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At least 793 records · Page 44Linked to original sources
PubMed1995

Control of luteinizing hormone-releasing hormone pulse generation in nonhuman primates.

1. The pulsatile release of luteinizing hormone-releasing hormone (LHRH) is critical for reproductive function. However, the exact mechanism of LHRH pulse generation is unclear. The purpose of this article is to review the current knowledge on LHRH pulse generation and to discuss a series of studies in our laboratory. 2. Using push-pull perfusion in the stalk-median eminence of the rhesus monkey several important facts have been revealed. There is evidence indicating that LHRH neurons themselves have endogenous pulse-generating mechanisms but that the pulsatility of LHRH release is also modulated by input from neuropeptide Y (NPY) and norepinephrine (NE) neurons. The release of NPY and NE is pulsatile, with their pulses preceding or occurring simultaneously with LHRH pulses, and the neuroligands NPY and NE and their agonists stimulate LHRH pulses, while the antagonists of the ligands suppress LHRH pulses. 3. The pulsatile release of LHRH increases during the estrogen-induced LH surge as well as the progesterone-induced LH surge. These increases are partly due to the stimulatory effects of estrogen and progesterone on NPY neurons. 4. An increase in pulsatile LHRH release occurs at the onset of puberty. This pubertal increase in LHRH release appears to be due to the removal of tonic inhibition from gamma aminobutyric acid (GABA) neurons and a subsequent increase in the inputs of NPY and NE neurons to LHRH neurons. 5. There are indications that additional neuromodulators are involved in the control of the LHRH pulse generation and that glia may play a role in coordinating pulses of the release of LHRH and neuromodulators. 6. It is concluded that the mechanism generating LHRH pulses appears to comprise highly complex cellular elements in the hypothalamus. The study of neuronal and nonneuronal elements of LHRH pulse generation may serve as a model to study the oscillatory behavior of neurosecretion.

Animals↗
PubMed1997

Vesicular neurotransmitter transporters. Potential sites for the regulation of synaptic function.

Neurotransmission depends on the regulated release of chemical transmitter molecules. This requires the packaging of these substances into the specialized secretory vesicles of neurons and neuroendocrine cells, a process mediated by specific vesicular transporters. The family of genes encoding the vesicular transporters for biogenic amines and acetylcholine have recently been cloned. Direct comparison of their transport characteristics and pharmacology provides information about vesicular transport bioenergetics, substrate feature recognition by each transporter, and the role of vesicular amine storage in the mechanism of action of psychopharmacologic and neurotoxic agents. Regulation of vesicular transport activity may affect levels of neurotransmitter available for neurosecretion and be an important site for the regulation of synaptic function. Gene knockout studies have determined vesicular transport function is critical for survival and have enabled further evaluation of the role of vesicular neurotransmitter transporters in behavior and neurotoxicity. Molecular analysis is beginning to reveal the sites involved in vesicular transporter function and the sites that determine substrate specificity. In addition, the molecular basis for the selective targeting of these transporters to specific vesicle populations and the biogenesis of monoaminergic and cholinergic synaptic vesicles are areas of research that are currently being explored. This information provides new insights into the pharmacology and physiology of biogenic amine and acetylcholine vesicular storage in cardiovascular, endocrine, and central nervous system function and has important implications for neurodegenerative disease.

Amino Acid Sequence↗
PubMed2001

SNAREs during development.

Soluble N-ethylmaleimide-sensitive factor attached protein receptor (SNARE) molecules are implicated in many fundamental cellular processes that require membrane fusion, and the interactions of the SNARE proteins, SNAP-25, syntaxin and VAMP/synaptobrevin, have been extensively studied. This review documents recent data on their role at different stages of development. SNARE proteins are expressed very early and play important roles in fertilization and in cell division during early embryogenesis. In the developing nervous system, they are important for neurite outgrowth and transformation of the growth cone into the mature synapse. In the neuroendocrine system, in addition to neurosecretion, they are involved in processes related to morphological plasticity. Although few data exist on regulation of SNARE proteins during development, growth factors, intracellular messengers and depolarization are known to modify their cellular expression. The putative importance of these factors during development is discussed.

Animals↗
PubMed2006

Treatment and prophylaxis of anthrax by new neurosecretory cytokines.

