Search PubMedSearch

Biomedical subjects

F Boudouresque

Publications and source records attributed to F Boudouresque.

At least 37 records · Page 2Linked to original sources

Effect of passive immunization against corticotropin-releasing factor (CRF) on the postadrenalectomy changes of CRF binding sites in the rat anterior pituitary gland.

The concentration of corticotropin-releasing factor (CRF)-binding sites decreases in the rat anterior pituitary after adrenalectomy; this change may be related either to a direct effect of the circulating glucocorticoids at the pituitary level or to a desensitization of CRF receptors through an increased CRG release in hypophysial portal blood. In order to examine the latter possibility we have measured plasma adrenocorticotropin hormone (ACTH) levels and the number of anterior pituitary CRF binding sites in sham-operated and 24-hour adrenalectomized rats after blockade of endogenous CRF by passive immunization with an antiserum anti-rat CRF (CRF-AS), or after injection of normal rabbit serum (NRS). In NRS-injected rats, after sham operation, plasma ACTH concentration increased (227 +/- 34 vs. 118 +/- 19 pg/ml in controls) without change in CRF-binding sites capacity (20.7 +/- 2.6 vs. 24.6 +/- 3.5 fmol/mg protein in controls). Adrenalectomy induced a large rise in plasma ACTH (785 +/- 89 pg/ml) and a decrease in the number of CRF-binding sites (12.2 +/- 1.7 fmol/mg protein). After CRF-AS injection, plasma ACTH was normalized in sham-operated animals (149 +/- 24 pg/ml) and significantly reduced in adrenalectomized rats (472 +/- 76 pg/ml); the adrenalectomy-induced decrease in the number of CRF-binding sites was unaffected by the CRF-AS administration (12.2 +/- 1.7 fmol/mg protein). The administration of dexamethasone to adrenalectomized rats significantly reduced plasma ACTH concentrations (23.3 +/- 10.6 pg/ml) and prevented the loss in CRF-binding sites capacity (20.7 +/- 1.3 fmol/mg protein).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy

Effects of chronic maternal dexamethasone treatment on the hormones of the hypothalamo-pituitary-adrenal axis in the rat fetus.

Different hormones of the hypothalamo-pituitary-adrenal axis (corticotropin-releasing factor, adrenocorticotropic hormone, corticosterone) were measured in brain pieces (stalk, median eminence, hypothalamus), hypophyses, adrenals and plasma of 21-day-old rat fetuses from mothers which were given either plain tap water or water containing dexamethasone acetate (10 micrograms/ml) from day 15 to 21 of gestation. Dexamethasone induced drastic reduction of body weight (-66% vs. controls), severe atrophy of the adrenals (-83%) and a sharp drop in their corticosterone content (-74%). Fetal plasma corticosterone levels were below the lower limit of detection of the competitive corticosteroid-binding globulin (CBG) radioassay (less than 0.01 microgram/ml). Both atrophy and severe reduction of the adrenal activity in fetuses from dexamethasone-treated females were in good correlation with a drastic decrease in plasma adrenocorticotropic hormone (ACTH) levels which were below the lower limit of detection of the radioimmunoassay (RIA) used (less than 10 pg/ml) and a significant reduction in pituitary ACTH content (-93%). The low corticostimulating activity of the fetal hypophyses was associated with a drop in both corticotropin-releasing factor (CRF) hypothalamic content (-57%) and concentration (-67%). The effects of dexamethasone on plasma and pituitary ACTH concentrations in 21-day-old fetuses were compared to those, previously reported, of encephalectomy and decapitation performed on day 16 of gestation. The reported data were consistent with the present results, suggesting both pituitary and hypothalamic sites for the in vivo inhibiting action of dexamethasone on the rat hypothalamic-pituitary-adrenal axis in late gestation.

Adrenocorticotropic Hormone

Evidence for high peptide alpha-amidation activity in the neonatal rat pancreas.

A high peptide alpha-amidating activity is present in a mitochondrial/secretory granules preparation from 3-day old rat pancreas. It is dependent on copper, ascorbate and molecular oxygen. This preparation is able to generate TRH when incubated with Pyroglu-His-Pro-Gly, a sequence present in the TRH precursor molecular. The peptide alpha-amidating activity may be involved in the high rate of TRH biosynthesis in the pancreas during the neonatal period. In the pancreas of adult rats which contain low levels of TRH, the peptide alpha-amidating activity is barely detectable.

Amidohydrolases

[Characterization and modulation of anterior pituitary binding sites for rat corticotropin releasing factor (r-CRF)].

