome P450 aromatase. DNA Cell Biol. 1997 Jun;16(6):769–777. doi: 10.1089/dna.1997.16.769. [DOI] [PubMed] [Google Scholar]
  7. Cody R. P., Bortone S. A. Masculinization of mosquitofish as an indicator of exposure to kraft mill effluent. Bull Environ Contam Toxicol. 1997 Mar;58(3):429–436. doi: 10.1007/s001289900352. [DOI] [PubMed] [Google Scholar]
  8. Gimeno S., Gerritsen A., Bowmer T., Komen H. Feminization of male carp. Nature. 1996 Nov 21;384(6606):221–222. doi: 10.1038/384221a0. [DOI] [PubMed] [Google Scholar]
  9. Godwin J., Crews D., Warner R. R. Behavioural sex change in the absence of gonads in a coral reef fish. Proc Biol Sci. 1996 Dec 22;263(1377):1683–1688. doi: 10.1098/rspb.1996.0246. [DOI] [PubMed] [Google Scholar]
  10. Gorski R. A., Harlan R. E., Jacobson C. D., Shryne J. E., Southam A. M. Evidence for the existence of a sexually dimorphic nucleus in the preoptic area of the rat. J Comp Neurol. 1980 Sep 15;193(2):529–539. doi: 10.1002/cne.901930214. [DOI] [PubMed] [Google Scholar]
  11. Guillette L. J., Jr, Crain D. A., Rooney A. A., Pickford D. B. Organization versus activation: the role of endocrine-disrupting contaminants (EDCs) during embryonic development in wildlife. Environ Health Perspect. 1995 Oct;103 (Suppl 7):157–164. doi: 10.1289/ehp.95103s7157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hutchison J. B. Aromatase: neuromodulator in the control of behavior. J Steroid Biochem Mol Biol. 1993 Mar;44(4-6):509–520. doi: 10.1016/0960-0760(93)90255-u. [DOI] [PubMed] [Google Scholar]
  13. Hutchison J. B., Steimer T. J., Hutchison R. E. Formation of behaviorally active estrogen in the dove brain: induction of preoptic aromatase by intracranial testosterone. Neuroendocrinology. 1986;43(3):416–427. doi: 10.1159/000124558. [DOI] [PubMed] [Google Scholar]
  14. Lephart E. D. A review of brain aromatase cytochrome P450. Brain Res Brain Res Rev. 1996 Jun;22(1):1–26. [PubMed] [Google Scholar]
  15. Mahendroo M. S., Mendelson C. R., Simpson E. R. Tissue-specific and hormonally controlled alternative promoters regulate aromatase cytochrome P450 gene expression in human adipose tissue. J Biol Chem. 1993 Sep 15;268(26):19463–19470. [PubMed] [Google Scholar]
  16. Matsumine H., Herbst M. A., Ou S. H., Wilson J. D., McPhaul M. J. Aromatase mRNA in the extragonadal tissues of chickens with the henny-feathering trait is derived from a distinctive promoter structure that contains a segment of a retroviral long terminal repeat. Functional organization of the Sebright, Leghorn, and Campine aromatase genes. J Biol Chem. 1991 Oct 25;266(30):19900–19907. [PubMed] [Google Scholar]
  17. Panzica G. C., Viglietti-Panzica C., Balthazart J. The sexually dimorphic medial preoptic nucleus of quail: a key brain area mediating steroid action on male sexual behavior. Front Neuroendocrinol. 1996 Jan;17(1):51–125. doi: 10.1006/frne.1996.0002. [DOI] [PubMed] [Google Scholar]
  18. Parsons B., Rainbow T. C., McEwen B. S. Organizational effects of testosterone via aromatization on feminine reproductive behavior and neural progestin receptors in rat brain. Endocrinology. 1984 Oct;115(4):1412–1417. doi: 10.1210/endo-115-4-1412. [DOI] [PubMed] [Google Scholar]
  19. Pasmanik M., Schlinger B. A., Callard G. V. In vivo steroid regulation of aromatase and 5 alpha-reductase in goldfish brain and pituitary. Gen Comp Endocrinol. 1988 Jul;71(1):175–182. doi: 10.1016/0016-6480(88)90308-5. [DOI] [PubMed] [Google Scholar]
  20. Roselli C. E., Abdelgadir S. E., Rønnekleiv O. K., Klosterman S. A. Anatomic distribution and regulation of aromatase gene expression in the rat brain. Biol Reprod. 1998 Jan;58(1):79–87. doi: 10.1095/biolreprod58.1.79. [DOI] [PubMed] [Google Scholar]
  21. Roselli C. E. Synergistic induction of aromatase activity in the rat brain by estradiol and 5 alpha-dihydrotestosterone. Neuroendocrinology. 1991 Jan;53(1):79–84. doi: 10.1159/000125701. [DOI] [PubMed] [Google Scholar]
  22. Schlinger B. A., Callard G. V. Aromatization mediates aggressive behavior in quail. Gen Comp Endocrinol. 1990 Jul;79(1):39–53. doi: 10.1016/0016-6480(90)90086-2. [DOI] [PubMed] [Google Scholar]
  23. Simpson E. R., Mahendroo M. S., Means G. D., Kilgore M. W., Corbin C. J., Mendelson C. R. Tissue-specific promoters regulate aromatase cytochrome P450 expression. J Steroid Biochem Mol Biol. 1993 Mar;44(4-6):321–330. doi: 10.1016/0960-0760(93)90235-o. [DOI] [PubMed] [Google Scholar]
  24. Simpson E. R., Michael M. D., Agarwal V. R., Hinshelwood M. M., Bulun S. E., Zhao Y. Cytochromes P450 11: expression of the CYP19 (aromatase) gene: an unusual case of alternative promoter usage. FASEB J. 1997 Jan;11(1):29–36. doi: 10.1096/fasebj.11.1.9034163. [DOI] [PubMed] [Google Scholar]
  25. Simpson E. R., Zhao Y., Agarwal V. R., Michael M. D., Bulun S. E., Hinshelwood M. M., Graham-Lorence S., Sun T., Fisher C. R., Qin K. Aromatase expression in health and disease. Recent Prog Horm Res. 1997;52:185–214. [PubMed] [Google Scholar]
  26. Tanaka M., Fukada S., Matsuyama M., Nagahama Y. Structure and promoter analysis of the cytochrome P-450 aromatase gene of the teleost fish, medaka (Oryzias latipes). J Biochem. 1995 Apr;117(4):719–725. doi: 10.1093/oxfordjournals.jbchem.a124768. [DOI] [PubMed] [Google Scholar]
  27. Tchoudakova A., Callard G. V. Identification of multiple CYP19 genes encoding different cytochrome P450 aromatase isozymes in brain and ovary. Endocrinology. 1998 Apr;139(4):2179–2189. doi: 10.1210/endo.139.4.5899. [DOI] [PubMed] [Google Scholar]
  28. Thompson E. A., Jr, Siiteri P. K. Utilization of oxygen and reduced nicotinamide adenine dinucleotide phosphate by human placental microsomes during aromatization of androstenedione. J Biol Chem. 1974 Sep 10;249(17):5364–5372. [PubMed] [Google Scholar]
  29. YAMAMOTO T. Artificial induction of functional sex-reversal in genotypic females of the medaka (Oryzias latipes). J Exp Zool. 1958 Mar;137(2):227–263. doi: 10.1002/jez.1401370203. [DOI] [PubMed] [Google Scholar]

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