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PubMed1988

Stimulated release of immunoreactive adrenocorticotropin and beta-endorphin from extrahypothalamic brain.

Although it has been suggested pro-opiomelancortin (POMC)-related peptides widely distributed throughout brain may be neurotransmitters or neuromodulators, little is known about their secretion from neurons because it is difficult to study neurosecretion in vivo. Previous work has shown that POMC-related peptides in hypothalamus may be released in response to potassium-induced depolarization. However, little attention has been directed toward studying secretion of POMC-related peptides in extrahypothalamic brain. To demonstrate the possibility that POMC peptides in extrahypothalamic brain may also be neuroregulators and can be released in response to a specific stimulus, the release of derivatives of POMC, immunoreactive (IR) adrenocorticotropic hormone (ACTH) and IR-beta-endorphin, from dissociated amygdala and cortical brain cells was studied in response to potassium-induced depolarization. Depolarizing concentrations of potassium in the presence of calcium stimulated significant increments in release of IR-ACTH/IR-beta-endorphin by amygdala (111/105%) and cortical (162/136%) cells. Stimulated release occurred following an experimental paradigm used to stimulate release of classical neurotransmitters and neuropeptides and suggested POMC-related peptides could be neuroregulators in extrahypothalamic brain.

Adrenocorticotropic Hormone↗
PubMed1989

Alterations in luteinizing hormone-releasing hormone release from the mediobasal hypothalamus of ovariectomized, steroid-primed middle-aged rats as measured by push-pull perfusion.

The spontaneous luteinizing hormone (LH) surge on proestrus as well as the steroid-induced LH surge and hypersecretion of LH following ovariectomy are attenuated in middle-aged female rats when compared to their young counterparts. It is generally assumed that the lower titers of serum LH measured in aging animals result, in part, from age-related alterations in luteinizing hormone-releasing hormone (LHRH) neurosecretion, yet no direct measurements of LHRH release from the hypothalamus of aging females are currently available. The present study utilized the push-pull perfusion technique to characterize and compare in vivo LHRH output from the mediobasal hypothalamus of ovariectomized middle-aged and young females during a steroid-induced LH surge. Twelve-minute perfusates were collected for a period of 6 h from middle-aged and young animals outfitted with push-pull cannulae resting in the mediobasal hypothalamus in close proximity to the median eminence. The overall pattern of LHRH release differed in the two age groups. Mean levels of LHRH measured in brain perfusates from middle-aged females were significantly lower than mean levels measured in young animals. Moreover, mean levels of LHRH detected in perfusates during the 1- and 2-hour intervals prior to and the 1-hour interval after the time of maximal LHRH output were lower in middle-aged animals, and a larger percentage of samples from middle-aged females contained levels of LHRH below the detectability of the assay. The mean amplitude of identified LHRH pulses and maximal LHRH output, however, did not differ in the two age groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1990

Synergistic interaction between opioid receptor blockade and alpha-adrenergic stimulation on luteinizing hormone-releasing hormone (LHRH) secretion in vitro.

The effects of opioid receptor blockade, alpha-adrenergic receptor stimulation and concomitant opioid blockade and adrenergic stimulation on LHRH neurosecretion was examined in tissue culture using perifused preoptic area-mediobasal hypothalamic (POA-MBH) explants. Blockade of opioid receptors using naloxone (NAL) resulted in increased (p less than 0.05) LHRH secretion from POA-MBH explants obtained from intact postpubertal female rats. After washout of the NAL-medium, basal release rate was reset to a lower baseline. Subsequent exposure of POA-MBH explants to phenylephrine (PHEN), an alpha-adrenergic agonist, resulted in a slight but statistically insignificant increase in LHRH release from adult explants. The attenuated response to PHEN may have been due to a sustained inhibition of LHRH release following the NAL exposure since PHEN not preceded by NAL resulted in a marked stimulation of LHRH release. In three separate experiments, the LHRH response in postpubertal rat explants to simultaneous PHEN and NAL was greater and more prolonged than the responses to either of the substances alone. This study demonstrates that the stimulatory effects of PHEN are much more profound in the presence of opioid receptor blockage. The observations of the stimulatory effects of PHEN and NAL potentiating each other also suggest that separate mechanisms of LHRH control by each class of neurotransmitter are present. Similar to the postpubertal rat explants, explants obtained from prepubertal rats increased LHRH release in response to NAL and showed a sustained inhibition of LHRH release following washout of NAL. Explants obtained from prepubertal rats also significantly increased LHRH release in response to PHEN.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Regulation of hypothalamic gonadotropin-releasing hormone secretion in experimental uremia: in vitro studies.

