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Biomedical subjects

J A Cabranes

Publications and source records attributed to J A Cabranes.

At least 37 records · Page 2Linked to original sources
PubMed1987

D-Trp6-luteinizing hormone-releasing hormone inhibits sulpiride-induced hyperprolactinemia in normal men.

The effect of a potent agonistic analog of LHRH, D-Trp6-LHRH, on hyperprolactinemia induced by sulpiride was studied in normal men. Six men received sulpiride (100 mg, twice daily, orally) for 44 days. D-Trp6-LHRH was given sc during the last 2 weeks of sulpiride administration; the dose was 500 micrograms on the first day and 100 micrograms daily for the subsequent 14 days. All men had high serum PRL levels before D-Trp6-LHRH administration (mean +/- SEM, 56 +/- 9 ng/mL), which decreased significantly after the first dose of the analog (45 +/- 5 ng/mL; P = 0.031) and also after 15 days of analog administration (41 +/- 6 ng/mL; P = 0.016). These data demonstrate that administration of LHRH agonist can inhibit the hyperprolactinemic effect of sulpiride, suggesting a direct action of the analog on the pituitary gland to modulate PRL secretion.

Follicle Stimulating Hormone↗
PubMed1987

Free fatty acids block growth hormone (GH) releasing hormone-stimulated GH secretion in man directly at the pituitary.

Increases in plasma FFA levels inhibit GH responses to a variety of pharmacological and physiological stimuli. To gain further insight into the mechanism by which FFA exert their effect, we studied the plasma GH responses to GHRH-(1-44) (1 microgram/kg, iv) in normal subjects in whom plasma FFA levels were raised by a lipid-heparin infusion (250 mL 10% Intralipid plus 2500 U heparin). Paired tests were performed in 10 normal subjects, with and without lipid-heparin pretreatment. Lipid-heparin infusion from -30 to 120 min increased mean FFA levels from 0.41 +/- 0.03 (+/- SEM) to 3.12 +/- 0.40 mmol/L at 120 min. The mean plasma GH levels after GHRH administration were lower at all times; however, the values were significantly different (P less than 0.05) only at the later times (45, 60, and 90 min). When considered individually, an all or none pattern was observed; 5 subjects had no plasma GH response to GHRH, and 5 had no reduction. To investigate the time relationships between the FFA peak and subsequent GH blockade, a different protocol of paired tests was performed with GHRH with or without a different lipid-heparin infusion protocol. Lipid-heparin was infused from -90 to 0 min, with an additional heparin pulse at -15 min, to obtain a higher and earlier (0 min) FFA increase. FFA increased from 1.06 +/- 0.19 to 11.61 +/- 0.83 mmol/L at zero time. The GHRH-induced GH secretory peak (15.8 +/- 3.5 ng/ml) at 15 min was completely blocked (0.9 +/- 0.2 ng/ml), and the mean plasma GH levels were also lower at 30, 45, and 60 min. To determine whether the FFA-induced blockade of GH secretion was exerted in the pituitary, a series of in vitro studies was conducted using monolayer cultures of rat anterior pituitary glands, with GHRH concentrations of both 10(-10) and 10(-8) M and 10(-5) M forskolin to stimulate GH release. Both caprylic and oleic acid inhibited basal GH release and GHRH- or forskolin-induced GH release. PRL release was not altered, nor were toxic actions noted on the cells. In conclusion, FFA are able to block GH secretion directly at the pituitary level.

Adult↗
PubMed1987

Low serum osteocalcin in acute alcohol intoxication: a direct toxic effect of alcohol on osteoblasts.

A direct effect of alcohol on bone cells has not been convincingly demonstrated, but numerous studies have postulated that alcohol inhibits osteoblastic activity. Since osteoblasts synthesize osteocalcin, we studied the serum levels of this protein in 15 patients with acute alcoholic intoxication to determine if alcohol has an effect on these cells, whether direct or indirect. We found lower osteocalcin levels in our alcoholics than in 15 normal individuals of similar age and sex (3.1 +/- 1.0 vs. 6.6 +/- 0.8 ng/ml; P less than 0.0001), evidence of the influence of alcohol on osteoblasts. This effect seems to be direct rather than mediated.

Alcoholism↗
PubMed1986

Atropine blockade of growth hormone (GH)-releasing hormone-induced GH secretion in man is not exerted at pituitary level.

