Impaired circadian rhythmicity of beta-lipotrophin, beta-endorphin and ACTH in heroin addicts

The circadian rhythm of plasma proopiocortin-related peptides was studied in 15 heroin addicts and in 6 sex- and age-matched controls. ACTH, beta-lipotrophin, (beta-LPH), beta-endorphin (beta-EP) and cortisol were measured by RIA either directly (cortisol), or after plasma extraction (ACTH) and Sephadex G-75 gel chromatography (beta-LPH and beta-EP) every 4 h from 8 a.m. to 8 p.m. and again at 8 a.m. the next morning. The means of the two 8 a.m. measurements of beta-LPH (2.67 +/- 0.34 fmol/ml, mean +/- SE), ACTH (2.74 +/- 0.71) and cortisol (218 +/- 31 pmol/ml) levels in heroin addicts were significantly lower than those in controls (6.28 +/- 0.61, 10.1 +/- 0.74 and 364 +/- 27, respectively, P less than 0.01) while beta-EP concentrations in heroin addicts (5.1 +/- 0.6) were similar to those of healthy volunteers (6.44 +/- 0.56). In controls, all three peptides and cortisol show a circadian rhythm of secretion, the lowest values being in the evening and the highest ones in the morning. Heroin addicts partially lack this phenomenon showing constant levels of the three proopiocortin-related peptides throughout the day, with a slight but significant decrease of plasma cortisol. In the 7 subjects who took heroin throughout the study, no systematic changes were observed in the three proopiocortin-related peptides, while it seems that this group of addicts shows a cortisol decrease in the evening to a lesser extent than subjects receiving methadone maintenance only.(ABSTRACT TRUNCATED AT 250 WORDS)     

Impairment of adrenergic-induced proopiomelanocortin-related peptide release in heroin addicts

The effects of iv stimulation with clonidine on plasma levels of beta-lipotropin (beta-LPH), beta-endorphin (beta-EP), cortisol, growth hormone (GH) and adrenocorticotrophic hormone (ACTH) were tested in a group of 10 healthy volunteers and in 8 heroin abusers. Hormones were measured either by direct radioimmunoassay (RIA) (GH, cortisol) or after plasma extraction and Sephadex G-75 column chromatography (beta-LPH and beta-EP) or by immunoradiometric assay (IRMA) (ACTH). Plasma levels of GH increased in a similar fashion in the two groups. In the controls, clonidine induced release of beta-LPH and beta-EP after 30 min (from 8.9 +/- 1.0 to 19.1 +/- 4.6 fmol/ml, P less than 0.01 and from 8.1 +/- 0.6 to 17.9 +/- 4.6, P less than 0.01) and of ACTH after 60 min (from 12.1 +/- 1.8 to 18.1 +/- 1.8, P less than 0.05) while in addicts beta-EP but not beta-LPH showed a significant increase (from 8.5 +/- 0.7 to 19.8 +/- 4.2, P less than 0.05), 90 min after the injection. In heroin addicts, plasma cortisol levels decreased continuously after clonidine stimulation while in controls they showed a biphasic pattern, decreasing until the 60th min (from 135.2 +/- 30.4 ng/ml to 74.0 +/- 13.3, P less than 0.05) and regaining basal levels 1 h later (122.0 +/- 24.8, P less than 0.05 vs 60th min value). These data demonstrate the existence in human beings of noradrenergic control of proopiomelanocortin (POMC)-related peptides and indicate that chronic opiate abuse greatly interferes with this control. Clonidine-induced release of plasma beta-EP may be of importance with regard to its therapeutic effects in detoxification.     

