Showing papers on "Hypothalamus published in 1991"
TL;DR: The hippocampus is capable of mediating inhibition over a wide range of steroid levels, and is distinguished from most potential feedback sites, including the hypothalamus and pituitary, by its high content of both type I and II corticosteroid receptors.
Abstract: There is considerable, although not entirely consistent, evidence that the hippocampus inhibits most aspects of HPA activity, including basal (circadian nadir) and circadian peak secretion as well as the onset and termination of responses to stress. Although much of the evidence for these effects rests only on the measurement of corticosteroids, recent lesion and implant studies indicate that the hippocampus regulates adrenocortical activity at the hypothalamic level, via the expression and secretion of ACTH secretagogues. Such inhibition results largely from the mediation of corticosteroid feedback, although more work is required to determine whether the hippocampus supplies a tonic inhibitory input in the absence of corticosteroids. It must be noted that the hippocampus is not the only feedback site in the adrenocortical system, since removal of its input only reduces, but does not abolish, the efficacy of corticosteroid inhibition, and since other elements of the axis appear eventually to compensate for deficits in feedback regulation. The importance of other feedback sites is further suggested not only by the presence of corticosteroid receptors in other parts of the brain and pituitary, but also by the improved prediction of CRF levels by combined hypothalamic and hippocampal receptor occupancy. The likelihood of feedback mediated by nonhippocampal sites underscores the need for future work to characterize hippocampal influence on HPA activity in the absence of changes in corticosteroid secretion. However, despite the fact that the hippocampus is not the only feedback site, it is distinguished from most potential feedback sites, including the hypothalamus and pituitary, by its high content of both type I and II corticosteroid receptors. The hippocampus is therefore capable of mediating inhibition over a wide range of steroid levels. The low end of this range is represented by corticosteroid inhibition of basal (circadian nadir) HPA activity. The apparent type I receptor specificity of this inhibition and the elevation of trough corticosteroid levels after hippocampal damage support a role for hippocampal type I receptors in regulating basal HPA activity. It is possible that basal activity is controlled in part through hippocampal inhibition of vasopressin, since the inhibition of portal blood vasopressin correlates with lower levels of hippocampal receptor occupancy, and the expression of vasopressin by some CRF neurons is sensitive to very low corticosteroid levels. At the high end of the physiological range, stress-induced or circadian peak corticosteroid secretion correlates strongly with occupancy of the lower affinity hippocampal type II receptors.(ABSTRACT TRUNCATED AT 400 WORDS)
1,672 citations
TL;DR: The presence of allopregnanolone and allotetrahydroDOC in brain is demonstrated and acute stress results in a rapid increase of these neuroactive steroids to levels known to modulate GABAA receptor function.
Abstract: A 3 alpha-hydroxy A-ring-reduced metabolite of progesterone, 3 alpha-hydroxy-5 alpha-pregnan-20-one (allopregnanolone), and one of deoxycorticosterone (DOC), 3 alpha,21-dihydroxy-5 alpha-pregnan-20- one (allotetrahydroDOC), are among the most potent known ligands of gamma-aminobutyric acid (GABA) receptors designated GABAA in the central nervous system. With specific radioimmunoassays, rapid (less than 5 min) and robust (4- to 20-fold) increases of allopregnanolone and allotetrahydroDOC were detected in the brain (cerebral cortex and hypothalamus) and in plasma of rats after exposure to ambient temperature swin stress. Neither steroid was detectable in the plasma of adrenalectomized rats either before or after swim stress. However, allopregnanolone, but not allotetrahydroDOC, was still present in the cerebral cortex (greater than 3 ng/g) after adrenalectomy. These data demonstrate the presence of allopregnanolone and allotetrahydroDOC in brain and show that acute stress results in a rapid increase of these neuroactive steroids to levels known to modulate GABAA receptor function.
917 citations
TL;DR: Findings of intense and dynamic NPY neurosecretory activity within a discrete hypothalamic site in association with an increased drive for food consumption demonstrate that NPY release in the PVN is an important orexigenic signal for periodic eating behavior.
Abstract: Feeding in mammals is a periodic behavior; however, knowledge of how the brain signals an intermittent eating pattern is scanty. Recent indirect evidence indicates that one of the signals encoded in the structure of neuropeptide Y (NPY) is to stimulate robust feeding. Therefore, two series of experiments were undertaken to characterize NPY secretion within the paraventricular nucleus (PVN) in association with eating behavior in the rat. Dynamic changes in NPY concentration in several hypothalamic sites and release in the PVN were assessed before and during the course of food consumption in rats trained to eat daily only for 4 h. Only in the PVN were NPY concentrations elevated before the introduction of food and, thereafter, levels decreased significantly during the course of eating. A similar temporal pattern in NPY release into the PVN interstitium was evident in samples collected by push-pull cannula perfusion in unrestrained rats. In addition, in food-deprived rats displaying a robust drive for feeding, NPY release in the PVN was also markedly enhanced in the shape of high-amplitude secretory episodes as compared to a lower release rate in rats receiving food ad libitum. The higher rate of NPY release in fasted rats returned to the control range after 24 h of ad libitum food supply. These findings of intense and dynamic NPY neurosecretory activity within a discrete hypothalamic site in association with an increased drive for food consumption demonstrate that NPY release in the PVN is an important orexigenic signal for periodic eating behavior. These results have important global implications for elucidating the underlying causes of the pathophysiology of eating disorders--anorexia nervosa, bulimia, and obesity--as well as constituting a specific contextual model for the formulation and testing of suitable NPY receptor agonists and antagonists for therapeutic intervention.