Defective regulation of hypothalamic gonadotropin-releasing hormone (GnRH) secretion is the primary defect leading to the inhibition of pituitary gonadotropin secretion and its consequences such as androgen deficiency and infertility in experimental uremia. Previous studies using indirect methods to study presumptive GnRH release and the function of GnRH-secreting neurons have suggested functional disturbances of GnRH neurosecretion; however, the precise biochemical mechanisms involved were not defined. Therefore, in order to clarify the mechanisms of aberrant regulation of hypothalamic GnRH secretion in experimental uremia, we examined basal secretion of GnRH from mediobasal hypothalamus (MBH) in vitro and the GnRH-secretory responses to naloxone, an opiate receptor antagonist in experimental uremia. Using a static incubation system, adult male rats, either intact or castrate, with subtotal nephrectomy demonstrated a significant reduction of GnRH secretion by 25% in intact and by 40% in castrate uremic male rats compared with their nonuremic controls. In contrast, hypothalamic GnRH content of uremic animals was increased significantly (6% in intact and 14% in castrate uremic rats). Despite the fall in basal GnRH release from MBH, the MBH GnRH release response to in vitro stimulation by an opioid blocker (naloxone) and a membrane-depolarizing agent (veratrine) were not diminished in uremic male rats. These findings suggest that the inhibition of pituitary gonadotropin secretion in experimental uremia is likely to be due to a functional defect in suprahypothalamic regulation of GnRH secretion rather than an intrinsic defect in the GnRH-secreting neurons. Further studies are required to clarify the nature of the neuromodulator interactions involved.

Animals↗
PubMed1993

Isotonic but not hypertonic ethanol stimulates LHRH secretion from perifused rat median eminence.

We utilized luteinizing hormone-releasing hormone (LHRH) secretion by perifused minced rat hypothalamic median eminence (ME) tissue to evaluate whether isotonic ethanol would stimulate neurosecretion as it does secretion from pituitary cells. Isotonic ethanol induced a dose-dependent burst of LHRH secretion which was maximal at 2-3 min and returned to near baseline by 10 min. In Ca(2+)-depleted media (< 2 microM Ca2+), stimulation of secretion by isotonic ethanol was enhanced, but secretion induced by depolarizing 30 mM K+ was abolished. Hypertonic ethanol was ineffective in stimulating LHRH secretion in either normal or Ca(2+)-free media. The secretory response of hypothalamic LHRH-secreting cells to ethanol and its negative modulation by medium Ca2+ is thus identical to that of normal anterior pituitary cells and presumably is caused by cell swelling resulting from influx of permeant ethanol molecules across the plasmalemma.

Animals↗
PubMed1995

A relative depletion of luteinizing hormone-releasing hormone was observed in the median eminence of young but not middle-aged rats on the evening of proestrus.

