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Biomedical subjects

R C Gaillard

Publications and source records attributed to R C Gaillard.

At least 127 records · Page 7Linked to original sources
PubMed1984

Topographical and ontogenetic study of the neurons producing growth hormone-releasing factor in human hypothalamus.

Neurons producing growth hormone-releasing factor have been characterized and analyzed by immunohistochemistry in the hypothalami of human fetuses, neonates, infants and adults, using two antibodies against human pancreatic GRF (hpGRF). One of the antibodies recognized both the hpGRF(1-40)OH and hpGRF(1-44)NH2 in the mid portion (between the 28th and 39th amino acid), the other one specifically recognized the C-terminal end of hpGRF(1-44)NH2. These two antibodies stain a single neuronal system with cell bodies mainly located in the infundibular (arcuate) nucleus, and in the ventromedial and lateralis tuber nuclei. These neurons project to the median eminence where they give numerous endings in contact with portal vessels. These neurons are distinct from those containing LH-RH, somatostatin, CRF or pro-opiocortin. In fetuses, neurons immunoreactive with hpGRF antibodies are first detected at the 29th week. They display a neuroblastic aspect which persists after birth. Immunoreactive fibers are detectable in the median eminence after the 31st week. These results demonstrate that the infundibular nucleus plays a major role in control of GH secretion in man and that secretion of GRF appears late during fetal life; this suggests that the first stages of differentiation and development of GH producing cells in the human fetus do not depend on hypothalamic GRF secretion.

Adult↗
PubMed1984

RU 486: a steroid with antiglucocorticosteroid activity that only disinhibits the human pituitary-adrenal system at a specific time of day.

RU 486 is a synthetic steroid hormone antagonist which acts at the receptor level. It has both intrinsic anti-progesterone and antiglucocorticosteroid properties in animals. We investigated the antiglucocorticosteroid activity in humans by evaluating the pituitary-adrenal response to RU 486 in men and in pregnant and nonpregnant women. In non-pregnant women, RU 486 (approximately equal to 1 mg/kg of body weight per day) produced an interruption of the luteal phase without affecting the pituitary-adrenal axis, thereby indicating a more potent anti-progesterone than antiglucorticosteroid effect. In the course of pregnancy interruption by RU 486 (approximately equal to 4 mg/kg per day), there was a significant increase in plasma corticotropin, beta-lipotropin, and cortisol concentrations. In normal men, RU 486 administration led to a dose-dependent stimulation of plasma corticotropin, beta-endorphin, and cortisol. This disinhibition of the pituitary-adrenal axis was only observed during the morning hours of the circadian rhythm. When administered concomitantly with 1 mg of dexamethasone at midnight, 6 mg of RU 486 per kg completely suppressed the dexamethasone inhibitory effect on the pituitary-adrenal axis. These results indicate that RU 486 is an antiglucocorticosteroid that disrupts the negative pituitary feedback of both the morning cortisol rise and administered dexamethasone. Furthermore, they demonstrate the possibility of optimizing the anti-progestational effect of the compound and its potential use for human fertility control by modifying the dose and the time of administration of the drug and thereby minimizing the antiglucocorticosteroid effect.

Abortifacient Agents, Steroidal↗
PubMed1984

Properties of rat anterior pituitary vasopressin receptors: relation to adenylate cyclase and the effect of corticotropin-releasing factor.

Crude plasma membrane fractions were prepared from female Wistar rat anterior pituitaries. These fractions contained a single population of specific 3H-labeled [8-lysine]vasopressin [( 3H]vasopressin) binding sites with a dissociation of constant (Kd) of 8 +/- 2 X 10(-9) M and maximal binding capacity of 244 +/- 45 fmol/mg of protein. The Kd values for a series of vasopressin structural analogues with selective vasopressor or antidiuretic activities were determined together with the corresponding corticotropin-releasing activities (isolated perfused pituitary cells were used). A good correspondence was found between the two sets of values, suggesting that the detected vasopressin binding sites are the receptors involved in vasopressin-induced corticotropin release. The order of potency of these analogues for the binding to hypophysial receptors was similar to that found for the binding to the receptors involved in the vasopressor response. Corticotropin-releasing factor and angiotensin did not affect vasopressin binding to pituitary membranes. Median eminence extracts inhibited [3H]vasopressin binding with an efficiency very close to that expected from their vasopressin content. Corticotropin-releasing factor activated, and angiotensin inhibited, the adenylate cyclase activity of pituitary membranes. Under the same experimental conditions, vasopressin did not influence adenylate cyclase activity nor did it affect the corticotropin-releasing factor-induced activation. These data support the view that vasopressin is one component of the multifactorial regulation of corticotropin release and that it acts through a cAMP-independent pathway. The potentiation by vasopressin of corticotropin-releasing factor-induced cAMP accumulation in intact cells very likely proceeds through indirect mechanisms, which are not expressed in broken cell preparations.