673 citations
TL;DR: Insight is provided into the neuroanatomical basis of the differential effects of drugs that act on D1 or D2 receptors by mapping the cellular expression of the corresponding mRNAs in rat brain by in situ hybridization histochemistry.
Abstract: Physiological and pharmacological criteria have divided dopamine receptors into D1 and D2 subtypes, and genes encoding these subtypes have recently been cloned Based on the sequences of the cloned receptors, we prepared oligodeoxynucleotide probes to map the cellular expression of the corresponding mRNAs in rat brain by in situ hybridization histochemistry These mRNAs showed largely overlapping yet distinct patterns of expression The highest levels of expression for both mRNAs were observed in the caudate-putamen, nucleus accumbens, and olfactory tubercle Within the caudate-putamen, 47 +/- 6% and 46 +/- 5% of the medium-sized neurons (10-15 microns) expressed the D1 and D2 mRNAs, respectively, and only the D2 mRNA was observed in the larger neurons (greater than 20 microns) The D1 and D2 mRNAs were expressed in most cortical regions, with the highest levels in the prefrontal and entorhinal cortices Within neocortex, D1 mRNA was observed primarily in layer 6 and D2 mRNA in layers 4-5 Within the amygdala, D1 mRNA was observed in the intercalated nuclei, and D2 mRNA in the central nucleus Within the hypothalamus, D1 mRNA was observed in the suprachiasmatic nucleus and D2 mRNA in many of the dopaminergic cell groups Within the septum, globus pallidus, superior and inferior colliculi, mammillary bodies, and substantia nigra only D2 mRNA was detected These data provide insight into the neuroanatomical basis of the differential effects of drugs that act on D1 or D2 receptors
473 citations
TL;DR: Comparisons with the effects of manipulation of glucocorticoid status, comparable analyses were carried out in separate groups of animals following adrenalectomy with and without corticosteroid replacement, suggesting that exposure to a novel environment can effect a decrease in CRF mRNA levels in the olfactory bulb.
Abstract: The regulation of corticotropin-releasing factor (CRF) mRNA expression in the rat brain by glucocorticoids and stress was examined by Northern blot analysis and in situ hybridization histochemistry. Rats either were exposed to a single electrical footshock session and killed 2, 4, 12, or 24 hr later (acute stress), or were subjected to the same regimen twice daily for 3 or 7 d and killed on the day following the last session (chronic stress). Rats placed in the experimental chamber but not administered shock comprised a “sham-handling” group. Chronic (7 d) intermittent footshock stress resulted in an 84 +/- 26% (P less than 0.05) increase in CRF mRNA levels in the whole hypothalamus as detected by Northern blot analysis and a 97 +/- 29% (P less than 0.05) increase in the paraventricular nucleus (PVN) as detected using in situ hybridization. No significant change in CRF mRNA levels was observed in the hypothalamus at any time up to 24 hr after a single exposure to footshock stress. A different pattern of results was obtained in other CRF-expressing cell groups. In Barrington's nucleus (a pontine micturition center), both acute and chronic stress produced significant increases in CRF mRNA, while in the olfactory bulb, both paradigms resulted in decreased levels. By Northern blot analysis, CRF mRNA in the olfactory bulb declined steadily, beginning at 4 hr after acute stress, and reached significance at 24 hr (69.2 +/- 1.9% of control, P less than 0.05). Levels from chronically (7 d) stressed animals declined to 54.1 +/- 5.1% of control value (P less than 0.05). Analysis of hybridization histochemical material revealed that both the number of positively hybridized cells and the number of silver grains per cell in the mitral and external plexiform layers of the bulb decreased following acute and chronic stress. However, CRF mRNA levels in the olfactory bulb were decreased to a comparable extent in the sham- handling group, suggesting that exposure to a novel environment can effect a decrease in CRF mRNA levels in the olfactory bulb. To provide comparisons with the effects of manipulation of glucocorticoid status, comparable analyses were carried out in separate groups of animals following adrenalectomy (ADX) with and without corticosteroid replacement. After ADX, CRF mRNA levels in the whole hypothalamus increased 60 +/- 5% (P less than 0.05) and were normalized following dexamethasone replacement. In contrast to the hypothalamus, no effects of steroid manipulation on CRF mRNA levels in the olfactory bulb, midbrain, cerebral cortex, or brain stem were detected.(ABSTRACT TRUNCATED AT 400 WORDS)
434 citations
TL;DR: The time-dependent effect of long-term imipramine administration on decreasing the gene expression of CRH in the hypothalamus and TH in the LC may be relevant to the therapeutic efficacy of this agent in depression.
