beta-LPH Levels Research Articles

Discrimination between beta-endorphin and beta-lipotrophin in human plasma using two-site immunoradiometric assays.

We wished to discriminate between the opioid peptide beta-endorphin (beta-EP) and its non-opioid precursor beta-lipotrophin (beta-LPH) in normal subjects and patients with ACTH-related disorders. We produced monoclonal antibodies to beta-EP and beta-LPH for the development of two-site immunoradiometric assays (IRMAs) which specifically quantitate beta-EP and beta-LPH. Samples were obtained from patients with a range of ACTH-related disorders and compared with 18 normal subjects. Peptide levels were also compared in six patients with Cushing's syndrome undergoing bilateral inferior petrosal sinus sampling with corticotrophin releasing hormone administration. In the beta-EP IRMA, antibody 6B2, specific for beta-EP 18-27, is radiolabelled and antibody 2E10, recognizing beta-EP 1-5, is coupled to Sephacryl S-300 as solid phase. The IRMA is specific for beta-EP (beta-LPH cross-reacts < 0.02%), has a detection limit of 1.4 +/- 0.7 pmol/l (n = 7) and has a within-assay coefficient of variation of < 10% between 4.9 and 1200 pmol/l. In the beta-LPH IRMA, antibody 6B2, which recognizes an epitope common to beta-LPH and beta-EP, is radiolabelled and paired with solid-phase antibody 5C11 which recognizes beta-LPH 39-56. The binding site of this antibody ensures that beta-EP cannot be measured in the beta-LPH assay. The detection limit is 0.8 +/- 0.1 pmol/l (n = 9) and the within-assay coefficient of variation is < 10% at concentrations 1.7-870 pmol/l. In normal subjects, beta-EP and beta-LPH levels were < 1.4-1.7 pmol/l (< 5-6 ng/l) and 2.5-6.7 pmol/l (29-77 ng/l) at 0930 h and < 1.4-1.7 pmol/l (< 5-6 ng/l) and 1.9-4.5 pmol/l (22-49 ng/l) at 1600 h, respectively. In patients with ACTH-related pathologies concentrations of beta-EP and beta-LPH paralleled those of ACTH. The ratio of beta-LPH:beta-EP in plasma varied between 3.2:1 and 38:1 in these patients demonstrating that beta-LPH is the major circulating peptide derived from the C-terminal of pro-opiomelanocortin in man. However, in two patients undergoing bilateral inferior petrosal sampling with corticotrophin releasing hormone for diagnosis of Cushing's disease beta-EP concentrations increased rapidly during the first 5 minutes of the test, resulting in a sharp decrease in the beta-LPH: beta-EP ratio. These results suggest that beta-EP is preferentially released in response to acute corticotrophin releasing hormone stimulation. It is concluded that two-site IRMAs for beta-EP and beta-LPH provide an easy approach to study the dynamic changes in processing of beta-LPH to beta-EP.

Longitudinal evaluation of adrenocorticotrophin and beta-lipotrophin plasma levels following bilateral adrenalectomy in patients with Cushing's disease.

Bilateral adrenalectomy may be indicated in patients with Cushing's disease in whom hypercortisolism is not resolved after pituitary microsurgery. However, Nelson's syndrome is a major long-term complication of such therapy. We have carried out a longitudinal study on patients with Cushing's disease who underwent bilateral adrenalectomy comparing plasma beta-lipotrophin (beta-LPH) with ACTH levels. Seven patients unsuccessfully treated by pituitary surgery for Cushing's disease underwent bilateral adrenalectomy. Blood samples were collected on days 8 and 15 and at 1, 2, 3, 6, 9, 12, 18 and 24 months after adrenalectomy in all patients. Five patients were followed up for the longer periods of 30, 33, 39, 72 and 84 months respectively. Plasma ACTH and beta-LPH were determined by RIA after extraction. Pituitary CT scan was done at 6-8 month intervals. A pituitary tumour was detected in three patients at 14, 24 and 26 months after adrenalectomy respectively. The basal ACTH (range 8-21 pmol/l) began to rise between 15 and 30 days and exhibited a sharp increase with a range of 36-114 pmol/l at 3 months and a range of 53-187 pmol/l at 6-9 months after adrenalectomy. The ACTH levels in the three patients who later presented with a pituitary tumour were indistinguishable from those observed in the other patients up to 12 months after adrenalectomy. Only at 12 months or thereafter were their ACTH levels higher than in the other patients (958 +/- 252 vs 205 +/- 22 pmol/l). beta-LPH concentrations changed in parallel with ACTH levels. The ACTH levels correlated positively with beta-LPH levels (r = 0.76). In patients with Cushing's disease undergoing bilateral adrenalectomy, plasma ACTH and beta-LPH concentrations cannot predict the development of pituitary tumours until 12 months after surgery.

