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Showing papers on "Hypothalamus published in 1992"


Journal ArticleDOI
TL;DR: The main regulation of the thyroid gland involves a positive control by pituitary TSH, which is generated in these cells from plasma T4 (1, 2) as discussed by the authors.
Abstract: I. Introduction IN classical physiology, the main regulation of the thyroid gland involves a positive control by pituitary TSH. The pituitary thyrotrophs that synthesize and secrete TSH are submitted to tonic stimulation by the hypothalamic TRH and to negative feedback by T3, which is generated in these cells from plasma T4 (1, 2). The predominant role of TSH in thyroid regulation is exemplified by physiological experiments and pathological situations. Hypophysectomy, or treatment with thyroid hormones that reduces plasma TSH levels without interfering with other pituitary functions, almost abolishes thyroid function and greatly reduces the weight and cell mass of the gland. Conversely, chronic inhibition of the synthesis of thyroid hormones, and thus of their secretion, which greatly enhances TSH plasma levels, enhances thyroid growth and iodine metabolism upstream from the inhibited step. In pathology, hyperthyrotropinemia caused by pituitary adenomas induces hyperthyroidism and goiter. Hypopituitarism ...

616 citations


Journal ArticleDOI
TL;DR: The projections of the ventral subiculum are organized differentially along the dorsoventral (or septotemporal) axis of this cortical field, with more ventral regions playing a particularly important role in hippocampal communication with the amygdala, bed nuclei of the stria terminalis, and rostral hypothalamus.
Abstract: The projections of the ventral subiculum are organized differentially along the dorsoventral (or septotemporal) axis of this cortical field, with more ventral regions playing a particularly important role in hippocampal communication with the amygdala, bed nuclei of the stria terminalis (BST), and rostral hypothalamus. In the present study we re-examined the projection of the ventral subiculum to these regions with the Phaseolus vulgaris leucoagglutinin (PHAL) method in the rat. The results confirm and extend earlier conclusions based primarily on the autoradiographic method. Projections from the ventral subiculum course either obliquely through the angular bundle to innervate the amygdala and adjacent parts of the temporal lobe, or follow the alveus and fimbria to the precommissural fornix and medial corticohypothalamic tract. The major amygdalar terminal field is centered in the posterior basomedial nucleus, while other structures that appear to be innervated include the piriformamygdaloid area, the posterior basolateral, posterior cortical, posterior, central, medial, and intercalated nuclei, and the nucleus of the lateral olfactory tract. Projections from the ventral subiculum reach the BST mainly by way of the precommissural fornix, and provide rather dense inputs to the anterodorsal area as well as the transverse and interfascicular nuclei. The medial corticohypothalamic tract is the main route taken by fibers from the ventral subiculum to the hypothalamus, where they innervate the medial preoptic area, "shell" of the ventromedial nucleus, dorsomedial nucleus, ventral premammillary nucleus, and cell-poor zone around the medial mammillary nucleus. We also observed a rather dense terminal field just dorsal to the suprachiasmatic nucleus that extends dorsally and caudally to fill the subparaventricular zone along the medial border of the anterior hypothalamic nucleus and ventrolateral border of the paraventricular nucleus. The general pattern of outputs to the hypothalamus and septum is strikingly similar for the ventral subiculum and suprachiasmatic nucleus, the endogenous circadian rhythm generator.

524 citations


Journal ArticleDOI
TL;DR: New studies in rat pups demonstrate that central OT selectively decreases the separation response, an effect which mimics social contact, and demonstrate that physiologic changes in gonadal steroids can alter receptor expression in anatomically discrete target fields and thereby direct responsiveness to endogenous neuropeptide release.

467 citations


Journal ArticleDOI
Akira Arimura1
TL;DR: Immunohistochemical study indicated that PACAP containing neural fibers are present throughout the brain, including both internal and external zones of the median eminence, in the hypothalamus and the supraoptic nucleus in various species.

458 citations


Journal ArticleDOI
TL;DR: The results suggest that olfactory inputs, possibly of vomeronasal origin, contribute to the activation of c-fos in the medial amygdala, and that afferent inputs from the central tegmental field and from the medial amy interact to promote cellular activity, and the resultant induction of c.fos, in the ipsilateral bed nucleus of the stria terminalis and medial preoptic area.