Abstract: Imipramine is the prototypic tricyclic antidepressant utilized in the treatment of major depression and exerts its therapeutic efficacy only after prolonged administration. We report a study of the effects of short-term (2 wk) and long-term (8 wk) administration of imipramine on the expression of central nervous system genes among those thought to be dysregulated in imipramine-responsive major depression. As assessed by in situ hybridization, 8 wk of daily imipramine treatment (5 mg/kg, i.p.) in rats decreased corticotropin-releasing hormone (CRH) mRNA levels by 37% in the paraventricular nucleus (PVN) of the hypothalamus and decreased tyrosine hydroxylase (TH) mRNA levels by 40% in the locus coeruleus (LC). These changes were associated with a 70% increase in mRNA levels of the hippocampal mineralocorticoid receptor (MR, type I) that is thought to play an important role in mediating the negative feedback effects of low levels of steroids on the hypothalamic-pituitary-adrenal (HPA) axis. Imipramine also decreased proopiomelanocortin (POMC) mRNA levels by 38% and glucocorticoid receptor (GR, type II) mRNA levels by 51% in the anterior pituitary. With the exception of a 20% decrease in TH mRNA in the LC after 2 wk of imipramine administration, none of these changes in gene expression were evident as a consequence of short-term administration of the drug. In the light of data that major depression is associated with an activation of brain CRH and LC-NE systems, the time-dependent effect of long-term imipramine administration on decreasing the gene expression of CRH in the hypothalamus and TH in the LC may be relevant to the therapeutic efficacy of this agent in depression.
348 citations
TL;DR: IL-6, like IL-1, can exert a potent enhancing effect on the HPA by acutely stimulating the secretion of CRH-41 from the hypothalamus at a site above the level of the median eminence, at concentrations known to occur in human plasma and cerebrospinal fluid.
Abstract: It has previously been shown that interleukin-1 (IL-1) directly stimulates the release of CRH-41 from rat hypothalamus in vitro, suggesting that cytokines may mediate the effects of changes in immune state on the hypothalamo-pituitary adrenal axis (HPA). However, it is likely that several cytokines can cause changes in neuroendocrine function, and we have now investigated a series of others for central activity on the HPA: IL-2, IL-6, IL-8, tumor necrosis factor (cachectin), interferon-alpha 2, and interferon-gamma. The static rat hypothalamic incubation system used involves fresh hypothalamic explants with consecutive 20-min incubation, and estimation of CRH-41 concentrations in the medium by a specific RIA; the acute effects of cytokines on ACTH release from rat dispersed pituitary cells were also measured. IL-6 increased hypothalamic CRH-41 secretion in the range 10-100 U/ml, but had no effect on isolated median eminences incubated in vitro under the same conditions. IL-6 (1-1000 U/ml) also had no effect on the secretion of ACTH from freshly dispersed rat anterior pituitary cells when administered in 10-min pulses. The effects of both IL-1 and IL-6 were antagonized by blockade of the eicosanoid cyclooxygenase pathway, but not by lipooxygenase blockade. Neither IL-2 (1-10000 U/ml), IL-8 (0.1-10 nM), tumor necrosis factor (10-1000 U/ml), interferon-alpha 2 (10-1000 U/ml) nor interferon-gamma (10-1000 U/ml) had any effect on hypothalamic CRH-41 release or pituitary ACTH release. It is therefore concluded that IL-6, like IL-1, can exert a potent enhancing effect on the HPA by acutely stimulating the secretion of CRH-41 from the hypothalamus at a site above the level of the median eminence, at concentrations known to occur in human plasma and cerebrospinal fluid. These effects are probably mediated by cyclooxygenase products. Acute stimulatory effects of the other cytokines investigated on the HPA are unlikely to be exerted through changes in either CRH-41 or ACTH directly.
344 citations
340 citations
TL;DR: Findings support possible multifunctional roles for PACAP as a posterior pituitary hormone, a hypophysiotrophic factor, and a neurotransmitter/neuromodulator in the rat forebrain.
