Biomedical subjects

R C Gaillard

Publications and source records attributed to R C Gaillard.

At least 91 records · Page 5Linked to original sources

PubMed1991

Dexamethasone treatment in man induces changes in 24-hour growth hormone (GH) secretion profile without altering total GH released.

Glucocorticoids inhibit growth in man and laboratory animals and reduce the GH response to the majority of exogenously administered stimuli. Recently, however, glucocorticoids have been shown to have varying effects on GH secretion depending on the time of administration and, furthermore, to be potent secretagogues in their own right. To investigate this further, we have carried out sampling over two 24-h periods in six normal male volunteers both before and directly after treatment with dexamethasone (DEX; 2 mg twice daily) for 96 h. After DEX administration, all volunteers showed an increase in mean GH secretion during the first 9 h of sampling (0900-1800 h) compared with pre-DEX control profiles (5.1 +/- 1.2 vs. 1.7 +/- 0.5 micrograms/L; P less than 0.001). DEX treatment also had the effect of delaying and attenuating the nocturnal peak; mean GH secretion between 0000-0200 h was significantly greater before DEX (13.6 +/- 2.7 micrograms/L) than after DEX (3.6 +/- 0.7 micrograms/L; P less than 0.001), whereas that between 0300-0800 h was greater after DEX (5.5 +/- 0.8 vs. 0.7 +/- 0.2 micrograms/L; P less than 0.001). Individual nocturnal peaks ranged from 7.0-56.8 micrograms/L, occurring between 0030-0200 h before DEX, and 2.6-21.2 micrograms/L, occurring between 0300-0400 h after DEX. Overall mean GH secretion was not significantly altered by DEX treatment (3.8 +/- 0.6 vs. 4.2 +/- 0.5 micrograms/L; P = NS). Total insulin-like growth factor-I (IGF-I) levels, measured after acid-ethanol extraction, were significantly increased by DEX treatment, with mean IGF-I over the 24-h sampling period rising from 292.2 +/- 31.8 to 425.9 +/- 37 micrograms/L (P less than 0.005). All individuals showed an increase in mean 24-h IGF-I of between 10-75%. In a second study, 12 male volunteers were treated with DEX in an identical manner, and blood was taken at 0800 h daily. Total IGF-I levels rose steadily from 307.9 +/- 13.3 micrograms/L, reached a plateau at 72 h and remained elevated at 96 h (424.9 +/- 16.5 micrograms/L; P less than 0.001). These results suggest that glucocorticoids alter the normal pattern of GH secretion with an increase in daytime levels, but a delaying and attenuating effect on the nocturnal pulse. Previous studies have suggested that IGF-I concentrations are decreased by steroid treatment, but these have been based on bioassay systems. Total IGF-I, measured by RIA, would appear to be consistently elevated; the apparent decrease seen in bioassay systems may be due to glucocorticoid-induced changes in binding protein concentrations.

Adult↗

PubMed1991

Effects of glucocorticoid treatment and acute passive immunization with growth hormone-releasing hormone and somatostatin antibodies on endogenous and stimulated growth hormone secretion in the male rat.