340 citations


Journal ArticleDOI
TL;DR: The present evidence suggests that, whereas MAO-A is found in noradrenergic and adrenergic neurons,MAO-B occurs in astrocytes, serotoninergic neuron, as well as ventricular cells, including most circumventricular organs.
Abstract: Monoamine oxidases A and B (MAO-A and MAO-B) oxidatively deaminate neurotransmitter and xenobiotic amines. Since the cellular localization of the isoenzymes in the CNS and peripheral organs determines to a large extent which substrate has access to which isoenzyme, knowledge of their tissue distribution and cellular localization is essential. Here we describe how reversible and selective inhibitors of MAO-A and MAO-B [Ro 41-1049 and Ro 19-6327 (lazabemide), respectively] can be used, as tritiated radioligands, to map the distribution and abundance of the enzymes in microscopic regions of the rat CNS and peripheral organs, and human brain by quantitative enzyme radioautography. The in vitro binding characteristics of both radiolabeled inhibitors revealed them to be selective, high-affinity ligands for the respective enzymes. KD and Bmax values for 3H-Ro 41-1049 in rat cerebral cortex were 10.7 nM and 7.38 pmol/mg protein, respectively, and for 3H-Ro 19-6327 were 18.4 nM and 3.45 pmol/mg protein, respectively. In accordance with their potencies as enzyme inhibitors, binding to MAO-A and MAO-B was competitively inhibited by clorgyline (IC50 = 1.4 nM) and L-deprenyl (selegiline; IC50 = 8.0 nM), respectively. The capacities of various rat and human tissues to bind the radioligands correlated extremely well with their corresponding enzyme activities. As revealed by the respective binding assays, the distribution and abundance of MAO-A and MAO-B in the tissues investigated differed markedly. MAO-A was most abundant in the locus coeruleus, paraventricular thalamus, bed nucleus of the stria terminalis, median habenular nucleus, ventromedial hypothalamus, raphe nuclei, solitary tract nucleus, inferior olives, interpeduncular nucleus, claustrum, and numerous peripheral tissues, including liver, vas deferens, heart, superior cervical ganglion, and exocrine and endocrine pancreas. In contrast, MAO-B was most abundant in the ependyma, circumventricular organs, olfactory nerve layer, periventricular hypothalamus, cingulum, hippocampal formation, raphe nuclei, paraventricular thalamus, mammillary nuclei, cerebellar Bergmann glia cells, liver, posterior pituitary, renal tubules, and endocrine pancreas. The cellular localization of the isoenzymes in both rat and human brain differs markedly and does not reflect the distribution of the presumed natural substrates, for example, absence of MAO-A in serotoninergic neurons. Indeed, the present evidence suggests that, whereas MAO-A is found in noradrenergic and adrenergic neurons, MAO-B occurs in astrocytes, serotoninergic neurons, as well as ventricular cells, including most circumventricular organs. The physiological roles of the enzymes are discussed in the light of these findings, some of which were unexpected.(ABSTRACT TRUNCATED AT 400 WORDS)

319 citations


Journal ArticleDOI
TL;DR: Understanding of how the central nervous system transduces information about nutritional status into neuroendocrine signals that control reproduction in cattle and sheep is limited by a lack of information concerning the nature of neurons controlling LHRH release in these species.
Abstract: Prolonged restriction of dietary energy delays onset of puberty, disrupts cyclicity in sexually mature animals, and lengthens the postpartum anestrous period in domestic ruminants One important mechanism by which energy restriction impairs reproductive activity seems to be suppression of the increase in LH pulse frequency that is necessary for growth of ovarian follicles to the preovulatory stage Under-nutrition apparently inhibits pulsatile secretion of LH by reducing LHRH secretion by the hypothalamus The ability of an animal to sustain a high-frequency mode of pulsatile LH release is related to its metabolic status Mechanisms linking metabolic status to LHRH secretion have not been fully characterized Changes in body fat have been associated with changes in reproductive activity, but it is unlikely that body fat per se regulates LHRH secretion It is possible that pulsatile LHRH release is regulated by specific metabolites and(or) metabolic hormones that reflect nutritional status Alternatively, availability of oxidizable metabolic fuels, such as glucose and nonesterified fatty acids, may influence activity of neurons that control LHRH release Our understanding of how the central nervous system transduces information about nutritional status into neuroendocrine signals that control reproduction in cattle and sheep is limited by a lack of information concerning the nature of neurons controlling LHRH release in these species

