Estradiol Modulates Density of Putative Oxytocin Receptors’ in Discrete Rat Brain Regions

Kloet, E. Ronald de; Voorhuis, Dorothy A.M.; Boschma, Ypie; Elands, Jack

doi:10.1159/000124680

Cited by 201 publications

(99 citation statements)

References 41 publications

(69 reference statements)

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“…Regulation of OTR by estrogens in VMN has been shown in females as well as males (16,18,(20)(21)(22)(23)(24)(25). A four-gene micronet theory featuring ER␣, ER␤, oxytocin, and OTR and has been proposed to explain how neurons in hypothalamus and amygdala cooperate to facilitate social behaviors in female rodents (26,27).…”

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confidence: 99%

Sex and estrogenic effects on coexpression of mRNAs in single ventromedial hypothalamic neurons

Devidze

Mong

Jasnow

et al. 2005

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

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(102, 14446-14451; first published September 26, 2005; 10.1073͞pnas.0507144102), the authors note that ''%'' was added after several numbers, due to a printer's error. On page 14449, right column, the second sentence under Estrogen Treatment Increases Number of ER␣, ER␤, OTR, and PKCs in Female Rats, ''In estrogen-treated animals, these numbers were higher than in the oil group, ER␣ (66% vs. 20%), ER␤ (39% vs. 14%), OTR (56% vs. 15%), PKC␦ (28% vs. 8%), PKC (30% vs. 8%), and PKC (44% vs. 12%) (P Ͻ 0.05 in all cases) (Tables 3 and 4),'' should read: ''In estrogen-treated animals, these numbers were higher than in the oil group, ER␣ (66 vs. 20 estrogen ͉ hypothalamus ͉ lordosis ͉ oxytocin ͉ PKC E strogens, steroid sex hormones, play important roles in the development and establishment of reproductive and sexual behaviors as well as many other nonreproductive functions (1-4). Although estrogens' actions in females are relatively well understood, its role in male CNS function is less studied (5). Estrogens are regulated by binding to specific nuclear estrogen receptors (ERs), ER␣ and ER␤, ligand-activated transcription factors (6). ER␣ and ER␤ belong to a large group of six subfamilies of transcription factors (7), one of which comprises the steroid receptors (8). ER expression in the brain varies by region (9) and can affect both female and male sexual behaviors (10-12). Both ER␣ and ER␤ are expressed in the hypothalamus, and particularly in ventromedial nucleus (VMN), which is well known to regulate female sexual behavior (13,14).In addition to regulating sexual behaviors, estrogens affect affiliative social behaviors by affecting mRNA levels for the oxytocin receptors (OTR) (15), which are expressed in VMN (4,(16)(17)(18)(19). Regulation of OTR by estrogens in VMN has been shown in females as well as males (16,18,(20)(21)(22)(23)(24)(25). A four-gene micronet theory featuring ER␣, ER␤, oxytocin, and OTR and has been proposed to explain how neurons in hypothalamus and amygdala cooperate to facilitate social behaviors in female rodents (26,27). OTRs are important for sex and anxiety behaviors (4). Regulation of OTR also requires second messenger-mediated kinases (28), one of which involves PKCs (29). Evidence shows that PKC␣ associates with OTR within 2 min of agonist stimulation (30).It has been demonstrated that estrogens have two types of actions: genomic and membrane (31-33). Although ERs play a major role in genomic actions of estrogens, nongenomic actions in neurons involve several signal transduction pathways (34). And although lordosis behavior requires genomic actions of estrogens in VMN (35), estrogen-induced membrane actions in VMN can potentiate these genomic actions in a manner involving PKC (14). Several in vitro studies show that activation of PKC is involved in the potentiating effect of the rapid membrane actions of estrogens (34,(36)(37)(38)(39). PKCs comprise a family of 12 related isozymes (40) that are divided into three groups: classical or calcium-dependent (PKC␣, -␤I, -␤II, and -␥); the n...