Despite causing marked inhibition of somatic growth, glucocorticoids enhance both the response to GH-releasing hormone (GHRH) and the amplitude of naturally occurring GH secretory pulses in the male rat. The relative contribution of the two major hypothalamic regulatory factors for GH (somatostatin and GHRH) to these observed effects remains speculative. In the present studies, we have investigated endogenous and stimulated GH release in rats pretreated with glucocorticoid or vehicle, and the effects of passive immunoneutralization of somatostatin or GHRH. In an initial study, four groups of eight rats were treated with either saline or various doses of a depot preparation of betamethasone: low dose, 0.85 mg; medium dose, 1.7 mg; high dose, 3.4 mg. All doses significantly suppressed body weight gain, total adrenal weight and concentrations of both plasma corticosterone and pituitary ACTH. Seven days after betamethasone treatment, GH responses to an i.v. injection of 1 microgram human GHRH(1-29) were evaluated during pentobarbitone anaesthesia. Compared with saline-treated controls (peak GH concentration of 506.0 +/- 68.5 micrograms/l), peak GH levels were enhanced by the low dose (704.4 +/- 47.8 micrograms/l, P less than 0.05), unaltered by the medium dose (543 +/- 65.8 micrograms/l) and suppressed by the high dose (312.7 +/- 55.2 micrograms/l, P less than 0.05) of betamethasone. Similarly, the area under the secretory curves was increased by 46% following the low dose (P less than 0.01), unaltered by the medium dose and reduced by 33% after the high dose of betamethasone. In a second study, rats were pretreated for 7 days before blood sampling with either the medium dose of betamethasone or saline. On day 5, 48 h before blood sampling, an indwelling venous catheter was fitted enabling sampling of conscious rats. On the day of study, blood samples were taken at 30-min intervals over an initial 2-h period (10.00-12.00 h). Following the sample at 12.00 h, rats were given the reconstituted and dialysed immunoglobulin fraction from either control sheep serum (NSIgG), sheep anti-rat GHRH serum (GHRHab) or sheep anti-somatostatin serum (SRIHab), and samples were taken for a further 90 min (12.30-14.00 h). Directly after the sample at 14.00 h, GH stimulation was effected in all rats using 1 microgram human GHRH(1-29) with samples taken at 5, 10, 20 and 40 min following stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1990

Regional distribution of neuropeptide Y-like immunoreactivity in human hypothalamus measured by immunoradiometric assay: possible influence of chronic respiratory failure on tissue levels.

The regional distribution of neuropeptide Y-like immunoreactivity (NPY-IR) in the human hypothalamus has been determined using a highly specific immunoradiometric assay. Hypothalami were removed during postmortem examination from 19 subjects. The pituitary stalk and 11 anatomically defined nuclei and areas were microdissected from one or both sides of each hypothalamus. NPY-IR was detectable in the acid extracts of tissue samples prepared from all the hypothalamic regions studied, with the highest concentrations being found in the infundibular nucleus (325 +/- 53 fmol/mg wet weight of tissue) and the ventromedial nucleus (217 +/- 22 fmol/mg). For the 11 subjects where both sides of the hypothalamus were dissected, values obtained for the areas in one half showed a good degree of symmetry with the corresponding areas on the contralateral side. The infundibular nucleus exhibited the greatest range of values (72-1,137 fmol/mg). Interestingly, variations in other parts of the hypothalamus were observed to parallel those of this nucleus. Expressed as correlation coefficients (r), levels in the infundibular nucleus appeared to be most closely related to those of the ventromedial nucleus (VM; r = 0.89) and paraventricular nucleus (PV; r = 0.84). In addition, retrospective analysis of the clinical histories showed that all patients with very high NPY levels in the infundibular nucleus (621.0 +/- 107.7 fmol/mg; n = 8) had suffered from respiratory failure or severe dyspnea of at least 10 days duration prior to death. The remaining patients (166.7 +/- 17.1 fmol/mg; n = 11) had either died 48 h from the onset of cardiorespiratory difficulties or of unrelated causes.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1990

Depletion of hypothalamic growth hormone-releasing hormone by neonatal monosodium glutamate treatment reveals an inhibitory effect of betamethasone on growth hormone secretion in adult rats.

Rats were treated with monosodium glutamate (MSG), 4 mg/g on alternate days for the first 10 days of life, to induce lesions of the arcuate nucleus and destroy the majority of growth hormone-releasing hormone (GHRH) neurones. At 10 weeks of age, control (n = 42) and MSG-treated (n = 36) male rats were used to test the effect of glucocorticoids on growth hormone (GH) secretion. Each treatment group was divided into six study groups to determine the effect of betamethasone (BM), administered either 3 or 20 h prior to sacrifice, alone and in combination with hypoglycaemia (insulin 0.1 U/100 g). BM treatment of male rats was without effect on plasma GH levels in control animals. In contrast, glucocorticoid administered either 3 h before sacrifice or the previous evening significantly reduced circulating GH (p less than 0.001) in MSG-treated animals. The difference in plasma GH response to BM pretreatment in control rats and those with lesions of the arcuate nucleus indicates a hypothalamic action of glucocorticoids, presumably on somatostatin and GHRH neurones. In control animals the effects appear to be counterbalancing, but following destruction of GHRH neurones an uncompensated inhibitory influence was observed. Male MSG-treated rats had lower body weight (-25%) and reduced hypothalamic GHRH (-89%) and pituitary GH content (-69%) compared to male controls. Female rats which had undergone the same neonatal MSG treatment (n = 40) when sacrificed 1 week after their male counterparts showed similar reductions in body weight (-15%), hypothalamic GHRH (-74%), and pituitary GH (-67%).(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1990