Impaired clearance of beta-lipotropin in uremia

Immunoreactive ACTH and beta-lipotropin (beta-LPH) plasma concentrations are elevated in clinically stable chronic renal failure patients on hemodialysis (LPH: patients, 271.8 +/- 35.7 fmol ml-1; normal subjects; 6.6 +/- 0.5; ACTH: patients, 56.4 +/- 15.3; normal subjects, 19.4 +/- 1.7). To begin to study the etiology of such elevated levels, the MCR, apparent volume of distribution, and fractional rate of disappearance of synthetic human ACTH and highly purified human beta-LPH were determined in two clinically stable chronic renal failure patients on hemodialysis, after bolus simultaneous injection of both peptides. Biphasic disappearance curves were obtained for beta-LPH; triphasic for ACTH. The MCR of ACTH was within the range seen in normal subjects, whereas the MCR of beta-LPH was less than one half the normal rate. The data indicate that a decrease in MCR (rather than an increase in pituitary secretory rate) may account for the higher plasma levels of beta-LPH in uremic patients.     

Serotoninergic agonists increase plasma levels of beta-endorphin and beta-lipotropin in humans

A pharmacological approach was used to investigate the serotoninergic control of plasma levels on beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH) in humans. Acute administration of L5-OH-triptophan, the physiologic precursor of serotonin (SE), induced a significant rise in plasma beta-EP and beta-LPH levels both when injected iv (20 and 40 mg) (four normal men) and when administered orally (200 and 400 mg) (seven normal men) (P less than 0.01 vs. placebo). The iv route of administration induced a prompt (mean peak values after 150 min) dose-dependent increase in beta-EP and beta-LPH levels. The responses evoked by oral administration (mean peak values after 130 and 240 min) were not dose dependent. Fluoxetine (15 and 30 mg orally) a blocker of SE reuptake, induced a significant dose-related rise in plasma beta-EP and beta-LPH levels in a group of seven normal men (P less than 0.01) (mean peak values after 150 min). Pretreatment with methysergide, a SE receptor antagonist (3 X 2.8 mg orally, five men), did not induce any significant changes in plasma beta-EP and beta-LPH levels, but blocked the increase in the two hormones evoked by L5-OH-triptophan (40 mg iv). Plasma cortisol levels changed similarly to those of beta-EP and beta-LPH in all the experiments, indicating that putative serotoninergic drugs exert a positive role on the various corticotropin-releasing hormone-mediated secretions.     

Plasma beta-endorphin and beta-lipotropin in the human fetus at delivery: correlation with arterial pH and pO2.

Beta-endorphin-like immunoactivity was measured in the umbilical cord plasma of 45 term human fetuses. Mean concentration was 91 +/- 16 (SEM) pg/ml,an the normal adult level of 30.7 +/- 2.7 pg/ml. This immunoactivity was further characterized in 10 cases by Sephadex G-50 chromatography to separate beta-endorphin from beta-lipotropin (beta-LPH). Mean beta-endorphin and beta-LPH concentrations were 57 +/- 12.8 and 455 +/- 101 pg/ml, respectively. Both were higher (P less than 0.01) than the mean beta-endorphin and beta-LPH concentrations reported in the adult. The mean molar beta-endorphin to beta-LPH ratio was 0.35 in the fetus and 0.36 in the adult. In 17 fetuses whose umbilical arterial and venous concentrations were measured separately, mean beta-endorphin-like immunoactivity was higher in the artery than in the vein. A highly significant negative correlation (r = -0.831; P less than 0.001) was present between umbilical arteiral pH and beta-endorphin-like immunoactivity. A negative correlation (r = -0.611; P less than 0.005) with arterial pO2 was also noted. We conclude that high levels of beta-endorphin-like immunoactivity, composed of both beta-endorphin and beta-LPH, circulate in the human fetus at term, and that hypoxia and secondary acidosis may be major stimuli to the release of these peptides.     