Adenylyl Cyclases↗
PubMed1983

Studies of the factors modulating antidiuretic hormone excretion in man in response to the osmolar stimulus: effects of oestrogen and angiotensin II.

The aim of this study was to assess the influence of hormones known to regulate fluid and electrolyte balance on the release of antidiuretic hormone induced by raising serum osmolality. The stimulus provoked by the infusion of a 2.5% NaCl solution induces an increase of urinary [arginine-8]-vasopressin from 1.12 to 2.64 ng/h in men and from 1.65 to 7.27 ng/h in women as has been previously reported. These results were compared to those obtained in males infused with angiotensin II (AII) before and during a hypertonic sodium load and in males infused with hypertonic saline on the fourth day of administration of ethinyl-oestradiol. During the combined infusion of AII and then hypertonic saline, the mean hourly urinary excretion of AVP increased from 2.8 to 5.67 ng/h. Within each group the increase of urinary AVP was highly significant. The rise of urinary AVP during AII infusion was significantly different from the rise observed both in untreated males and untreated females, lying in between. The mean hourly excretion rate of AVP increased before and after hypertonic saline loading from 2.65 to 5.3 ng/h in males pre-treated with ethinyl-oestradiol. The significant difference observed between males and females is reduced when males treated with oestrogen were compared to female subjects. In each group plasma renin activity decreased to low values during the salt-loading test. During oestrogen treatment PRA and plasma renin substrate rose, while urinary aldosterone remained almost unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1982

Opiate modulation of the pituitary-adrenal axis: effects of stress and circadian rhythm.

The opiate control of the pituitary-adrenal axis has been investigated in normal subjects. The infusion of 1 mg of the met-enkephalin analogue, DAMME, led to a fall in circulating cortisol in spite of a fall in blood pressure. Conversley, 16 mg of the opiate antagonist, naloxone led to brisk and pronounced elevations in plasma ACTH, lipotrophin (LPH) and cortisol. The rise above basal levels was consistent, irrespective of whether the infusion was given at 09.00, 18.00, or 23.00 h; the peak response obtained was significantly less at 23.00 h than at either 09.00 or 18.00 h. Finally, insulin-induced hypoglycaemia (0.15 u/kg) or naloxone (25 mg) produced a similar rise in plasma cortisol which was no different when the two stimuli were combined. It is suggested that there is a constant tonic inhibition of the pituitary-adrenal axis by endogenous opiates throughout 24 h, and that the circadian rhythm of ACTH/LPH secretion is not due to changes in opiate tone. However, disinhibition of this tone is likely to be responsible, at least in part, for the rise in cortisol in response to hypoglycaemic stress.

Adolescent↗
PubMed1982

Binding and activation properties of angiotensin II in dispersed rat anterior pituitary cells.

The properties of angiotensin II receptors were studied in isolated rat anterior pituitary cells prepared by trypsin digestion. Angiotensin II bound in a time- and temperature-dependent manner to pituitary cells, with Kd of 4.1 x 10(-9) M. The heptapeptide, des-Asp1-angiotensin II, had only one-tenth of the affinity of the octapeptide (Ki = 5.5 x 10(-8) M). These two peptides displayed a similar potency ratio in their ability to stimulate ACTH release from pituitary cells. These results indicate that angiotensin II may play a regulatory role in controlling ACTH secretion from the pituitary gland.

Angiotensin II↗
PubMed1981

The opioid control of LH and FSH release: effects of a met-enkephalin analogue and naloxone.