Computer-assisted analysis was used to examine LHRH reaction product in the median eminence of young and middle-aged rats prior to and after the expected peak of the LH surge on proestrus. The area of LHRH reaction product was analyzed in 5 rostral-caudal levels (A-E) of the median eminence. The relative depletion of LHRH in the median eminence of young females on the evening compared to the afternoon of proestrus suggested LHRH neurosecretion in conjunction with the preovulatory LH surge. The pattern of depletion observed further suggested that LHRH release may occur preferentially from restricted regions of the median eminence or in a coordinated wave-like pattern. Four of the five levels of the median eminence exhibited a relative decrease in LHRH on the evening of proestrus in young females, and this time-related difference in LHRH reaction product was statistically significant in median eminence levels B and C. In contrast, little evidence of a relative depletion in LHRH reaction product from early to late proestrus was observed in the median eminence of aging animals. Moreover, the concentration of the densest LHRH reaction product appeared diminished in the median eminence of middle-aged compared to young females at the time points examined in the present study. The age-related differences observed in LHRH reaction product in the median eminence may contribute to the attenuated LH surge documented in middle-aged female rats. Whether these changes in LHRH immunoreactivity can be attributed to age-related alterations in afferents received by LHRH neuronal cell bodies or terminals or to intrinsic deficits in signalling mechanisms within LHRH neurons remains to be determined. Computer-assisted analysis of the immunocytochemical data enabled the assessment of relative changes in reaction product within specific elements of LHRH neurons in precise regions of the median eminence.

Aging↗
PubMed1996

Evidence for the presence of receptors for pituitary adenylate cyclase-activating polypeptide in the neurohypophysis that are positively coupled to cyclic AMP formation and neurohypophyseal hormone secretion.

This study examines the neural lobe of the pituitary gland for the presence of receptors for pituitary adenylate cyclase-activating polypeptide (PACAP) and their possible involvement in the regulation of neurosecretion. The presence of PACAP receptors of type I was revealed in the neural lobe, as well as in anterior and intermediate lobes, by means of RT-PCR amplification using selective oligonucleotide pairs of primers. They appeared to be expressed in the tissues as a short form together with an isoform of heavier molecular weight. Activation of receptors in the presence of PACAP stimulated both formation of cyclic AMP (cAMP) and secretion of arginine vasopressin (AVP) in neural lobes, in a dose-related fashion, with half-maximum (EC50) values of 1.0 +/- 0.2 x 10(-9) M and 1.4 +/- 0.3 x 10(-8) M, respectively. Parallel with AVP, PACAP also stimulated oxytocin (OXT) output, with an EC50 value of 0.6 +/- 0.1 x 10(-8) M. In an attempt to localize receptors on cells (mainly astrocyte-like glials or pituicytes) and/or on nerve fibers of the gland, we used cultures of neural lobe cells and explants (in which nerve fibers undergo degeneration), as well as isolated nerve endings. In both cells and nerve terminals, PACAP enhanced accumulation of cAMP, while it triggered AVP secretion from the latter. The stimulatory effect of PACAP on both AVP and OXT release was mimicked by dbcAMP and blocked by H89, an inhibitor of cAMP-dependent protein kinase. We conclude that in the neural lobe, PACAP receptors are localized on both nerve terminals and pituicytes, which participate in the modulation of secretion of neurohypophyseal hormones in an interactive way and mainly through the cAMP signalling route.

Animals↗
PubMed1975

Histological and histochemical study on the ependyma of Bradypus tridactylus.

Histological and histochemical aspects of the whole encephalic ventricular system of eight specimens of Bradypus tridactylus were studied. After anesthesia and perfusion, the encephalons were obtained by craniotomy. Transverse serial sections of the encephalon, stained according to Azan (Heidenhain's method) or Kluver-Barrera for nerve cells and myelinated nerve fibers; silver impregnation was carried out according to Cajal-De Castro's or Palmgren's methods. The following histochemical reactions were used: PAS (McManus), metachromasia, acid phosphatase (Gomori), Brachet's and Gomori's trichromic reaction (modified by Bargmann for neurosecretion). Histologically, different characteristics of the ependymal cells in different areas were observed, which would be related to functional peculiarities of each area of the encephalic ventricles. The ependymal cells showed discrete apical basophilia due to the presence of RNA which disappears after treatment with crystalline ribonuclease. The PAS reaction indicated the presence of a small quantity of PAS-positive substances in the apical zone of the ependymal cells and the subependymal tissue. These substances disappeared after the salivary amylase test, indicating the presence of glycogen. The acid phosphatase reaction was negative.

