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M Grino

Publications and source records attributed to M Grino.

At least 37 records · Page 2Linked to original sources
PubMed1998

The hormonal response to stress is not modified by the dramatic decrease in prolactin plasma concentration during surgery for microprolactinoma.

OBJECTIVES: To determine the endocrine response to surgical stress in a homogeneous population of 36 women with microprolactinomas, particularly to evaluate the effect of the sharp decrease in plasma prolactin on stress induced hormonal secretion. In addition, the effects of exogenous opiates on prolactin secretion were studied. METHODS: The plasma kinetics of cortisol, prolactin, ACTH, GH, and beta-endorphin like immunoreactivity (beta-ELI) were analysed by including patients operated on with strict anaesthetic and surgical protocols, and by sampling blood every 10 minutes, starting at premedication up to 3 hours after induction. RESULTS AND CONCLUSIONS: (a) Surgical stress or opiate administration did not induce prolactin release in patients with microprolactinoma. (b) The dramatic decrease in prolactin concentrations have apparently no effect on the release of other hormones involved in stress. (c) The existence of an early GH peak, independently of any surgical procedure, strongly suggests that GH is released by surgical stress whereas beta-endorphin is secreted in response to pain. Thus GH may be a useful marker of surgical stress.

Adolescent↗
PubMed1998

An in situ hybridization histochemistry technique allowing simultaneous visualization by the use of confocal microscopy of three cellular mRNA species in individual neurons.

We present a specific and sensitive method for simultaneous detection of three mRNA species in individual neurons. The method relies on the use of riboprobes labeled with [35S]-UTP, digoxigenin-UTP, or biotin-UTP. The nonradioactive probes were sequentially revealed by incubation with anti-digoxigenin immunoglobulins or streptavidin conjugated to peroxidase, followed by the use of fluorochrome-labeled tyramides as peroxidase substrates. The radioactive probe was revealed by conventional autoradiography. There was no interaction among the different probes or the various detection systems. We demonstrate the use of this method by illustrating on laser scanning confocal microscopy the co-localization of the mRNAs coding for corticotropin-releasing factor (CRF), arginine vasopressin (AVP), or peptidylglycine alpha-amidating monooxygenase (PAM) in rat hypothalamic paraventricular nucleus (PVN) and its modulation by endogenous glucocorticoids. Our results suggest that this method could be used not only to study the regulation of the hypothalamo-pituitary-adrenal axis but also in various models in which mRNAs are present at low concentrations.

Adrenal Glands↗
PubMed1998

Consequences of prenatal morphine exposure on the hypothalamo-pituitary-adrenal axis in the newborn rat: effect of maternal adrenalectomy.

The hypothalamo-pituitary-adrenal axis is already functional in rat fetuses in late gestation. We have reported previously that prenatal morphine exposure induced a severe atrophy of the adrenals and a decrease of corticosterone release in newborn rats at birth and during the early postnatal period. The first aim of the present study was to determine the effects of prenatal morphine exposure (1) on corticotrophin releasing factor (CRF) content of the hypothalamus, CRF immunofluorescence in the median eminence, CRF mRNA in the paraventricular nucleus (PVN) and pro-opiomelanocortin (POMC) mRNA in the anterior pituitary gland; (2) on CRF-induced ACTH release from the anterior pituitary gland in vitro; and (3) on ACTH-induced corticosterone release by the adrenals in vitro. Moreover, as morphine is a hepatotoxic factor, we determined the effects of prenatal morphine on liver weight and plasma corticosteroid binding globulin (CBG) binding capacity in newborn rats. Since acute administration of morphine stimulates corticosterone secretion in adult rats and since maternal corticosterone can cross the placental barrier, we also measured both adrenal weight and glucocorticoid activity in newborns from adrenalectomized mothers treated with morphine. The present results show that prenatal morphine given to intact mothers induced adrenal atrophy and hypoactivity in newborns but did not affect the responsiveness of the anterior pituitary gland to CRF or that of the adrenal gland to ACTH. Prenatal morphine reduced both CRF content in the newborn hypothalamus and CRF immunofluorescence in the median eminence without a significant effect on CRF mRNA expression in the PVN. Moreover, morphine induced a significant decrease of POMC mRNA in the anterior pituitary gland. However, morphine did not significantly affect the weight of the liver, or the plasma CBG binding capacity for corticosterone, in rat pups. In contrast, morphine treatment of the adrenalectomized mothers did not induce adrenal atrophy in newborns and did not impair adrenal activation during the early postnatal period. Maternal adrenalectomy also prevented the effects of prenatal morphine on hypothalamic content of CRF, CRF immunofluorescence in the median eminence, and POMC mRNA in the anterior pituitary gland. However, adrenal atrophy was observed at term in newborns of adrenalectomized mothers treated with both morphine and corticosterone or only corticosterone. In conclusion, morphine given to pregnant rats induced inhibition of the hypothalamo-pituitary-adrenal axis in pups at term. As maternal adrenalectomy prevented these effects, we speculate that an adrenal factor of maternal origin, probably corticosterone, mediated these drug effects on newborns.