292 citations


Journal ArticleDOI
TL;DR: It is indicated that CRF-BP is expressed predominantly in the cerebral cortex, including all major archi-, paleo-, and neocortical fields, and could serve to modify the actions of CRF by intra- and intercellular mechanisms, inCRF-related pathways in the central nervous system and pituitary.
Abstract: In recent studies to clone and characterize genes coding for the corticotropin-releasing factor-binding protein (CRF-BP), analysis of the tissue distribution of the CRF-BP gene indicated a high level of expression in the rat brain. We have now characterized by immunohistochemical and hybridization histochemical means the cellular localization of CRF-BP protein and mRNA expression, respectively. Results from both approaches converged to indicate that CRF-BP is expressed predominantly in the cerebral cortex, including all major archi-, paleo-, and neocortical fields. Other prominent sites of mRNA and protein expression include subcortical limbic system structures (amygdala, bed nucleus of the stria terminalis), sensory relays associated with the auditory, olfactory, vestibular, and trigeminal systems, severe raphe nuclei, and a number of cell groups in the brainstem reticular core. Expression in the hypothalamus appears largely limited to the ventral premammillary and dorsomedial nuclei; only isolated CRF-BP-stained cells are apparent in neurosecretory cell groups. Dual immunostaining for CRF and CRF-BP revealed a partial colocalization in some of these regions. In addition, prominent CRF-BP-stained terminal fields have been identified in association with CRF-expressing cell groups in circumscribed hypothalamic and limbic structures. In the anterior pituitary, CRF-BP mRNA and immunoreactivity were colocalized with corticotropin-immunoreactivity in a majority of corticotropes. Thus, CRF-BP could serve to modify the actions of CRF by intra- and intercellular mechanisms, in CRF-related pathways in the central nervous system and pituitary.

288 citations


01 Jan 1992
TL;DR: Neurochemical data indicate that high alcohol-seeking behavior is associated with lower contents of 5-HT in certain limbic regions, while neuronal tolerance to alcohol appears to develop in both these monoamine pathways, and an attenuated effect on metabolite levels by a challenge dose of ethanol given to P rats that had been chronically drinking alcohol.
Abstract: Neurochemical and neuropharmacological studies were undertaken to assess the involvement of CNS serotonin (5-HT), dopamine (DA) and GABA systems in regulating the alcohol-drinking behavior of two lines of rats selectively bred for their high alcohol-seeking behavior, namely the alcohol-preferring P line and the high alcohol-drinking HAD line of rats. Neurochemical data indicate that high alcohol-seeking behavior (when compared with data from rats with low alcohol-seeking characteristics) is associated with: a) lower (10-20%; p less than 0.05) contents of 5-HT in certain limbic regions (e.g., nucleus accumbens, frontal cortex, hypothalamus and hippocampus); b) a lower (10-15%; p less than 0.05) content of DA in the nucleus accumbens; c) higher (20-35%; p less than 0.05) densities of 5-HT1A binding sites in some limbic regions (e.g., medial nucleus accumbens, medial prefrontal cortex and ventral hippocampus); and d) a greater (20-50%) density of GABA axon terminals in the nucleus accumbens. Furthermore, the acute administration of high doses of ethanol appears to increase the activity of the 5-HT and DA projections to the nucleus accumbens of the P line of rats (as indicated by the 20-30% elevated tissue levels of 5-HT and DA metabolites following IP ethanol administration); neuronal tolerance to alcohol appears to develop in both these monoamine pathways, as suggested by an attenuated effect on metabolite levels by a challenge dose of ethanol given to P rats that had been chronically drinking alcohol.(ABSTRACT TRUNCATED AT 250 WORDS)

282 citations


Journal ArticleDOI
TL;DR: A brief history of Corticotropin-Releasing Hormone (CRH) and Vasopressin as Mediators of Pituitary-Adrenal Activation in Humans and their role in regulating anterior pituitary function is presented.
Abstract: I. A Brief History of Corticotropin-Releasing Hormone (CRH) and Vasopressin as Mediators of Pituitary-Adrenal Activation in Humans HARRIS' 1948 hypothesis (1) that anterior pituitary function is regulated by hypothalamic factors released into and carried by the hypothalamic-hypophysial portal blood to the adenohypophysis was not lost upon clinical investigators. Soon thereafter G. W. Liddle, for example, referred to this regulatory influence of the central nervous system as the “pituitary driving mechanism” (2), recognizing that such a mechanism was essential for explaining the diurnal rhythm in pituitary-adrenal axis function and its response to stress. According to this concept, the pituitary driving mechanism was the variable force against which cortisol exerted its negative feedback inhibitory action on ACTH secretion. Long before CRH [ovine CRH (oCRH) mol wt = 4671; human CRH (hCRH) mol wt = 4758] was isolated, characterized, and synthesized (3), vasopressin [either arginine vasopressin (AVP) or lysi...