Abstract: Pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) are structurally similar, share the same high affinity site in same peripheral tissues and increase the intracellular content of adenylate cyclase. To establish which neural circuits are signaling with each of these two peptides, we systematically compared the immunohistochemical distribution of PACAP and VIP in selected rat forebrain regions using previously characterized antiserum. The PACAP antiserum recognized both PACAP27 and PACAP38, and PACAP immunoreactivity was unaffected by preincubation with various other peptides. PACAP-immunoreactive perikarya and fibers were observed in both hypothalamic and extrahypothalamic regions. In the hypothalamus PACAP perikarya were located in the supraoptic, paraventricular, anterior commissural, periventricular, and perifornical nuclei. In intact rats PACAP immunolabeled fibers were present in the internal zone of the median eminence and posterior pituitary. One week after hypophysectomy the intensity of staining in the internal zone was enhanced and immunoreactive fibers appeared in the external zone of the median eminence. Two or 3 weeks later a dense fiber network was observed around the portal capillaries in the external zone, and immunoreactive material further accumulated in the fibers of the internal zone. PACAP-immunoreactive perikarya and fibers were also observed in several extrahypothalamic regions including central thalamic nuclei, amygdaloid complex, bed nucleus of stria terminalis, septum, hippocampus and cingulate, and entorhinal cortices. In the lateral septum and entorhinal cortex PACAP fibers surrounded unstained neuronal cell bodies and small blood vessels. In intact rats, VIP-immunoreactive perikarya were present in all regions of the cerebral cortex, hippocampus, amygdaloid complexus and in the suprachiasmatic nucleus, but not in the paraventricular and supraoptic nuclei. In colchicine-treated rats the VIP perikarya appeared in the preoptic area and paraventricular nucleus. The fibers were organized in two main pathways: the stria terminalis and an ascending pathway from the suprachiasmatic nucleus to the paraventricular area. Hypophysectomy induced the appearance of VIP-immunoreactive fibers in the internal zone of the median eminence and perikarya in the supraoptic and paraventricular nuclei in addition to the suprachiasmatic nucleus. The dissimilar distributions of PACAP and VIP suggest that PACAP neural circuits are independent of that of VIP in the rat forebrain. These findings support possible multifunctional roles for PACAP as a posterior pituitary hormone, a hypophysiotrophic factor, and a neurotransmitter/neuromodulator.
260 citations
TL;DR: In this brief review, ongoing attempts to delineate these pathways are summarized and evidence for plasticity and local modulation of magnocellular reflexes in response to prolonged stimulation, such as chronic dehydration and lactation, is presented.
257 citations
TL;DR: It is proposed that neurons containing estrogen receptor, SP, and NKB mRNAs participate in the hypothalamic circuitry regulating estrogen negative feedback in the human.
Abstract: We have previously described hypertrophy of neurons containing estrogen receptor mRNA in the infundibular nucleus of postmenopausal women. In the present investigation we identified peptide mRNAs in the hypertrophied neurons and determined whether postmenopausal neuronal hypertrophy was accompanied by changes in gene expression. In the first study in situ hybridization was performed on sections from hypothalami of postmenopausal women (n = 3) using synthetic 35Slabeled cDNA probes complementary to mRNAs encoding estrogen receptor, substance-P (SP), neurokinin-B (NKB), POMC, cholecystokinin, dynorphin, CRF, enkephalin, galanin, neuropeptide-Y, GH-releasing hormone, and tyrosine hydroxylase. Neuronal cross-sectional areas and cell densities were measured with the aid of a computer microscope system. Neurons labeled with the NKB and SP probes were comparable in size, morphology, and distribution to the hypertrophied neurons containing estrogen receptor mRNA. In contrast, neurons labeled with other cDNA probe...
TL;DR: This work has used two antisera against peptide sequences derived from the cDNA of the human Type I corticosteroid receptor to map the regional distribution and cortiosteroid regulation of the intracellular location of Type I Corticosteroids receptor‐like immunoreactivity (Type I‐ir) in the rat CNS.
Abstract: Previous maps of Type I corticosteroid receptor binding in the rat central nervous system (CNS) revealed a restricted distribution of the receptor in limbic regions, hypothalamus, and circumventricular organs. More recent studies have shown a more widespread expression of the receptor, with high levels of Type I receptor mRNA in limbic, motor, and sensory systems. We have used two antisera against peptide sequences derived from the cDNA of the human Type I corticosteroid receptor to map the regional distribution and corticosteroid regulation of the intracellular location of Type I corticosteroid receptor-like immunoreactivity (Type I-ir) in the rat CNS.
Neurons showing Type I-ir were observed at all levels of the CNS. Highest densities of immunoreactive neurons were observed in limbic regions, isocortex, and some thalamic nuclei. Motor, sensory, and visceral systems often showed moderate densities of immunoreactive neurons. Type I-ir glia were observed in some fiber systems, e.g., corpus callosum, medial lemniscus, cerebral peduncles, spinal trigeminal tract, and funiculi of the spinal cord. In the majority of neurons and in glia, Type I-ir showed a diffusely nuclear and cytoplasmic location, Long-term adrenalectomy reduced immunoreactivity in most neurons and glia. Neuronal Type I-ir was localized mainly in the cytoplasm after long-term adrenalectomy. Nuclear immunoreactivity was retained in some neurons in the globus pallidus, motor trigeminal nucleus, and laminae 8 and 9 of the spinal cord. Acute treatment with corticosterone or aldosterone restored neuronal and glial Type I-ir to densities below that seen in intact rats.