Specific binding sites for rat CRF (r-CRF) have been characterized on rat anterior pituitary membranes. The binding of the radioiodinated analog of r-CRF (125I Tyr-r-CRF) was time, temperature, pH and protein dependent. No interaction was found with other neurohormones except with Arginine Vasopressin, but at supra physiological levels. Two classes of specific binding sites (high affinity and low affinity) for r-CRF were identified. Bilateral adrenalectomy provoked, since the 24th hour and up to 7 days, in addition of an increase of ACTH plasmatic levels, an abolition of the high affinity binding site; corticosterone treatment reversed these changes. This finding suggests that circulating glucocorticoids may control the anterior pituitary binding sites for CRF, either by a direct action on the anterior pituitary, or by a modulatory effect on hypothalamic CRF secretion.

Adrenalectomy

[Demonstration of a TRH precursor in the pancreas of the newborn rat].

This study allows the indirect demonstration of a precursor for TRH in pancreatic extracts of 2-days old rats. The sequential treatment of these extracts with trypsin and carboxypeptidase A is followed by a large increase in Pyroglutamyl Histidine Proline (TRH-OH). The molecular weight of the protein that gives rise to TRH-OH after enzymatic treatment ranges between 30,000 and 40,000 daltons. During ontogenesis. TRH levels decrease earlier and more rapidly than that of TRH-precursor levels. These data suggest that changes in the processing of TRH-precursor play a role in the diminution of TRH concentrations that is observed during the first two weeks of life.

Animals

TRH and TRH-OH in the pancreas of adult and newborn rats.

TRH and its metabolite TRH-OH have been measured by specific radioimmunoassays in acid extracts of pancreas in adults and developing rats. TRH and TRH-OH immunoreactivity had the same ontogenic pattern with a maximal concentration on day 4 followed by a progressive return towards adult levels on day 20. A significant linear correlation was found between TRH levels and the TRH/TRH-OH ratio. The range of TRH/TRH-OH ratio varied from 136 +/- 1.6, at the peak of concentrations of both peptides, to 18 +/- 3.9 on day 20. Pancreatic TRH and TRH-OH had the same elution pattern as corresponding synthetic peptides both on Biogel P2 and high-pressure liquid chromatography. The origin of TRH-OH as well as its potential function need further investigations.

Age Factors

Evidence for a precursor for TRH in the neonatal rat pancreas.

Immunoreactive TRH-OH is present at low concentrations in acid extracts from 2- days old rat pancreas. The sequential treatment of these extracts with trypsin and carboxypeptidase A is followed by a three- and ten-fold increase in TRH-OH IR respectively. The molecular weight of the protein that gives rise to TRH-OH after enzymatic treatment ranges between 30000 and 40000 daltons. The appearance of TRH-OH in the tryptic digest suggests that TRH-OH is the COOH-terminal sequence of this protein. These results are the first evidence that TRH biosynthesis occurs through a large molecule precursor. However, this is an indirect demonstration since TRH cannot be generated under these conditions due to the lack of enzymatic amidation activity.

Animals

[Corticotropin releasing factor].

The search for a neurohormone specifically controlling ACTH secretion resulted in the discovery of the corticotropin-releasing factor (CRF). This factor, located mainly in a paraventricular-infundibular hypothalamic tract, stimulates ACTH synthesis and secretion through a cAMP-dependent mechanism. The corticotropin-releasing factor is the predominant component of a complex control system of adrenal cortex secretion, which also includes catecholamines and the antidiuretic hormone. Its specificity as stimulant of the corticotropic function makes it an extremely useful tool for physiological and physiopathological studies of the hypothalamus-pituitary-adrenal cortex axis regulation.

Adrenocorticotropic Hormone

[Caudal epidural anesthesia in children. Study of endocrine changes].

Changes in serum levels of corticotrophin (ACTH), immunoreactive beta-endorphin, antidiuretic hormone and cortisol were compared in children undergoing minor surgery under either general anaesthesia with halothane or epidural anaesthesia by the caudal route. A rapid and major increase in hormone levels was observed under general anaesthesia but not under epidural anaesthesia.

Adrenocorticotropic Hormone

Interaction of opiates with opioid binding sites in the bovine adrenal medulla: I. Interaction with delta and mu sites.