281 citations


Journal ArticleDOI
TL;DR: It is shown that the sexually dimorphic neurotensin neurons in the preoptic area possess oestrogen receptors and that female rats have larger number of neurons co-localizing neurotens in and oestrogens receptors.

Journal ArticleDOI
01 May 1992-Peptides
TL;DR: The results suggest the amygdala and the bed nucleus of the stria terminalis are a major forebrain source of CRF, neurotensin, somatostatin, and substance P terminals in the midbrain central gray.

Journal ArticleDOI
TL;DR: In situ hybridization histochemistry was used to examine the effects of short-term and long-term administration of 3 different classes of activating antidepressant drugs which tend to be preferentially effective in treating atypical depressions, on the expression of central nervous system genes thought to be dysregulated in major depression.

Journal Article
TL;DR: A review of the literature reveals that NPY may modulate the secretion of other pituitary hormones through a similar combination of hypothalamic and pituitaries actions, and is integrated into an overall hypothesis for induction of the preovulatory LH surge on proestrus requiring an interplay between NPY and other neuronal networks.

Journal ArticleDOI
21 Feb 1992-Science
TL;DR: In Brattleboro rats, injection into the hypothalamus of purified mRNAs from normal rat hypothalami or of synthetic copies of the vasopressin mRNA leads to selective uptake, retrograde transport, and expression of vasoppressin exclusively in the magnocellular neurons.
Abstract: Messenger RNAs occur within the axons of magnocellular hypothalamic neurons known to secrete oxytocin and vasopressin. In Brattleboro rats, which have a genetic mutation that renders them incapable of vasopressin expression and secretion and thus causes diabetes insipidus, injection into the hypothalamus of purified mRNAs from normal rat hypothalami or of synthetic copies of the vasopressin mRNA leads to selective uptake, retrograde transport, and expression of vasopressin exclusively in the magnocellular neurons. Temporary reversal of their diabetes insipidus (for up to 5 days) can be observed within hours of the injection. Intra-axonal mRNAs may represent an additional category of chemical signals for neurons.

Journal ArticleDOI
TL;DR: It is demonstrated, for the first time, that androgen receptors can be detected by immunocytochemistry in the avian brain and the results are in general agreement with the binding data obtained by autoradiography with tritiated dihydrotestosterone.
Abstract: The distribution of androgen receptors was studied in the brain of the Japanese quail (Coturnix japonica), the zebra finch (Taeniopygia guttata), and the canary (Serinus canaria) by immunocytochemistry with a polyclonal antibody (AR32) raised in rabbit against a synthetic peptide corresponding to a sequence located at the N-terminus of the androgen receptor molecule. In quail, androgen receptor-immunoreactive cells were observed in the nucleus intercollicularis and in various nuclei of the preoptic-hypothalamic complex, namely, the nucleus preopticus medialis, the ventral part of the nucleus anterior medialis hypothalami, the nucleus paraventricularis magnocellularis, the nucleus ventromedialis hypothalami, and the tuberal hypothalamus. In the two songbird species, labeled cells were also observed in various nuclei in the preoptic-hypothalamic region, in the nucleus taeniae, and in the nucleus intercollicularis. Additional androgen receptor-immunoreactive cells were present in the androgen-sensitive telencephalic nuclei that are part of the song control system. These immunoreactive cells filled and outlined the boundaries of the hyperstriatum ventrale, pars caudalis, nucleus magnocellularis neostriatalis anterioris (both in the lateral and medial subdivisions), and nucleus robustus archistriatalis. The immunoreactive material was primarily present in cell nuclei but a low level of immunoreactivity was also clearly detected in cytoplasm in some brain areas. These studies demonstrate, for the first time, that androgen receptors can be detected by immunocytochemistry in the avian brain and the results are in general agreement with the binding data obtained by autoradiography with tritiated dihydrotestosterone. Immunocytochemical methods offer several advantages over autoradiography and their use for the study of the androgen receptor will greatly facilitate the analysis of steroid-sensitive systems in the avian brain.