The effect of long-acting analogue of met-enkephalin (DAMME) and naloxone on gonadotrophin secretion has been investigated in man. In menopausal women DAMME induced a progressive fall in LH to approximately 60% of basal levels at 3 h, which was blocked by naloxone; there was a smaller fall in FSH that did not attain statistical significance. However, the LHRH-induced rise in LH and FSH in young male volunteers was unaffected by pretreatment with a high-dose DAMME infusion. Naloxone infusion in young male and female normal subjects produced a significant rise in both LH and FSH. Long-term infusion of naloxone appeared to increase the rate, and possibly the amplitude, of LH pulsatility. These results suggest that met-enkephalin-like opioid peptides exert a tonic inhibitory control of LH release in both menopausal and young subjects of both sexes. This control is most likely to be at the level of the hypothalamus, and involves modulation of pulsatile LHRH release.

Adolescent↗
PubMed1981

Studies off the opiate control of prolactin, GH and TSH.

Opiate peptides are known to influence the secretion of several anterior pituitary hormones under basal conditions. Further studies on prolactin, GH and TSH have therefore been performed in normal subjects, under basal and stimulated conditions, using an opiate agonist and antagonist. Sixteen mg naloxone had no effect on the basal release of prolactin or GH, but lowered TSH. An infusion of the met-enkephalin analogue DAMME (1 mg) increased GH, and produced an exaggerated response of both prolactin and TSH to 200 micrograms TRH i.v. The peak responses of both prolactin and GH to hypoglycaemia were unaffected by pretreatment with either low-dose (0.4 mg) or high-dose (25 mg) naloxone, or DAMME (0.25 mg). These results suggest that opiate peptides are unlikely to play a major role in the tonic or hypoglycaemia-stimulated release of prolactin and GH, although they may be of importance in the control of TSH.

Adolescent↗
PubMed1981

The effects of a met-enkephalin analogue on ACTH, beta-LPH, beta-endorphin and MET-enkephalin in patients with adrenocortical disease.

Thirteen patients with either Addison's disease, or Cushing's disease treated by bilateral adrenalectomy, were infused with the long-acting met-enkephalin analogue DAMME. In patients with Addison's disease significant and pronounced falls in ACTH and N- and C-terminal beta-LPH were seen; chromatography suggested that beta-endorphin fell concomitantly. Three out of four patients with Cushing's disease who had not received pituitary irradiation, also showed a decrease in plasma ACTH and N- and C-terminal beta-LPH; however, no change was seen in any of the irradiated patients. The changes were naloxone reversible. The levels of plasma met-enkephalin were normal and did not change after DAMME in any group of patients. These results are interpreted as suggesting that there are inhibitory opiate receptors controlling the release of ACTH, beta-LPH, and beta-endorphin.

Addison Disease↗
PubMed1981

Angiotensin II stimulates the release of ACTH from dispersed rat anterior pituitary cells.

In a rat anterior pituitary dispersed cell system, angiotensin II was found to stimulate the release of ACTH at concentrations ranging from 100 pmol/l to 1 mumol/l, with a maximal response being given by 10 nmol/l. The angiotensin II antagonist, saralasin, was able to block completely at a concentration of 1 mumol/l the stimulation of ACTH induced by 10 nmol/l angiotensin II, but had no effect on the basal release. The log dose-response curve for ACTH release by angiotensin II was shifted to the right in a parallel fashion by saralasin 10 nmol/l, suggesting competitive antagonism. The stimulation of ACTH release by a rat stalk-median eminence extract or by arginine vasopressin was unaffected by saralasin. The data are interpreted as suggesting that rat corticotrophs contain angiotensin II receptors, and that these may be involved in ACTH release in response to hypovolaemic stress.

Adrenocorticotropic Hormone↗
PubMed1976

Effect on plasma aldosterone, renin activity and cortisol of acute volume depletion induced by ethacrynic acid under constant infusion of angiotensin II and dexamethasone in man.

The influence on plasma aldosterone of acute volume depletion induced by ethacrynic acid was studied in man. The experiments were performed during the morning in supine healthy males receiving a control infusion of 5% glucose or an infusion of angiotensin II (AII) to suppress endogenous renin production or an infusion of dexamethasone to suppress endogenous ACTH. Ethacrynic acid induced in all circumstances a similar diuresis and volume depletion. The rise of plasma renin activity (PRA) was effectively suppressed by AII and the rise of plasma cortisol by dexamethasone. Plasma aldosterone (PA) rose markedly even when the elevation of PRA or cortisol were suppressed. Yet when both endogenous renin and ACTH secretion were blocked, PA rose much less after ethacrynic acid. This residual increase could be attributed mainly to a decrease of the metabolic clearance rate (MCR) of aldosterone which had been measured before and after ethacrynic acid administration. The data presented indicate that multiple factors influencing PA after acute volume depletion could be dissected out and that renin, ACTH and a decrease of the MCR each contribute to the elevation of PA.