Adrenal Glands↗
PubMed1997

Effect of excitatory amino acids on rat hypothalamic somatostatin secretion in vitro.

We studied the effect of various agonists of excitatory amino acid (EAA) receptor subtypes on somatostatin (SRIF) release from incubated rat hypothalamic slices. N-Methyl-D-aspartic acid (NMDA) and L-glutamate (1 x 10(-7) to 1 x 10(-3) M) stimulated, in a dose-dependent fashion, SRIF release. The maximal effect was obtained at a concentration of 1 x 10(-4) M for both drugs. The IC50 was 3.2 x 10(-5) M and 2.1 x 10(-5) M for NMDA and L-glutamate, respectively. Incubation with 2.5 x 10(-4) M D-2-amino-5-phosphonovalerate (a NMDA receptor antagonist) or 2-amino-4-phosphonobutyrate (a metabotropic receptor antagonist) was without significant effect on basal SRIF secretion and completely blocked the increase in SRIF release induced by 5 x 10(-5) M NMDA or L-glutamate, respectively. Incubation with 1 x 10(-4) M kainate or 0.5 x 10(-4) M alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) did not change basal SRIF secretion. Incubation with 2 x 10(-4) M gamma-D-glutamylglycine (a specific antagonist of kainate and AMPA receptors) had no effect under basal conditions or during exposure to kainate or AMPA. Our data demonstrate that EAAs stimulate SRIF secretion in vitro, by an action through NMDA and metabotropic receptors but not kainate or AMPA receptors.

Animals↗
PubMed1997

Glutamate and N-methyl-D-aspartate stimulate rat hypothalamic corticotropin-releasing factor secretion in vitro.

It is known that in vivo excitatory amino acids (EAA) stimulate the hypothalamo-pituitary-adrenal axis. However their site of action is not fully understood. We investigated the possibility of a direct action of EAA on the secretion of the major adrenocorticotropin hormone (ACTH) secretagogue: corticotropin-releasing factor (CRF) from incubated rat hypothalamic slices. N-methyl-D-aspartic acid (NMDA) or L-glutamate (1 x 10(-7) to 1 x 10(-3) M) stimulated in a dose-dependent fashion CRF release. The maximal effect was obtained at a concentration of 1 x 10(-4) M for both drugs. The IC50 was 1.3 x 10(-5) M and 3.3 x 10(-5) M for NMDA and L-glutamate, respectively. Incubation with 2.5 x 10(-4) M D-2-amino-5-phosphonovalerate (a NMDA receptor antagonist) or 2-amino-4-phosphonobutyrate (a metabotropic receptor antagonist) was without significant effect on basal CRF secretion and completely blocked the increase in CRF release induced by 5 x 10(-5) M NMDA or L-glutamate, respectively. Incubation with 1 x 10(-4) M kainate or 0.5 x 10(-4) M AMPA did not change basal CRF secretion. Incubation with 2 x 10(-4) M gamma-D-glutamylglycine (a specific antagonist of kainate and AMPA receptor) had no effect under basal conditions or during exposure to kainate or AMPA. Our data demonstrate that EAA could stimulate directly CRF secretion, by an action through NMDA and metabotropic receptors, but not kainate or AMPA receptors. These findings may be relevant to the regulation of the hypothalamo-pituitary adrenal axis, both under basal conditions and during exposure to stress.

Animals↗
PubMed1996

The modulatory role of estrogens on corticotropin-releasing factor gene expression in the hypothalamic paraventricular nucleus of ovariectomized rats: role of the adrenal gland.