In the present study we examined the interaction of opiates with the delta and mu opioid binding sites in the bovine adrenal medulla. [3H][D-Ala2, D-Leu5]-enkephalin ( [3H]DADLE) in the presence of saturating concentrations of morphiceptin was used to analyze delta site interactions, whereas either [3H]DADLE in the presence of saturation concentrations of [D-Ser2, Leu5]-enkephalin-Thr6 (DSLET) or [3H][D-Ala2, Me-Phe4, Gly5-ol]-enkephalin ( [3H]DAGO) was used for the determination of mu sites. Both binding sites were found to interact stereoselectively with opiates. The binding was affected differentially by proteolytic enzymes (trypsin, alpha-chymotrypsin, pepsin), N-ethylmaleimide, and A2-phospholipase. Kinetic and equilibrium binding studies revealed that in each case radiolabeled opiates interact with one class of binding sites, following simple second-order bimolecular kinetics. Competition for binding by opiates and opioid peptides confirmed the delta and mu selectivity of these sites. Monovalent (Na+, Li+, K+) and divalent (Mg2+, Mn2+, Ca2+) ions interacted differentially with these two binding sites: In general, monovalent cations affected preferentially the apparent number of binding sites, whereas divalent ions modified the equilibrium dissociation constant. Furthermore, positive or negative cooperativity and an apparent heterogeneity of binding sites were detected under some ionic conditions.

Adrenal Medulla

Interaction of opiates with opioid binding sites in the bovine adrenal medulla: II. Interaction with kappa sites.

In this study we examined the interaction of opiates with kappa binding sites in the bovine adrenal medulla. [3H]Ethylketocyclazocine (EKC), [3H]etorphine, and [3H]bremazocine stereoselective bindings were used to assay these interactions. The kappa sites were found to be heterogeneous: [3H]bremazocine identified with high affinity all subtypes of these sites. [3H]EKC, in the presence of saturating concentrations of [D-Ala2, D-Leu5]-enkephalin (DADLE) (5 microM), was used to identify kappa 1 sites, on which dynorphin A (1-13) bound with high affinity. Either [3H]EKC or [3H]etorphine in the presence of 5 microM DADLE identified the kappa 2 subtype. This subtype was found to interact with beta-endorphin and especially with the octapeptide Met5-enkephalyl-Arg6-Gly7-Leu8. Furthermore, [3H]etorphine identified in the bovine adrenal medulla a third high-affinity component, in the presence of 5 microM DADLE. This residual interaction was found to be equally stereoselective and presenting kappa selectivity. Met5-enkephalyl-Arg6-Phe7 interacted preferentially with this site. The three kappa subtypes interacted differentially with monovalent (Na+, K+, and Li+) and divalent (Ca2+, Mg2+, and Mn2+) ions by modification of the apparent concentration of the accessible sites and/or by changes of the apparent KD for radioligands. Modifying agents (proteolytic enzymes, thiol-modifying reagents, and A2-phospholipase) produced different effects on each subtype of the kappa site, suggesting a different protein (or protein-lipid?) composition.

Adrenal Medulla

Characterization of enkephalins and related peptides in rat hypophysial portal blood.

Rat hypophysial portal blood, collected from the pituitary stalk, was extracted and enkephalins were assayed by different RIA. Met-Enk-IR and Leu-Enk-IR levels were 1635 +/- 470 pg/ml and 125 +/- 50 pg/ml, respectively. Using HPLC characterization, the presence in portal blood of Met-Enk, Leu-Enk, proenkephalins fragments and dynorphin1-17 has been demonstrated. An unidentified Met-Enk-IR peptide has also been found.

Animals

[Effects of adrenal medullectomy and passive immunization with an anti-CRF antiserum on the corticotropin secretion in response to stress in Long-Evans rats].

Ether stress-induced ACTH and corticosterone secretion is similar in 60 days adrenal medullectomized and intact Long-Evans Rats. Passive immunisation with a 41-CRF antiserum impairs corticotropic function after stress. This decrease is more pronounced in adrenal medullectomized than in intact animals. These results suggest that epinephrine plays a minor role on the stress induced ACTH secretion. This role can be demonstrated only after immunoneutralisation of endogenous 41-CRF.

Adrenal Medulla

Adrenal medullary opiate receptors. Pharmacological characterization in bovine adrenal medulla and a human pheochromocytoma.