Insulin resistance in uraemic insulin-dependent diabetics. Effect of dialysis therapy as assessed by the artificial endocrine pancreas

Twenty-four hour insulin requirements were measured in 5 uraemic insulin-dependent diabetics using a glucose controlled insulin infusion system (artificial endocrine pancreas). All patients were studied twice: initially 14 (1-27) days before institution of dialysis treatment and again after a mean of 46 (21-98) days on chronic dialysis therapy. At near normal blood glucose level the daily insulin requirements decreased from 44.8 +/- 2.9 U pre-dialysis to 35.0 +/- 2.3 U post-dialysis (P less than 0.001). The reduction included the prandial as well as the basal requirements. Consistent with this, the mean plasma free insulin level was higher pre-dialysis than post-dialysis (42 +/- 12 microU/ml vs 31 +/- 7 microU/ml) especially during daytime (49 +/- 11 microU/ml vs 37 +/- 9 microU/ml, P less than 0.03), suggesting that a decreased insulin degradation was not a major factor in the difference in insulin requirements. The effect of an acute change in azotaemia on insulin requirements was also evaluated in 4 uraemic diabetics on chronic haemodialysis the day prior to and the day after a routine dialysis (serum creatinine 922 +/- 59 mumol/l vs 555 +/- 109 mumol/l). No difference in insulin administration on the two days was observed (42.5 +/- 6.1 U vs 43.2 +/- 5.6 U). It is concluded that insulin resistance is present in uraemic insulin-dependent diabetics analogous to the insulin resistance widely prevalent in non-diabetic uraemic patients. The abnormality is at least partly reversible after several weeks on chronic dialysis, but not acutely. The pathophysiologic mechanisms underlying the insulin resistance in uraemia in the diabetic remain to be clarified.     

gamma-Aminobutyric acid inhibits beta-endorphin secretion from the anterior pituitary but not the neurointermediate lobe in the rat

We have evaluated the role of gamma-aminobutyric acid (GABA) in the neuroendocrine control of beta-endorphin (beta-EP) secretion in the rat. Plasma beta-EP and beta-lipotropin (beta-LPH) levels and beta-EP-like immunoreactivity (beta-EPLI) in the anterior pituitary (AP) and neurointermediate lobe (NIL) were determined after administration of GABA antagonist or agonist drugs in male rats under resting conditions or after potent physical stresses. Bicuculline (0.1-0.8 mg/kg BW ip), a GABA receptor antagonist, induced a dose-related rise in plasma beta-EP and beta-LPH levels and a concomitant decrease in beta-EPLI concentrations in the AP but not in the NIL. Muscimol, a potent GABA-mimetic drug, did not alter baseline plasma beta-EP and beta-LPH levels, whether given systemically (1.0-2.0 mg/kg BW ip) or intracerebroventricularly (500 ng/kg BW), but prevented the effect of bicuculline on plasma and AP-beta-EP and beta-LPH concentrations. Administration of foot shock or restraint stress induced a clear-cut activation of the AP-related beta-EP secretion, an effect that was prevented by pretreatment with muscimol. Together, these data show that GABA-ergic mechanisms, probably operating at a central nervous system level, exert an inhibitory action on resting and stimulated beta-EP and beta-LPH secretion. Since no alterations in beta-EP concentrations in the NIL occurred after manipulations with GABA-ergic drugs or stress, and these were detected only in the AP, an interaction between GABA-ergic neurons and CRF neurons is the most likely explanation for the reported findings.     

Beta-endrophin immunoreactivity during human pregnancy.