In vitro, estrogens stimulate corticotropin-releasing factor (CRF) gene transcription. In ovariectomized (OVX) rats, estrogens have a negative effect on CRF mRNA levels in the hypothalamic paraventricular nucleus. This suggests that the stimulatory influence of estrogens found in vitro may be masked in vivo by an inhibitory effect mediated through neural and/or humoral factors. Glucocorticoids may be involved in this phenomenon since estrogens increase circulating corticosterone levels in OVX rats. We studied the effect of 7-day 17 beta-estradiol (E2) treatment on CRF gene expression in the paraventricular nucleus of 2-week OVX mature rats after sham operation or adrenalectomy (ADX) with or without corticosterone replacement. In sham ADX animals, E2 administration increased plasma corticosterone concentrations, did not change the binding capacity or the affinity of circulating corticosteroid binding globulin, and decreased hypothalamic CRF gene expression. Following ADX, CRF mRNA levels increased and were normalized by corticosterone treatment. Estrogens induced a significant build up in CRF mRNA concentrations in both ADX or ADX corticosterone-replaced animals. Our data demonstrate that the positive effect of estrogens on CRF gene expression found in vitro or in vivo after ADX is antagonized, in vivo when the adrenal glands are intact, by a negative influence. They strongly suggest that the increased circulating corticosterone levels induced by E2 administration mediate the inhibitory effect of estrogens on CRF mRNA levels. These observations may explain the gender related differences in the basal and stress-induced hypothalamo-pituitary-adrenal activity.

Adrenal Glands↗
PubMed1995

[Regulation of corticotropic function in stressful situations].

ACTH secretion is mainly controlled by two hypothalamic neurohormones: corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP). Both peptides are synthesized in the hypothalamic paraventricular nucleus (PVN) (in parvo-cellular neurons for CRH and in magnocellular neurons for most AVP). Under basal conditions, some CRH neurons coexpress AVP (CRH+/AVP+ neurons). This colocalisation represents a form of functional plasticity since the number of CRH+/AVP+ neurons increases after acute or repeated stress exposure. Experiments in sheep and rat (studies on the secretion of both peptides in hypophysial portal blood, effects of anti-CRH and anti-AVP immunisation upon ACTH secretion) indicate that stress-induced ACTH stimulation involves both CRH and AVP. Unlike CRH which participates also in the maintenance of basal ACTH and glucocorticoids secretion, the role of AVP appears to be limited to corticotropic response to stress.

Adrenocorticotropic Hormone↗
PubMed1994

Effect of chronic treatment with the antidepressant tianeptine on the hypothalamo-pituitary-adrenal axis.

The effects of acute and chronic administration of tianeptine, a novel antidepressant agent, on the hypothalamo-pituitary-adrenal axis were studied in the adult male rat. A single injection of tianeptine did not alter the activity of the hypothalamo-pituitary-adrenal axis. In contrast, chronic administration of tianeptine (10 mg/kg twice a day for 15 days) induced a significant decrease in the concentration of corticotropin-releasing factor (CRF) in the hypothalamus and adrenocorticotropin (ACTH) in the anterior lobe of the pituitary. Chronic tianeptine treatment did not modify CRF levels in the cerebral cortex and hippocampus, and did not alter alpha-melanocyte-stimulating hormone and beta-endorphin levels in the neurointermediate lobe of the pituitary. Using the in situ hybridization technique, we observed that chronic administration of tianeptine did not modify CRF mRNA levels in the paraventricular nucleus of the hypothalamus. The effect of chronic tianeptine treatment on the neuroendocrine response to stress was also investigated. Tube restraint stress for 30 min induced a significant depletion of hypothalamic CRF and a substantial increase of plasma ACTH and corticosterone. Tianeptine abolished the stress-induced reduction of hypothalamic CRF concentration and markedly reduced the stress-induced increase in plasma ACTH and corticosterone levels. Taken together, these results suggest that tianeptine acts primarily at the level of the hypothalamus: (1) in unstressed rats, tianeptine reduces hypothalamic CRF and pituitary ACTH contents; (2) in stressed animals, tianeptine attenuates the activation of the hypothalamo-pituitary-adrenal axis.

Animals↗
PubMed1994

Blockade of alpha 2-adrenoceptors stimulates basal and stress-induced adrenocorticotropin secretion in the developing rat through a central mechanism independent from corticotropin-releasing factor and arginine vasopressin.