Aminosalicylic Acids↗
PubMedDate not supplied

Human chromogranin A. Purification and characterization from catecholamine storage vesicles of human pheochromocytoma.

Chromogranin A is the quantitatively major soluble protein in catecholamine storage vesicles of the adrenal medulla and sympathetic nerve, and has been a useful index of exocytosis during sympathoadrenal neurosecretion. To probe human catecholamine storage and release, we isolated chromogranin A from chromaffin tissue in human pheochromocytoma, and compared it to chromogranin A isolated from chromaffin tissue in bovine adrenal medulla. The preparation included catecholamine storage vesicle isolation by sucrose gradient centrifugation, removal of dopamine-beta-hydroxylase by affinity chromatography on Concanavalin A-Sepharose, and preparative polyacrylamide gel electrophoresis. Human and bovine chromogranin A displayed considerable interspecies homology. Human chromogranin A is a 68,000 dalton monomeric protein with an unusual amino acid composition (31.53 weight % glutamic acid); an acidic, microheterogeneous isoelectric point (4.57-4.68); a characteristic tryptic digest peptide map; and marked dissimilarity to dopamine-beta-hydroxylase in all properties studied. A new probe of human sympathoadrenal function is available in chromogranin A.

Adrenal Gland Neoplasms↗
PubMed2001

Ultrastructural localization of vesicle-associated membrane protein(s) to specialized membrane structures in human pericytes, vascular smooth muscle cells, endothelial cells, neutrophils, and eosinophils.

Vesicle-associated membrane proteins (VAMPs) are important to the trafficking of vesicles between membrane-bound intracytoplasmic organelles, in the facilitation of neurosecretion, and in constitutive and regulated secretion in non-neuronal cells. We used a pre-embedding ultrastructural immunonanogold method to localize VAMPs to subcellular sites in human cells of five lineages known to have cytoplasmic vesicles that may function in vesicular transport. We found VAMPs localized to caveolae in pericytes, vascular smooth muscle cells, and endothelial cells of venules, to the vesiculo-vacuolar organelle, recently defined in venular endothelial cells, to the vesicle-rich intergranular cytoplasm and secretory granule membranes of neutrophils, and to perigranular cytoplasmic secretory vesicles and secretory granule membranes in eosinophils. These specific localizations in five human vascular and granulocyte lineages support the notion that VAMPs have vesicle-associated functions in these cells.

Adult↗
PubMed1998

Cellular localization of calmodulin-dependent protein kinases I and II to A-cells and D-cells of the endocrine pancreas.

Ca2+/calmodulin-dependent protein kinases I and II, initially identified in brain on the basis of their ability to phosphorylate synapsin I, have been implicated in the regulation of Ca2+-dependent synaptic neurosecretion. Specific recombinant and synthetic peptide antibodies were used to examine the distribution of CaM kinases I and II in the rat pancreas and other tissues. The CaM kinase I antibodies detected a doublet of cytosolic proteins of approximately 38 and approximately 42 kD by immunoblot. CaM kinase I was observed in glucagon-containing A-cells at the periphery of the islet of Langerhans but had little or no overlap with pancreatic polypeptide or somatostatin cells. In contrast, CaM kinase II was localized to somatostatin-containing D-cells. CaM kinase I co-localized with glucagon secretory granules. CaM kinase II was not associated with the somatostatin granule but rather was enriched in areas of the cells that contained relatively little somatostatin. Because glucagon secretion is Ca2+-dependent, it is attractive to speculate that CaM kinase I may play a regulatory role in glucagon secretion. Glucagon and somatostatin cells both utilize intracellular Ca2+ for signaling. Therefore, specific CaM kinases may act as effectors of Ca2+ in these different cell types.

Animals↗
PubMed2003

Astrocytes and brain function: implications for reproduction.