The human placenta has been implicated as a source of numerous peptide hormones during pregnancy. Since the immunoassay detection of the proopiomelanocortin derived peptide beta-endorphin (beta E) in placental extracts in 1978, it has remained uncertain whether placental beta E immunoreactivity (IR) is 1) secreted into the maternal circulation and 2) opiate receptor active during pregnancy. To elucidate the nature of beta E IR in the placenta, both beta E IR and N-alpha-acetylated beta E (Ac beta E) IR were simultaneously measured in extracts of human pituitaries, placentas, and plasma by two homologous RIAs. Pituitary extracts (n = 6) contained 38 +/- 7 nmol beta E IR per g wet wt tissue (mean +/- SEM), of which only 20 +/- 4 pmol/g were Ac beta E IR. Term placental extracts (n = 19) had 201 +/- 30 fmol/g wet wt total beta E IR and 30 +/- 3 fmol/g wet wt total Ac beta E IR, which comprised 15% of total beta E IR in placental extracts. Total plasma beta E IR rose from 28 weeks gestation (8.5 +/- 0.3 fmol/mL, n = 159) to peak at labor (50 +/- 4 fmol/mL, n = 98; P < 0.01) but total Ac beta E IR was found in only four 28-week (1.7 +/- 0.9 fmol/mL) and 42 labor plasma samples (0.9 +/- 0.1 fmol/mL). Gel filtration chromatography of placental and pituitary extracts showed that while less than 1% of the beta E31-size material was acetylated in the pituitary, up to 60% of the beta E31-size material in placental extracts was acetylated. In pooled third trimester plasma extracts, however, only 4% of the beta E31-size material was acetylated. Furthermore, the ratio of beta E31:beta-lipotropin in pituitary extracts (n = 3) was 0.5; pooled plasma-0.5, and placental extracts (n = 5)-1.2. These data indicate that 1) the placenta extensively N-alpha-acetylates beta E31 destroying its opiate bioactivity while the pituitary does not; 2) beta E IR in pregnant women's plasma is similar to pituitary beta E IR, being mostly nonacetylated and similar in size to beta-lipotropin. These findings are consistent with a pituitary source for the elevated plasma beta E IR found during late pregnancy which may, in turn, be a consequence of elevated plasma concentrations of placentally secreted plasma corticotropin-releasing factor IR present during the third trimester.     

Plasma beta-endorphin, free fatty acids and blood lipid changes in type 2 (non-insulin dependent) diabetic patients

A lipolytic activity for beta-endorphin (beta EP) has been recently suggested both in vitro and in vivo. In our study we evaluated the relationship between beta EP and blood lipid pattern in Type 2 (non-insulin dependent) diabetic patients. Plasma beta EP, together with plasma beta-lipotropin (beta LPH), ACTH, cortisol and plasma insulin (IRI), was measured by RIA after silicic acid plasma extraction and Sephedex G-75 column chromatography. Although reduced beta EP (7.12 +/- 3.8 fmol/ml) and increased beta LPH (9.3 +/- 3.7 fmol/ml) levels were found in diabetic patients, compared to controls (8.53 +/- 3.3 fmol/ml, p less than 0.05 and 8.34 +/- 2.6 fmol/ml, p less than 0.05, respectively), higher plasma beta EP concentrations were demonstrated in hyperlipidemic diabetic patients (10.3 +/- 3.9 fmol/ml) than in patients with normal blood lipid pattern (4.85 +/- 1.45 fmol/ml, p less than 0.001). Several positive correlations between beta EP, plasma free fatty acids (r = 0.75, p less than 0.001), triglycerides (r = 0.84, p less than 0.001) and VLDL (r = 0.80, p less than 0.001) were found in our patients independently of overweight, hypoglycemic treatment, plasma IRI levels and of the degree of metabolic control. A higher prevalence of micro- and macrovascular complications was demonstrated in hyperlipidemic than in normolipidemic patients. Blood lipid disorders might therefore be associated with increased plasma beta EP levels in Type 2 diabetes.     

Specific radioimmunoassay of human beta-endorphin in unextracted plasma.

With an antiserum against human beta-endorphin (beta-EP) crossreacting less than 2% with human beta-lipotropin (beta-LPH) by weight we have developed a radioimmunoassay that can detect 1 pg beta-EP in diluted raw plasma. In a.m. fasting plasma of 14 normal subjects beta-EP ranged from less than 5 to 45 pg/ml. beta-EP was elevated in untreated, but normal in successfully treated Cushing's disease; undetectable in a patient with adrenal adenoma; extremely high in Nelson's syndrome; and elevated in a patient with bronchogenic carcinoma before, but undetectable after tumor resection. In subjects with intact hypothalamic-pituitary-adrenal axis, beta-EP was undetectable after dexamethasone and increased after metyrapone administration and insulin-induced hypoglycemia. beta-EP concentration was considerably lower in serum than in simultaneously collected plasma, but increased in serum left unfrozen for several hours after clot removal. Thus, beta-EP behaves like a hormone responding to the same stimuli as ACTH and beta-LPH and blood appears to contain enzymes both generating and destroying immunoreactive beta-EP.     

