Estrogen Receptor Messenger RNA Expression in Rat Hypothalamus as a Function of Genetic Sex and Estrogen Dose*

Lauber, Andrea H.; Mobbs, CV; Muramatsu, Masami; Pfaff, Donald W.

doi:10.1210/endo-129-6-3180

Cited by 208 publications

(133 citation statements)

References 37 publications

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“…EB replacement of OVX females, indeed, had a significant effect: the reduction of ER␣-ir cells. Modulatory effect of acute E treatment on the ER␣ mRNA levels in the mediobasal hypothalamus of OVX females has been reported (21). In the current study, acute EB replacement also reduced ER␣-ir in SGN of OVX females.…”

Section: Discussionsupporting

confidence: 71%

“…However, we have reduced the chance of this mechanism by careful selecting an antibody directed against the amino acids 580-599, an epitope in F domain near the C-terminals of the ER␣. Considering the half-life of ER␣ protein is 2 to 4 h, and the evidence for the acute effect of E on ER␣ mRNA levels, the reduction of ER␣-ir may reflect E-induced down-regulation of ER␣ mRNA (21).…”

Section: Discussionmentioning

confidence: 99%

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A recently identified hypothalamic nucleus expressing estrogen receptor α

Mori¹,

Matsuda²,

Pfaff³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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We report evidence for the existence of a unique nucleus in the rat hypothalamus. This nerve cell group is situated in the interstitial area between the arcuate nucleus and ventromedial nucleus of the hypothalamus, and is primarily oriented sagittally, in a spindle shape. This nucleus was a well defined structure in Nissl-stained sections because of its location in an otherwise cell-poor zone. This sagittalis nucleus of the hypothalamus (SGN) exhibits significant sex differences in its volume and cell numbers, as defined by Nissl staining and estrogen receptor (ER) ␣ immunoreactivity (ir), being significantly larger in males than in females. Treatment of neonatal females with testosterone eliminated these sex differences. It is noteworthy that adult female rats have estrous cycle-related variations in the ER␣-ir cell distribution, decreasing during the proestrus phase of the cycle. Pharmacological experiments demonstrated that the single injection of estradiol benzoate had a significant effect on the ER␣-ir cell count, suggesting the hormonal responsiveness of SGN neurons. This unique hypothalamic nucleus with its morphological sex differences and hormonal responsiveness is embedded in a region important for the regulation of endocrine functions and sexual behaviors.sexual difference ͉ estrous cycle ͉ calbindinD-28k ͉ sagittalis nucleus A fter the comprehensive neuroanatomical charting of neurons expressing mRNAs for estrogen receptors (1) and subsequent estradiol binding (2), it was assumed that the understanding of the neuroanatomy of estrogen action in the brain was fairly complete. Here, however, we have discerned a hitherto unrecognized cell group that expresses estrogen receptor (ER) ␣ and exhibits sex differences.A number of important sex differences have already been described in the mammalian brain (3, 4). Most of these are organized by the action of the gonadal steroids in the critical period: during the few days before to after birth in rodents (4). In this period, an elevated amount of testosterone (T) is secreted from the male fetal testes and converted to estradiol (E) by the enzyme aromatase in the hypothalamus. Formation of E causes permanent masculinization of the brain (5). This masculinization is also experimentally induced in females by the administration of E in the critical period (3, 6). These morphological sex differences in the brain are likely among the neuroanatomical mechanisms for the physiological sex differences in adult brain function (7,8).At the age of puberty, the functional sex-related differences begin to appear, indicated by a sudden rise in the secretion of gonadotrophic hormones: luteinizing hormone (LH) and follicle-stimulating hormone, followed by an increase in gonadal steroids (9). The gonadal steroids, particularly E, orchestrate the neuroendocrine circuits that coordinate sex-specific behaviors. This E signaling is importantly mediated by ERs (3), which are in fact abundant in the sexual dimorphic nuclei in the hypothalamus, such as the anteroventral periventricular ...

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Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 99%

A recently identified hypothalamic nucleus expressing estrogen receptor α

Mori¹,

Matsuda²,

Pfaff³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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“…It has been reported that castration leads to an up-regulation of ER mRNA, 49 whereas acute estradiol treatment down-regulates ER mRNA. 35 In the present study, castration has presumably led to an up-regulation of ER in both ATD and control males, although the possibility cannot be ruled out that the ER-21 antiserum could be more efficient at detecting unoccupied ERs in the rat brain as opposed to the guinea-pig brain. If ER levels were up-regulated by castration, then the ER levels in the present study represent the maximal capacity rather than physiological levels.…”

Section: Ref 1)mentioning

confidence: 50%

“…17,18 Sex differences have also been found in basal estrogen receptor (ER) mRNA levels in the ventrolateral portion of the VMH and in the Arc, with female rats showing higher concentrations than male rats. 35 The sex differences in ER biosynthesis are already present early in development. 24,33 Using immunocytochemical procedures, sex differences have been found in both newborn and adult rats, with females showing a higher density of ER immunoreactivity (ER-IR) than males.…”

mentioning

confidence: 99%

Quantitative estimation of estrogen and androgen receptor-immunoreactive cells in the forebrain of neonatally estrogen-deprived male rats