In 1881, Louis Pasteur described the Bacillus anthracis vaccine, which plays an important role for the treatment and prophylaxis of anthrax. Currently, treatment for anthrax infection involves the use of several different antibiotics, used in combination with vaccines, which possess potential virulence in white mice and guinea pigs. We discovered several new immunomodulators cytokines (polypeptides) produced by the neurosecretory cells of hypothalamus, some of which can be used as drugs for the treatment and prophylaxis of the anthrax. The proline-rich polypeptides, which consist from 10 to 15 amino acids and four proline residues, are of the special interest; one of them (PRP-1), which consist of 15 amino acids and has the following primary structure ALa-GLy-ALa-Pro-GLu-Pro-Ala-GLu-Pro-Ala-GLn-Pro-GLy-Val-Tyr (AGAPEPAEPAQPGVY) possesses antibacterial activity, and a new proline-rich peptide described by Galoyan and called Gx-NH2. Both were tested for treatment against the anthrax bacillus or anthrax strain N55 vaccine in guinea pigs and mice in vivo, and in vitro preparations. The results of experiments show that these hypothalamic neurosecretory cytokines have a strong prophylaxis and therapeutic properties towards animals infected by episodic strain of anthrax and anthrax vaccine N55. The conventional concepts concerning the function of hypothalamic neurosecretion and hypothalamic mechanisms of adaptation have to be reconsidered.

Amino Acid Sequence↗
PubMed1981

A retinopetal nucleus in the preoptic area in a teleost, Navodon modestus.

Following horseradish peroxidase (HRP) applications to the optic nerve of a teleost (Navodon modestus), a retinopetal nucleus was identified in the contralateral preoptic area. The nucleus was composed of small (7-10 microns) round cells. Centrifugal fibers from the nucleus were traced to the inner nuclear layer of the ipsilateral retina by both orthograde HRP and Fink-Heimer methods. The cells in the nucleus showed no neurosecretion. The retinopetal nucleus or neurons could not be found in Carassius carassius. No retinopetal neurons were found in the optic tectum in both species.

Afferent Pathways↗
PubMed1982

Inhibition of dopamine release by melatonin: regional distribution in the rat brain.

Dopamine release evoked by electrical field stimulation of slices from various regions of rat brain was assessed in the presence of 10-10-10-5 M melatonin. Inhibition of dopamine release by melatonin was observed in the ventral hippocampus, medulla pons, preoptic area and median and posterior hypothalamus. No inhibitory effect of melatonin on dopamine release was observed in the cerebral cortex, cerebellum, dorsal hippocampus and striatum. Equal concentrations of melatonin were needed to produce half-maximal inhibition in all the regions affected. The results indicate that the brain sites for inhibitory effect of melatonin on dopamine neurosecretion overlap the sites reportedly involved in its modulation of neuroendocrine functions.

Animals↗
PubMed1982

Cultured neurones from the mature bovine mediobasal hypothalamus contain LHRH but not catecholamine.

The in vitro culture of mature neurones from bovine mediobasal hypothalamus (MBH) is reported, providing a model for studies of mammalian neurosecretion at the cellular level. Explant tissue cultures of mature bovine MBH containing the arcuate nucleus were examined for LHRH, ACTH and catecholamines with a view to investigating the control of prolactin and gonadotropin secretion. LHRH immunoreactivity was found in both neuronal and non-neuronal cells in the outgrowth monolayer region of the explant. Neurones in this region appeared able to attach to a substrate and regenerate, in monolayer culture, well developed neurites characterized by beaded swellings as observed in vivo. Neither ACTH immunoreactivity nor catecholamine fluorescence was detected. Cultured neurones and astrocytes were labelled by tetanus toxin and anti-GFAP, respectively. Double labelling of cultures with tetanus toxin and anti-LHRH demonstrated the neuronal nature of many LHRH-immunoreactive cells. Radio-immunoassay data confirmed the presence of LHRH in the cultures but application of 60 mM KC1 failed to evoke hormone release. These studies have confirmed the view of previous workers that hypothalamic control of prolactin secretion in the bovine may be very different from that thought to occur in non-ruminants such as the rat and guinea pig. Finally, this work demonstrates that a cultured system from the mature bovine may prove a good model for study of neuronal regulation of gonadotropin secretion by the bovine mediobasal hypothalamus.

Adrenocorticotropic Hormone↗
PubMed1985

Electron microscopic examination of the catecholaminergic innervation of neurophysin- or vasopressin-containing neurons in the rat hypothalamus.