Tumor necrosis factor alpha inhibits the hormonal response of the pituitary gland to hypothalamic releasing factors.

Tumor necrosis factor alpha (TNF alpha), a monokine produced by activated macrophages and monocytes, may be an essential mediator of the pathogenesis and of the hormonal response to endotoxic shock. It has been suggested that an elevated level of TNF alpha is a marker for morbidity and mortality during septic shock, and that treatment with antibodies against TNF alpha decreases mortality. Because monokines have been shown to interact at the hypothalamic-pituitary level, we have studied the effect of TNF alpha on basal and stimulated hormone release from normal rat anterior pituitary cells. After 3 days of incubation, primary cultures of rat anterior pituitary cells were stimulated with either 0.5 ng/ml CRF, 3 ng/ml AVP, 10 ng/ml angiotensin II (AII), 10(-6) M TRF, 10(-8) M LHRH, or 10(-8) M GHRH, alone or in the presence of 20 or 50 ng/ml human or murine recombinant TNF alpha. The culture media were analyzed for ACTH, GH, LH, and PRL content. Each experiment was performed in triplicate and was repeated 3 to 8 times. Time-course experiments (n = 3) demonstrated that TNF alpha inhibited CRF-stimulated ACTH production over a period of 8, 16, and 24 h, but had no effect before a period of 4 h. At doses ranging from 1 to 100 ng/ml, TNF alpha did not affect basal ACTH secretion but inhibited CRF-stimulated ACTH release in a dose-dependent manner (ED50 approximately 10 ng/ml). At a dose of 50 ng/ml, TNF alpha inhibited AVP-stimulated ACTH release by 30% and blocked the effect of AII. TNF alpha (20 and 50 ng/ml) completely prevented the CRF-AVP potentiation of ACTH release. Similarly, TNF alpha inhibited the stimulated release of GH (100% inhibition), LH (35% inhibition), and PRL (100% inhibition). TNF alpha had no effect on the basal secretion of GH or LH but inhibited basal PRL in a dose-dependent manner. The administration of the monokine did not cause any cellular damage because 48 h after removal of the TNF alpha treatment the cells showed normal basal and stimulated hormone levels in response to their specific stimuli. Incubation of TNF alpha solutions with antibody to TNF alpha reversed all TNF alpha actions. These data suggest that TNF alpha inhibits the secretion of pituitary hormones and particularly suppresses the response of the corticotroph cells. This inhibitory effect may contribute to the increased mortality observed in cases of severe septic shock with high circulating TNF alpha levels.

Adrenocorticotropic Hormone↗

PubMed1990

Stimulation of growth hormone release in man by the potent D2-dopamine agonist CV 205-502: comparison of responses to intravenous and oral administration.