Journal ArticleDOI
TL;DR: The present results imply that the SCN can influence the daily corticosterone rhythm through its VP-containing projection to the paraventricular/dorsomedial nucleus of the hypothalamus.

Journal ArticleDOI
TL;DR: The results of these studies demonstrate that estrogen receptor mRNA levels are sexually dimorphic, vary during the estrous cycle, and increase after ovariectomy, and suggest that factors other than endogenous estrogen levels differentially modulate estrogen receptor RNA expression in the hypothalamus.
Abstract: Variations in levels of estrogen receptor mRNA were investigated in the medial preoptic nucleus, arcuate nucleus, and ventromedial nucleus of the hypothalamus throughout the phases of the female estrous cycle and compared with those in ovariectomized female and intact male rats. Female Wistar rats were killed during estrus, metestrus, diestrus, or proestrus or 72 h after ovariectomy as were a group of intact male rats. Brains were removed and frozen, and 20-microns cryostat sections were thaw-mounted onto slides and hybridized with a 35S-labeled antisense estrogen receptor probe. Section-mounted slides were processed, apposed to x-ray film, then dipped in liquid emulsion, and quantified. After exposure, estrogen receptor mRNA was detected in several brain regions, including the medial preoptic nucleus, arcuate nucleus, and ventromedial nucleus of the hypothalamus. Estrogen receptor mRNA levels in the medial preoptic nucleus were highest during estrus and metestrus, attenuated at diestrus, and low during proestrus. In contrast, the hybridization signal in the arcuate and ventromedial nuclei was low during estrus and then gradually increased throughout the cycle until it peaked during proestrus. Ovariectomized females exhibited an elevated level of estrogen receptor mRNA in all brain regions investigated. Hybridization signal in male medial preoptic nucleus and ventromedial nucleus was reduced compared with those in both intact and ovariectomized females. Estrogen receptor mRNA levels in the arcuate nucleus were similar to those in intact females, but less than those in ovariectomized animals. The results of these studies demonstrate that estrogen receptor mRNA levels are sexually dimorphic, vary during the estrous cycle, and increase after ovariectomy. Furthermore, these results indicate that the magnitude and direction of change observed during the estrous cycle are region specific and suggest that factors other than endogenous estrogen levels differentially modulate estrogen receptor mRNA expression in the hypothalamus.

Journal ArticleDOI
TL;DR: In situ hybridization histochemistry showed high levels of V1aR transcripts in the liver and the renal medulla among the vascular bundles, and subcloned DNA fragments containing the region encoding the putative 5/6 transmembrane loops of these receptors demonstrated that kidney expresses mRNAs encoding V 1a and V2 vasopressin receptors.
Abstract: The hepatic, vascular-type (V1aR) and the renal, antidiuretic-type (V2R) vasopressin receptor cDNAs were recently cloned from rat liver and kidney libraries, respectively. DNA fragments containing the region encoding the putative 5/6 transmembrane loops of these receptors were subcloned, separately, into RNA polymerase promoter-containing vectors from which 35S-labeled sense and antisense riboprobes were synthesized. In situ hybridization histochemistry showed high levels of V1aR transcripts in the liver and the renal medulla among the vascular bundles. Sparser labeling was found in the renal cortex, but there were no grains over the glomeruli. V1aR mRNA was detected in many brain areas, including the hippocampal formation, central amygdala, dorsolateral septum, lateral hypothalamus, suprachiasmatic, ventromedial, dorsomedial, and arcuate nuclei of the hypothalamus, nucleus of the solitary tract, cerebellum, spinal nucleus of the trigeminal tract, reticular formation, inferior olivary nucleus, and choroid...