The ultrastructural relationships between neurophysin (NP)- or vasopressin (VP)-containing neurons and catecholamine terminals in the paraventricular nucleus and supraoptic nucleus of the rat were observed by means of a technique combining immunocytochemistry using NP I/II or VP antiserum with autoradiography after [3H]noradrenaline (NA) injection or 5-hydroxydopamine (5-OHDA) uptake. NP- or VP-like immunoreactive nerve cell bodies and fibers received synaptic contacts from a large number of immunonegative axon terminals. The presynaptic elements that innervate the neurosecretory neurons were studied. Axon terminals labeled with [3H]NA or 5-OHDA made synaptic contacts with NP- or VP-like immunoreactive nerve cell bodies and fibers. Furthermore, axodendritic and/or axo/axonic and axosomatic synapses occurred between the same NP- or VP-like immunoreactive neurons. These findings suggest that at least NA- and 5-OHDA-containing neurons play some important role in the control of neurosecretion in the NP- or VP-producing neurons of the rat hypothalamus and that the axon collaterals of NP- and VP-containing neurons make synaptic contacts with the same kind of neurons to form a recurrent collateral circuit.

Animals↗
PubMed1986

Discordant changes between immunoreactive ACTH and beta-endorphin in rat brain and pituitary during early development.

UNLABELLED: Discordant changes in brain concentrations of immunoreactive (IR-) adrenocorticotropic hormone (ACTH) or beta-endorphin, peptides derived from pro-opiomelanocortin (POMC), have been reported during the latter part of development and with subsequent aging. These changes were believed to be due to age-related alterations in the regulation of metabolism of POMC-related peptides. However, concentrations of IR-ACTH and IR-beta-endorphin have not been simultaneously studied during early development when many changes in brain development and behavior are occurring. To determine whether concentrations of IR-ACTH and IR-beta-endorphin change during early development and whether changes are discordant, concentrations of IR-ACTH and IR-beta-endorphin were measured in several brain regions and pituitary in rats at 10, 29 and 80 days after birth. Whereas IR-ACTH in extrahypothalamic brain increased at day 29, and decreased at day 80, it did not change in hypothalamus and pituitary. Between day 10 and 29, IR-beta-endorphin rose in all brain regions, but subsequent changes in different tissues were variable at day 80. Because concentration changes can be mediated by alterations in one or more regulatory mechanisms, chromatographic profiles of hypothalamus and amygdala and molar ratios of all tissues were subsequently studied to give further insight into the mechanisms of the discordant changes. Molecular profiles of hypothalamic IR-ACTH and amygdalar IR-beta-endorphin exhibited lesser proportions of large molecular forms and greater proportions of ACTH and beta-endorphin during development. Molar ratios of IR-ACTH/IR-beta-endorphin in all tissues and ratios of ACTH1-39/beta-endorphin in hypothalamus and amygdala changed during development. CONCLUSIONS: (1) changes in IR-ACTH and IR-beta-endorphin occur in rat pituitary and several brain regions at different ages during early development and are frequently discordant; (2) molecular profiles suggested that the activity of processing enzymes for POMC and its derivatives vary in hypothalamus and amygdala with respect to type of derivative, brain region, and developmental age; and (3) changes in some molecular profiles and changes in molar ratios of IR-ACTH/IR-beta-endorphin and ratios of ACTH1-39/beta-endorphin suggest that changes in processing and possibly changes in neurosecretion and degradation contribute to concentration changes independent of possible alterations in biosynthesis of POMC.

Adrenocorticotropic Hormone↗
PubMed1986

Binding of 125I-cholecystokinin-octapeptide in the paraventricular but not the supraoptic nucleus is increased by ovariectomy.

Specific, high affinity binding of 125I-cholecystokinin-octapeptide (CCK) in the paraventricular nucleus was found to be confined to the anterior pole of the posterior magnocellular subdivision (PVHpm). Tissue sampled from intact male and female rats revealed only low CCK binding in the PVHpm; however, binding was greatly increased by ovariectomy. By contrast, binding was uniformly high throughout the supraoptic nucleus of intact males and females and was unaffected by ovariectomy. These results are interpreted in terms of the potential influence of CCK and estrogen on neurosecretion of oxytocin and CCK.

Animals↗
PubMed1992

A selective sexually dimorphic response in the median eminence neuropeptide Y.

