Brain Aromatase: Roles in Reproduction and Neuroprotection

Overview

Journal J Steroid Biochem Mol Biol

Specialties Biochemistry
Molecular Biology

Date 2007 Jul 24

PMID 17643294

Citations 39

Authors

Charles F Roselli

Affiliations

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Abstract

It is well established that aromatization constitutes an essential part of testosterone's signaling pathway in brain and that estrogen metabolites, often together with testosterone, organize and activate masculine neural circuits. This paper summarizes the current understanding regarding the distribution, regulation and function of brain aromatase in mammals. Data from our laboratory are presented that highlight the important function of aromatase in the regulation of androgen feedback sensitivity in non-human primates and the possible role that aromatase plays in determining the brain structure and sexual partner preferences of rams. In addition, new data is presented indicating that the capacity for aromatization in cortical astrocytes is associated with cell survival and may be important for neuroprotection. It is anticipated that a better appreciation of the physiological and pathophysiological functions of aromatase will lead to important clinical insights.

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References

Roselli C, Larkin K, Resko J, Stellflug J, Stormshak F . The volume of a sexually dimorphic nucleus in the ovine medial preoptic area/anterior hypothalamus varies with sexual partner preference. Endocrinology. 2003; 145(2):478-83. DOI: 10.1210/en.2003-1098. View

Roselli C, Stadelman H, Horton L, Resko J . Regulation of androgen metabolism and luteinizing hormone-releasing hormone content in discrete hypothalamic and limbic areas of male rhesus macaques. Endocrinology. 1987; 120(1):97-106. DOI: 10.1210/endo-120-1-97. View

Evrard H . Estrogen synthesis in the spinal dorsal horn: a new central mechanism for the hormonal regulation of pain. Am J Physiol Regul Integr Comp Physiol. 2006; 291(2):R291-9. DOI: 10.1152/ajpregu.00930.2005. View

Heimer L, Alheid G . Piecing together the puzzle of basal forebrain anatomy. Adv Exp Med Biol. 1991; 295:1-42. DOI: 10.1007/978-1-4757-0145-6_1. View

Gorski R, Gordon J, Shryne J, Southam A . Evidence for a morphological sex difference within the medial preoptic area of the rat brain. Brain Res. 1978; 148(2):333-46. DOI: 10.1016/0006-8993(78)90723-0. View

Naftolin F, Horvath T, Jakab R, Leranth C, Harada N, Balthazart J . Aromatase immunoreactivity in axon terminals of the vertebrate brain. An immunocytochemical study on quail, rat, monkey and human tissues. Neuroendocrinology. 1996; 63(2):149-55. DOI: 10.1159/000126951. View

Resko J, Quadri S, Spies H . Negative feedback control of gonadotropins in male rhesus monkeys: effects of time after castration and interactions of testosterone and estradiol-17beta. Endocrinology. 1977; 101(1):215-24. DOI: 10.1210/endo-101-1-215. View

Sanghera M, Simpson E, McPhaul M, Kozlowski G, Conley A, Lephart E . Immunocytochemical distribution of aromatase cytochrome P450 in the rat brain using peptide-generated polyclonal antibodies. Endocrinology. 1991; 129(6):2834-44. DOI: 10.1210/endo-129-6-2834. View

Roselli C, Stormshak F, Resko J . Distribution of aromatase mRNA in the ram hypothalamus: an in situ hybridization study. J Neuroendocrinol. 2000; 12(7):656-64. DOI: 10.1046/j.1365-2826.2000.00496.x. View

10.

Levay S . A difference in hypothalamic structure between heterosexual and homosexual men. Science. 1991; 253(5023):1034-7. DOI: 10.1126/science.1887219. View

11.

Lephart E . A review of brain aromatase cytochrome P450. Brain Res Brain Res Rev. 1996; 22(1):1-26. View

12.

Tobet S, Zahniser D, Baum M . Sexual dimorphism in the preoptic/anterior hypothalamic area of ferrets: effects of adult exposure to sex steroids. Brain Res. 1986; 364(2):249-57. DOI: 10.1016/0006-8993(86)90837-1. View

13.

Balthazart J, Ball G . New insights into the regulation and function of brain estrogen synthase (aromatase). Trends Neurosci. 1998; 21(6):243-9. DOI: 10.1016/s0166-2236(97)01221-6. View

14.

Roselli C, Klosterman S, Resko J . Anatomic relationships between aromatase and androgen receptor mRNA expression in the hypothalamus and amygdala of adult male cynomolgus monkeys. J Comp Neurol. 2001; 439(2):208-23. DOI: 10.1002/cne.1343. View

15.

Alexander B, Rose J, Stellflug J, FitzGerald J, Moss G . Fos-like immunoreactivity in brain regions of domestic rams following exposure to rams or ewes. Physiol Behav. 2001; 73(1-2):75-80. DOI: 10.1016/s0031-9384(01)00441-3. View

16.

Peterson R, Saldanha C, Schlinger B . Rapid upregulation of aromatase mRNA and protein following neural injury in the zebra finch (Taeniopygia guttata). J Neuroendocrinol. 2001; 13(4):317-23. DOI: 10.1046/j.1365-2826.2001.00647.x. View

17.

Clancy A, Zumpe D, MICHAEL R . Intracerebral infusion of an aromatase inhibitor, sexual behavior and brain estrogen receptor-like immunoreactivity in intact male rats. Neuroendocrinology. 1995; 61(2):98-111. DOI: 10.1159/000126830. View

18.

Roselli C, Resko J . Sex differences in androgen-regulated expression of cytochrome P450 aromatase in the rat brain. J Steroid Biochem Mol Biol. 1997; 61(3-6):365-74. View

19.

Perkins A, FitzGerald J . Luteinizing hormone, testosterone, and behavioral response of male-oriented rams to estrous ewes and rams. J Anim Sci. 1992; 70(6):1787-94. DOI: 10.2527/1992.7061787x. View

20.

Baum M . Mammalian animal models of psychosexual differentiation: when is 'translation' to the human situation possible?. Horm Behav. 2006; 50(4):579-88. DOI: 10.1016/j.yhbeh.2006.06.003. View