Recent evidence suggests that astrocytes have important neuroregulatory functions in addition to their classic functions of support and segregation of neurons. These newly revealed functions include regulation of neuron communication, neurosecretion, and synaptic plasticity. Although these actions occur throughout the brain, this review will focus on astrocyte-neuron interactions in the hypothalamus, particularly with respect to their potential contribution to the regulation of gonadotropin-releasing hormone (GnRH) secretion and reproduction. Hypothalamic astrocytes have been documented to release a variety of neuroactive factors, including transforming growth factors-alpha and -beta, insulin-like growth factor-1, prostaglandin E2, and the neurosteroid, 3 alpha-hydroxy-5 alpha-pregnane-20-one. Each of these factors has been shown to stimulate GnRH release, and receptors for each factor have been documented on GnRH neurons. Astrocytes have also been implicated in the regulation of synaptic plasticity in key areas of the hypothalamus that control GnRH release, an effect achieved by extension and retraction of glial processes (i.e., glial ensheathment). Through this mechanism, the number of synapses on GnRH neurons and GnRH regulatory neurons can potentially be modulated, thereby influencing the activation state of GnRH neurons. The steroid hormone 17beta-estradiol, which triggers the GnRH and luteinizing hormone surge, has been shown to induce the astrocyte-regulated changes in hypothalamic synaptic plasticity, as well as enhance formation and release of the astrocyte neuroactive factors, thereby providing another potential mechanistic layer for astrocyte regulation of GnRH release. As a whole, these studies provide new insights into the diversity of astrocytes and their potential role in reproductive neuroendocrine function.

Animals↗
PubMed2005

IGF-1 in the brain as a regulator of reproductive neuroendocrine function.

Given the close relationship among neuroendocrine systems, it is likely that there may be common signals that coordinate the acquisition of adult reproductive function with other homeostatic processes. In this review, we focus on central nervous system insulin-like growth factor-1 (IGF-1) as a signal controlling reproductive function, with possible links to somatic growth, particularly during puberty. In vertebrates, the appropriate neurosecretion of the decapeptide gonadotropin-releasing hormone (GnRH) plays a critical role in the progression of puberty. Gonadotropin-releasing hormone is released in pulses from neuroterminals in the median eminence (ME), and each GnRH pulse triggers the production of the gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). These pituitary hormones in turn stimulate the synthesis and release of sex steroids by the gonads. Any factor that affects GnRH or gonadotropin pulsatility is important for puberty and reproductive function and, among these factors, the neurotrophic factor IGF-1 is a strong candidate. Although IGF-1 is most commonly studied as the tertiary peripheral hormone in the somatotropic axis via its synthesis in the liver, IGF-1 is also synthesized in the brain, within neurons and glia. In neuroendocrine brain regions, central IGF-1 plays roles in the regulation of neuroendocrine functions, including direct actions on GnRH neurons. Moreover, GnRH neurons themselves co-express IGF-1 and the IGF-1 receptor, and this expression is developmentally regulated. Here, we examine the role of IGF-1 acting in the hypothalamus as a critical link between reproductive and other neuroendocrine functions.

Animals↗
PubMed1990

Detection of sialic acid residues in the axonal reticulum of rat superior cervical ganglion cells by lectin-gold cytochemistry.

Highly glycosylated compounds have been demonstrated in the axonal reticulum elements of the superior cervical ganglion cells of the rat, and this is considered to suggest a connection of the reticulum with the trans Golgi side. In the present study, the axonal reticulum and the Golgi elements were further characterized by post-embedding methods of lectin-gold cytochemistry to determine their carbohydrate residues and to see, more specifically, if sialic acid residues could be detected in the axonal reticulum elements. Therefore, the affinity of neuronal cell structures for Limax flavus agglutinin (LFA), wheat germ agglutinin (WGA), and Ricinus communis agglutinin I (RCA-I) was tested in ultra-thin sections of glycolmethacrylate-embedded material, counterstained with phosphotungstic acid (PTA) at low pH. The trans Golgi network, the Golgi-associated axonal reticulum, the reticulum within axons, the large dense-cored vesicles, and the plasma membranes were reactive for all three lectins used. We conclude that the axonal reticulum elements carry sialic acid residues, relating them to the trans Golgi network. The present results support the concept that the axonal reticulum is an extension of the trans network of the Golgi apparatus specialized for neurosecretion.