RAPID ESCAPE OF CORTISOL FROM SUPPRESSION IN RESPONSE TO I. V. DEXAMETHASONE IN ANOREXIA NERVOSA*

The suppressive effect of dexamethasone (Dex) on plasma cortisol and beta-lipotrophin (beta LPH) was investigated in patients with anorexia nervosa. Dex was given either orally, 1 mg at 2400 h, with blood sampling at 0800 h on the days before and after Dex, or by i.v. infusion starting at 1100 h (1 mg/h) for 4 h with sampling at 0800, 1100, 1500, 2000 and 2400 h and at 0800 h the following day. The plasma cortisol and beta LPH levels during oral or i.v. Dex administration were compared between patients and normally menstruating women of normal weight. The results showed that Dex administration depressed cortisol significantly (P less than 0.0001) during oral or i.v. infusion in most patients, without, however, suppressing it entirely as is the case in normal women. Moreover, during i.v. Dex infusion, the concentrations of cortisol escaped suppression and were higher than in normal women (less than 50 nmol/l) by 0800 h on the day following infusion. In the patients who were reinvestigated after re-feeding and weight gain (n = 9), a normal suppression of cortisol in response to i.v. Dex infusion was observed in only five cases and a slight failure to suppress, although concentrations were lower than before refeeding, was still evident in four. We concluded that, in anorexia nervosa, cortisol concentration rapidly escapes suppression by Dex administration, and that this escape is not related to the degree of starvation.

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.

The influence of fitness on neuroendocrine responses to exhaustive treadmill exercise

Neuroendocrine and sympathoadrenal responses to exhaustive graded treadmill exercise were examined in 17 male subjects of varying degrees of fitness. The mean duration of exercise to exhaustion was 15.2 +/- 0.7 (+/- SE) min. Exercise duration was inversely correlated with baseline heart rate (P less than 0.05). Compared to standing baseline values, mean plasma norepinephrine and epinephrine levels increased 339% and 301%, respectively, in an integrated 2-min blood sample collected immediately after completion of exercise. Mean adrenocorticotrophic hormone (ACTH), beta-endorphin (beta-EP), beta-lipotropin (beta-LPH), and prolactin levels increased 282%, 720%, 372%, and 211%, respectively, in an integrated 4-min blood sample beginning 2 min after completion of exercise. Cortisol levels increased 183% in the sample collected 17-21 min after exercise. The magnitude of these neuroendocrine responses to exercise was similar among individuals at the same relative intensity of exhaustive exercise, regardless of the duration of exercise. The exercise-induced increases of the pro-opiomelanocortin (POMC)-derived peptides, ACTH, beta-EP, and beta-LPH, were highly correlated with each other (P values less than 0.001), and were correlated with prolactin increases, (P values less than 0.05). During a 20-min recovery period after exercise, changes in heart rate, ACTH, and beta-LPH levels were correlated with duration of exercise, (P less than 0.01, P less than 0.03, and P less than 0.03, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

CSF-endorphines in acute and chronic brain lesions.