The role of acetylcholine (Ach) in the regulation of human GH secretion was assessed using atropine, which selectively blocks cholinergic muscarinic receptors. Paired tests were performed in seven normal subjects using GH-releasing hormone (GHRH) 1-44 (1 microgram/kg iv), with and without atropine pretreatment (1 mg im). The GHRH 1-44-induced GH secretory peak [20.7 +/- 4.5 (SEM) ng/ml] was completely blocked by atropine administration (2.3 +/- 0.6 ng/ml) (P less than 0.01). To determine whether this atropine blockade was at the pituitary level, a series of in vitro studies were conducted using monolayer cultures of cells from bovine anterior pituitary glands. GHRH 1-44 (10(-8) M) stimulated bovine GH release (11.1 +/- 1.5 micrograms/ml) as compared to control values (5.1 +/- 0.4 microgram/ml) (P less than 0.01). This response was not altered by 10(-6) M atropine (14.9 +/- 0.9 microgram/ml). Similar results were obtained with GHRH, 10(-9) M, with or without atropine, 10(-7) M. Addition of 10(-6) M Ach to the incubation medium significantly increased bovine GH release (12.7 +/- 1.2 microgram/ml) and the effect of 10(-6) M Ach and 10(-8) M GHRH was additive (20.9 +/- 2.1 micrograms/ml) (P less than 0.01). Similar results were obtained with Ach, 10(-5) M, and GHRH, 10(-9) M. Atropine or eserine alone did not alter basal GH secretion, and atropine blocked Ach-stimulating activity. In conclusion, atropine blockade of GHRH-induced GH secretion appears to be exerted at a site other than pituitary.

Acetylcholine↗
PubMed1986

Evidence of abnormal dopaminergic control of prolactin in patients with hypothalamic and pituitary tumors.

Prolactin secretion was investigated in an attempt to identify the patterns of responses in different types of tumors. Forty four patients were studied: thirty patients with prolactinomas (Group 2); nine patients with growth-hormone (GH)-adrenocorticotropic hormone (ACTH)-secreting pituitary tumors and hypothalamic tumors (Group 3); and five patients with non-secreting pituitary tumors (Group 4). A control group (Group 1) consisted of 60 healthy subjects (30 males and 30 females). All were submitted to testing by nomifensine (Nom), domperidone (Dom) and thyrotropin releasing hormone (TRH). The prolactin levels were measured by radioimmunoassay (RIA). In group 2 the suppression of PRL with Nom and the stimulation with Dom and TRH were significantly lower than in the control group (p less than 0.001). There was no statistically significant difference between groups 2 and 3 in the suppression with Nom. The increase with Dom in group 3 was significantly greater than that in group 2 (p less than 0.001) and less than that in the control group (p less than 0.005). The rise in PRL with TRH was also significantly higher in group 3 than in group 2 (p less than 0.001) and similar to that of the control group. Group 4 gave the same results as the control group to all 3 tests. Our results indicate a dopaminergic irregularity in the hypothalamic and GH-ACTH-secreting pituitary tumors, thus supporting a hypothalamic etiopathogenesis of these tumors. The normality of the GH-ACTH-secreting pituitary tumors and hypothalamic tumor responses to TRH is one more factor in differentiating these from prolactinomas. The normal response of the non-secreting tumors may involve a primary pituitary etiology of these tumors.

Adrenocorticotropic Hormone↗
PubMed1985

Increased blood cortisol in alcoholic patients with aseptic necrosis of the femoral head.

Although aseptic necrosis of the femoral head secondary to alcoholism is a very frequent entity, its etiology remains unknown. The same pathogenic mechanism is thought to be shared both by aseptic necrosis secondary to alcoholism and steroid therapy. Since alcohol stimulates adrenal steroid secretion, we have studied serum cortisol and urinary free-cortisol levels in 8 patients with aseptic necrosis of the femoral head due to alcoholism and compared them with those found in 8 age-matched patients with aseptic necrosis of idiopathic origin. Serum cortisol levels and urinary free-cortisol levels were significantly higher in the alcoholic than in the idiopathic group: serum 227 +/- 21.7 vs 154 +/- 22.1 ng/ml, P less than 0.001; urine 0.20 +/- 0.002 vs 0.13 +/- 0.04 micrograms/mg Cr/day, P less than 0.001. The data indicate that alcohol-induced aseptic necrosis of the femoral head results, at least in part, from increased circulating cortisol.

Adult↗
PubMed1985

Dexamethasone suppression test and familial subtypes of unipolar depression.

We have studied the suppression of plasma cortisol after dexamethasone (1 mg) and the peak post-dexamethasone cortisol values in 84 hospitalized patients with a diagnosis of primary unipolar depression. The non-suppressor responses in the three familial subgroups (Winokur) were: 11/22 in familial pure depressive disorder (FPDD), 21/49 in sporadic depressive disease (SDD) and 1/13 in depression spectrum disease (DSD) (FPDD vs. SDD, p less than 0.05; SDD vs. DSD, p less than 0.05). When considering the peak post-dexamethasone cortisol value, or the 8.30-9.00-hour values, the results in the DSD group were lower than in the other two groups (p less than 0.05). These results suggest a different behaviour of DSD as compared with FPDD and SDD.