TL;DR: In both male and female animals, the overall density of labeling found over individual cells in emulsion-dipped autoradiograms was consistently lower in hormone-treated animals compared with that over cells in gonadectomized controls, suggesting that the observed decreases in ER mRNA hybridization measured over the ARH and VMHvl are due to changes in cellular levels of ER mRNA.
Abstract: Sex steroid hormone receptors are thought to mediate the actions of their respective hormones by functioning as ligand-activated nuclear transcription factors that alter the expression of specific sets of hormone-responsive genes. Particularly high densities of estrogen receptor (ER)-containing neurons are located in the arcuate nucleus (ARH) and ventrolateral part of the ventromedial nucleus (VMHvl) of the hypothalamus, and these cell groups are thought to play key roles in the neuroendocrine control of reproductive function. Thus, hormonal regulation of ER gene expression in ARH and VMHvl neurons represents a direct mechanism by which circulating sex steroids could affect the responsiveness of these neurons to hormonal activation. We used in situ hybridization histochemistry to evaluate the influence of estradiol and testosterone on levels of ER mRNA within the ARH and VMHvl of adult male and female rats. In female rats, estradiol treatment reduced levels of ER mRNA in the ARH and VMHvl within 24 h relative to levels in both ovariectomized control animals and intact estrous females. Comparable results were obtained in male rats, except that testosterone did not significantly attenuate ER mRNA hybridization in the VMHvl until after 3 days of hormone treatment, and only a minor decrease was noted in the ARH, which was not statistically significant. In both male and female animals, the overall density of labeling found over individual cells in emulsion-dipped autoradiograms was consistently lower in hormone-treated animals compared with that over cells in gonadectomized controls, suggesting that the observed decreases in ER mRNA hybridization measured over the ARH and VMHvl are due to changes in cellular levels of ER mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: In transgenic mice expression of the simian virus 40 T antigen, driven by the promoter of human GnRH gene, resulted in central hypogonadism due to an arrest in neuronal migration during development and tumor formation along the migratory pathway.
Abstract: Gonadotropin-releasing hormone (GnRH) is important in reproduction, although the mechanism of central hypogonadism in humans remains unclear. Because the GnRH neuron originates from the olfactory placode and migrates to the hypothalamus during development, central hypogonadism in humans could be caused by failure in normal migration of GnRH neurons to the hypothalamus. We report that in transgenic mice expression of the simian virus 40 T antigen, driven by the promoter of human GnRH gene, resulted in central hypogonadism due to an arrest in neuronal migration during development and tumor formation along the migratory pathway. This system appears to be an important animal model of hypogonadotropic hypogonadism in humans. Additionally, olfactory bulb tumors from these animals were dispersed, and a GnRH-secreting neuronal cell line (GN cell line) was established.
TL;DR: Differences in basal levels and regulation of ER mRNA could be a substrate for sex differences in ER concentrations in the hypothalamus of the rat, and further raise the possibility ofsex differences in concentrations of nuclear proteins related to the control of ER gene expression.
Abstract: Previously, we showed that estrogen receptor (ER) messenger RNA (mRNA) levels are decreased in cells of the mediobasal hypothalamus of ovariectomized (OVX) female rats following an acute estradiol treatment. Here, we examined whether the level of ER mRNA remains depressed in the continued long-term presence of estradiol, and questioned if there is a systematic relationship between the concentration of estradiol and the decrease in ER mRNA level. OVX female rats were implanted for 2 weeks with silastic capsules containing various concentrations of estradiol. Tissue sections were hybridized with a [3H] single-stranded DNA probe prepared from the region of the rat ER complementary DNA corresponding to the steroid binding domain, and relative mRNA level was assessed by counting grains over cells in specific hypothalamic nuclei. Estradiol induced a dose-dependent decrease in ER mRNA levels. Message levels declined in the ventrolateral aspect of the ventromedial nucleus (VLVM) by 57% and in the arcuate nucleus ...
TL;DR: Investigation of the ultrastructure of GnRH neurons in the preoptic area and medial basal hypothalamus of rhesus monkeys provided strong evidence that alterations in the gonadal steroid milieu can produce morphological changes in the GnRH neuron and its immediate environment in the primate.
Abstract: The secretion of the gonadotropins is modulated by the gonadal steroids, but the means by which these effects are mediated are not well understood. The present anatomical study was undertaken to investigate the possibility that the GnRH system responds to alterations in the gonadal steroid environment with reversible changes in synaptic input and glial wrapping such as have been observed in other neuroendocrine systems. The ultrastructure of GnRH neurons was studied in the preoptic area and medial basal hypothalamus of rhesus monkeys in various steroid conditions including five intact cycling, four long-term ovariectomized animals, two long-term ovariectomized animals with steriod replacement (LtOVX+), and two animals replaced with steroid at the time of ovariectomy (StOVX+). Electron micrographic montages of GnRH neuronal profiles were analyzed using computerized morphometrics, and the percentages of the length of perikaryal membrane immediately apposed by glial processes and that with postsynaptic modif...