Animals↗
PubMed2002

Estrogen-astrocyte interactions: implications for neuroprotection.

BACKGROUND: Recent work has suggested that the ovarian steroid 17beta-estradiol, at physiological concentrations, may exert protective effects in neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and acute ischemic stroke. While physiological concentrations of estrogen have consistently been shown to be protective in vivo, direct protection upon purified neurons is controversial, with many investigators unable to show a direct protection in highly purified primary neuronal cultures. These findings suggest that while direct protection may occur in some instances, an alternative or parallel pathway for protection may exist which could involve another cell type in the brain. PRESENTATION OF THE HYPOTHESIS: A hypothetical indirect protective mechanism is proposed whereby physiological levels of estrogen stimulate the release of astrocyte-derived neuroprotective factors, which aid in the protection of neurons from cell death. This hypothesis is attractive as it provides a potential mechanism for protection of estrogen receptor (ER)-negative neurons through an astrocyte intermediate. It is envisioned that the indirect pathway could act in concert with the direct pathway to achieve a more widespread global protection of both ER+ and ER- neurons. TESTING THE HYPOTHESIS: We hypothesize that targeted deletion of estrogen receptors in astrocytes will significantly attenuate the neuroprotective effects of estrogen. IMPLICATIONS OF THE HYPOTHESIS: If true, the hypothesis would significantly advance our understanding of endocrine-glia-neuron interactions. It may also help explain, at least in part, the reported beneficial effects of estrogen in neurodegenerative disorders. Finally, it also sets the stage for potential extension of the hypothetical mechanism to other important estrogen actions in the brain such as neurotropism, neurosecretion, and synaptic plasticity.

Animals↗
PubMed1993

Mandatory neuropeptide-steroid signaling for the preovulatory luteinizing hormone-releasing hormone discharge.

In this article I have examined various aspects of the complex spatio-temporal patterning of peptidergic signaling that lead to synchronized development of neural events for the preovulatory LHRH discharge on proestrus. Undoubtedly, the integration of these events is orchestrated by both ovarian steroids, E2 and P. Evidence accumulated in recent years has failed to affirm the perceived notion that E2 is an adequate peripheral signal for the timely, robust discharge of LHRH on proestrus. The current understanding is shaped by the thesis that the concerted central actions of E2 and P are mediated by a host of regulatory peptides produced locally in the hypothalamus, and steroids, in general, augment the production and release of both inhibitory and excitatory peptides in a timely fashion to facilitate the preovulatory LHRH discharge. Since these peptidergic pathways appear mandatory for signal transfer, considerable recent research has been devoted first to identifying the signals that selectively participate in the induction of preovulatory LHRH (LH) surge, and then to trace the route of signal transmission that ultimately leads to LHRH hypersecretion on the afternoon of proestrus (Fig. 1). The peptidergic pathways that propagate and transmit impulses for the preovulatory LHRH discharge reside in the SCN-MPN-MPOA-ARC-ME neural complex (Fig. 1). The timely initiation of these impulses is entrained to the photo-periodic input reaching the SCN by the retino-hypothalamic tract. The evidence is already in place to show that further information processing is transduced in the MPN; however, the nature of neurochemical signaling between the two sites remains to be deciphered. The available evidence favors a mandatory participation of inhibitory (EOP and NPK) and excitatory (NPY, GAL, NT, and AII) messenger molecules within the SCN-MPN-MPOA-ARC-ME complex (Fig. 1). It is possible that the relevant information from the SCN-MPN is conveyed caudally to the ARC in order to initiate a chain of events for disinhibition/excitation of the NPY-EOP network and to affect LHRH neurosecretion at the perikaryal level in the MPOA and at axon terminals in the ME. Also, either concurrently or on a time-delayed basis, the relevant information from the MPN may be relayed to the MPOA via the local peptidergic network comprised of NT, EOP, NPK, and GAL. This transmission may initially be critical for elicitation of antecedent neurosecretory events in the ME and to ultimately evoke the preovulatory LHRH surge.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2003

Seasonal plasticity within the gonadotropin-releasing hormone (GnRH) system of the ewe: changes in identified GnRH inputs and glial association.