Journal ArticleDOI
TL;DR: The time course of the neuroendocrine response of Piebald-Viral-Glaxo (PVG) rats during the development of mycobacterially induced adjuvant arthritis is determined and a common paradox of a marked increase in adenohypophyseal POMC mRNA not associated with increased CRF mRNA or peptide release is shown.
Abstract: We have determined the time course of the neuroendocrine response of Piebald-Viral-Glaxo (PVG) rats during the development of mycobacterially induced adjuvant arthritis. Anterior pituitary POMC mRNA increased at the time of onset of mycobacterially induced arthritis, but, paradoxically, coincident with the first signs of arthritis there was a consistent fall in CRF mRNA in the hypothalamic paraventricular nucleus. Coincident with this fall in CRF message, there was a corresponding decrease in CRF-41 peptide release into the hypophysial portal blood (HPB). In contrast, however, vasopressin release into the HPB was increased. There was an increase in adrenal weight associated with the development of arthritis, reflecting chronic activation of the HPA axis, which was reflected by increased circulating corticosterone concentrations. The synthetic adjuvant CP20961, which has different antigenic determinants, also caused an increase in POMC mRNA in the anterior pituitary, a decrease in CRF mRNA in the hypothala...

Journal ArticleDOI
01 Oct 1992-Neuron
TL;DR: Results suggest that TGF-alpha of glial origin is a component of the developmental program by which the brain controls mammalian sexual maturation.

Journal ArticleDOI
TL;DR: The evidence suggests that the ventral premammillary nucleus receives two major inputs‐one from the sexually dimorphic circuit, and the other from the blood in the form of gonadal steroid hormones‐and gives rise to two major outputs: one (perhaps feed‐forward) to the neuroendocrine zone of the hypothalamus, and
Abstract: The projections of the ventral premammillary nucleus (PMv) have been examined with the Phaseolus vulgaris leucoagglutinin (PHAL) method in adult male rats. The results indicate that the nucleus gives rise to two major ascending pathways and a smaller descending pathway. One large ascending pathway terminates densely in most regions of the periventricular zone of the hypothalamus, with the notable exception of the suprachiasmatic, suprachiasmatic preoptic, and median preoptic nuclei. This pathway is in a position to influence directly many cell groups known to regulate anterior pituitary function. The second large pathway ascends through the medial zone of the hypothalamus and densely innervates the ventrolateral part of the ventromedial nucleus and adjacent basal parts of the lateral hypothalamic area, medial preoptic nucleus, principal nucleus of the bed nuclei of the stria terminalis, ventral lateral septal nucleus, posterodorsal part of the medial nucleus of the amygdala, posterior nucleus, and immediately adjacent regions of the posterior cortical nucleus of the amygdala. It is already known that these regions are major components of the sexually dimorphic circuit, and, interestingly, that they provide the major neural inputs to the PMv. The smaller descending projection from the PMv seems to innervate preferentially the posterior hypothalamic nucleus, although a small number of fibers appear to end in the tuberomammillary nucleus, supramammillary nucleus, specific regions of the medial mammillary nucleus, interfascicular nucleus, interpeduncular nucleus, periaqueductal gray, dorsal nucleus of the raphe, laterodorsal tegmental nucleus, Barrington's nucleus, and locus coeruleus. Relatively sparse terminal fields associated with ascending fibers were also observed in the dorsomedial nucleus of the hypothalamus; in the nucleus reuniens, parataenial nucleus, paraventricular nucleus of the thalamus, and mediodorsal nucleus; in the central nucleus of the amygdala, anterodorsal part of the medial nucleus of the amygdala, posterior part of the basomedial nucleus of the amygdala; and in the ventral subiculum and adjacent parts of hippocampal field CA1, and the infralimbic and prelimbic areas of the medial prefrontal cortex. Taken as a whole, the evidence suggests that the PMv receives two major inputs--one from the sexually dimorphic circuit, and the other from the blood in the form of gonadal steroid hormones--and gives rise to two major outputs: one (perhaps feed-forward) to the neuroendocrine (periventricular) zone of the hypothalamus, and the other (perhaps feed-back) to the sexually dimorphic circuit.

Journal ArticleDOI
TL;DR: Results demonstrate that repeated stress activates AVP synthesis in CRF neurons, which leads to a 5-fold elevation in the number of AVP containing CRF cell bodies.