It is well known that dopaminergic agents are stimulators of GH release in man, and although responses are sometimes unreliable, oral L-dopa and iv dopamine have frequently been employed in the evaluation of GH-deficient states. To assess the effects on GH secretion of a new potent D2-dopamine agonist, the octahydrobenzo(g)quinoline CV 205-502 (CV) we have investigated the GH responses in healthy male volunteers to four different iv doses. For this purpose 3 separate groups of 9 subjects were studied. The respective groups were administered on separate occasions 10 micrograms CV and placebo (group 1), 5 micrograms, 2.5 micrograms, and placebo (group 2), and 1 microgram and placebo (group 3). Each subject received drug and placebo in a double blind randomly assigned order, with at least 5 days between their administration. Active compound or placebo was infused over 30 min, and blood sampling was carried out for 72 h after cessation of infusion. Peak GH levels occurred between 45-60 min after the end of the infusion; the observed maximum GH concentrations were 19.2 +/- 2.9 micrograms/L (10 micrograms, iv; P less than 0.001 vs. placebo), 9.61 +/- 2.1 (5 micrograms, iv; P less than 0.001 vs. placebo), 4.7 +/- 1.7 (2.5 micrograms, iv; P less than 0.05 vs. placebo), and 1.9 +/- 0.8 micrograms/L (1 micrograms, iv; P = NS vs. placebo). The mean integrated GH secretion expressed in arbitrary units [area under the response curve (AUC)] up to 3 h postinfusion showed a typical dose-response relationship. Mean values were 1715 +/- 269.4 (10 micrograms, iv; P less than 0.001 vs. placebo), 956.1 +/- 189.9 (5 micrograms, iv; P less than 0.001 vs. placebo), 312.8 +/- 105.8 (2.5 micrograms, iv), and 162.8 +/- 47.5 (1 microgram, iv). In a second study with a separate group of 18 volunteers, we compared the GH response to an oral dose of 100 micrograms CV with those to 5 micrograms CV given iv and placebo treatment. Peak GH values in this study were 20.3 +/- 5.5 micrograms/L (100 micrograms, orally; P less than 0.01 vs. placebo) and 14.6 +/- 2.8 (5 micrograms, iv; P less than 0.001 vs. placebo). Maximum levels occurred 45 min after the infusion and 90 min after ingestion (60 min relative to the end of the infusion).(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗

PubMed1989

Empty sella syndrome associated with diabetes insipidus: case report and review of the literature.

Alteration of posterior pituitary function in the empty sella syndrome is rare. A case of central diabetes insipidus and clear-cut deficiency of gonadotropins associated with an empty sella is described. Although computed tomographic scan revealed a defect of the diaphragma sellae, other pathogenic mechanisms are considered. Previously documented cases of empty sella syndrome associated with diabetes insipidus are reviewed.

Adult↗

PubMed1989

A physiological role for neuropeptide Y in regulating the estrogen/progesterone induced luteinizing hormone surge in ovariectomized rats.

To test the hypothesis that neuropeptide Y (NPY) is involved in the regulation of the estrogen/progesterone-induced luteinizing hormone (LH) surge in ovariectomized rats, we passively immunized animals against NPY by administering purified immunoglobulins raised against the peptide directly into the central nervous system. Ovariectomized rats were prepared with an intracerebroventricular (i.c.v.) guide cannula and an intravenous catheter prior to experimentation. On day 1 of the experiment the animals received a 5-microliters i.c.v. injection of a highly specific immunoglobulin against NPY (NPY-ab) and a 50-micrograms injection of estradiol benzoate. The antibody injection was repeated on days 2 and 3 of the experiment. On day 3, animals received a 2.5-mg injection of progesterone. Control animals were treated in exactly the same fashion except that a nonspecific control immunoglobulin was injected i.c.v. rather than the NPY-ab. As expected, the steroid-primed animals treated with the control antibodies exhibited large surges in LH secretion approximately 4 h following the progesterone injection. Concentrations rose from 4.2 +/- 1.0 to 27.9 +/- 9.9 ng/ml. In marked contrast, the NPY-ab-treated animals demonstrated no increase in LH concentrations. Baseline values were 3.1 +/- 0.3 ng/ml and remained unchanged (maximum concentrations were 3.8 +/- 1.9 ng/ml) following the progesterone injection. These results demonstrate that hypothalamic NPY plays a role in mediating the estradiol/progesterone-induced gonadotropin surge and suggests that this neuropeptide plays a physiological role in normal ovulatory surges of LH and FSH.

Animals↗

PubMed1989

Neuroendocrine mechanisms regulating growth hormone and prolactin secretion during lactation.

