Gonadal Hormones Affect Spine Synaptic Density in the CA1 Hippocampal Subfield of Male Rats

Léránth, Csaba; Petneházy, Örs; MacLusky, Neil J.

doi:10.1523/jneurosci.23-05-01588.2003

Cited by 376 publications

(354 citation statements)

References 46 publications

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“…In females, estrogens can also increase CA1 PSSD, though they have no effect in males (Leranth et al, 2003;MacLusky et al, 2005). This result indicates that the androgeninduced increase in PSSD in males may be mediated through ARs.…”

Section: Hippocampusmentioning

confidence: 84%

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: Hippocampusmentioning

confidence: 84%

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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“…A prior electrophysiological study had investigated whether sex differences may exist in rapid estrogen actions within the hippocampus and, as found here for pCREB, no sexual dimorphism was evident (Fugger et al, 2001). This indicates that the established sex difference in the ability of estrogen to modulate dendritic spine density in the CA1 (Woolley and McEwen, 1992;Leranth et al, 2003), is unlikely to depend simply on sex differences in CREB phosphorylation. The intracellular pathways mediating the effects of estrogen upon CREB phosphorylation in the hippocampus are currently under examination.…”

Section: Absence Of Sex Differences In Rapid Estrogen Actions In Thementioning

confidence: 96%

“…In addition, clear sex differences have been observed in the effects of estrogen on networks involved in regulating male and female sexual behavior (Pfaff et al, 1994;Flanagan-Cato, 2000). Interestingly, these sexually differentiated actions of estrogen are not confined solely to circuits involved in the modulation of reproductive function but also exist within brain regions such as the hippocampus (Woolley, 2000;Leranth et al, 2003).The mechanisms underlying the sexually dimorphic effects of estrogen on brain function in the adult are unclear. As one possibility, estrogen may regulate different numbers or populations of cells within a specific brain region of males and females.…”

mentioning

confidence: 99%

Major sex differences in non-genomic estrogen actions on intracellular signaling in mouse brain in vivo

Ábrahám

Herbison

2005

Neuroscience

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Abstract-Rapid effects of estrogen have now been identified throughout the brain but the extent to which these actions may be different in males and females is unknown. Previous work has shown that estrogen rapidly phosphorylates Ser 133 of cAMP responsive element binding protein (CREB) through a non-genomic mechanism. Using this indicator, we have examined here whether non-genomic estrogen actions occur in a sexually dimorphic manner within the adult brain. Male and female mice were gonadectomized and 3 weeks later treated with 17-␤-estradiol or vehicle for 1 h prior to perfusion fixation and subsequent CREB and phosphorylated CREB (pCREB) immunostaining of brain sections. The numbers of cells expressing CREB immunoreactivity were not altered by estrogen treatment or different in males and females in any of the brain regions examined. However, estrogen treatment significantly (P<0.05) increased pCREB-immunoreactive cell numbers in the medial preoptic area, ventrolateral division of the ventromedial nucleus, medial septum and CA1 region of the hippocampus of female mice. In contrast, estrogen increased pCREB levels in the medial septum and CA1 but not in the preoptic area or ventromedial nucleus of male mice. To evaluate the extent to which non-genomic estrogen actions may be sexually differentiated within a single neuronal phenotype, dual labeling immunocytochemistry was undertaken to evaluate the gonadotropin-releasing hormone ( A variety of neuronal circuits in the mammalian brain exhibit robust sex differences in structure and function (De Vries, 1990;Simerly, 2002). Hypothalamic regions such as the medial preoptic area (mPOA) and ventromedial nucleus (VMN) contain key sexually differentiated neuronal circuits responsible for controlling reproductive function (Pfaff et al., 1994;Flanagan-Cato, 2000;Simerly, 2002). For example, the GnRH neurons within the mPOA represent the final output neurons of the network involved in regulating gonadal function (Levine, 2003). Whereas estrogen stimulates a massive increment in GnRH secretion to induce ovulation in the female mammal, it has no similar effect in males (Herbison, 1998). In addition, clear sex differences have been observed in the effects of estrogen on networks involved in regulating male and female sexual behavior (Pfaff et al., 1994;Flanagan-Cato, 2000). Interestingly, these sexually differentiated actions of estrogen are not confined solely to circuits involved in the modulation of reproductive function but also exist within brain regions such as the hippocampus (Woolley, 2000;Leranth et al., 2003).The mechanisms underlying the sexually dimorphic effects of estrogen on brain function in the adult are unclear. As one possibility, estrogen may regulate different numbers or populations of cells within a specific brain region of males and females. This is likely to be the case for the sexually dimorphic nucleus of the preoptic area and the spinal nucleus of the bulbocavernosus in the rat (for review see Simerly, 2002) where major sex differences in neuronal n...

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“…A further intriguing complication arises from the apparent ability of the brain itself to synthesize gonadal hormones, as in Figure 1 (Mukai et al, 2006) and the reduction of this ability with aging and Alzheimer's disease (Schumacher et al, 2003). Leranth et al (2003) in rats and in monkeys (2004), spurred by apparent parallels between the actions of estrogren and androgens on dendritic spine density, investigated this possibility in orchidectomized rats and monkeys. In accord with their hypothesis, testes removal induced a steep reduction of spine synaptic density in CA1.…”

Section: Androgensmentioning

confidence: 99%

Can endocrine disruptors influence neuroplasticity in the aging brain?

Weiss

2007

NeuroToxicology

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Only within the last two decades has the adult mammalian brain been recognized for its ability to generate new nerve cells and other neural structures and in essence to rewire itself. Although hippocampal structures have received the greatest scrutiny, other sites, including the cerebral cortex, also display this potential. Such processes remain active in the aging brain, although to a lesser degree. Two of the factors known to induce neurogenesis are environmental enrichment and physical activity. Gonadal hormones, however, also play crucial roles. Androgens and estrogens are both required for the preservation of cognitive function during aging and apparently help counteract the risk of Alzheimer's disease. One overlooked threat to hormonal adequacy that requires close examination is the abundance of environmental endocrine-disrupting chemicals that interfere with gonadal function. They come in the form of estrogenic mimics, androgen mimics, anti-estrogens, antiandrogens, and in a variety of other guises. Because our brains are in continuous transition throughout the lifespan, responding both to environmental circumstances and to changing levels of gonadal steroids, endocrine-disrupting chemicals possess the potential to impair neurogenesis, and represent a hazard for the preservation of cognitive function during the later stages of the life cycle.

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Gonadal Hormones Affect Spine Synaptic Density in the CA1 Hippocampal Subfield of Male Rats

Cited by 376 publications

References 46 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

Major sex differences in non-genomic estrogen actions on intracellular signaling in mouse brain in vivo

Can endocrine disruptors influence neuroplasticity in the aging brain?

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