Alteration in Sex-Specific Behaviors in Male Mice Lacking the Aromatase Gene

Μatsumoto, Takahiro; Honda, Shin‐ichiro; Harada, Nobuhiro

doi:10.1159/000071313

Cited by 104 publications

(79 citation statements)

References 34 publications

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“…Males lacking aromatase (ArKO) are unable to synthesize E but have normal receptors. Fewer ArKO males mounted, intromitted, and ejaculated, and had longer latencies when they did; however, about one-third of them were able to sire litters when placed with a female for a prolonged time (Bakker et al, 2002;Matsumoto et al, 2003).…”

Section: Steroid Receptor Mutantsmentioning

confidence: 98%

Sexual behavior in male rodents

Hull

Domínguez

2007

Hormones and Behavior

395

272

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The hormonal factors and neural circuitry that control copulation are similar across rodent species, although there are differences in specific behavior patterns. Both estradiol (E) and dihydrotestosterone (DHT) contribute to the activation of mating, although E is more important for copulation and DHT for genital reflexes. Hormonal activation of the medial preoptic area (MPOA) is most effective, although implants in the medial amygdala (MeA) can also stimulate mounting in castrates. Chemosensory inputs from the main and accessory olfactory systems are the most important stimuli for mating in rodents, especially in hamsters, although genitosensory input also contributes. Dopamine agonists facilitate sexual behavior, and serotonin (5-HT) is generally inhibitory, though certain 5-HT receptor subtypes facilitate erection or ejaculation. Norepinephrine agonists and opiates have dose-dependent effects, with low doses facilitating and high doses inhibiting behavior.

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Section: Steroid Receptor Mutantsmentioning

confidence: 98%

Sexual behavior in male rodents

Hull

Domínguez

2007

Hormones and Behavior

395

272

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“…The masculinization and defeminization of male sexual behavior in rodents are traditionally believed to rely on the conversion of androgens to estrogens and the subsequent activation of ERs during the perinatal period, a hypothesis most recently supported by data from mice deficient in either aromatase or ERs (Ogawa et al, 2000;Matsumoto et al, 2003;Ogawa et al, 1997). However, newborn male rats administered an aromatase inhibitor retain masculine sexual behaviors (Dominguez-Salazar et al, 2002), while genetically produced AR knockout mice (ARKO) show less masculine sexual behavior (Sato et al, 2004), suggesting that ARs are also involved in male sexual behavior.…”

Section: Sexual/social Behaviormentioning

confidence: 99%

The role of androgen receptors in the masculinization of brain and behavior: What we've learned from the testicular feminization mutation

Zuloaga

Puts

Jordan

et al. 2008

Hormones and Behavior

213

156

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Many studies demonstrate that exposure to testicular steroids such as testosterone early in life masculinizes the developing brain, leading to permanent changes in behavior. Traditionally, masculinization of the rodent brain is believed to depend on estrogen receptors (ERs) and not androgen receptors (ARs). According to the aromatization hypothesis, circulating testosterone from the testes is converted locally in the brain by aromatase to estrogens, which then activate ERs to masculinize the brain. However, an emerging body of evidence indicates that the aromatization hypothesis cannot fully account for sex differences in brain morphology and behavior, and that androgens acting on ARs also play a role. The testicular feminization mutation (Tfm) in rodents, which produces a nonfunctional AR protein, provides an excellent model to probe the role of ARs in the development of brain and behavior. Tfm rodent models indicate that ARs are normally involved in the masculinization of many sexually dimorphic brain regions and a variety of behaviors, including sexual behaviors, stress response and cognitive processing. We review the role of ARs in the development of the brain and behavior, with an emphasis on what has been learned from Tfm rodents as well as from related mutations in humans causing complete androgen insensitivity. Keywordscomplete androgen insensitivity syndrome -CAIS; vasopressin; anxiety; spatial memory; bed nucleus; medial amygdala; SDN-POA; sexual behavior; aggression; VMH Exposure to testicular steroids such as testosterone (T) early in life masculinizes the developing brain, leading to permanent changes in behavior in a wide variety of animal models (Morris et al., 2004). According to the aromatization hypothesis, T is converted by aromatase into 17-β estradiol (E2), which then acts on estrogen receptors (ERs) to masculinize the brain (Naftolin et al., 1975). Traditionally, aromatization is believed to be the mechanism by which the rodent brain becomes masculinized and defeminized. Some sexually dimorphic regions within the hypothalamus adhere well to this hypothesis, including the sexually dimorphic nucleus of the preoptic area (SDN-POA) and anteroventral periventricular nucleus (AVPV). T spares neuronsCorresponding author: Damian Zuloaga, Neuroscience Program, 108 Giltner Hall, Michigan State University, East Lansing, MI 48824, Phone: Fax: (517) 432-2744, Email: E-mail: zuloagad@msu.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript from death in the SDN-POA...

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“…Under normal conditions, aromatase expression in the avian and mammalian central nervous system is restricted to specific neuronal populations. These neuronal groups are mainly located in the hypothalamic/preoptic (medial preoptic nucleus, ventromedial nucleus) and limbic system (bed nucleus of stria terminalis, amygdala, hippocampus, septum, etc), but more scattered populations of aromatase expressing neurons are also present in the cerebral cortex [24,160,215,216,252,271]. In zebra finches and canaries, aromatase is also detected in high concentrations in parts of the nidopallium adjacent to the song control nucleus HVC [14,166,222].…”

Section: The Fast Effects Of Estrogens: Systemic or Central Origin Ofmentioning

confidence: 99%

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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Alteration in Sex-Specific Behaviors in Male Mice Lacking the Aromatase Gene

Cited by 104 publications

References 34 publications

Sexual behavior in male rodents

Sexual behavior in male rodents

The role of androgen receptors in the masculinization of brain and behavior: What we've learned from the testicular feminization mutation

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

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