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A Sarrieau

Publications and source records attributed to A Sarrieau.

At least 37 records · Page 2Linked to original sources
PubMed1995

Steroid effects on brain functions: an example of the action of glucocorticoids on central dopaminergic and neurotensinergic systems.

It is now clearly established that steroid hormones released from peripheral endocrine glands may, through specific receptors in the brain, directly regulate brain function. These effects may be rapid or involve long-term modifications at the genomic level. Concerning the glucocorticoids, their receptors are found in most neuronal cells, an observation which can be related to their widespread effects on neuronal metabolism. Furthermore, glucocorticoids are often related to stress. We have previously demonstrated that neonatal handling of the rat prevented excessive endocrine response to stress. In adults, this action appeared to protect the animal from potential damaging effects of glucocorticoids and from related impairment of cognitive functions. The effects of glucocorticoids are thought to involve an interaction of several central neurotransmitter systems. One such neurotransmitter is neurotensin, a neuropeptide which was reported to be closely related to central dopaminergic system regulation. This paper presents a rapid overview of the central effects of glucocorticoids and possible evidence for the interrelationship between these steroids, dopamine and neurotensin systems in the regulation of the hypothalamo-pituitary-adrenal axis. It provides a new way to approach stress responses and to develop new substances that may become potential drugs in the treatment of some psychiatric disorders.

Adrenocorticotropic Hormone↗
PubMed1994

Localization and developmental pattern of vasoactive intestinal polypeptide binding sites in the human hypothalamus.

Using a quantitative in vitro autoradiographic approach, vasoactive intestinal polypeptide (VIP) binding site densities were compared in the post-mortem hypothalamus of human neonate/infant and adult. The densities were similar during development in most of the hypothalamic nuclei and areas examined underlying the stability of 125I-VIP binding sites in the post-mortem hypothalamus of young and adult individuals. However, the ventral part of the medial preoptic area, the medial, lateral, and supramammillary nuclei were characterized by an increase of 125I-VIP binding with age. In young and adult individuals, the highest densities of hypothalamic 125I-VIP binding sites were detected in the supraoptic and infundibular nuclei; the ependyma; the organum vasculosum of the lamina terminalis; the horizontal limb of the diagonal band of Broca; the ventral part of the medial preoptic area (in adult); the suprachiasmatic, paraventricular, and periventricular nuclei; and the medial and lateral mammillary nuclei in adult. Moderate densities were found in the vertical limb of the diagonal band of Broca, the bed nucleus of the stria terminalis, the ventral part of the medial preoptic area in neonate/infant, the medial and lateral mammillary nuclei in neonate/infant, the supramammillary nucleus in adult, the dorsal hypothalamic area, and the ventromedial nucleus. Low to moderate binding site densities were observed in the other hypothalamic regions of young or adult individuals. The nonspecific binding ranged from 15% of the total binding in the anterior hypothalamus to 20% in the mediobasal and posterior hypothalamic levels. Taken together, these results provide evidence for a large distribution of VIP binding sites in neonate/infant and adult human hypothalamus suggesting the implication of VIP in the development of this brain structure and the maintenance of its various functions.

Adult↗
PubMed1993

Regulation of interleukin-1 receptor expression in mouse brain and pituitary by lipopolysaccharide and glucocorticoids.

Interleukin-1 (IL-1) receptors have been characterized in mouse pituitary and brain. Previous studies have demonstrated that IL-1 receptor density is high in the dentate gyrus in the hippocampus and that lipopolysaccharide (LPS) injection caused an 80% decrease in the number of hippocampal IL-1 receptors, while pituitary receptors in the anterior pituitary were unaffected. In order to investigate on the role of glucocorticoids (GC) in the control of IL-1 receptor expression in the brain and pituitary, the effect of stress, exogenous GC administration or adrenalectomy (ADX) on IL-1 receptor density was determined. Assays were achieved under basal and LPS-stimulated conditions by in situ quantitative autoradiography technique using human recombinant 125I-IL-1 alpha as a tracer. An increase of GC concentration in serum, following immobilization stress or dexamethasone (DEX) treatment (short and long term), did not modify, in the hippocampus, the density of IL-1 receptors under basal conditions or after peripheral LPS injection. On the contrary, ADX significantly decreased IL-1 receptor density in LPS-treated animals. In the anterior pituitary, a significant increase in the density of basal IL-1 receptors was observed 6 h following immobilization stress or after 7 days of DEX treatment while short-term DEX treatments are ineffective. In contrast to what was observed in the hippocampus, no changes in pituitary receptor densities were observed in ADX mice. These results indicate that hippocampal and pituitary IL-1 receptor expressions are differentially regulated by GC. Therefore, this report constitutes the first demonstration of an in vivo regulation of IL-2 receptors in the pituitary.

