Estrogen-Induced Remodeling of Hypothalamic Neural Circuitry

Flanagan‐Cato, Loretta M.

doi:10.1006/frne.2000.0204

Cited by 46 publications

(26 citation statements)

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“…Neural circuits within the mPOA and VMN are critical sites of estrogen action in the regulation of sexually differentiated sexual behavior (Pfaff et al, 1994;Flanagan-Cato, 2000). The mPOA, in particular, exhibits a wide variety of neurochemical and structural sexual dimorphisms that are thought to underlie elements of male reproductive behavior (reviewed in De Vries, 1990;Simerly, 2002).…”

Section: Sex Differences In Rapid Estrogen Actions Upon Reproductive mentioning

confidence: 99%

“…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).…”

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confidence: 99%

“…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).…”

mentioning

confidence: 99%

“…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).…”

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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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Section: Sex Differences In Rapid Estrogen Actions Upon Reproductive mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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

Ábrahám

Herbison

2005

Neuroscience

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“…15 Catherine Woolley 16 and her colleagues have shown, probably consequent to the phenomena above, a stimulatory effect of estrogen treatment on dendritic growth. In the female rat hypothalamus, Maya Frankfurt 17 and Lori Flanagan 18,19 have reported that estrogens foster dendritic growth and an increased number of synapses. 20 Therefore, in VMH cells which control lordosis behavior circuitry, estrogens apparently provide the structural basis for increased synaptic activity and, therefore, greater sex-behavior-facilitating output.…”

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confidence: 99%

Hormonal symphony: steroid orchestration of gene modules for sociosexual behaviors

Mong

Pfaff

2004

Mol Psychiatry

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Genes induced by estrogens in the mammalian forebrain influence a variety of neural functions. Among them, reproductive behavior mechanisms are very well understood. Their functional genomics provide a theoretical paradigm for linking genes to neural circuits to behavior. We propose that estrogen-induced genes are organized in modules: Growth of hypothalamic neurons; Amplification of the estrogen effect by progesterone; Preparative behaviors; Permissive actions on sex behavior circuitry; and Synchronization of mating behavior with ovulation. These modules may represent mechanistic routes for CNS management of successful reproduction. Moreover, new microarray results add estrogen-dependent genes, including some expressed in glia, suggesting possible hormone-dependent neuronal/ glial coordination. Molecular Psychiatry (2004) 9, 550-556. doi:10.1038/sj.mp.4001493Keywords: sex; estrogen; gene; hypothalamus; lordosis; arousal; noradrenalin; acetylcholine; oxytocin; enkephalin; opioid; GnRH; LHRH; neurotrophic; anxiety Sexual behaviors are important for psychiatry. Not only hypersexual disorders but also concerns about lack of sexual desire are prominent, internationally, in the psychiatric landscape. Further, in some traditions of psychiatric theory, sexual problems are held to be at the root of apparently unrelated syndromes. Finally, biological thought has held that sexual affiliations provide the bauplan, the structural precedent, for a wide variety of other social relations, both normal or abnormal. Fortunately, the molecular analysis of stereotyped sexual behaviors has benefited greatly from several strategic advantages: Even in mammals, simple stimuli and responses permit neural net analysis. Steroid hormones acting through nuclear receptors which are transcription factors invoke regulated gene expression, for example, in hypothalamic neurons.1 In turn, these neurons control mating behavior circuits.Drawing hormone-regulated gene expression into the explanation of mammalian sex behavior has proceeded rapidly. Here we theoretically propose a gene network-really, a micronet-downstream of estrogen action in the forebrain responsible for courtship and lordosis behavior in females. Not a massive review of the literature or an original data report, this paper comprises an attempt to draw different transcriptional systems into a new theoretical formulation. These efforts to explain hormone-driven behaviors have benefited from Rosenfeld's example of genetic network control over pituitary gland development.2 Both direct and indirect causal routes are depicted below.Causal routes, downstream from genomic action; a modular system emergent The primary sex behavior of female quadrupeds, lordosis, depends on defined physical signals: cutaneous stimuli and estrogens þ progestins 1 (E þ P). The neural circuit has been worked out; estrogen-dependent transcription in ventromedial hypothalamic cells allows permissive signals to the midbrain central gray, thus enabling the rest of the circuit. In the absence of fear or anxiety-pro...

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Alterations of sex‐typical microanatomy: Prenatal stress modifies the structure of medial preoptic area neurons in rats

Gerecke

Kishore

Jasnow

et al. 2011

Developmental Psychobiology

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Prenatal stress disrupts normal sexual differentiation and behavior with concomitant alterations in brain development; however, its effects on the cytoarchitecture of neurons in the sexually dimorphic medial preoptic area (mPOA) of the hypothalamus is not known. Morphometric analysis of the mPOA of adult rats showed sex differences as neurons from control females had significantly greater numbers of basal dendritic branches and cumulative basal dendritic length as compared to control male neurons. Prenatal stress significantly altered these sexual dimorphisms, as prenatally stressed (P-S) males had increased measures of cell body area, perimeter, cumulative basal dendritic length, and branch point numbers as compared to control males. Prenatal stress also altered the cytoarchitecture in the female mPOA neurons as P-S female neurons had significantly greater measures for primary dendritic branch number and a trend towards significance for several additional measures as compared to control females. Therefore, there are significant effects of both sex and prenatal stress on neuronal architecture in the mPOA that may help to explain the well-documented alterations in reproductive behaviors observed in P-S animals.

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Estrogen-Induced Remodeling of Hypothalamic Neural Circuitry

Cited by 46 publications

References 127 publications

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

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

Hormonal symphony: steroid orchestration of gene modules for sociosexual behaviors

Alterations of sex‐typical microanatomy: Prenatal stress modifies the structure of medial preoptic area neurons in rats

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