Androgen receptor blockade in the MPOA or VMN: effects on male sociosexual behaviors

Harding, Shannon M.; McGinnis, Marilyn Y.

doi:10.1016/j.physbeh.2004.03.008

Cited by 80 publications

(48 citation statements)

References 45 publications

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“…In this instance, it is easier to infer how demasculinization of sex behavior-related circuitry could lead to a demasculinization of behavior. Ultrasonic vocalizations, which are disrupted in Tfm males, appear to rely heavily on androgens acting in the VMH (Harding and McGinnis, 2003;Harding and McGinnis, 2004), so the demasculinization of this nucleus in Tfm males (Dugger et al, 2007) may contribute to this deficit in masculine behavior. Furthermore, along with its role in sexual behavior, the BST is also an important component of the circuitry involved in the regulation of the HPA axis and anxiety-related behavior.…”

Section: Structure/function Relationships In Tfm Rodentsmentioning

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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Section: Structure/function Relationships In Tfm Rodentsmentioning

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

View full text Add to dashboard Cite

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“…Regions inhibiting male sexual behavior have not been noted. While the role of the VMN in males has been less well studied, McGinnis and colleagues have shown that activity within subregions of this nucleus is also required for hormone-dependent copulatory behaviors in males (McGinnis et al, 1996;Harding and McGinnis, 2004). In both sexes, the mPOA is a key site for the integration of sensory input and the regulation of sexual performance (for review, Meisel and Sachs, 1994;Pfaff et al, 1994;Paredes and Baum, 1997;Blaustein and Erskine, 2002;Hull et al, 2002), as well as partner preference and motivation (Baum, 2006;Guarraci and Clark, 2006).…”

Section: Forebrain and Hypothalamic Regions Regulating The Expressionmentioning

confidence: 99%

Steroid modulation of GABAA receptor-mediated transmission in the hypothalamus: Effects on reproductive function

Henderson

2007

Neuropharmacology

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The hypothalamus, the seat of neuroendocrine control, is exquisitely sensitive to gonadal steroids. For decades it has been known that androgens, estrogens and progestins, acting through nuclear hormone receptors, elicit both organizational and activational effects in the hypothalamus and basal forebrain that are essential for reproductive function. While changes in gene expression mediated by these classical hormone pathways are paramount in governing both sexual differentiation and the neural control of reproduction, it is also clear that steroids impart critical control of neuroendocrine functions through nongenomic mechanisms. Specifically, endogenous neurosteroid derivatives of deoxycorticosterone, progesterone and testosterone, as well and synthetic anabolic androgenic steroids that are self-administered as drugs of abuse, elicit acute effects via allosteric modulation of γ-aminobutyric acid type A receptors. GABAergic transmission within the hypothalamus and basal forebrain is a key regulator of pubertal onset, the expression of sexual behaviors, pregnancy and parturition. Summarized here are the known actions of steroid modulators on GABAergic transmission within the hypothalamus/basal forebrain, with a focus on the medial preoptic area and the supraoptic/paraventricular nuclei that are known to be central players in the control of reproduction.

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“…It is possible that the absence of functional AR in some other brain region led, via any of several possible pathways including changes in neuronal activity, neurotrophic factor release, etc., to the decrease in VMH volume and soma size. While local blockade of ARs within the VMH impairs male copulatory behavior (Harding and McGinnis, 2004), there is no data to date about whether such treatments also alter VMH volume and/ or neuronal somata size.…”

Section: Possible Mechanismmentioning

confidence: 99%

“…Some data support this view. For example, pharmacologically blocking ARs in the VMH of adult male rats inhibits copulation (Harding and McGinnis, 2004). However, there is no published data to date on whether ARs, either in the VMH or elsewhere, have a role in its sexual differentiation.…”

Section: Introductionmentioning

confidence: 99%

Androgen receptors are required for full masculinization of the ventromedial hypothalamus (VMH) in rats

Dugger

Morris

Jordan

et al. 2007

Hormones and Behavior

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The ventromedial hypothalamus (VMH) is one of several sexually dimorphic nuclei that regulate mating behavior, and is rich in steroid hormone receptors and aromatase activity. We looked at the contribution of the androgen receptor (AR) to the volume of the VMH in rats by measuring each of the four subdivisions of the VMH in 90 day old male, female, and XY male rats carrying a mutant AR allele (tfm), which renders animals largely unresponsive to androgens. Confirming published reports, total VMH volume was greater in wild-type males than in females (p < 0.01). The mean total volume of the VMH in TFM males was intermediate, but not significantly different from either females or males (Ps > 0.10). The sex difference in VMH volume was primarily accounted for by the ventrolateral subdivision (VMHvl), which in both females and TFM males was significantly smaller than in wild-type males (Ps < 0.005). There was no significant sex difference in the volume of the other three subdivisions of the VMH. Neuronal somata were larger in males than females in VMHvl, central VMH (VMHc) and the dorsomedial VMH (VMHdm), with TFM males having feminine neuronal somata in the VMHdm and VMHc. These data suggest that AR plays a role during sexual differentiation of the VMH, imparting its greatest effect in the VMHvl. ARs may regulate aromatase expression or activity to affect estrogen receptor activation, or may act independently of estrogen receptors to influence VMH morphology.

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Androgen receptor blockade in the MPOA or VMN: effects on male sociosexual behaviors

Cited by 80 publications

References 45 publications

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

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

Steroid modulation of GABAA receptor-mediated transmission in the hypothalamus: Effects on reproductive function

Androgen receptors are required for full masculinization of the ventromedial hypothalamus (VMH) in rats

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