Androgen-insensitive rats are defeminised by their testes

Kl, Olsen

doi:10.1038/279238a0

Cited by 54 publications

(23 citation statements)

References 21 publications

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“…The aromatization hypothesis also seems to hold for the development of some sexual and nonsexual rodent behaviors. Defeminization of rat sexual behavior, as measured by the proclivity to show lordosis (the female posture of sexual receptivity), and masculinization of aggressive behavior in rodents are largely controlled by estrogenic metabolites of T acting on ERs (Olsen, 1979;Vreeburg et al, 1977;Ogawa et al, 2000;Scordalakes and Rissman, 2004).…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

“…In rats, defeminization of sexual behavior appears to be AR-independent. Olsen (1979) found that neonatally castrated Tfm male rats, compared to intact Tfm males, showed an increased display of lordosis, indicating that functional ARs are not necessary for the defeminization of this behavior, but rather androgens normally act through another mechanism (presumably ERs) to defeminize lordosis. The role of ARs in the development of masculine sexual behavior (i.e., mounting behavior), however, is not as clear.…”

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confidence: 97%

“…In this regard, the Tfm rat resembles untreated humans with CAIS, who also have circulating T levels in the high-male range (Vague, 1983). In both rat and mouse Tfm models, indirect evidence suggests that T levels are near the normal male range in the perinatal period (Olsen, 1979;Goldstein and Wilson, 1972), but no one has actually measured circulating androgens in perinatal Tfm rodents.Aromatase activity is also decreased in several areas of the adult Tfm brain compared to wt males (Roselli et al, 1987;Rosenfeld et al, 1977), so differences between wt males and Tfm males in brain morphology and behaviors associated with these regions may be caused by reduced ER activation. Therefore in the survey that follows, as we find evidence that the Tfm allele of the AR gene affects brain and behavior, we must keep in mind that such findings do not disprove a role for ER, since AR may be acting in part by affecting aromatase.…”

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confidence: 99%

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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

210

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: Nih-pa Author Manuscriptmentioning

confidence: 99%

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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

210

156

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“…So the demasculinization of the VMH cannot be due to lack of circulating testosterone, and therefore loss of substrate to be aromatized into estrogens to act upon ERs, in adulthood. We also know that the perinatal testes of TFM males secrete some hormone, because Olsen (Olsen, 1979) found that neonatal castration of TFM rats averted the defeminization of their brains as measured by the propensity to display lordosis behavior. But we do not know whether the perinatal testes of TFM males produce as much androgen as those of WT males.…”

Section: Provisos and Cautionsmentioning

confidence: 99%

“…In rats, testicular development and testosterone secretion appear to be normal in TFM males, but somatic tissues show little or no response to androgens. TFM males do not display lordosis despite their feminine appearance (Olsen, 1979), so they are defeminized, presumably by aromatized metabolites of testosterone acting on estrogen receptors. They also show infrequent and incomplete male copulatory responses to receptive females (Beach and Buehler, 1977), but that could be due to either incomplete masculinization of brain sites such as the VMH or to the absence of normal male genitalia.…”

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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Play fighting in androgen-insensitivetfm rats: Evidence that androgen receptors are necessary for the development of adult playful attack and defense

Field

Whishaw²,

Watson

2006

Dev. Psychobiol.

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The frequency of playful attack and the style of playful defense, are modifiable by gonadal steroids and change after puberty in male and female rats. The present study examined the play behavior exhibited by testicular feminized mutation (tfm)-affected males, who are insensitive to androgens but can bind estrogens aromatized from androgens, to determine the relative contributions of androgens and estrogens to the age-related changes in play behavior. tfm males did not exhibit a decrease in playful attack with age and were more likely to maintain the use of complete rotations, a juvenile form of playful defense, into adulthood. tfm males did however, show age related changes in the use of partial rotations and upright postures, two other forms of playful defense, that were similar to normal males. These data suggest that the development of play fighting and defense in males is dependent on both androgen-and estrogenreceptor-mediated effects. ß 2006 Wiley Periodicals, Inc. Dev Psychobiol 48: 111-120, 2006.

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Androgen-insensitive rats are defeminised by their testes

Cited by 54 publications

References 21 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

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

Play fighting in androgen-insensitivetfm rats: Evidence that androgen receptors are necessary for the development of adult playful attack and defense

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