TL;DR: It is suggested that brain is the source of circulating estrogens in the male zebra finch and that estrogen actions on the song system result from local rather than peripheral aromatization.
Abstract: The neural system controlling song in passerine birds can undergo striking morphological and functional changes during both development and adulthood, and many of these changes are regulated by estrogenic hormones. Estrogens circulate at high levels in blood of male songbirds and persist after castration. We measured the activity of aromatase, the enzyme that converts androgens to estrogens, in various tissues from adult male and female zebra finches. As expected, aromatase activity was present in male hypothalamus/preoptic area and pituitary and female ovary, but aromatase was unusually active in whole telencephalon of males and females. By contrast, activity was undetected in testes, adrenals, or other tissues of males. These results suggest that brain is the source of circulating estrogens in the male zebra finch and that estrogen actions on the song system result from local rather than peripheral aromatization.
TL;DR: It is indicated that chronic ethanol ingestion generally reduces the synthesis of vasopressin, and that increased vasopressingin synthesis is not necessary in order for the peptide to affect ethanol tolerance.
TL;DR: The studies demonstrate that the pattern of c‐fos expression in hypothalamic magnocellular neurons following systemic CCK administration mirrors the neurosecretory response of these neurons, both with regard to specificity for the peptides secreted as well as intensity of secretion.
Abstract: The effect of systemically-administered Cholecystokinin octapeptide (CCK) on hypothalamic oxytocin, vasopressin, and corticotropin-releasing hormone neurons was studied by analysis of c-fos antigen expression in immunocytochemically-characterized neurons in the supraoptic and paraventricular nuclei. CCK (100mug/kg intraperitoneally) caused a marked increase in nuclear c-fos immunocytochemical staining, which peaked at 60 to 90 min after injection. C-fos expression was found in most magnocellular oxytocin neurons in the supraoptic nucleus and in all magnocellular subdivisions of the paraventricular nucleus, but in no vasopressin neurons in either area. C-fos expression was also found in several parvocellular subdivisions of the paraventricular nucleus: in oxytocin neurons within the medial and lateral, but not the dorsal, parvocellular subdivisions, and in corticotropin-releasing hormone neurons in the medial parvocellular subdivision. Injection of lower doses of CCK showed that c-fos expression closely paralleled the pattern of pituitary oxytocin secretion in response to CCK, with a threshold for activation at 1 mug/kg, near maximal responses by 10 mug/kg, and maximal responses by 100 mug/kg. These studies demonstrate that the pattern of c-fos expression in hypothalamic magnocellular neurons following systemic CCK administration mirrors the neurosecretory response of these neurons, both with regard to specificity for the peptides secreted as well as intensity of secretion. They also demonstrate that systemic CCK administration activates c-fos expression in parvocellular oxytocin and corticotropin-releasing hormone neurons, and therefore likely causes secretion of oxytocin and corticotropin-releasing hormone within the brain at the terminal fields of these neurons.
TL;DR: The colocalization and cosecretion of GAL and LHRH and the cooperative action at the level of the anterior pituitary afford important evidence for the functional significance of coexistence of neurotransmitters in neurons of the central nervous system.
Abstract: Galanin (GAL) is widely distributed in the peripheral and the central nervous systems. In the brain, the highest GAL concentrations are observed within the hypothalamus and, particularly, in nerve terminals of the median eminence. This location, as well as GAL actions on prolactin, growth hormone, luteinizing hormone (LH), and LH-releasing hormone (LHRH) secretion, suggest the possibility that GAL may act as a putative hypothalamic-hypophysiotropic hormone. To establish this, GAL and LHRH levels were measured in hypophyseal portal plasma samples using specific radioimmunoassays. Rat galanin (rGAL) concentrations in portal blood were approximately 7-fold higher than those observed in peripheral plasma in male and female (estrus, diestrus) rats, indicating an active secretory process of rGAL into the portal vasculature. Frequent (10 min) sampling revealed that rGAL and LHRH were secreted into the portal circulation in a pulsatile manner with a pulse frequency of one pulse per hour. Interestingly, both hormone series depicted a high degree of coincident episodes. In fact, the probability of random coincidence, calculated by the algorithm HYPERGEO, was less than 0.01. Moreover, the retrograde tracer Fluoro-Gold, when given systemically, was taken up by GAL neurons in the hypothalamus, including a subset of neurons expressing rGAL and LHRH, strengthening the notion of the existence of a GAL neuronal system connected to the hypophyseal portal circulation. These observations reinforce the concept that GAL regulates pituitary hormone secretion. To analyze this in further detail, the effects of rGAL on LH secretion were evaluated under basal and stimulated conditions. rGAL induced a small but dose-dependent increase in LH secretion from cultured, dispersed pituitary cells. Interestingly, rGAL enhanced the ability of LHRH to stimulate LH release. The tight link between GAL and LHRH neuronal systems is strengthened by the observation that during the estrous cycle of the rat, rGAL and LHRH contents in the median eminence show an identical profile (r = 1.00). These data indicate that GAL should be considered as a hypothalamic-hypophysiotropic hormone and as an important neuromodulator of LHRH secretion and action. The colocalization and cosecretion of GAL and LHRH and the cooperative action at the level of the anterior pituitary afford important evidence for the functional significance of coexistence of neurotransmitters in neurons of the central nervous system.