In order to answer the question of an opioid influence on consciousness, a radio-immuno-assay (n = 852) of beta-endorphin and beta-LPH (beta-lipotropic hormone) in both ventricular CSF and blood plasma was carried out in 101 neurosurgical patients. The following results were obtained: I) beta-END and beta-LPH levels were found to be lower in the CSF than in blood plasma. II) beta-END and beta-LPH in the CSF was the same in both sexes. III) beta-END levels in the CSF decreased with age. IV) beta-END and beta-LPH levels showed a diurnal rhythm with a maximum in the late a. m. hours. V) beta-END levels in the ventricular CSF tend to decrease parallel to a drop in conciousness as well as with longlasting comatous states. VI) beta-END in ventricular CSF becomes higher with increasing systolic arterial blood pressure. VII) beta-END and beta-LPH levels in ventricular CSF are not correlated with the type of the disease, CSF pressure, body temperature or respiratory changes.

Evidences for a dopamine-regulated peripheral source of circulating beta-endorphin.

Circulating beta-endorphin (beta EP) and beta-lipotropin (beta LPH) concentrations increase after the administration of acetylcholine or serotonin agonist drugs. In this study we examined the effect of dopamine receptor agonists and/or antagonists on plasma beta EP, beta LPH, cortisol, and PRL levels in normal subjects. Neither direct dopamine (DA) agonist drugs, DA (1 microgram/kg min for 120 min), bromocriptine (2.5 mg po), L-dopa (500 mg po) or an indirect DA agonist, nomifensine (200 mg po), significantly altered plasma beta EP and beta LPH levels. The administration of metoclopramide, a DA antagonist (10 mg iv), significantly increased plasma beta EP, beta LPH, PRL, and cortisol levels. This effect was completely reversed by pretreatment with L-dopa (500 mg po) and only partially antagonized by DA infusion. Domperidone (10 mg iv), a DA antagonist which does not cross the blood brain barrier, increased only plasma beta EP levels, an effect inhibited both by L-dopa and DA. After dexamethasone (2 mg/day for 2 days) domperidone still increased plasma beta EP and PRL levels. The concomitant increase of beta EP, beta LPH, and cortisol after metoclopramide suggests that endogenous DA inhibits the secretion of proopiomelanocortin-related peptides. Moreover, since domperidone increases only beta EP and this effect is not altered by dexamethasone, there may be a corticotropin-releasing hormone-independent source of circulating beta EP in humans, which is inhibited by DA.

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.

Effects of neuroleptic treatments on peripheral opioid secretion.

The effects of short- and long-term neuroleptic therapy on peripheral secretion of beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH) were examined in 25 chronic schizophrenic patients. Haloperidol was given to 8 patients for 10 days (group A: 0.1 mg/kg b.w./day) and to another group of 8 patients for 30 days (group B: 10-18 mg/day). The other 9 patients were given a combination of haloperidol (6-30 mg/day) with either chlorpromazine (25-75 mg/day), clotiapine (40-60 mg/day), or fluphenazine decanoate (25-75 mg/month) for 14-18 months (group C). beta-EP and beta-LPH levels were assayed before and after each treatment. Haloperidol plasma levels were assayed in group B patients at the end of treatment. beta-EP mean basal levels were higher in patients than in controls; however, beta-LPH mean basal levels were higher only for group A patients. After treatment, the mean levels did not differ from those prior to therapy in groups A and B, while beta-LPH levels were significantly higher in group C. Level increases or decreases in single patients did not correlate with drug dose or duration of treatment, with baseline peptide levels or with the clinical effects of the various treatments.

Beta-endorphin/beta-lipotropin release and gonadotropin secretion after acute exercise in normal males.