The annual reproductive cycle in sheep may reflect a functional remodeling within the GnRH system. Specifically, changes in total synaptic input and association with the polysialylated form of neural cell adhesion molecule have been observed. Whether seasonal changes in a specific subset(s) of GnRH inputs occur or whether glial cells specifically play a role in this remodeling is not clear. We therefore examined GnRH neurons of breeding season (BS) and nonbreeding season (anestrus) ewes and tested the hypotheses that specific (i.e. gamma-aminobutyric acid, catecholamine, neuropeptide Y, or beta-endorphin) inputs to GnRH neurons change seasonally, and concomitant with any changes in neural inputs is a change in glial apposition. Using triple-label immunofluorescent visualization of GnRH, glial acidic fibrillary protein and neuromodulator/neural terminal markers combined with confocal microscopy and optical sectioning techniques, we confirmed that total numbers of neural inputs to GnRH neurons vary with season and demonstrated that specific inputs contribute to these overall changes. Specifically, neuropeptide Y and gamma-aminobutyric acid inputs to GnRH neurons increased during BS and beta-endorphin inputs were greater during either anestrus (GnRH somas) or BS (GnRH dendrites). Associated with the changes in GnRH inputs were seasonal changes in glial apposition, glial acidic fibrillary protein density, and the thickness of glial fibrils. These findings are interpreted to suggest an increase in net stimulatory inputs to GnRH neurons during the BS contributes to the seasonal changes in GnRH neurosecretion and that this increased innervation is perhaps stabilized by glial processes.

Animals↗
PubMed2005

Astrocyte-derived transforming growth factor-{beta} mediates the neuroprotective effects of 17{beta}-estradiol: involvement of nonclassical genomic signaling pathways.

17beta-Estradiol (E2) and selective estrogen receptor modulators (SERMs), such as tamoxifen, mediate numerous effects in the brain, including neurosecretion, neuroprotection, and the induction of synaptic plasticity. Astrocytes, the most abundant cell type in the brain, influence many of these same functions and thus may represent a mediator of estrogen action. The present study examined the regulatory effect and underlying cell signaling mechanisms of E2-induced release of neurotropic growth factors from primary rat cortical astrocyte cultures. The results revealed that E2 (0.5, 1, and 10 nm) and tamoxifen (1 mum) increased both the expression and release of the neuroprotective cytokines, TGF-beta1 and TGF-beta2 (TGF-beta), from cortical astrocytes. The stimulatory effect of E2 was attenuated by the estrogen receptor (ER) antagonist, ICI182,780, suggesting ER dependency. The effect of E2 also appeared to involve mediation by the phosphotidylinositol 3-kinase (PI3K)/Akt signaling pathway, because E2 rapidly induced Akt phosphorylation, and pharmacological or molecular inhibition of the PI3K/Akt pathway prevented E2-induced release of TGF-beta. Additionally, the membrane-impermeant conjugate, E2-BSA, stimulated the release of TGF-beta, suggesting the potential involvement of a membrane-bound ER. Finally, E2, tamoxifen, and E2-BSA were shown to protect neuronal-astrocyte cocultures from camptothecin-induced neuronal cell death, effects that were attenuated by ICI182,780, Akt inhibition, or TGF-beta immunoneutralization. As a whole, these studies suggest that E2 induction of TGF-beta release from cortical astrocytes could provide a mechanism of neuroprotection, and that E2 stimulation of TGF-beta expression and release from astrocytes occurs via an ER-dependent mechanism involving mediation by the PI3K/Akt signaling pathway.

Animals↗