Journal ArticleDOI
TL;DR: The results suggest that neurons may use prostaglandins as intracellular or perhaps paracrine, but probably not synaptic, mediators in the normal brain.
Abstract: Evidence from tissue culture studies suggests that glial cells are the principal source of prostaglandins in the brain. We have used immunohistochemistry, Western blot analysis, and enzyme activity assays to localize cyclooxygenase (COX), the enzyme responsible for the conversion of arachidonic acid to prostaglandins, in situ in the normal ovine brain. We observed very few immunoreactive glial cells. In contrast, an extensive distribution of COX-like immunoreactive (ir) neuronal cell bodies and dendrites and a corresponding pattern of COX enzyme activity were observed. COXir neurons were most abundant in forebrain sites involved in complex, integrative functions and autonomic regulation such as the cerebral cortex, hippocampus, amygdala, bed nucleus of the stria terminalis, substantia innominata, dorsomedial nucleus of the hypothalamus, and tuberomammillary nucleus. Moderate populations were observed in other regions of the central nervous system implicated in sensory afferent processing, including the dorsal column nuclei, spinal trigeminal nucleus, and superior colliculus, and in structures involved in autonomic regulation, such as the nucleus of the solitary tract, parabrachial nucleus, and the periaqueductal gray matter. We did not observe COXir axons or terminal fields, however. Our results suggest that neurons may use prostaglandins as intracellular or perhaps paracrine, but probably not synaptic, mediators in the normal brain.

Journal Article
Fuller Rw1
TL;DR: Measurement of ACTH or cortisol levels in humans after administration of a direct- or indirect-acting serotonin agonist provides one means of probing the functional state of brain serotonergic systems in disease or after drug treatment.

Journal ArticleDOI
TL;DR: Growth hormone secretion by the pituitary gland is dependent on the dual regulation exerted by growth hormone-releasing hormone and somatostatin, which are the final integrative pathways for several signals reaching the hypothalamus.

Journal ArticleDOI
TL;DR: Male Wistar rats living in hierarchically structure male/female colonies were used to investigate the effects of chronic psychosocial stress on the hypothalamus-pituitary-adrenal system and subordinate rats showed suppressed hypothalamic, pituitary and adrenal responses to interaction with the dominant male, which may reflect suppressive actions of elevated corticosterone on CRF neurons or suprahypothalamic centers.
Abstract: Male Wistar rats living in hierarchically structure male/female colonies were used to investigate the effects of chronic psychosocial stress on the hypothalamus-pituitary-adrenal system. Colony-housed subordinates were compared to control rats housed in male-female pairs. Classical parameters of chronic stress (thymus involution, impaired somatic growth, and elevated resting plasma corticosterone level) were found in all subordinate rats. Changes in vasopressin (AVP) and CRF stored in the external zone of the median eminence (ZEME) were measured by quantitative immunocytochemistry. Chronic psychosocial stress for 19-28 days increased AVP immunostaining in the ZEME to 160-190% of that in pair-housed controls, whereas CRF immunostaining in the ZEME remained unchanged. Within colonies, subordinates differed in avoidance behavior and aggression received (subordinate status). This intracolony subordination rank was correlated with AVP in the ZEME (P less than 0.01). Although resting corticosterone was elevated in subordinate rats (P less than 0.01), the increase in AVP was not associated with detectable secretion of AVP and/or CRF from the ZEME, as measured after blockade of axonal transport. In control rats, interaction with a dominant male increased plasma ACTH and corticosterone levels and caused depletion of AVP, but not CRF, from the ZEME. Subordinates showed suppressed hypothalamic (AVP depletion), pituitary (plasma ACTH) and adrenal (plasma corticosterone) responses to interaction with the dominant male, which may reflect suppressive actions of elevated corticosterone on CRF neurons or suprahypothalamic centers.