Recent studies show that neuropeptide Y (NPY) is widely distributed in the hypothalamus and that it stimulates luteinizing hormone-releasing hormone (LHRH) release from the medial basal hypothalamus (MBH) of male and female rats. The neuroendocrine factors that regulate NPY neurosecretion in two sexes are not well understood. We have previously observed that orchidectomy (orch) in male rats decreased and testosterone (T) replacement increased NPY levels selectively in the median eminence (ME), arcuate nucleus (ARC) and ventromedial nucleus (VMN) and the KCl-evoked in vitro release of NPY from the MBH was likewise decreased after orch and restored by testosterone replacement. Now we report that these NPY responses are different in female rats following removal of the ovaries. Ovariectomy (ovx) decreased NPY concentrations in the ARC and VMN and not in the ME. Estrogen replacement restored NPY concentrations in the ARC and VMN, however, in the ME NPY concentration decreased significantly. Further, the KCl-evoked NPY release in vitro from either the MBH or ME of intact and ovx rats was similar. In an additional concurrent comparative study in male and female rats, we observed that of the 6 microdissected hypothalamic sites, NPY levels were approximately 50% less in the ME of intact females than in those of intact male rats. Again, in male rats there was a significant decrease in NPY levels in the ME, ARC and VMN after orch, whereas in female rats, NPY levels in the ARC and VMN, but not in the ME decreased after ovx.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Characterization of neurochemical phenotypes in cultured hypothalamic neurons with immunohistochemistry and in situ hybridization.

The expression of neurochemical phenotypes was studied in long-term cultures of dissociated embryonic neurons from rat hypothalamus. With time in culture, these neurons establish a complex dendritic and axonal network, as indicated by staining with antibodies against microtubulin-associated protein (MAP2) and neurofilaments (SMI32 and SMI33) as well as GABA and glutamate decarboxylase mRNA immunoreactivity. Neurons expressing neuropeptide Y (NPY) mRNA and NPY peptide and opioid-like peptides as well as vasopressin were observed. Further, weakly acetylcholinesterase- and NADPH diaphorase (nitric-oxide synthase)-labelled neurons were present. In conclusion, the neurochemical phenotypes reported for hypothalamic neurons in vivo can be observed in these cultures. This indicates that the culture conditions allow morphological and molecular differentiation. These findings support the view that long-term hypothalamic cultures provide a valuable model for studying mechanisms of neurosecretion in hypothalamic networks.

Acetylcholinesterase↗
PubMed1995

The organisation of the axonal reticulum at a ligation, in in vitro incubated bovine splenic nerves.

From previous studies we concluded that in noradrenergic neurons the axonal reticulum can be considered to be an extension of the Golgi apparatus, directly involved in the condensation and packaging of neurosecretion. But the precise ultrastructure of the organisation of the axonal reticulum in relation to neurosecretory granule formation remained to be elucidaded. This conversion was studied in ligated bovine splenic nerve incubated in vitro for three hours. The ultrastructure of the material accumulating proximally and distally was examined and its nature was determined by phosphotungstic acid staining and immunocytochemistry on glycolmethacrylate sections. Proximal to the ligation predominantly electron-lucent vesicles and tubules were found. Tubules of intermediate electron density appeared in between. The latter, especially in thicker sections, were seen to form complexes with tubules and granules of high electron density. All those elements were shown to be positive for dopamine-beta-hydroxylase and cytochrome b561. In the distal part multivesicular bodies accumulated and they were also positive for both enzymes. From these findings it is concluded that the different types of structures accumulating proximally belong to a neurosecretory axonal reticulum. At a block the axonal reticulum is triggered to generate a reticular differentiation, in which granular densities of different size are found. This configuration compares well with that in nerve terminals and strongly suggests that granule formation is basically a local process.

Animals↗
PubMed1985

Phorbol ester and calcium act synergistically to enhance neurotransmitter release by brain neurons in culture.

Preincubation of intact fetal brain neurons in culture with the phorbol ester TPA (12-O-tetradecanoyl phorbol-13-acetate) in the presence of calcium, resulted in the enhancement of the depolarization-induced, Ca2+-dependent neurotransmitter release by the cells. This effect was due to a marked decrease in the concentration of extracellular Ca2+ required to provoke the release. The concentration of Ca2+ needed to produce half-maximal release shifted from approx 0.1 mM in the absence of TPA to 0.018 mM in its presence. This activity of TPA was concentration-dependent (half-maximal effect at 4 nM TPA) and was also dependent on the presence of calcium during the preincubation period. The TPA-induced enhancement of the stimulated release was also observed when Ca2+ entry into the depolarized cells was partially inhibited by Co2+. The results suggest that TPA acts synergistically with Ca2+ to activate neuronal component(s) involved in Ca2+-dependent neurosecretion.

Animals↗
PubMed1991

Identification of a peptide arising from the specific post-translation processing of secretogranin II.