Adrenalectomy↗
PubMed1992

Quantitative autoradiographic study of somatostatin and neurotensin binding sites in medulla oblongata of SIDS.

Quantitative autoradiography analysis of neurotensin (NT) and somatostatin (SS) binding sites was performed on coronal sections of the medulla oblongata from 2 fetuses, 6 controls and 7 victims of Sudden Infant Death Syndrome (SIDS). Throughout the first postnatal year, mean SS binding site density was similar in controls and SIDS in all structures of the medulla oblongata. The density of neurotensin binding sites was significantly higher in the nucleus of tractus solitarius (NTS) of SIDS than in controls, but there was no significant differences in the other areas of the medulla oblongata. Our findings suggest an immature developmental pattern of increased NT binding sites the NTS of SIDS. This alteration may be related to an abnormal central cardiorespiratory and arousal control which is thought to be present in SIDS.

Autoradiography↗
PubMed1992

Distribution of cells expressing vasoactive intestinal peptide/peptide histidine isoleucine-amide precursor messenger RNA in the rat brain.

The distribution of cells expressing vasoactive intestinal peptide/peptide histidine isoleucine-amide precursor messenger RNA was investigated in the rat brain and pituitary by in situ hybridization using a synthetic 35S-labeled oligonucleotide probe. Detection of labeled neurons by light-microscopic radioautography revealed a selective repartition of the messenger RNA-expressing cells. Several major vasoactive intestinal peptide/peptide histidine isoleucine-amide messenger RNA-containing cell groups were demonstrated including layers II-VI of the cerebral cortex, the suprachiasmatic nucleus and various thalamic structures such as the ventrolateral, posterior, lateral reticular, paracentralis and gelatinosus nuclei. Positive cells, to a lesser extent, were also found in the limbic system, medial preoptic area, superior and inferior colliculi as well as in the central gray matter. They were totally absent in the pituitary and the pineal gland of normal rats. The results of the present study provide a detailed mapping of neurons expressing vasoactive intestinal peptide/peptide histidine isoleucine-amide messenger RNA in the adult rat brain. The predominance of vasoactive intestinal peptide/peptide histidine isoleucine-amide messenger RNA-containing neurons in the cerebral cortex, suprachiasmatic nucleus and thalamus suggest that vasoactive intestinal peptide is mainly involved in the control of cortical informations, circadian rhythms and sensory perception in agreement with several physiological data.

Animals↗
PubMed1991

Characterization and distribution of [3H]ohmefentanyl binding sites in the human brain.

Binding properties and localization of [3H]ohmefentanyl, a new ligand for mu opioid receptors, were investigated on normal human brain sections. Binding assays performed at the level of the basal ganglia revealed: (1) a steady-state binding reached after 60 min incubation at room temperature, (2) the presence, in saturation experiments, of an apparent single class of binding sites with a Kd = 1.68 +/- 0.45 nM and a Bmax = 162 +/- 9 fmol/mg protein, (3) an order of potency to inhibit [3H]ohmefentanyl binding as follows: ohmefentanyl greater than [D-Ala2, MePhe4, Gly-ol5] enkephalin (DAGO) greater than ethylketocyclazocine (EKC) much greater than Tyr-D-Ser(OtBu)-Gly-Phe-Leu-Thr(OtBu) (BUBU) and U-50,488H. Quantitative autoradiography showed an heterogeneous distribution of [3H]ohmefentanyl binding sites with the highest densities in amygdala, medical geniculate body, thalamus, and caudate nucleus. Binding characteristics and anatomical distribution also show that [3H]ohmefentanyl may bind to a small proportion of additional sites called "DAGO-inaccessible [3H]ohmefentanyl specific binding sites." [3H]Ohmefentanyl binding to these sites can be partly inhibited by sigma ligands such as 1,3-di-o-tolylguanidine (DTG) and haloperidol. However, unlabeled DAGO inhibited more than 80% of [3H]ohmefentanyl specific binding in most of the human brain regions studied, suggesting that the major population of sites labeled by [3H]ohmefentanyl represented mu opioid receptors.