Adrenocorticotropic Hormone↗
PubMed1975

Radioimmunoassay of (8-arginine)-vasopressin. II. Application to determination of antidiuretic hormone in urine.

A radioimmunoassay for [8-arginine]-vasopressin (AVP), previously described (Czernichow et al. 1975) has been used for the determination of antidiuretic hormone in a 4 ml urine sample. AVP is extracted from acidified urine with a cation exchanger (Amberlite CG 50) with an overall recovery of 72%. The blank value measured in extracted samples of urine was 0.29 pg/ml +/- 0.21 (SEM) and calculated by extrapolation of the regression line of the recovery experiment was 0.49 pg/ml. The coefficient of variation within-assay was 13% and between-assay 18%. Addition of the amounts of AVP found in each specimen of urine voided gave results nearly identical to those of the amounts found in 24 h pool of urine, indicating that the assay was not affected by changes in concentration of the other urinary components during the day. The daily urinary excretion of AVP measured in 34 subjects was found to be 34 ng in 17 women and 70 ng in 17 men, a significant difference. Urinary concentration and excretion rate of AVP rose during thirst test and during Carter-Robbins test performed in 13 healthy subjects. In the latter test it was observed that the women displayed a strikingly more pronounced AVP elevation after the osmolar stimulus than the men. In both sexes a significant correlation was found between AVP excretion rate and plasma osmolality as well as free water clearance. Three cases of complete or incomplete diabetes insipidus and potomania could be clearly differentiated according to the total output of AVP during the thirst test. Extremely high values of AVP were found in the urine of 5 subjects with Schwartz-Bartter syndrome associated with bronchogenic tumours.

Arginine Vasopressin↗
PubMedDate not supplied

Sexual dimorphism in the hypothalamo-pituitary-adrenal (HPA) axis and TNFalpha responses to phospholipase A2-related neurotoxin (from crotalus durissus terrifcus) challenge.

Neuroendocrine-immune interactions are vital for the individual's survival in certain physiopathological conditions such as sepsis and tissular injury. It is known that several snake venoms (SV) are potent neurotoxic compounds and that their main component is a specific phospholipase type 2 (PLA2). It has been recently described that the venom from crotalus durissus terrificus (SV) possesses a cytotoxic effect in different in vitro and in vivo animal models. In the present study we investigated whether SV is able to stimulate both TNFalpha and neuroendocrine functions in a sexual dimorphic fashion. For this purpose the modulatory role of endogenous sex steroids during neurotoxemia was evaluated. Our results indicate that SV (25 microg/animal) stimulates the hypothalamo-pituitary-adrenal axis and TNFalpha secretion when administered (ip) to adult male mice, such responses were characterized by a time-related enhance in plasma glucose, ACTH, corticosterone and TNFalpha levels. SV-stimulated glycemia, corticosteronemia and adrenal glucocorticoid were sexually dimorphic. Twenty-day gonadectomized mice showed a similar sexual dimorphism to that found in intact animals, however, they additionally showed a sexual dimorphic pattern in cytokine release in plasma 30 min post-SV. Estradiol (E2) treatment, in gonadectomized mice, abolished some characteristics of the sexual dimorphism, such as hyperglycemia, hypercorticosteronemia and hypercytokinemia. Finally, in vitro experiments indicate that: a) gonadectomy increased spontaneous and SV-stimulated cytokine output by incubated peripheral mononuclear cells (PMNC), regardless of the sex; and b) despite E2 treatment, in gonadectomized, did not modify the pattern of basal and SV-elicited TNFalpha secretion induced by orchidectomy, fully reversed the enhance in basal and SV-stimulated cytokine release found after ovariectomy alone. Our results further indicate that neurotoxemia, due to SV challenge, induces several symptoms common to those of inflammatory stress; they also strongly support that both gender and endogenous sex steroids are responsible for neuroendocrine-immunological sexual dimorphism.

Adrenal Glands↗