The maternal plasma concentrations of GH and PRL increase dramatically upon the initiation of lactation in the rat. In light of the fact that these two hormones have evolved from one common precursor, we sought to determine if the neuroendocrine mechanisms regulating their concomitant increase during lactation are common or if they are functionally distinct. To evaluate this, lactating rats were passively immunized with antiserum raised against GHRH and then monitored for changes in GH and PRL secretion in response to suckling. On day 9 or 10 postpartum, pups were removed from their mothers at 0800 h. At 1100 h mothers were injected with normal rabbit serum (NRS) or GHRH antiserum (GHRH-ab). At 1400 h a control blood sample was drawn. Pups were then returned to their mothers, with subsequent blood samples drawn over the next 60 min. Plasma concentrations of GH significantly increased to 12.3 +/- 1.0 ng/ml (mean +/- SEM) in NRS-treated females after the return of the pups. In contrast, there was no change in GH concentrations in the females treated with the GHRH-ab. Plasma PRL concentrations rose approximately 200 ng/ml in both the NRS-treated animals and the GHRH-ab-treated ones. Body weight gains of the pups during the 60-min period of lactation were similar in both groups. These results suggest that the neuroendocrine mechanisms regulating the increases in GH and PRL during lactation are distinct and that GHRH is the hypothalamic factor responsible for the increase in GH. Furthermore, these results suggest that acutely interrupting the increase in GH secretion that occurs during lactation does not compromise nursing behavior and performance.

Animals↗

PubMed1989

Specific effect of CV 205-502, a potent nonergot dopamine agonist, during a combined anterior pituitary function test.

CV 205-502, an octahydrobenzo[g]quinoline, is a dopamine agonist compound that is not an ergot or ergoline derivative. To investigate the site of action of CV 205-502, three groups of five men were given single daily doses of CV 205-502 (0.04, 0.06, or 0.08 mg/day, doses that suppress plasma PRL by 60-80% for 24 h) for 5 days; on day 6 a combined anterior pituitary function test using iv administration of four hypothalamic releasing hormones (TRH, 200 micrograms; GHRH, 100 micrograms; CRH, 100 micrograms; LHRH, 100 micrograms) was performed. One month later the challenge tests were repeated to obtain control values. The following hormones were measured by RIA in plasma: TSH, ACTH, cortisol, PRL, GH, LH, FSH, and testosterone. With the exception of plasma PRL levels, basal and releasing hormone-stimulated values were similar after CV 205-502 administration and after the 1-month washout period. Basal plasma PRL was lower after CV 205-502 administration, and the response to TRH was attenuated by all three doses of CV 205-502 (the mean percent inhibition values were 76%, 93%, and 94%, respectively). All three doses of CV 205-502 were well tolerated, and another group of men well tolerated 0.1 mg daily. The results confirm that CV 205-502 is a potent dopamine agonist, which directly inhibits lactotropic cells but has no effect on other pituitary cell types.

Adult↗

PubMed1988

Plasma levels of beta-endorphin, prolactin and gonadotropins in male athletes after an international nordic ski race.

Plasma beta-endorphin, prolactin (PRL), FSH and LH were measured in 17 volunteer male subjects at rest and under the stress caused by a long-distance nordic ski race. The race induced increased levels of beta-endorphin and PRL in all skiers. The changes in PRL with exercise were significantly related to the changes in beta-endorphin (r = 0.69, p less than 0.001). Furthermore, the highly trained skiers training over 150 km.week-1 of nordic ski showed consistently higher post-exercise beta-endorphin and PRL levels than the moderately trained skiers who trained for 20 km.week-1. In addition the race induced slight falls in FSH and LH; however plasma gonadotropin levels did not show any correlation with plasma beta-endorphin concentrations and did not differ between the two groups of skiers. These results suggest that endogenous opioid peptides may modulate PRL secretion in heavy exercise, since they are of minor importance in the release of FSH and LH in such a situation. The observations also suggest that the degree of previous training and the exercise intensity do seem to be responsible for the hormonal changes.

Gonadotropins↗

PubMed1988

Hormonal effects of CV 205-502, a novel octahydrobenzo [g] quinoline with potent dopamine agonist properties.