We have characterized the opiate binding sites on the membranes of bovine adrenal medulla and human pheochromocytoma, using 3H-labeled D-Ala2-D-Leu5-enkephalin ( [3H]DADLE), [3H]etorphine, and [3H]ethylketocyclazocine ( [3H]EKC). Binding was stereoselective in both membrane preparations. Association and dissociation kinetics showed that steady state was achieved after 20-25 min of incubation at 37 degrees. Saturation experiments were performed in the absence or in the presence of morphiceptin (1 microM), which masks the mu sites, D-Ser2-Leu-enkephalin-Thr6 (100 nM), which masks delta sites, or DADLE (5 microM), which was found to mask the delta, mu, and benzomorphan receptor. Taking into consideration the affinities of the three radioligands used (DADLE identifying the delta and mu sites when used in the nanomolar range; etorphine identifying the delta, mu, and benzomorphan sites; EKC identifying the delta, mu, kappa, and benzomorphan receptors) we have characterized pharmacologically the opiate sites present on bovine and human membranes. Human pheochromocytoma membranes contained (a) mu binding sites (15 fmoles/mg of protein, KD [3H]etorphine 1.0 nM, [3H]EKC 5.4 nM, [3H]DADLE 5.6 nM); (b) kappa sites (41 fmoles/mg of protein, KD [3H]EKC 1.0 nM); (c) benzomorphan sites (115 fmoles/mg of protein, KD [3H]etorphine and [3H]EKC 1.0 nM). On bovine membranes we have detected (a) delta binding sites (10 fmoles/mg of protein, KD [3H]DADLE 0.7 nM); (b) mu sites (24 fmoles/mg of protein, KD [3H]DADLE 2.9 nM, [3H]etorphine 0.2 nM, [3H]EKC 3.4 nM); (c) kappa sites (12 fmoles/mg of protein, KD [3H]EKC 0.4 nM); (d) benzomorphan sites (80 fmoles/mg of protein, KD [3H]etorphine 0.2 nM, [3H]EKC 1.3 nM); (e) a residual high-affinity (20 fmoles/mg of protein, KD 0.2 nM) site identified by [3H]etorphine in the presence of 5 microM DADLE. The relative proportions of benzomorphan sites were equal in both tissues (65% of the high-affinity sites) whereas kappa receptors were more abundant on human membranes (25%) than on bovine membranes (9% of the high-affinity sites).

Adrenal Gland Neoplasms

Opiate binding sites spectrum on bovine adrenal medullas and six human pheochromocytomas.

Opiate binding sites have been characterized on membranes from bovine adrenal medullas and six human pheochromocytomas. In human tumors, large variations in site distribution were observed. Kappa and benzomorphan sites represented the majority of the sites detected. The heterogeneity of the opiate sites on these tissues could explain the observed differences in the pharmacological responses to opiates of cultured cells from these tissues. Furthermore, adrenal medullas could be a good model for the study of the kappa site action at the cellular level.

Adrenal Gland Neoplasms

[Effects of electric stimulation of the para-ventricular nucleus on corticotropin function in Long-Evans and Brattleboro rats].

Two peptides have a strong corticotropin releasing factor (CRF) activity: arginine vasopressine (AVP) and a 41-residue peptide (41-CRF). Both peptides are present in high concentration in the PVN of the Rat, a zone of the hypothalamus at which electrical stimulation elicits ACTH release. Since homozygous Brattleboro Rats (Di/Di) congenitally lack endogenous AVP, it was of interest to compare the ACTH and corticosterone release after electrical stimulation of the PVN in Long-Evans (L.E.) and Di/Di Rats. In both L.E. and Di/Di Rats, there is a significant increase in plasma ACTH and corticosterone after electrical stimulation of the PVN. However, corticosterone levels are significantly lower in Di/Di than in L.E. Rats whether the Rats have been stimulated or not. It is concluded that a physiological CRF activity is present in the PVN of Di/Di Rats independently of the CRF like activity of AVP.

Adrenocorticotropic Hormone

[Effect of passive immunization with an antiCRF antiserum on the secretion of ACTH in rats].

A peptide with 41-residue having CRF activity both in vivo and in vitro has recently been isolated from ovine hypothalami (41-CRF). Passive immunization of Sprague-Dawley Rats with an antiserum against this peptide is followed by a significant decrease in plasma ACTH and cortisosterone levels under basal conditions as well as after ether-stress and adrenalectomy. These data demonstrate that 41-CRF plays a major role in the physiological regulation of ACTH secretion.

Adrenocorticotropic Hormone

Influence of endogenous somatostatin on growth hormone and thyrotropin secretion in neonatal rats.

When gestating rats were injected iv with an antiserum to somatostatin (SRIF-AS) during the last week of gestation, serum GH levels in fetuses and 6-h-old newborn rats were not significantly different from controls. Similarly, 2 h after the ip administration of SRIF-AS, no change in serum GH concentration was observed in 2-h-old rats. However, under the same conditions, a significant increase in serum GH was observed in 24-h-old rats and in 2- to 60-day-old rats. The injection of SRIF-AS neither changed basal serum TSH levels during the neonatal development nor in the adult stage. A significant increase in TRH-induced TSH release was observed after the third postnatal day. It is concluded that endogenous SRIF plays a physiological role in GH release by 24 h of age in the rat and that the fall in GH secretion that normally occurs during the first week of life is due to the development of inhibitory mechanisms mediated by hypothalamus SRIF. Additionally the results suggest that the influence of SRIF upon TSH secretion is present before that of TRH.

Aging