Adrenocorticotropic Hormone↗
PubMed1984

Cholinergic mediation of growth hormone secretion elicited by arginine, clonidine, and physical exercise in man.

The role of acetylcholine in human GH secretion was studied with atropine, which selectively blocks cholinergic muscarinic receptors and crosses the blood-brain barrier. Paired tests were performed in 22 normal subjects divided into 4 groups. The stimuli employed were arginine (30 g/30 min, iv), clonidine (300 micrograms, orally), physical exercise for 20 min, and saline. In the second test, atropine (1 mg, im) was administered before GH stimulation. Arginine elicited a GH secretory peak of 16.6 +/- 5 ng/ml (mean +/- SEM), which was completely blocked when atropine was administered with arginine (0.9 +/- 0.1 ng/ml). Atropine did not, however, modify the PRL secretory response; peak levels after arginine and atropine plus arginine were 16.3 +/- 3.1 and 16.8 +/- 2.5 ng/ml, respectively. Clonidine elicited a GH secretory peak (11.8 +/- 2.7 ng/ml) which also was blocked by pretreatment with atropine (1.2 +/- 0.2 ng/ml). Neither clonidine nor clonidine plus atropine altered PRL secretion. GH levels also were sharply increased after physical exercise, with a peak level of 19.4 +/- 4.9 ng/ml. Atropine completely blocked exercise-induced GH secretion (2 +/- 0.9 ng/ml). Atropine alone did not modify GH or PRL values compared with saline administration. The potency of the atropine-induced suppression of GH secretion by three different stimuli, each with presumably different mechanisms of action, suggests that acetylcholine plays an important role in the regulation of GH secretion.

Acetylcholine↗
PubMed1984

Selective inhibition of sleep related growth hormone release by Phe-4-somatostatin.

We have compared the effects of somatostatin (SS) and the somatostatin analog Phe-4-SS on nocturnal GH secretion in three normal male volunteers, 20 to 23 years of age. Subjects were studied in our sleep laboratory on 5 consecutive nights. Nights 1 and 2 were used for adaptation. On the third night (control night), all patients exhibited a typical GH peak accompanying slow-wave sleep, with maximum GH levels from 9.2 to 27 ng/ml. Insulin, glucagon and glucose levels were episodic and sleep-independent. On night 4, subjects received SS infusion at a rate of 3 micrograms/min, which inhibited GH levels consistently below 2.4 ng/ml. In two cases a post-infusion rebound of GH levels was observed. During SS infusion all three subjects showed a significant decrease in insulin levels (p less than 0.0005), followed by an immediate rebound after infusion was stopped. Glucagon levels fell significantly during infusion (p less than 0.001, p less than 0.025 and p less than 0.00025 respectively). Glucose was significantly higher than on control night in subject No. 3 (p less than 0.0005) and similar to control night in subjects 1 and 2. On the fifth night, Phe-4-SS was infused at a rate of 0.75 microgram/min. GH levels decreased significantly as compared to control night in all three subjects and remained virtually constant throughout the night. Insulin levels were diminished in subject No. 1 (p less than 0.0005), but were comparable to control values in subjects 2 and 3. Cessation of analog infusion was followed by a rebound in insulin levels in all three subjects. Glucagon values were not significantly lowered and the rebound effect was not apparent. Glucose levels were higher in response to Phe-4-SS than on control night, and fell below infusion values (p less than 0.001) after administration was discontinued. It was concluded that Phe-4-SS inhibits nocturnal secretion of GH more selectively than SS, but its effect is not more prolonged than that of SS.

Adult↗
PubMed1984

Inhibition of growth hormone and glucagon release by Phe-4-somatostatin in patients with acromegaly.

We have studied growth hormone (GH), insulin (I), glucagon (Gl) and glucose in basal conditions, after somatostatin (SS) (3 micrograms/ml) and Phe-4-SS (0.75 microgram/ml) infusion and IV bolus of the latter in 3 acromegalic patients. In two patients, Phe-4-SS inhibited glucagon and growth hormone secretion in a similar way as SS, without modifying insulin secretion. These effects were short-lived and ceased after the infusion was stopped. From these results it appears that Phe-4-SS is both more potent and more specific than SS with respect to inhibition of GH and glucagon release, but it does not have prolonged biological action. Lack of suppression of GH by SS or Phe-4-SS in the acromegalic patient with post-surgical recurrence of the disease could be due to the existence of receptor abnormalities, and suggests a diversity in the physiopathology of the disease.

Acromegaly↗