Plasma and urine concentrations of atrial natriuretic peptide in patients with diabetes mellitus

To examine whether plasma and urine concentrations of human atrial natriuretic peptide (hANP) are altered in patients with diabetes mellitus (DM), plasma and urine hANP concentrations were evaluated in 86 patients with diabetes mellitus using an extraction procedure. The mean recovery rate of extraction was 71.8 +/- 0.6% (mean +/- SEM). The major immunoreactive component of hANP in extracted plasma and urine appeared to be identical to synthetic alpha hANP as judged by reverse-phase high-performance liquid chromatography (HPLC). The patients were divided into three groups according to their renal complications. The patients in group 1 had no apparent abnormality in serum creatinine, serum or urine beta 2-microglobulin (beta 2-MG), or urine N-acetyl-beta-D-glucosaminidase (NAG); those in group 2 showed either beta 2-MG or NAG abnormality but no creatinine abnormality. The patients in group 3 were though to have an established diabetic nephropathy and showed a serum creatinine increase. Plasma ANP concentrations in groups 1, 2, and 3 were 10.7 +/- 2.1, 19.9 +/- 5.6, and 39.2 +/- 9.9 fmol/ml, respectively. These values in groups 2 and 3 were significantly higher than the control values (p less than 0.05 or p less than 0.01 versus 6.2 +/- 0.7 fmol/ml). Urine ANP concentrations in group 1 were also within normal range, though those in groups 2 and 3 markedly increased in comparison with normal values.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma beta-endorphin and beta-lipotropin levels increase in well trained athletes after competition and non competitive exercise

Plasma beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH) levels were measured in 15 healthy trained marathon runners. These hormones were evaluated in two different conditions: 1-before (1h) and after a marathon race (n = 10); 2-before, during and after a prolonged (90 min) submaximal exercise (bicycle ergometer at 50% VO2 max) (n = 5). In these latter group plasma beta-EP and beta-LPH levels were measured every 15 min for 165 min. In all the athletes, both plasma beta-EP and beta-LPH levels were significantly higher after the end of the marathon race than in basal conditions (p less than 0.01). The prolonged exercise with bicycle ergometer significantly stimulated plasma beta-EP and beta-LPH levels. Starting 60 min after the beginning of the exercise, plasma beta-EP and beta-LPH levels resulted significantly higher than basal values until the end of the exercise (p less than 0.01 at 60, 75 and 90 min). These data confirming that marathon running is a potent stress stimulus, showed that the duration and related factors but not the work load may be considered critical in stimulating beta-EP and beta-LPH release during physical exercise.     

Secretion of beta-endorphin into the maternal circulation by uteroplacental tissues in response to hypoglycaemic stress

The placenta has been shown to contain ACTH and beta-endorphin but the roles of these peptides are unknown. To investigate whether they are released into the maternal circulation from the placenta in response to physiological stimuli the effects of hypoglycaemic stress were investigated. Plasma samples were collected from the femoral artery (FA) and uterovarian (UV) vein of nine pregnant sheep before and during hypoglycaemia induced by intravenous insulin (100U). Plasma concentrations of ovine beta-endorphin (o beta-EP) were measured by radioimmunoassay. Concentrations of o beta-EP rose in both vessels by 60 min after insulin. The peak concentrations of o beta-EP (pmol/l) were 122 +/- 29 (mean +/- SEM, n = 8) in the UV and 96 +/- 24 (n = 9) fmol/ml in the FA 60 min after insulin injection. There was no difference between the concentrations of o beta-EP in the vessels before insulin injection but at 60 and 120 min after insulin the concentrations of o beta-EP were significantly higher in the UV than FA (P less than 0.02, analysis of variance). This indicates that the pregnant uterus or placenta can respond to hypoglycaemia by secreting beta-EP into the maternal circulation. It is therefore possible that placental pro-opiomelanocortin (POMC) peptides may have a role in maternal endocrinology and metabolism.     

