Regulation of Aromatase Gene Expression in the Adult Rat Brain

Roselli, Charles E.; Abdelgadir, Salah E.; Resko, John A.

doi:10.1016/s0361-9230(97)00214-1

Cited by 106 publications

(82 citation statements)

References 38 publications

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“…In line with our data, administration of E2 with DHT to castrated males, but not E2 alone, induced the same levels of masculine sexual behavior as those observed after treatment with T or in intact males (Cooke et al, 2003;BurnsCusato et al, 2004;Arteaga-Silva et al, 2007). Nevertheless, as it has been previously shown that androgens upregulate aromatase expression (Yamada et al, 1993;Roselli et al, 1997), it would be interesting to examine whether brain aromatase expression is affected in AR NesCre mice. In conclusion, we report here a pertinent genetic model that allows exploring the specific involvement of central AR in T-induced effects in the nervous system.…”

Section: Sexual and Aggressive Behaviors Of Gonadectomized And T-treasupporting

confidence: 88%

Conditional Inactivation of Androgen Receptor Gene in the Nervous System: Effects on Male Behavioral and Neuroendocrine Responses

Raskin¹,

Gendt²,

Duittoz³

et al. 2009

J. Neurosci.

190

221

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Testosterone (T) profoundly influences central sexual differentiation and functions. In the brain, T signals either directly through androgen receptor (AR) or indirectly through estrogen receptor (ER) following aromatization into E2 (17-␤-estradiol).As T, through AR, also controls peripheral male sexual differentiation, the relative contribution of central AR in T-mediated regulation of behavioral and neuroendocrine responses still remains unclear. To address this question, we generated, by using Cre-loxP technology, mice selectively lacking AR expression in the nervous system. The mutant male urogenital tract was normally developed, and mice were able to produce offspring. Nonetheless, sexual motivation and performance as well as aggressive behaviors were affected. Only a low percentage of males displayed a complete sexual behavior and offensive attacks. The latency to show masculine behaviors was increased and copulation length prolonged. Erectile activity during mating was also altered. These alterations occurred despite increased levels of T and its metabolites, and an unaffected number of ER␣-immunoreactive cells. Olfactory preference and neuronal activation, mapped by Fos immunoreactivity, following exposure to estrus female-soiled bedding were also normal. At comparable T levels, greater differences in masculine behaviors were observed between gonadectomized control and mutant males. AR invalidation in the nervous system also disrupted the somatotropic axis since mutant males exhibited growth retardation and decreased serum levels of insulin-like growth factor I. Our findings show that central AR is required in T-induced regulation of male-typical behaviors and gonadotrope and somatotropic axes. This genetic model offers a unique opportunity in the understanding of AR's role in cerebral functions of T.

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Section: Sexual and Aggressive Behaviors Of Gonadectomized And T-treasupporting

confidence: 88%

Conditional Inactivation of Androgen Receptor Gene in the Nervous System: Effects on Male Behavioral and Neuroendocrine Responses

Raskin¹,

Gendt²,

Duittoz³

et al. 2009

J. Neurosci.

190

221

View full text Add to dashboard Cite

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“…It has traditionally been assumed that brain aromatase activity, as opposed to aromatase expressed in ovaries or adipose tissue, is regulated by sex steroids which act as transcription factors after binding to their cognate receptor to regulate the transcription of the enzyme. Treatment of castrates with testosterone markedly increases aromatase activity in several brain regions including the preoptic/hypothalamic area in birds and mammals [213,217,231]. Testosterone similarly increases the concentration of the aromatase protein and the corresponding messenger RNA supporting the idea that testosterone induced changes in brain aromatase activity result of an increase in gene transcription [1,23].…”

Section: Brain Synthesized Estrogensmentioning

confidence: 75%

Functional significance of the rapid regulation of brain estrogen action: Where do the estrogens come from?

2006

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Estrogens exert a wide variety of actions on reproductive and non-reproductive functions. These effects are mediated by slow and long lasting genomic as well as rapid and transient non-genomic mechanisms. Besides the host of studies demonstrating the role of genomic actions at the physiological and behavioral level, mounting evidence highlights the functional significance of non-genomic effects. However, the source of the rapid changes in estrogen availability that are necessary to sustain their fast actions is rarely questioned. For example, the rise of plasma estrogens at pro-estrus that represents one of the fastest documented changes in plasma estrogen concentration appears too slow to explain these actions. Alternatively, estrogen can be synthesized in the brain by the enzyme aromatase providing a source of locally high concentrations of the steroid. Furthermore, recent studies demonstrate that brain aromatase can be rapidly modulated by afferent inputs, including glutamatergic afferents. A role for rapid changes in estrogen production in the central nervous system is supported by experiments showing that acute aromatase inhibition affects nociception as well as male sexual behavior and that preoptic aromatase activity is rapidly (within min) modulated following mating. Such mechanisms thus fulfill the gap existing between the fast actions of estrogen and their mode of production and open new avenues for the understanding of estrogenic effects on the brain.

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“…T is converted by an enzyme complex termed aromatase (27), which has been shown to be present in various tissues including endothelial cells (13,14) and vascular smooth muscle (27). Local formation of estrogens from circulating androgens via aromatase has been implicated as a regulatory effect of androgens on various functions in the brain (28,29) and ovary (27). However, the role of aromatase in the vascular wall and in modulating atherogenesis has not been assessed previously.…”

Section: Discussionmentioning

confidence: 99%

Testosterone inhibits early atherogenesis by conversion to estradiol: Critical role of aromatase

Nathan

Shi

Dinh

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

225

161

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The effects of testosterone on early atherogenesis and the role of aromatase, an enzyme that converts testosterone to estrogens, were assessed in low density lipoprotein receptor-deficient male mice fed a Western diet. Castration of male mice increased the extent of fatty streak lesion formation in the aortic origin compared with testes-intact animals. Administration of anastrazole, a selective aromatase inhibitor, to testes-intact males increased lesion formation to the same extent as that observed with orchidectomized animals. Testosterone supplementation of orchidectomized animals reduced lesion formation when compared with orchidectomized animals receiving the placebo. This attenuating effect of testosterone was not observed when the animals were treated simultaneously with the aromatase inhibitor. The beneficial effects of testosterone on early atherogenesis were not explained by changes in lipid levels. Estradiol administration to orchidectomized males attenuated lesion formation to the same extent as testosterone administration. Aromatase was expressed in the aorta of these animals as assessed by reverse transcription-PCR and immunohistochemistry. These results indicate that testosterone attenuates early atherogenesis most likely by being converted to estrogens by the enzyme aromatase expressed in the vessel wall.atherosclerosis ͉ androgens ͉ anastrazole ͉ mice ͉ estrogen

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Regulation of Aromatase Gene Expression in the Adult Rat Brain

Cited by 106 publications

References 38 publications

Conditional Inactivation of Androgen Receptor Gene in the Nervous System: Effects on Male Behavioral and Neuroendocrine Responses

Conditional Inactivation of Androgen Receptor Gene in the Nervous System: Effects on Male Behavioral and Neuroendocrine Responses

Functional significance of the rapid regulation of brain estrogen action: Where do the estrogens come from?

Testosterone inhibits early atherogenesis by conversion to estradiol: Critical role of aromatase

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