Adult↗
PubMed1991

The effects of neonatal handling on the development of the adrenocortical response to stress: implications for neuropathology and cognitive deficits in later life.

Several years ago Levine, Denenberg, Weininger, Ader, and others described the effects of postnatal "handling" on the development of behavioral and endocrine responses to stress. The handling procedure usually involved removing rat pups from their cages, placing the animals together in small containers, and 15-20 min later, returning the animals to their cages and their mothers. The manipulation was performed daily for the first 21 days of life. As adults, handled (H) rats exhibited attenuated fearfulness (e.g., decreased freezing, increased exploration) in novel environments and a less pronounced increase in the secretion of adrenal glucocorticoids in response to a variety of stressors. These findings clearly demonstrated that the development of rudimentary, adaptive responses to stress could be modified by environmental events. We have followed on these earlier handling studies, convinced that this paradigm provides a marvelous opportunity to examine how subtle variations in the early environment alter the development of specific biochemical systems in the brain, leading to stable individual differences in biological responses to stimuli that threaten homeostasis. In this work we have shown how early handling influences the neurochemical development of certain brain regions that regulate the adrenocortical response to stress. Neonatal handling increases the efficiency of this endocrine response to stress, preventing excessive exposure to the highly catabolic adrenal steroids. In later life, this effect appears to protect the animal from potentially damaging effects of these steroids, ensuring the anatomical integrity of brain structures involved in cognitive functioning.

Adrenal Cortex↗
PubMed1991

Cell-specific expression of the glucocorticoid receptor within granular convoluted tubules of the rat submaxillary gland.

The submaxillary gland, a heterogeneous tissue composed essentially of two functionally distinct cell types (tubular epithelial and acinar), offers an interesting system in which to study the mechanisms of steroid-dependent growth and differentiation. One cell type, the granular convoluted tubular (GCT) cell, secretes a large number of physiologically important polypeptides, including epidermal and nerve growth factors. Two steroids, androgens and glucocorticoids, greatly influence the growth, differentiation, and secretory activity of GCT cells. Because glucocorticoids can partially mimic or potentiate androgen effects, it has been thought that glucocorticoids act via androgen receptors. Since the presence of glucocorticoid receptors is a prerequisite for glucocorticoid action, we have investigated the presence and cellular distribution of glucocorticoid receptors within the rat submaxillary gland. Binding experiments using [3H]dexamethasone revealed the presence of high affinity binding sites in rat submaxillary tissue homogenates. Most of these sites were specifically competed by dexamethasone, corticosterone, and a pure glucocorticoid agonist RU 28362. Neither testosterone nor dihydrotestosterone competed for glucocorticoid binding. The cellular distribution of glucocorticoid receptors within the submaxillary gland was investigated by immunocytochemistry, using two highly specific glucocorticoid receptor antibodies. The receptor was localized in the GCT cells, but not in the acinar cells of rat and mouse submaxillary tissue sections. In GCT cells, the glucocorticoid receptor colocalized with several secretory polypeptides, including epidermal growth factor, nerve growth factor, alpha 2u-globulin, and atrial natriuretic factor. These data suggest that the submaxillary gland is a target for glucocorticoid action and that at least part of the glucocorticoid effects on this tissue are mediated by bona fide glucocorticoid receptors.

Adrenalectomy↗
PubMed1990

Estrogen-like effects of 7,12-dimethylbenz(a)anthracene on the female rat hypothalamo-pituitary axis.