Plasma concentrations of angiotensin metabolites in young male normotensive and mild hypertensive subjects.

The plasma concentrations of angiotensin (Ang) I, Ang II, and their metabolites (Ang (3-8), (4-8), (5-8), and (3-4)) following in vitro ACE inhibitory activity were examined in young male normotensive (NT) (n = 7), and mild hypertensive (HT) volunteers (n = 6). There were no differences in supine plasma levels of Ang I, Ang II, and Ang (5-8) between the NT and HT groups: Ang I, 304 +/- 43 fmol/ml vs. 293 +/- 15 fmol/ml; Ang II, 32 +/- 6 fmol/ml vs. 43 +/- 10 fmol/ml; Ang (5-8), 176 +/- 22 fmol/ml vs. 133 +/- 32 fmol/ml. In addition, there were no significant differences between groups in any of these Ang levels when measured after standing for 60 min. However, the HT group showed significantly reduced supine and upright plasma Ang (3-8) and Ang (3-4) levels as compared to the NT group. In particular, the supine plasma level of Ang (3-4) (71 +/- 13 fmol/ml-plasma) in the HT group was significantly (1/3-fold) lower than that in the NT group (197 +/- 35 fmol/ml-plasma). An inverse correlation between the plasma level of Ang (3-4) and the upright systolic blood pressure (r = -0.627, p < 0.02, n = 13) was observed, indicating that the metabolism of Ang (3-4) might have been associated with the change in blood pressure.     

Beta-lipotropin and beta-endorphin in physiological and surgical menopause

Beta-lipotropin (beta-LPH) and beta-endorphin (beta-EP) plasma levels were characterized by a significant decrease in postmenopausal females (22 subjects aged from 56 to 70 yr) when compared to fertile women (22 subjects from 31 to 45 yr). On the contrary, ACTH plasma levels determined in 10 of the premenopausal and 13 of the postmenopausal subjects reported above showed constant levels in both groups. A significant increase in the beta-LPH/beta-EP molar ratio was observed in postmenopausal females. The plasma beta-LPH and beta-EP levels studied before and 6 months after ovariectomy, showed a significant decrease in 8 out of 10 patients, while they remained constant in the other 2. Two subjects, in whom postsurgical samples were taken during a flushing episode, showed beta-LPH and beta EP plasma levels which were both higher than the corresponding preovariectomy values. The results suggest that these changes may be important in explaining modifications in behavior and mood frequently found in postmenopausal females and in patients undergoing surgical castration in the fertile age.     

TRH-immunoreactivity in chronic pancreatitis.

Thyrotropin-releasing hormone (TRH) is abundantly present in the pancreas. We studied the circulating TRH-immunoreactivity (IR) in 27 patients with chronic pancreatitis (CP) and different degrees of exocrine pancreatic insufficiency (EPI), as well as in 23 normal subjects. Furthermore we examined the effect of oral administration of 100 g glucose on peripheral TRH-IR in normal subjects (n = 5) and in patients with severe exocrine insufficiency (SEI, n = 5). Basal TRH-IR plasma levels in the CP group (20.8 +/- 7 fmol/ml, mean +/- SD) were significantly lower (p < 0.005) as compared with the normal subjects (38 +/- 14). TRH-IR plasma levels in patients with CP and SEI (15.8 +/- 3) were significantly lower (p < 0.05) than in patients with normal pancreatic function (28.1 +/- 8), but were no different from those in patients with CP and moderate exocrine insufficiency (18.7 +/- 5). In normal controls TRH-IR rose 120-180 min after glucose ingestion from 33 +/- 5 to 64 +/- 20 fmol/ml, while no increase in TRH-IR levels was observed in patients with SEI. We conclude that circulating TRH-IR levels are mainly of pancreatic origin. Patients with SEI have very low peripheral TRH-IR, indicating that CP does indeed influence TRH-release.     