In the neonatal rat, the response of the hypothalamo-pituitary-adrenal axis to stressful stimuli is markedly reduced during the first 2 weeks of life [stress-hyporesponsive period (SHRP)]. In this report, we studied the effect of idazoxan (an alpha 2-adrenergic antagonist) on plasma ACTH and corticosterone levels in 8-day-old rats. Indeed, it is known that in the adult rat, blockade of alpha 2-adrenoceptors increases ACTH secretion stimulated by CRF and arginine vasopressin (AVP) injection. Injection of 2.5 micrograms/g idazoxan induced a rapid (within 30 min) increase in basal plasma ACTH and corticosterone levels that lasted for 60 min. Injection of increasing doses of idazoxan led to a dose-dependent stimulation of ACTH and corticosterone levels. Administration of 2.5 micrograms/g idazoxan significantly increased the ACTH response to insulin-induced hypoglycemia, whereas it potentiated and accelerated the ACTH response to ether exposure stress. We next examined ACTH secretion from superfused anterior pituitary glands. Neither the alpha 2-adrenergic agonist clonidine nor idazoxan changed the basal ACTH secretory rate. Idazoxan had no effect on CRF- and AVP-stimulated ACTH secretion. This indicates that in vivo, idazoxan acts at a suprapituitary level. To investigate a possible effect of idazoxan on presynaptic alpha 2-adrenoceptors, we studied the effect of idazoxan on the concentrations of norepinephrine (NE) and L-DOPA in punches of locus coeruleus after dopa-decarboxylase blockade. Idazoxan injection induced a decrease in the NE content, without changing L-DOPA levels, indicating that idazoxan can act at the level of presynaptic alpha 2-adrenoceptors, inducing an increased release and/or degradation of NE without any effect on catecholamines synthesis. Finally, we investigated a possible involvement of CRF and AVP in mediating the effect of alpha 2-adrenoceptor blockade on ACTH secretion. Passive immunization against CRF or AVP did not change the ACTH response to idazoxan administration, whereas idazoxan pretreatment had simply an additive effect on CRF- and lysine vasopressin-stimulated ACTH secretion. In conclusion, our data demonstrate that during the SHRP, blockade of alpha 2-adrenoceptors induces an increase in both basal and stress-induced ACTH secretion. They suggest that a decreased catecholaminergic tone, consecutive to an increased occupation of alpha 2-adrenoceptors, acting through a central mechanism independent from CRF and AVP may be responsible for the SHRP in the developing rat.

Adrenergic alpha-Antagonists↗
PubMed1994

Insulin-induced hypoglycaemia increases colocalization of corticotrophin-releasing factor and arginine vasopressin mRNAs in the rat hypothalamic paraventricular nucleus.

The regulation of ACTH secretion during stress is a multifactorial process that mainly involves two hypothalamic neurohormones: corticotrophin-releasing factor (CRF) and arginine vasopressin (AVP). In this report we measured, using semiquantitative in situ hybridization, the concentrations of CRF and AVP mRNA in hypophyseotrophic paraventricular parvocellular cell bodies of male rats after an acute (3-h) exposure to insulin-induced hypoglycaemia. Insulin injection (2.5 IU/kg) induced a significant decrease in blood glucose levels and a strong increase in plasma ACTH concentrations. The concentration of CRF mRNA in the paraventricular nucleus (PVN) was significantly increased after insulin-induced hypoglycaemia (150% of control levels), while the number of CRF mRNA-containing cell bodies was not changed. Double-labelling experiments demonstrated that the number of CRF mRNA-containing cell bodies that also contained AVP mRNA was doubled after insulin injection. These data demonstrate that the established increased colocalization of AVP immunoreactivity in nerve terminals immunoreactive for CRF after exposure to stress follows a pretranslational activation of AVP synthesis. Cell-by-cell analysis indicated that the mean CRF hybridization signal was increased in double-labelled cells (about 150% of control levels), suggesting that the increase in CRF gene expression occurs equally in the AVP-synthesizing and in the AVP-deficient CRF mRNA-containing cell bodies. The mean AVP hybridization signal in the double-labelled cells was decreased, suggesting that the amount of AVP mRNA was unchanged in the cell bodies that expressed both CRF and AVP in the basal state and that AVP mRNA levels in the cell bodies recruited after insulin-induced hypoglycaemia were below control values.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1994

Effect of POMC-derived peptides on corticosterone secretion during the stress hypo-responsive period in rat.