et al. 1997

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Abstract--Using quantitative immunocytochemical procedures, the total number of estrogen and androgen receptors was estimated in a large number of hypothalamic and limbic nuclei of male rats, in which brain estrogen formation was inhibited neonatally by treatment with the aromatase inhibitor 1,4,6-androstatriene-3,17-dione. The highest densities of estrogen receptor immunoreactivity were observed in the periventricular preoptic area and the medial preoptic area. Neonatally estrogen-deprived males showed a higher estrogen receptor immunoreactivity than control males in the periventricular preoptic area and the ventrolateral portion of the ventromedial nucleus of the hypothalamus, i.e. those brain areas in which sex differences have been reported, with female rats showing a greater estrogen binding capacity than male rats. The highest densities of androgen receptor immunoreactivity were found in the septohypothalamic nucleus, the medial preoptic area, the posterior division of the bed nucleus of the stria terminalis and the posterodorsal division of the medial amygdaloid nucleus. No significant differences in distribution or total numbers of androgen receptors were found between neonatally estrogen-deprived males and control males.These findings suggest that neonatal estrogens, derived from the neural aromatization of testosterone, are involved in the sexual differentiation of the estrogen receptor system in the periventricular preoptic area and the ventromedial hypothalamus. The role of neonatal estrogens in the development of the forebrain androgen receptor system is less clear. 1997 IBRO. Published by Elsevier Science Ltd.Key words: neonatal ATD treatment, androgen receptor, estrogen receptor, estrogens, hypothalamus, preoptic area.In mammals, testosterone and estradiol derived from neural aromatization of testosterone act synergistically in the developing male brain to organize its structures and functions, i.e. to masculinize and defeminize the neural substrates that later control sexual behavior and neuroendocrine function. In the rat brain, masculinization results in the display of male-typical sexual behavior (mounts, intromissions and ejaculations) in adulthood. Defeminization results in a loss of cyclic release of gonadotropins necessary for ovulation and a loss of female-typical sexual behavior (lordosis, presenting, ear wiggling, hop and dart) in adulthood (e.g., Ref. 37). Thus, gonadally intact male rats display the complete pattern of male coital behavior when pair tested with an estrous female and no female-typical sexual behavior when pair tested with a sexually active male. However, lordosis behavior can be induced in castrated male rats by administering estradiol and progesterone, although the behavior displayed is usually less intense than that of females, and considerably more estradiol is required for its stimulation. 20,42,54 The development of the female rat brain is generally believed to proceed in the absence of testosterone and estradiol. Gonadally intact female rats display periods of be...

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“…Hybridization signals of ER mRNA in ( VMN were lower compared with those in both intact and ovariectomized & rats (22). Moreover, E can influence ER mRNA expression in VMN in a sex-dependent way (23). We speculate that the sex difference of E regulation of neuronal activity may be related to sex differences in E-influenced ER expression.…”

Section: Discussionmentioning

confidence: 76%

Sex differences in estrogenic regulation of neuronal activity in neonatal cultures of ventromedial nucleus of the hypothalamus

Zhang

Pfaff

Chen

2005

Proc. Natl. Acad. Sci. U.S.A.

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Estrogenic effects have been implicated in sexual differentiation of brain and behavior, in part by affecting neuronal activity in the ventromedial nucleus of the hypothalamus (VMN). We report here a remarkable sex difference in estrogenic regulation of neuronal activity in male vs. female neural networks. Spontaneous synaptic currents originating from a population of neurons were recorded in primary VMN cultures using the whole-cell patch-clamp technique. Treatment with 17␤-estradiol (E2, 10 nM) for 24 h induced opposite effects in the two sexes: the frequency of spontaneous synaptic events decreased significantly in neurons derived from males but increased in those from females. Interestingly, the 24-hour E2 effect was partially reversed by an acute application (5 min) of a second dose of E2 (10 nM), suggesting an interaction between extended (24-hr) and acute (5-min) effects of E2 in VMN neurons. To understand the underlying mechanism of this sexually dimorphic action of E2, we analyzed the E2 effect on GABAergic neurotransmission by recording miniature inhibitory postsynaptic currents. After 24-hour E2 treatment, both the amplitude and frequency of miniature inhibitory postsynaptic currents increased in neurons derived from males but decreased in those from females. These results suggest that E2-induced changes in GABAergic inhibition could at least partially explain E2 effects on neuronal activity. We conclude that E2 may have sexually dimorphic effects on the synaptic output of VMN neurons by modulating GABAergic neurotransmission.GABA ͉ sexual dimorphism ͉ steroid hormone E strogens (E) play important roles in a variety of neurobiological processes, including neural development and adult behaviors (1). The functional outcomes of these processes are coordinated with physiological events that are fundamentally different in males (() and females (&). These physiological events involve E interactions with nuclear E receptors (ERs), as well as interactions at several cellular levels, including signal transduction systems. One focus of these interactions is on hypothalamic neuronal activity. During a perinatal sensitive period, E exposure enhances neuronal excitability in the ( hypothalamus by affecting amino acid neurotransmitters, which might be a crucial mechanism in the process of masculinization of the ( brain (2). E plays a fundamental role in lordosis via actions in the ventromedial nucleus of the hypothalamus (VMN) (3, 4). Previous studies (5, 6) have demonstrated that an increase in VMN neuronal activity is a mechanism by which E acts through VMN to induce lordosis. However, the questions of exactly how E increases VMN neuronal activity and how sex differences might arise here remain to be elucidated.GABA plays an important role in VMN development (7), and GABAergic neurotransmission has been implicated in E's effects on several important functions, such as sexual differentiation during neural development (8) and lordosis behavior (9). E has been shown to affect many aspects of GABAergic transmission, ...

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Estrogen Receptor Messenger RNA Expression in Rat Hypothalamus as a Function of Genetic Sex and Estrogen Dose*

Cited by 208 publications

References 37 publications

A recently identified hypothalamic nucleus expressing estrogen receptor α

A recently identified hypothalamic nucleus expressing estrogen receptor α

Quantitative estimation of estrogen and androgen receptor-immunoreactive cells in the forebrain of neonatally estrogen-deprived male rats

Sex differences in estrogenic regulation of neuronal activity in neonatal cultures of ventromedial nucleus of the hypothalamus

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