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confidence: 99%

Sex and estrogenic effects on coexpression of mRNAs in single ventromedial hypothalamic neurons

Devidze

Mong

Jasnow

et al. 2005

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

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“…As a result, mRNA and functional protein levels of the oxytocin receptor (OT R ) are increased. 67 The medial and cortical nuclei of the amygdala receive pheromonal inputs from the vomeronasal system. 68 Such inputs are crucial for directing neuroendocrine events and social behavior.…”

Section: Microarray Results Implicate Glial-expressed Genesmentioning

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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“…Specific oxytocin binding sites, which are present in this nucleus only after puberty (I), a r e probably involved in t h e regulation o f steroid hormone-dependent sexual receptivity (26,27). Estradiol can induce oxytocin binding sites in the rat ventromedial nucleus of thc hypothalamus (28)(29)(30) particularly in its vcntrolateral aspect which contains high numbers of estrogen-concentrating cells (31,32). It remains t o be shown however whether t h e expression of oxytocin binding in the hypothalamic ventromedial nucleus is regulated by t h e s a m e mechanism in the guinea-pig.…”

Section: Discussionmentioning

confidence: 99%

Oxytocin Excites Neurons Located in the Ventromedial Nucleus of the Guinea‐Pig Hypothalamus

Inenaga

Karman

Yamashita

et al. 1991

J Neuroendocrinology

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The area of the ventromedial nucleus of the hypothalamus in the guinea-pig was shown in autoradiographs to contain high affinity binding sites for oxytocin. In order to ascertain whether these sites may represent neuronal receptors, single-cell extracellular recordings were obtained from ventromedial neurons in coronal slices of t h e hypothalamus of adult guinea-pigs. Oxytocin applied in the nanomolar range excited about half of the neurons tested; none were inhibited. The response to the peptide was reversible and concentration-dependent. It was exerted directly since it persisted under t h e condition of synaptic isolation. Moreover, the effect was specific since it could be mimicked by a selective oxytocin agonist and since vasopressin was usually at least 10-fold weaker than oxytocin. These findings suggest that the binding sites for oxytocin detected by light microscopic autoradiography in the guinea-pig hypothalamic ventromedial nucleus represent functional receptors.In the rat brain, specific high affinity binding sites for oxytocin could be detected in various areas by light microscopic autoradiography, both in developing ( I ) and adult animals (2-5). In several of these areas, oxytoci?, was shown to excrt a neuronal effect ( I , 6 12), corroborating the view that binding sites detected by autoradiography represent, at least in part, functional receptors associated with neurons.Unexpectedly, when other species were examined, marked regional differences in the distribution of oxytocin binding sites were found ( 1 3). Thus, the ventral hippocampus and the dorsal motor nucleus of the vagus nerve were labelled in the rat but not in the guinea-pig (9, 11). In accordance with these autoradiographical data, electrophysiological recordings showed that neurons in the hippocampus and in the dorsal vagal nucleus of the rat were excited by oxytocin; in contrast, no neuronal sensitivity to this peptide was observed in the homologous area in the guinea-pig brain (9, 1 I).Amongst the regions of the rat brain which are most intensely labelled by [3H]oxytocin and by the radioiodinated selective oxytocin antagonist [1251]OTA (l4), is the hypothalamic ventromedial nucleus ( 1 , 4, 5). In the present study, we assessed whether the hypothalamic ventromedial nucleus also contains oxytocin binding sites in the guinea-pig. Moreover, in order to determine whether hypothalamic ventromedial neurons in this species are sensitive to oxytocin, we have carried out extracellular recordings from hypothalamic slices. The specificity of the neuronal action of oxytocin was ascertained by using a synthetic structural analogue, acting as a selective agonist (15). Part of these data have been presented a t scientific meetings (16,17).

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Estradiol Modulates Density of Putative Oxytocin Receptors’ in Discrete Rat Brain Regions

Cited by 201 publications

References 41 publications

Sex and estrogenic effects on coexpression of mRNAs in single ventromedial hypothalamic neurons

Sex and estrogenic effects on coexpression of mRNAs in single ventromedial hypothalamic neurons

Hormonal symphony: steroid orchestration of gene modules for sociosexual behaviors

Oxytocin Excites Neurons Located in the Ventromedial Nucleus of the Guinea‐Pig Hypothalamus

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