Journal ArticleDOI
TL;DR: A possible regulatory role for serotonin is investigated by examining its effect, when applied at projection sites, on the circadian rhythm of neuronal activity in rat SCN in vitro and finding no effect on the timing of the electrical activity rhythm.
Abstract: 1. The suprachiasmatic nucleus (SCN) of the hypothalamus is the primary pacemaker for circadian rhythms in mammals. The 24 h pacemaker is endogenous to the SCN and persists for multiple cycles in the suprachiasmatic brain slice. 2. While serotonin is not endogenous to the SCN, a major midbrain hypothalamic afferent pathway is serotonergic. Within this tract the dorsal raphe nucleus sends direct projections to the ventrolateral portions of the SCN. We investigated a possible regulatory role for serotonin in the mammalian circadian system by examining its effect, when applied at projection sites, on the circadian rhythm of neuronal activity in rat SCN in vitro. 3. Eight-week-old male rats from our inbred colony, housed on a 12 h light: 12 h dark schedule, were used. Hypothalamic brain slices containing the paired SCN were prepared in the day and maintained in glucose and bicarbonate-supplemented balanced salt solution for up to 53 h. 4. A 10(-11) ml drop of 10(-6) M-serotonin (5-hydroxytryptamine (5-HT) creatinine sulphate complex) in medium was applied to the ventrolateral portion of one of the SCN for 5 min on the first day in vitro. The effect of the treatment at each of seven time points across the circadian cycle was examined. The rhythm of spontaneous neuronal activity was recorded extracellularly on the second and third days in vitro. Phase shifts were determined by comparing the time-of-peak of neuronal activity in serotonin- vs. media-treated slices. 5. Application of serotonin during the subjective day induced significant advances in the phase of the electrical activity rhythm (n = 11). The most sensitive time of treatment was CT 7 (circadian time 7 is 7 h after 'lights on' in the animal colony), when a 7.0 +/- 0.1 h phase advance was observed (n = 3). This phase advance was perpetuated on day 3 in vitro without decrement. Serotonin treatment during the subjective night had no effect on the timing of the electrical activity rhythm (n = 9). 6. The specificity of the serotonin-induced phase change was assessed by treating slices in the same manner with a microdrop of serotonergic agonists, 5-carboxamidotryptamine, that targets the 5-HT1 class of receptors, or 8-hydroxy-dipropylaminotetralin (8-OH DPAT), that acts on the 5-HT1A receptor subtype.(ABSTRACT TRUNCATED AT 400 WORDS)

Journal ArticleDOI
TL;DR: The current results imply that the dual effects of NPY on LH secretion may involve modulation of LHRH secretion, both by the direct route and indirectly through the hypothalamic beta END system.
Abstract: Central administration of neuropeptide-Y (NPY) inhibits pituitary LH release in ovariectomized rats and stimulates LH release in intact and ovariectomized rats pretreated with ovarian steroids. Although the precise neural mechanism of this dual effect of NPY is not known, experimental evidence suggests an underlying interaction between hypothalamic NPY and the inhibitory beta-endorphin (beta END) systems in the neuroendocrine regulation of pituitary LH release in the rat. The present study was undertaken to examine the morphological basis of the interaction between these two peptidergic systems in the hypothalamus. Sections of the mediobasal hypothalamus of colchicine-pretreated female rats were double immunostained for NPY and beta END and examined by light and electron microscopy. The light brown diaminobenzidine reaction was used to visualize beta END cells, while NPY neurons were labeled with a dark blue nickel ammonium sulfate-intensified diaminobenzidine reaction. Under the light microscope, a dense network of NPY-immunoreactive axons and axon terminals was observed in close apposition with beta END-immunoreactive neurons throughout the medial basal hypothalamus. Electron microscopic examination revealed that NPY-immunoreactive boutons formed axosomatic and axo-dendritic synaptic connections with beta END cells. A majority of these synaptic membrane specializations appeared asymmetrical [corrected]. In light of the previous evidence of excitatory and inhibitory effects on LH release and the existence of direct synaptic connections between NPY and LHRH neurons in the hypothalamus, the current results imply that the dual effects of NPY on LH secretion may involve modulation of LHRH secretion, both by the direct route and indirectly through the hypothalamic beta END system.

Journal ArticleDOI
TL;DR: It is demonstrated that increased expression of CRF mRNA is preceded by c-fos mRNA induction in the PVN after stress suggesting a role of c- fos in the activation ofCRF gene expression.
Abstract: CRF plays a role in coordinating endocrine, physiological, and behavioral responses to stressful stimuli. Several kinds of stressors have been reported to induce an increase in CRF mRNA expression in the paraventricular nucleus of the hypothalamus (PVN). Recently, the expression of c-fos mRNA has shown promise as a useful tool for metabolic mapping at the cellular level, because various types of stimulation induce c-fos mRNA expression in specific neuron populations in various brain regions. The aim of the present study is to clarify a possible anatomical-temporal correlation between the early induction of c-fos and the enhanced expression of CRF mRNA after stress. Wistar male rats were exposed to immobilization stress for 60 min and killed before and 15, 30, 60, 90, 120, and 180 min after the beginning of immobilization. In situ hybridization was performed by hybridizing sections with 35S-labeled prepro-CRF and c-fos cRNA probes. Relative levels of CRF and c-fos mRNA were compared by estimating the numbe...