During the stress hyporesponsive period (postnatal days 2-10), the stimulation of corticosterone secretion by ACTH is very low. In our study, we have observed that administration of ACTH during 3 consecutive days is followed by a striking increase in corticosterone response to an acute ACTH test. A comparable potentiation of corticosterone secretion was observed after a similar treatment with Lys gamma 3-MSH. The 3 day-treatment with each peptide induced an increase in adrenal weight. Similar data were obtained with alpha-MSH. However, corticosterone response to ACTH was not significantly altered following the same pattern of alpha-MSH administration.

Adrenal Cortex↗
PubMed1993

Passive immunization and hypothalamic peptide secretion.

Passive immunization is a common approach used to eliminate the biological activity of an endogenous substance by its binding to a specific antibody (Ab). Surprisingly little information has been gathered on the mechanisms involved. Moreover, the possibility that immunoneutralization could affect also the secretion of the antigen itself has been mostly ignored. To study hypothalamic neuropeptide secretion under the condition of passive immunization, labeled and unlabeled monoclonal antibody (MoAb) against arginine vasopressin (AVP) was injected intravenously. After 2 h a similar amount of 125I-MoAb was found in hypophyseal portal and peripheral (femoral artery) plasma, showing a distribution volume of 73.2 ml/kg. Assessment of the MoAb dilution in the same plasma samples from the binding studies revealed substantially higher dilutions (800-5,700 ml/kg). Such a MoAb dilution (saturation) would be attained by the binding of 130-290 pmol AVP/ml plasma. The calculated amount of plasma AVP decreased by one half within the interval from 2 to 24 h after Ab injection, similarly as did the 125I-MoAb content. Intravenous injection of polyclonal corticotropin-releasing hormone (CRH) Ab resulted in a decrease of plasma adrenocorticotropin and corticosterone levels. After 24 h the dilution of the Ab in portal plasma exceeded two times that in peripheral plasma. CRH concentrations of 0.6-2.5 pmol/ml were found by specific radioimmunoassay after its dissociation from the Ab in plasma. The CRH concentration was higher in portal than in peripheral plasma and was related to the amount of the Ab injected. CRH mRNA levels in the paraventricular nucleus were significantly increased in CRH Ab as compared with normal rabbit serum injected rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

In situ hybridization of arginine vasopressin (AVP) heteronuclear ribonucleic acid reveals increased AVP gene transcription in the rat hypothalamic paraventricular nucleus in response to emotional stress.

The regulation of anterior pituitary adrenocorticotropin hormone (ACTH) secretion during stress involves several hypothalamic neurohormones, including arginine vasopressin (AVP). In situ hybridization techniques have been used to study the regulation of neuropeptide messenger ribonucleic acids in the hypothalamus. Owing to the relatively slow time course of the changes in cytoplasmic messenger ribonucleic acid concentrations, rapid alterations in the level of neuropeptide gene transcription could not be detected. Because of its rapid processing, the nuclear level of the heteronuclear ribonucleic acid should reflect the rate of its synthesis, namely the transcription of the gene. We have used in situ hybridization with a probe complementary to a portion of an intronic sequence of the rat AVP gene to study rapid changes in the level of AVP gene transcription during emotional stress. The specificity of our technique was demonstrated by the localization of the hybridization signals in the paraventricular nucleus, the supraoptic nucleus and the suprachiasmatic nucleus, and was confirmed by the nuclear localization of the labeling. Isolation and exposure of male rats to a novel environment induced an activation of the pituitary-adrenal axis and an increase in AVP heteronuclear ribonucleic acid concentrations in the paraventricular nucleus 2 h after the onset of the stress, suggesting that an increased AVP gene transcription may play a role in the activation of the pituitary-adrenal axis in response to emotional stress.

Animals↗
PubMed1993

[Stress. Neuroendocrine aspects].

All kind of stress produce an endocrine response. These hormonal responses can serve as stress indicators. The main peripheral endocrine responses to stress are the activation of adrenal corticoids, the stimulation of Growth Hormone (GH) and prolactin secretion, and the inhibition of insulin and gonadal secretion. Except for the inhibition of insulin release, all these hormonal variations depend on the adenohypophysis activity: stimulation of Adrenocorticotrophin hormone (ACTH), GH and prolactin, and inhibition of gonadotrophins (LH-FSH) secretions. Several lines of evidence demonstrate that specific hypothalamic Neuro-hormones stimulate or inhibit the hypophysial activity in response to stress. However, due to methodological difficulties, only measurements of peripheral hormones can be used as stress indicators.

Adrenocorticotropic Hormone↗