The plasma beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH) response to acute exercise and the relationship of these opioid peptides to basal and luteinizing hormone-releasing hormone (LRH)-stimulated luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion was studied in eight normal male volunteers. Acute exercise resulted in a rise in plasma beta-LPH levels that returned to base line when measured 60 min after exercise. Plasma beta-EP levels did not demonstrate any rise when measured immediately after 20 min of exercise or at 60 min after exercise. Serum LH concentrations in individual volunteers declined to nadir values 60-180 min after exercise after which they showed a rebound to levels higher than the preexercise values in three of five volunteers in whom nadir LH levels were attained before the final (180 min) measurement. Serum FSH concentrations were unaltered by exercise. Acute exercise similarly did not alter the LH/FSH response to exogenous LRH stimulation. Pretreatment of the volunteers with the narcotic antagonist, naloxone, failed to alter the postexercise or LRH-stimulated LH and FSH release. The data suggest that beta-EP does not exert a suppressive effect on LH secretion after acute exercise in normal human males. Whether the suppression of LH secretion after acute exercise in unconditioned males is due to factor(s) cosecreted with beta-LPH, an increase in brain beta-EP or to alternate mechanisms such as alteration in central dopaminergic or GABAergic tone remains to be established.

Beta-lipotropin and cortisol responses to an intravenous infusion dexamethasone suppression test in Cushing's syndrome and obesity.

An i.v. infusion dexamethasone (Dex) test was used to investigate the ACTH feedback response in 9 normal subjects, 12 obese patients, and 11 patients with Cushing's syndrome. Dex phosphate was infused iv for 4 h, starting at 1100 h (1 mg/h). Plasma concentrations of beta-lipotropin (beta LPH) and cortisol were measured every 20 min between 0900 and 1600 h, then every 2 h until midnight and at 0900 h the next day. In normal subjects and obese patients, plasma beta LPH and cortisol concentrations fell rapidly to less than 40 ng/liter and 3 micrograms/dl, respectively, at the end of Dex infusion. Subsequent values remained low through 0900 h the next day. In 7 patients with Cushing's disease, basal plasma beta LPH and cortisol concentrations declined by greater than 50% during the Dex infusion. In these patients, rapid escape from suppression occurred between 1600 and 2400 h; by 0900 h the following day, beta LPH and cortisol levels were higher than 100 ng/liter and 10 micrograms/dl, respectively. In 3 patients with adrenal tumors, beta LPH concentrations were low, and cortisol concentrations did not decline during the Dex infusion. In 1 patient with ectopic ACTH secretion, beta LPH concentrations were high and were not suppressed by the Dex infusion. We conclude that the iv infusion Dex suppression test can distinguish patients with Cushing's syndrome from normal or obese subjects and can aid in the etiological diagnosis of Cushing's syndrome.

Neuroendocrine effects of flunarizine treatment in postmenopausal women.

Flunarizine (10 mg/day for 60 days) was given to eight postmenopausal women with common migraine. Plasma LH pulsatility fluctuation, peripheral concentrations of prolactin (PRL), cortisol, beta-endorphin (beta-EP), beta-lipotropin (beta-LPH) and Pain Total Index (PTI) were evaluated before and after treatment. PTI was significantly reduced by flunarizine, which did not affect beta-LPH, beta-EP and cortisol plasma levels. On the contrary, both PRL values and amplitude, and length of LH pulses had increased at the end of treatment. Flunarizine reduced head pain in postmenopausal women. However, the enhancement of both PRL and LH release indicates that this calcium antagonist might interfere with the dopaminergic tonus.

Proopiocortin-related peptide plasma levels throughout prepuberty and puberty.