We have recently demonstrated that 7,12-dimethylbenz(a)anthracene (DMBA), a potent inducer of mammary tumors in rodents, can in vitro decrease the number of membrane dopamine D2 receptors and stimulate prolactin (PRL) release, by direct estrogen-like actions on anterior pituitary. In the present study, we tested the ability of DMBA to mimic the in vivo estradiol (17 beta E2) effects on pituitary D2 receptors and on PRL as well as LH release. We have found that DMBA, like 17 beta E2, when injected to ovariectomized rats, induced a decrease in the number of anterior pituitary D2 receptors, a release of PRL and exerted a biphasic (acute negative and longer term positive) action on LH secretion. We thus examined the ability of DMBA to interact with 17 beta E2 receptors in the hypothalamo-pituitary axis: DMBA binds to the pituitary cytosolic estrogen receptors with an affinity 0.001% that of 17 beta E2. Finally [3H]DMBA binds to hypothalamus-containing brain sections. This binding was displaced partially by RU 2858 a pure estrogen agonist and totally by tamoxifen, a purported estrogen antagonist. No competition for [3H]DMBA binding was observed with an androgen (RU 1881) or a glucocorticoid (RU 26988) agonist. From these data, it may be concluded that DMBA can act as a partial estrogen in pituitary and hypothalamic tissues.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1990

Androgen binding sites in human temporal cortex.

We have characterized putative androgen receptor binding sites in five separate biopsy samples of human temporal cortex from epilepsy patients using an in vitro exchange assay with soluble fractions and [3H]5 alpha-dihydrotestosterone as radioligand. The results revealed highly specific, saturable binding with an apparent affinity constant (Kd) of approximately 2 nM with a moderate capacity (Bmax) of approximately 50 fmol/mg protein. In competition studies, we found that only testosterone and 5 alpha-dihydrotestosterone competed effectively (i.e. at low nanomolar concentrations) for [3H]5 alpha-dihydrotestosterone binding sites. These data indicate the presence of androgen receptors in human cortex that are pharmacologically very similar to that previously described in rodent and infrahuman primate CNS, and suggest the existence of a possible mechanism whereby circulating androgens might influence neuronal events in human cortex.

Adolescent↗
PubMed1989

Neonatal handling alters adrenocortical negative feedback sensitivity and hippocampal type II glucocorticoid receptor binding in the rat.

Adult rats handled (H) daily for the first 3 weeks of life show a dramatically altered adrenocortical response to stress. We found that H animals secreted less ACTH and corticosterone (B) during and following the termination of stress than did nonhandled (NH) controls. In contrast, H and NH animals did not differ in basal B secretion at any point in the diurnal cycle, nor in adrenocortical responses to exogenously administered oCRF or ACTH. Moreover, the clearance rate for B was similar in H and NH animals. H animals were more sensitive than NH animals to the inhibitory effects of either B or dexamethasone on stress-induced adrenocortical activity. In a dose-response study, both glucocorticoids administered 3 h prior to testing suppressed the adrenocortical response to a 20-min restraint stress to a greater extent in the H animals. Handling increased type II, glucocorticoid receptor binding capacity in the hippocampus of adult animals (approximately 50% increase in capacity, with no change in affinity). There were no handling-induced changes in type II receptor binding capacity in the hypothalamus or pituitary, nor in type I receptor binding capacity in the hippocampus. Following chronic (5 mg/kg/day) treatment with B, hippocampal type II receptor binding capacity was significantly reduced in the B-treated H animals, compared with saline-treated H animals, and indistinguishable from saline-treated NH animals. Down-regulated H animals, like NH animals, hypersecreted B following the termination of stress in comparison to the saline-treated H animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗
PubMed1988

Autoradiographic localization of glucocorticosteroid binding sites in rat brain after in vivo injection of [3H]RU 28362.

The autoradiographic distribution of glucocorticosteroid binding sites in the brain of adrenalectomized rats was studied following in vivo injection of a potent synthetic glucocorticosteroid agonist [3H]RU 28362. Analysis of the autoradiograms revealed a specific and dense labeling in the pyramidal cell layer of the Ammon's horn and in the granular cell layer of the dentate gyrus of the hippocampus. In the hypothalamus, the labeling was particularly high in the paraventricular nucleus (site of CRF synthesis), the arcuate, periventricular and the supraoptic nuclei as well as in the median eminence. Autoradiograms also revealed the presence of [3H]RU 28362 binding sites in several brain regions including the amygdala, the pineal gland, the entorhinal cortex, the interpeduncular, interfascicular and dorsal raphe nuclei, the central grey and the substantia nigra suggesting possible effects of glucocorticosteroids in these structures.

Adrenalectomy↗
PubMed1988

Postnatal development and environmental regulation of hippocampal glucocorticoid and mineralocorticoid receptors.