Following the success of ergot alkaloids and their synthetic derivatives in treating a variety of pathophysiological disturbances, efforts have been concentrated on the synthesis of new derivatives and partial structures with the aim of dissecting out a specifically dopaminomimetic pharmacophore. Accordingly CV 205-502, a structure which superposes the linear benzo [g] quinoline segment of apomorphine on the substituted pyrrolo [3,4- g] quinoline moiety of the ergolines was designed. This study was performed in normal young volunteers to investigate the effect of single oral doses of CV 205-502 on plasma prolactin levels and on other endocrine parameters (GH, LH, FSH, TSH and cortisol) as well as on tolerability. 10 volunteers participated in a dose-ranging study. They received single oral doses of 0.01 to 0.09 mg CV 205-502, in order to assess the prolactin suppressant action. 6 volunteers were given a dose of 0.06 mg CV 205-502 in order to determine the endocrine profile of the compound. The duration of action of 0.06 mg CV 205-502 was investigated in 6 subjects by measuring plasma PRL and GH levels for 48 h. The results show strong dose-dependent suppression of PRL appearing following doses between 0.04 and 0.09 mg of CV 205-502. PRL was markedly suppressed for more than 24h. and the peaks of the normal sleep profile were abolished. Intermittent transient GH increases occurred during the first 6 hours; sleep profiles were normal. Compared with placebo values, no changes were seen in the levels of any other hormone except TSH, which decreased. Tolerability was good and no drug attributable changes in safety measures occurred. This study demonstrates that CV 205-502 is a potent and long acting PRL suppressant compound and suggest that this novel octahydrobenzo [g] quinoline will prove to be a therapeutically useful dopaminomimetic compound.

Adult↗

PubMed1988

Isolation and sequence of rat peptide YY and neuropeptide Y.

Rat peptide YY and rat neuropeptide Y have been isolated in parallel from colon and brain extracts respectively, using salt fractionation, gel filtration chromatography, cation-exchange HPLC, and reverse phase phenyl-silica HPLC. Immunoreactivity was identified using a combination of 3 NPY immunoassays which exhibit differing cross-reactivities for PYY (90%, less than 0.01% and 30% respectively). The yield at the final purification step was 1.2 nmol rPYY and 0.5 nmol rNPY. Half of each purified peptide was subjected to complete microsequence analysis. This showed that while rat NPY was structurally identical to human NPY, the sequence of PYY from rat colon was the same as porcine PYY isolated from extracts of duodenum.

Amino Acid Sequence↗

PubMed1988

Dexamethasone treatment increases neuropeptide Y levels in rat hypothalamic neurones.

Immunoreactive glucocorticoid receptors (GR) have previously been demonstrated in neuropeptide Y (NPY) neurones of the rat hypothalamus. To determine whether NPY synthesis is influenced by glucocorticoids, the effect of dexamethasone (DEX) on the levels of immunoreactive NPY in rat hypothalamic neurones was investigated in vivo and in vitro. Daily injections of DEX (0.1 mg/day) for 5 days increased the NPY content of the mediobasal hypothalamus in female rats by 117% (p less than 0.002). Primary cultures of hypothalamic neurones were also sensitive to the effect of glucocorticoids. Intracellular NPY levels were significantly increased (p less than 0.001) compared to control values by 151%, 222% and 268% when cultures were maintained in a defined serum free medium containing DEX 10(-9), 10(-8) and 10(-7) M respectively.

Animals↗

PubMed1988

Corticotropin releasing factor activity of CRF 41 in normal man is potentiated by angiotensin II and vasopressin but not by desmopressin.

Multiple hypothalamic factors seem to influence ACTH release. In vitro and/or in vivo animal models have shown that angiotensin II, vasopressin and some of its analogs are ACTH secretagogues capable of potentiating the corticotropin releasing activity of CRF41. Since these effects are controversial in man, we investigated in 3 groups of volunteers the corticotropin releasing activity of a 2h-infusion of angiotensin II (7 ng/kg/min), vasopressin (1 ng/kg/min) and desmopressin (1 ng/kg/min) given alone or in combination with a bolus injection of 100 micrograms CRF41 by measuring plasma concentrations of ACTH, cortisol, dehydroepiandrosterone and delta 4-androstenedione. Given alone angiotensin II and desmopressin had no significant effect in contrast to vasopressin which increased significantly the ACTH and steroid levels. Angiotensin II and vasopressin were both able to potentiate the corticotropin releasing activity of CRF41, whereas desmopressin was unable to produce such a potentiation. These results suggest that in man vasopressin and angiotensin II may well regulate the responsiveness of the pituitary-adrenal axis in various physiological or pathophysiological situations.