TL;DR: Sexual dimorphic synaptic organization seems to be critical from the developmental period to adulthood for organizing and reorganizing the neuronal circuitry driving neuroendocrine and behavioral functions.
Journal Article•
TL;DR: Evidence will be presented that the serotonergic system plays a major role in the maturation of the brain by interacting with the 5-HT1A receptors which are most dense during these early developmental periods.
Abstract: The serotonergic neurons of the mammalian brain comprise one of the most expansive chemical systems known The cell bodies are largely confined to the midline (raphe) region of the brain stem in two general clusters: a superior group that consists of the dorsal raphe nucleus (B-7 and B-6), median raphe nucleus (B-8 and B-5), caudal linear nucleus (rostral B-8), and supralemniscal nucleus (B-9), and an inferior group that consists of nucleus raphe obscurus (B-2), nucleus raphe pallidus (B-1), nucleus raphe magnus (B-3), ventral lateral medulla (B-1/B-3), and the area postrema The axons from these cells project throughout the neuroaxis from the spinal cord to the olfactory bulb and from the cerebral cortex to the hypothalamus The development of this giant system begins very early in gestation and is influenced by a variety of growth regulatory factors, including the astroglial protein S-100 beta Evidence will be presented that the serotonergic system plays a major role in the maturation of the brain by interacting with the 5-HT1A receptors which are most dense during these early developmental periods The 5-HT1A receptor is located on both neurons and astrocytes, and in the latter cells may serve to stimulate release of S-100 beta The developmental role of 5-HT appears to become dormant as the brain matures, and during aging and Alzheimer's disease, 5-HT receptors are significantly depressed However, specific damage to 5-HT fibers in the adult brain by 5,7-dihydroxytryptamine produces a sharp fall in the levels of 5-HT which seems to reactivate the developmental signals in the brain Not only are the serotonergic fibers encouraged to sprout and expand their territory, but the stimulation of the astrocytic growth factor by a 5-HT1A agonist is reinstated The ability to recall developmental processes in the adult brain by interrupting the 5-HT fibers may provide important tools for understanding and treating the aged brain
TL;DR: The most dense collections of estrogen receptor‐immunoreactive cells were found in medial preoptic, medial hypothalamic, and limbic nuclei (amygdala, bed nucleus of the stria terminals, lateral septum) and also in the midbrain (central gray).
Abstract: We mapped the distribution of estrogen receptor-containing cells in the forebrain of the adult female guinea pig. Cellular estrogen receptor content was detected using monoclonal antibody H222, directed against the estrogen receptor, and the avidin-biotin method with nickel-intensified diaminobenzidine as the chromagen. A complete set of deletion, titration, and adsorption controls established the specificity of the staining. The most dense collections of estrogen receptor-immunoreactive cells were found in medial preoptic, medial hypothalamic, and limbic nuclei (amygdala, bed nucleus of the stria terminalis, lateral septum). Numerous estrogen receptor-immunoreactive cells were also found in additional, specific subregions of the remainder of the preoptic area, hypothalamus, and limbic system, and also in the midbrain (central gray). Elsewhere, estrogen receptor-immunoreactive cells were present in smaller numbers or were absent. This map confirms and extends previous maps based on estrogen binding. The majority of estrogen receptor-immunoreactive cells are found in areas known to be involved in some aspect of reproduction. In addition, many estrogen receptor-immunoreactive cells are found in areas not typically considered to have a primary role in reproductive behavior or neuroendocrine function.
TL;DR: Results indicate that DuP 753 and WL 19 are highly selective for angiotensin II binding site subtypes in the brain and that, in general these subtypes are compartmentalized in distinct brain regions.
TL;DR: It is concluded that the reduction in circulating T3 after food deprivation appears to be due primarily to decreased hypothalamic TRH synthesis and release.