We report here on developmental changes in [3H]RU 28362 (glucocorticoid receptor) and [3H]aldosterone (mineralocorticoid receptor) binding capacity in soluble fractions prepared from hippocampal tissue. [3H]RU 28362 binding was low on Day 3 of life (less than 30% of that observed in adults) and increased towards adult values during the second and third weeks of life, a pattern virtually identical to that previously reported for dexamethasone binding. In contrast, [3H]aldosterone binding on Day 3 of life was only slightly lower than that observed in adults and reached adult values by Day 7. Postnatal handling of rat pups, which has been shown to increase dexamethasone binding in hippocampus, resulted in a significant increase in [3H]RU 28362 binding capacity in hippocampus, but had no effect on [3H]aldosterone binding.

Adrenalectomy↗
PubMed1988

Glucocorticoid binding sites in human temporal cortex.

This work describes the presence of glucocorticoid binding sites in human temporal cortex obtained following partial lobectomy in two epileptic patients. Using [3H]dexamethasone as radioligand and cold cortisol or RU 28362 as competitor we found an apparent Kd of approximately 2.8 nM with a Bmax of approximately 34 fmol/mg protein. The order of potency of various unlabeled steroids to compete for [3H]dexamethasone binding was as follows: RU 28362 = RU 38486 = cortisol = dexamethasone greater than progesterone greater than spironolactone greater than estradiol. These data provide evidence for an intracellular mechanism by which circulating glucocorticoids might regulate neuronal function in the human cortex.

Adult↗
PubMed1986

Characterization and autoradiographic distribution of vasoactive intestinal peptide binding sites in the rat central nervous system.

Biochemical characteristics and topographical distribution of mono-[125I )vasoactive intestinal peptide (VIP) binding sites in rat brain were studied on tissue sections and by quantitative autoradiography. Biochemical investigations show two classes of binding sites with a dissociation constant of 1.03 +/- 0.11 nM and 68 +/- 14 nM and a maximal binding capacity of 43.3 +/- 5.1 fmol/mg protein and 713 +/- 117 fmol/mg protein respectively. The order of potency of various peptides to inhibit 125I-VIP binding to brain sections is: VIP greater than PHI greater than secretin greater than VIP greater than hGRF. Autoradiography reveals the highest densities of binding sites in the pineal gland, the dentate gyrus of the hippocampus, the central amygdaloid nucleus and in various thalamic nuclei such as the mediodorsal, lateral posterior, submedius, dorsolateral and medial geniculate nuclei. Similar high densities are observed in the olfactory bulbs as well as in the suprachiasmatic and dorsomedial nuclei of the hypothalamus and in the superior colliculus. These data together with the distribution of the endogenous peptide suggest a physiological role for VIP both in the regulation of CNS activities and pituitary functions.

Animals↗
PubMed1986

Effect of an inhibitor of aromatization, 1,4,6 androstatriene-3,17-dione (ATD) on LH release and steroid binding in hypothalamus of adult female rats.

Prevention of testosterone aromatization in the female rat pups by perinatal treatment with 1,4,6 androstatriene-3,17-dione (ATD) induces an important defeminization as shown by a reduction of fluctuations of LH release after castration and estradiol implantation. The fact that, under our in vitro experimental conditions, ATD is able to displace testosterone binding in the hypothalamus whereas estradiol does not, confirms the hypothesis that ATD acts on aromatase. The most attractive explanation for the defeminization effect of ATD is then an estrogen-like action of ATD.

Androstatrienes↗
PubMed1986

Autoradiographic localization of glucocorticosteroid and progesterone binding sites in the human post-mortem brain.

The presence of glucocorticosteroid and progesterone binding sites in the human brain has been investigated with an in vitro autoradiographic approach using [3H]RU 38486. The present data revealed that the hippocampus, the entorhinal cortex, the subiculum, the fimbria and the amygdala showed a different pattern of [3H]RU 38486 labeling using various unlabeled steroids (RU 38486, RU 28362, cortisol, RU 27987 and dexamethasone). RU 38486 is the best competitor in all these structures. The hippocampus seems to possess mainly glucocorticosteroid binding sites whereas the entorhinal cortex and the subiculum reveal the presence of both glucocorticosteroid and progesterone binding sites. Furthermore, the amygdaloid complex and the fimbria show a high density of glucocorticosteroid binding sites.

Autopsy↗