Adrenocorticotropic Hormone↗

PubMed1988

Human recombinant interleukin-1 beta and -alpha, but not recombinant tumor necrosis factor alpha stimulate ACTH release from rat anterior pituitary cells in vitro in a prostaglandin E2 and cAMP independent manner.

The pituitary-adrenal axis is known to be stimulated during the acute-phase response. As cytokines play a central role in mediating the constellation of host response occurring during the acute-phase response it was of interest to assess the ability of cytokines to stimulate ACTH secretion from normal pituitary cells in culture. We used human recombinant interleukin-1 beta and -alpha (hrIL1 beta, hrIL1 alpha) and human recombinant tumor necrosis factor alpha (hrTNF alpha) to analyze the ability of these cytokines to induce ACTH secretion from normal rat anterior pituitary cells in culture. We also investigated the possible roles of prostaglandin E2 (PGE2) and cAMP in the cellular transduction mechanism. After 3 days of incubation primary cultures of rat anterior pituitary cells were stimulated for 24 h with either hrIL1 beta, hrIL1 alpha or hrTNF alpha alone or with the addition of dexamethasone or indomethacin. The culture media were analyzed for ACTH, PGE2 and cAMP content. At doses ranging from 0.03 to 30 nM, hrIL1 beta stimulated the release of ACTH and PGE2 in a dose-dependent manner. In contrast, at doses ranging from 3 to 60 nM, hrTNF alpha was unable to stimulate ACTH secretion although it stimulated PGE2 synthesis. Time-course experiments demonstrated that hrIL1 beta (3 nM) stimulates ACTH production over a period of 8, 16 and 24 h, but not after a period of 4 h. In these experiments, hrIL1 beta failed to cause any change in the secretions of growth hormone and luteinizing hormone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

PubMed1988

Hormonal effects of CQP 201-403, a new dopamine agonist.

CQP 201-403 is a propylergoline derivative with strong dopamine stimulant properties in animals models. It was developed in order to meet the need for a dopamine agonist compound which would offer longer action and improved tolerability. In this study, we tested CQP 201-403 m healthy male volunteers in order to assess its PRL suppression action and other hormonal effects as well as its duration of action and tolerability. Twenty-one volunteers participated in a dose-range study conducted according to a double-blind cross-over design with placebo control. The PRL suppression effect of single oral doses ranging from 0.05 mg to 0.035 mg were investigated. The duration of action of CQP 201-403 was tested in 6 other volunteers receiving a single oral dose of 0.025 mg or placebo. Blood was sampled over 48 h for PRL and GH measurements. An endocrine profile was performed in 6 volunteers receiving either 0.025 mg CQP 201-403 as a single oral dose or placebo. Blood was sampled over 8 h for measuring plasma PRL, GH, LH, FSH, TSH and cortisol. The results show strong dose-dependent PRL suppression (P less than 0.001) beginning 2 h after ingestion. PRL suppression lasted for more than 24 h and the normal sleep PRL surges were abolished. GH was transiently stimulated during the first few hours; the GH sleep profile was normal. All other hormones were not affected by the administration of CQP 201-403. Tolerability was good and no drug attributable changes in safety measures occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1987

Identification of human synenkephalin-like immunoreactivity in phaeochromocytoma tissue using a novel carboxy-terminal radioimmunoassay.

An antiserum raised against the synthetic tyrosinylated carboxy-terminal sequence of synenkephalin (Tyr-Glu-Glu-Ser-His-Leu-Leu-Ala) has been used to chromatographically characterize the human synenkephalin-like immunoreactivity extracted from 3 adrenal medullary phaeochromocytomas. Gel filtration chromatography identified in each tumor a single peak of 8 kDa which on subsequent ion-exchange chromatography had the elution characteristics of an acidic polypeptide. These results are compatible with the human synenkephalin sequence predicted from cDNA studies, and indicate that this is the authentic peptide.

Adrenal Gland Neoplasms↗