Abstract: Food deprivation in laboratory rats induces profound changes in the neuroendocrine system. We have investigated the hypothalamic and pituitary responses of the hypothalamo- pituitary thyroid axis to 48-h food deprivation in Sprague- Dawley rats. Peripheral T3 and hypophysial portal TRH were measured by RIA, and TSHβ, PRL, and pro-TRH mRNA were measured using in situ hybridization histochemistry. Peripheral total T3 was greatly reduced in food-deprived rats. Hypothalamic portal blood TRH levels declined significantly with time in control animals. The initial level of TRH in the portal blood of food-deprived rats was significantly reduced compared to that in controls, but did not fall further with time. In situ hybridization histochemistry revealed significantly lower pro-TRH mRNA in the paraventricular nucleus of food-deprived animals, while pro-TRH mRNA in the reticular nucleus remained unaltered. Furthermore, in the anterior pituitary, TSHβ mRNA decreased significantly in food-deprived animals, while PRL...
TL;DR: The results suggest that an endogenous y-aminobutyric acid system exerts a tonic inhibitory effect on the sympathetic nervous system at the level of the paraventricular nucleus of the hypothalamus.
Abstract: The present study was undertaken to determine whether gamma-aminobutyric acid in the paraventricular nucleus contributes to the regulation of cardiovascular function. Blood pressure and heart rate were recorded and plasma catecholamines were measured in conscious rats receiving microinfusions of either artificial cerebrospinal fluid or a gamma-aminobutyric acid antagonist, bicuculline methiodide, bilaterally into the paraventricular nucleus. Artificial cerebrospinal fluid had no effect on any of the recorded variables. In contrast, infusion of bicuculline into the region of the paraventricular nucleus produced increases in blood pressure (20 +/- 2 mm Hg), heart rate (110 +/- 11 beats/min), and plasma concentrations of norepinephrine (640 +/- 107 pg/ml) and epinephrine (1,266 +/- 267 pg/ml). Pretreatment with a ganglionic blocking agent abolished both the blood pressure (-1 +/- 2 mm Hg) and heart rate (5 +/- 18 beats/min) effects. Bilateral adrenal medullectomy reduced the changes in plasma norepinephrine concentrations (81 +/- 14 pg/ml) significantly and abolished the changes in plasma epinephrine concentrations (5 +/- 4 pg/ml). Conversely, adrenal medullectomy reduced the pressor effects (18 +/- 2 mm Hg) only slightly while the heart rate responses were attenuated (42 +/- 9 beats/min) by approximately 50%. These results suggest that an endogenous gamma-aminobutyric acid system exerts a tonic inhibitory effect on the sympathetic nervous system at the level of the paraventricular nucleus of the hypothalamus.
TL;DR: The concept of axonal mRNA transport is supported by embryonic developmental studies showing that appearance of vasopressin transcripts in the hypothalamus and the pituitary anlage is correlated and during axonal transport the respective mRNAs are subject to specific modification at the poly(A) tails.
Abstract: Hypothalamic vasopressin and oxytocin transcripts have been detected in the posterior pituitary suggesting either transcription of the respective genes in pituicytes or axonal mRNA transport from the hypothalamus to the nerve terminals of the posterior pituitary. The concept of axonal mRNA transport is supported firstly, by Northern blot and in situ hybridization analysis indicating that vasopressin and oxytocin mRNAs are also present in the neural stalk; secondly, by intron analysis and transcription run on experiments demonstrating the absence of primary vasopressin and oxytocin transcripts in non-neuronal cells of the posterior pituitary; thirdly, by embryonic developmental studies showing that appearance of vasopressin transcripts in the hypothalamus and the pituitary anlage is correlated. Furthermore, during axonal transport the respective mRNAs are subject to specific modification at the poly(A) tails.
TL;DR: Central nervous system binding sites (receptors) for melatonin and CorticaI structures in the anterior hypothalamus and other areas are studied.
TL;DR: It is suggested that photic induction of Fos-lir in most of the SCN depends on activation of an NMDA-type receptor which is sensitive to MK-801, but that Fos’s immunoreactivity in one portion of theSCN is induced by a mechanism which is not antagonized byMK-801.
TL;DR: The present studies suggest that the PVN, which represents the predominant hypothalamic nucleus controlling the response of the HPA axis to a number of stimuli, does not appear to be necessary for the antireproductive effects of intermittent footshock or immune activation.
Abstract: The documented ability of physical stress and cytokines to increase the secretion of corticotropin-re lea sing factor CRF by the paraventricular nucleus of the hypothalamus (PVN), coupled with our earlier demonstration that CRP acts within the brain to interfere with reproductive functions, led us to investigate the effect of lesions of the PVN on LH, testosterone, ACTH, and corticosterone (CORT) secretion. Bilateral lesions of the PVN were done electrolytically, and 2 weeks later a series of acute and chronic experiments were performed in intact or castrated male rats bearing indwelling jugular and/or intracerehroventricularcannulas. The first study involved a single 2-h exposure of intact male rats to footshocks (2 mA, 2-sec duration, 4 per min). Although PVN lesions did not measurably alter the ability of intermittent footshock to lower plasma testosterone levels, this treatment attenuated the rise in plasma ACTH and CORT. In a second study, which was done in castrated rata, shocks were delivered 2 h d...