Estrogen Increases Proenkephalin Messenger Ribonucleic Acid Levels in the Ventromedial Hypothalamus of the Rat

Romano, Gary; Harlan, Richard E.; Shivers, Brenda D.; Howells, Richard D.; Pfaff, Donald W.

doi:10.1210/mend-2-12-1320

Cited by 176 publications

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“…In addition, hormones such as thyroid hormone and glucocorticoids may regulate the transcription of the preproenkephalin gene in the central nervous system (Ahima et al, 1992;Zhu et al, 1996). As will be described in more detail later, estrogens also have the ability to regulate enkephalin gene expression in certain brain regions (Priest et al, 1995;Romano et al, 1988).…”

Section: The Endogenous Opioid Systemmentioning

confidence: 99%

“…In the forebrain and hypothalamus, estradiol administration to ovariectomized animals has been shown to increase preproenkephalin mRNA expression, the concentration of endogenous opioids, and the release of endogenous opioids (Eckersell et al, 1998;Hammer et al, 1993;Priest et al, 1995;Romano et al, 1988). There are functional EREs that bind ER located in the promoter region of the rat preproenkephalin gene (Zhu and Pfaff, 1995) indicating a putative direct regulatory effect of estrogens on enkephalin gene transcription.…”

Section: Estrogen Receptor Neurons and The Endogenous Opioid Systemmentioning

confidence: 99%

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Estrogenic influences in pain processing

Amandusson

Blomqvist

2013

Frontiers in Neuroendocrinology

111

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Gonadal hormones not only play a pivotal role in reproductive behavior and sexual differentiation, they also contribute to thermoregulation, feeding, memory, neuronal survival, and the perception of somatosensory stimuli. Numerous studies on both animals and human subjects have also demonstrated the potential effects of gonadal hormones, such as estrogens, on pain transmission. These effects most likely involve multiple neuroanatomical circuits as well as diverse neurochemical systems and they therefore need to be evaluated specifically to determine the localization and intrinsic characteristics of the neurons engaged. The aim of this review is to summarize the morphological as well as biochemical evidence in support for gonadal hormone modulation of nociceptive processing, with particular focus on estrogens and spinal cord mechanisms.

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Section: The Endogenous Opioid Systemmentioning

confidence: 99%

Section: Estrogen Receptor Neurons and The Endogenous Opioid Systemmentioning

confidence: 99%

Estrogenic influences in pain processing

Amandusson

Blomqvist

2013

Frontiers in Neuroendocrinology

111

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“…Analgesia The enkephalin gene is turned on rapidly, in female mouse and rat hypothalamic neurons, by estrogens, [45][46][47] within about 30 min, and this is proven by in vitro transcription assays to represent a hormone-facilitated transcriptional facilitation. 48 The route of action upon lordosis, of the enkephalin gene product, would theoretically be indirect, through other behaviors.…”

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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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“…Estrogen administration rapidly induces high levels of enkephalin mRNA in the ventromedial nucleus of the hypothalamus (VMH), a nerve-cell group essential for lordosis behavior (13,14). This induction includes a transcriptional facilitation by estradiol (15-17) and is greater in females than in males (18).…”

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confidence: 99%

Female preproenkephalin-knockout mice display altered emotional responses

Ragnauth¹

2001

Proceedings of the National Academy of Sciences

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The endogenous opioid system has been implicated in sexual behavior, palatable intake, fear, and anxiety. The present study examined whether ovariectomized female transgenic preproenkephalin-knockout (PPEKO) mice and their wild-type and heterozygous controls displayed alterations in fear and anxiety paradigms, sucrose intake, and lordotic behavior. To examine stability of responding, three squads of the genotypes were tested across seasons over a 20-month period. In a fear-conditioning paradigm, PPEKO mice significantly increased freezing to both fear and fear ؉ shock stimuli relative to controls. In the open field, PPEKO mice spent significantly less time and traversed significantly less distance in the center of an open field than wild-type controls. Further, PPEKO mice spent significantly less time and tended to be less active on the light side of a dark-light chamber than controls, indicating that deletion of the enkephalin gene resulted in exaggerated responses to fear or anxiety-provoking environments. These selective deficits were observed consistently across testing squads spanning 20 months and different seasons. In contrast, PPEKO mice failed to differ from corresponding controls in sucrose, chow, or water intake across a range (0.0001-20%) of sucrose concentrations and failed to differ in either lordotic or female approach to male behaviors when primed with estradiol and progesterone, thereby arguing strongly for the selectivity of a fear and anxiety deficit which was not caused by generalized and nonspecific debilitation. These transgenic data strongly suggest that opioids, and particularly enkephalin gene products, are acting naturally to inhibit fear and anxiety. E ndogenous opioid systems are involved intimately in fearrelated behaviors. For example, the work of Fanselow and coworkers has established an opioidergic modulation of freezing responses in rodents, which is a basic species-specific response to threatening stimuli (1-5). It would be hypothesized then that gene deletion of an endogenous enkephalin opioid peptide gene should alter the ability of the animal to respond appropriately to fear-or threat-inducing stimuli as evidenced in paradigms ostensibly measuring these responses including the open-field, dark-light transition, and conditioned shock paradigms.Opioid agonists have been shown also to potently stimulate intake of sweet solutions (6-12), ostensibly by increasing the hedonic value of the solution. It then would be hypothesized that loss of an endogenous enkephalin opioid peptide should blunt the proingestive actions of sucrose over a range of sucrose concentrations.Finally, previous molecular data lead to a prediction about possible effects of an enkephalin gene knockout on estrogendependent lordosis behavior. Estrogen administration rapidly induces high levels of enkephalin mRNA in the ventromedial nucleus of the hypothalamus (VMH), a nerve-cell group essential for lordosis behavior (13,14). This induction includes a transcriptional facilitation by estradiol (15-17) and is greate...

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Estrogen Increases Proenkephalin Messenger Ribonucleic Acid Levels in the Ventromedial Hypothalamus of the Rat

Cited by 176 publications

References 0 publications

Estrogenic influences in pain processing

Estrogenic influences in pain processing

Hormonal symphony: steroid orchestration of gene modules for sociosexual behaviors

Female preproenkephalin-knockout mice display altered emotional responses

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