Response of the beta-adrenergic system to maximal dynamic exercise in congestive heart failure secondary to idiopathic dilated cardiomyopathy

In congestive heart failure (CHF), prolonged exposure to high plasma catecholamine levels may reduce the responsiveness of the adrenergic system to physiologic stimuli. In healthy subjects, exercise is known to induce a rapid up-regulation of lymphocytic beta adrenoceptors. Lymphocytic beta-adrenoceptor density, lymphocytic basal and isoproterenol-stimulated cyclic adenosine monophosphate (cAMP) response, plasma catecholamine concentrations and plasma cAMP levels were studied during maximal ergometer exercise in 11 patients with CHF secondary to dilated cardiomyopathy and in 6 healthy control subjects. At rest, there was no difference in the lymphocytic beta-adrenoceptor levels between the patients and control subjects (48 +/- 3 vs 42 +/- 5 fmol/mg protein, respectively). However, the exercise-induced increase in lymphocytic beta adrenoceptors was attenuated in patients when compared with controls (26 +/- 6 fmol/mg protein [56%] vs 75 +/- 16 fmol/mg protein [204%], respectively, p less than 0.02). A subgroup of 4 patients with the lowest exercise capacity (peak oxygen uptake less than 12.5 ml/min/kg) had even more reduced up-regulation compared with the other 7 patients (13 +/- 1 fmol/mg protein [29%] vs 34 +/- 9 fmol/mg protein [71%], p less than 0.05). The lymphocytic cAMP response at rest and during exercise tended to be lower in patients compared with controls, but the differences did not reach statistical significance. The plasma levels of epinephrine and norepinephrine at rest were higher in patients compared with controls, but no difference was found in the exercise values. The plasma levels of cAMP correlated closely with plasma catecholamine levels at rest, but not during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Correlation between plasma levels of ACTH and beta-endorphin in the first seven days of postnatal life

Plasma adrenocorticotropic hormone (ACTH) and beta-endorphin (beta-EP) concentrations were measured by radioimmunoassay in 122 newborns, born vaginally after spontaneous labor between the 38th and the 41st week of pregnancy. Blood samples were taken from umbilical cord in 10 newborns and from antecubital vein in the remaining 112 newborns, divided into 8 groups aged from 12 h to 7 days. The mean (+/- SE) ACTH concentrations in cord plasma were 81.87 +/- 10.16 pg/ml and decreased significantly (p less than 0.01) at the 24th h of life (49.09 +/- 6.93 pg/ml). Afterwards mean ACTH plasma concentrations fluctuated around the latter values. The mean (+/- SE) B-EP concentrations in cord plasma were 21.96 +/- 3.12 pmol/l and decreased significantly at the 24th h of life (13.43 +/- 2.08 pmol/l; p less than 0.01). From the 24th h to the 7th day the mean plasma concentrations of beta-EP were not significantly different. ACTH and beta-EP plasma levels were positively correlated (p less than 0.001) at delivery and during the first seven days of life.     

Thyrotropin releasing hormone (TRH) immunoreactivity and thyroid function in obesity

Circulating TRH-immunoreactive levels, the thyrotropin response to a TRH intravenous stimulation (200 micrograms) and thyroid hormone concentrations have been determined in 43 overweight subjects (body mass index 45 +/- 12 kg/m2, mean +/- s.d.) and 46 (body mass index 22 +/- 2 kg/m2) normal weight controls. The TRH levels measured by a recently developed, highly specific radioimmunoassay were similar among both groups (44 +/- 16 vs 40 +/- 12 fmol/ml, n.s.). The pattern of response of TSH to TRH was normal in the obese and no significant difference was observed between the peak TSH values of the obese and the normal group (8.3 +/- 2.8 vs 8.7 +/- 2.2 microU/ml, n.s.). No correlations were found between the degree of obesity and the concentrations of TRH, TSH and peripheral thyroid hormone levels. Three obese patients showed a delta-TSH of 18, 19 and 21 microU/ml at normal thyroid hormone concentrations as sign of latent hypothyroidism. These data indicate that in obesity: (a) the TSH response to i.v. TRH is not impaired, (b) circulating TRH-IR levels are not significantly changed and (c) the incidence of overt hypothyroidism is not increased.     

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)