The biological role of secrotogranin II is unknown but it has been suggested that the protein may function as a precursor of one or more biologically active neuroendocrine peptides. We have isolated a 33 amino acid-residue peptide from the brain of the frog Rana ridibunda that shows strong (82%) homology with human presecretogranin II-(182-204)-peptide. This region of secretogranin II has also been very strongly conserved in the rat and bovine proteins. Analysis of the nucleotide sequence of the mammalian secretogranin II cDNAs indicates that the peptide sequence is flanked by two Lys-Arg dibasic residue processing sites. It is proposed, therefore, that this fragment represents a specific product of the post-translational processing of secretogranin II and, by analogy with peptides derived from chromogranin A, may be important in the regulation of neurosecretion.

Amino Acid Sequence↗
PubMed1988

Gonadal steroids and neuropeptide Y-opioid-LHRH axis: interactions and diversities.

We report that the two classes of regulatory neuropeptides, neuropeptide Y (NPY) and endogenous opioid peptides (EOP), modulate luteinizing hormone (LH) release in diverse fashion in gonad-intact rats. Each neuropeptide acts at two loci, the hypothalamus and pituitary, to excite (NPY) or inhibit (EOP) LH release. At the hypothalamic level, NPY stimulates luteinizing hormone releasing hormone (LHRH) release, a response mediated by alpha 2-adrenoreceptors and amplified in the presence of adrenergic agonists. At the pituitary level, NPY acts in concert with LHRH to amplify the LH response. In contrast, EOP inhibit LHRH release by decreasing the supply of excitatory adrenergic signals in the vicinity of LHRH neurons in the preoptic-tuberal pathway, and at the pituitary level, they decrease LH release in response to LHRH. Further, the gonadal steroidal milieu facilitates NPY neurosecretion and postsynaptic expression of NPY in concert with adrenergic system; a similar clear-cut facilitatory effect of gonadal steroids on EOP secretion is not yet obvious. Our additional studies imply that the EOP system has the potential to increase sensitivity towards gonadal steroids and that to induce the preovulatory LH surge the neural clock may decrease the inhibitory EOP tone prior to the critical period on proestrus. This antecedent neural event allows the excitatory adrenergic and NPY signals to evoke LHRH secretion at a higher frequency approximating that seen in ovariectomized rats. Further studies are under way to delineate the steroid-induced subcellular events that integrate the action of these regulatory peptides in the control of the episodic LHRH secretion pattern which sustains basal and cyclic gonadotropin release in the rat.

Androgens↗
PubMed1992

MacMARCKS, a novel member of the MARCKS family of protein kinase C substrates.

MARCKS is a specific protein kinase C (PKC) substrate that binds both calmodulin and actin and is phosphorylated during phagocyte activation, neurosecretion, and growth factor-dependent mitogenesis. We report here on MacMARCKS, a MARCKS homolog, whose synthesis is dramatically increased in macrophages when these cells are exposed to bacterial lipopolysaccharide. We have purified rabbit MacMARCKS and cloned its cDNA from rabbit and mouse. The effector domains of MacMARCKS and MARCKS are nearly identical, and both proteins bind calmodulin in a phosphorylation-regulated manner. MacMARCKS and MARCKS also share a second, highly conserved region also found in the internalization domain of the mannose-6-phosphate receptor. Our data suggest the existence of a family of PKC substrates that are targeted to different subcellular locations and that function to integrate PKC and calcium/calmodulin-dependent signals in the control of the plastic actin cytoskeleton.

Actins↗
PubMed1989

Calcium signalling in non-excitable cells: notes on oscillations and store refilling.

Technical advances in studying cellular calcium concentrations, and discoveries about many aspects of signal transduction have transformed this field of biology since this Journal was launched a decade ago. At that time monitoring of the key variable, cytoplasmic free Ca2+ concentration [Ca2+]i, was possible with aequorin or arsenazo ill mainly in large invertebrate cells, though pioneering work with aequorin micro-injection into cardiac and smooth muscle had just started. At that time there was also intense activity by a few groups aiming to make Ca-selective micro-electrodes selective and sharp enough to measure [Ca2+]i in small cells. Also the use of electropermeabilized cells had begun to allow the defining of the concentrations of Ca2+ required to activate secretion in mammalian cells. Nearly all this work and all the relevant electrophysiology relating to calcium signalling had been done in excitable cells, basically muscle and nerve, and was aimed at understanding contraction, transmitter release and neurosecretion, and the control of membrane permeability. Recent advances have now allowed [Ca2+]i to be measured in non-excitable cells.

Benzofurans↗