The plasma patterns of ACTH, beta-lipotropin (beta LPH) and beta-endorphin (beta EP), in addition to those of cortisol and dehydroepiandrosterone sulfate (DHAS), were studied in 139 prepubertal children (subdivided into different age groups) and 38 adolescents (subdivided according to Tanner's pubertal stages) aged 10-16 yr. The adult control group was composed of 23 females and 12 males aged 17-40 yr. No sex differences were found in ACTH, beta LPH, beta EP, and cortisol plasma levels. ACTH plasma levels were slightly lower in the 1- to 3-yr-old groups than in males at 4-5 yr and females at 8-9 yr. No further significant differences were observed in any of the age or pubertal groups, the concentrations being constantly in the adult range. beta LPH and beta EP plasma levels were lowest at 1-3 yr in both males (beta LPH: 2.1 +/- 0.25, beta EP: 1.85 +/- 0.59 fmol/ml, mean +/- SE) and females (beta LPH: 2.8 +/- 0.31; beta EP: 2.41 +/- 0.41 fmol/ml); plasma levels of both hormones increased progressively in both sexes until Puberty 1 stage of sexual maturation, at which time levels were 7.3 +/- 0.78 and 8.69 +/- 1.0 fmol/ml in males and 7.1 +/- 0.34 and 6.76 +/- 0.13 fmol/ml in females; these levels are similar to adult values. A highly significant linear correlation was found between both beta LPH and beta EP concentrations and the age of the subjects; this was not true for ACTH plasma levels. Cortisol plasma levels were similar in all groups. DHAS plasma levels increased progressively from 1-3 yr to the end of sexual maturation when adult values were reached. During prepuberty, DHAS levels were significantly correlated with both beta LPH and beta EP, but not ACTH. These data indicate that plasma beta LPH and beta EP concentrations, in contrast to ACTH levels, increase progressively throughout prepuberty and suggest that the processing of the parent proopiocortin molecule or secretion of the processed peptides from the anterior pituitary (or other sources) may change from early infancy to adulthood. Furthermore, the correlation between both beta LPH and beta EP with DHAS plasma levels in prepuberty suggests a role of proopiocortin-related peptides in adrenarche.

Beta-lipotrophin and beta-endorphin plasma levels during pregnancy.

beta-lipotrophin (beta-LPH) and beta-endorphin (beta-EP) plasma levels were measured by radioimmunoassay after glass powder extraction and Sephadex G-75 column chromatography in plasma samples from controls (ten healthy males and twenty-six young women in early follicular phase), from eighty-two pregnant women in weeks 9-40 after their last menstrual period, from nine women just after delivery and the cord blood of their neonates, in fifteen mixed cord blood samples and in seven amniotic fluid samples obtained by amniocentesis. No sex differences were found in beta-LPH (120.6 +/- 8.5 pg/ml) or beta-EP (31.1 +/- 2.4 pg/ml) plasma levels or in their molar ratio (1.34 +/- 0.09) (MR). beta-LPH plasma levels increased in early pregnancy (13-16 weeks) (185.0 +/- 27.1 pg/ml) and remained high until weeks 21-24, then declining to levels similar to those of controls. beta-EP plasma levels were significantly depressed in weeks 9-12 (20.7 +/- 5.3 pg/ml), subsequently increasing to a maximum at weeks 36-37 (42.7 +/- 6.8 pg/ml). beta-LPH/beta-EP molar ratio was about double normal in early pregnancy and decreased to normal in the second half. The present data indicate that beta-LPH and beta-EP present different patterns throughout pregnancy and that beta-EP levels increase progressively, reaching the highest concentrations at term. At delivery, both beta-LPH and beta-EP showed maximum values (beta-LPH: 230.2 +/- 20.4 pg/ml; beta-EP: 78.0 +/- 7.4 pg/ml) and a MR of 1.02 +/- 0.10 indicating that stressful situations, such as labour, stimulate a simultaneous rise in beta-LPH and beta-EP plasma levels. Cord blood specimens showed a wide range of values (beta-LPH:75-347 pg/ml; beta-EP: 16-287 pg/ml) with a MR of 1.21 +/- 0.14. Amniotic fluid samples obtained late in the third trimester of pregnancy were characterized by beta-LPH levels of 119.4 +/- 26.4 pg/ml and beta-EP levels of 29.6 +/- 7.5 pg/ml.

Beta-Endorphin and beta-lipotropin plasma levels in hirsute women: correlation with body weight.

Based on the findings of elevated circulating beta-endorphin (beta-END) levels in genetically obese (fa/fa) fats and the reversal of the overeating of genetically obese (ob/ob) mice by naloxone, circulating beta-END and beta-lipotropin (beta-LPH) levels were measured in 8 hirsute, hyperandrogenic, oligo-amenorrheic women of varying weights. Circulating beta-END and beta-LPH levels were significantly elevated (p less than .001) above the levels in nonobese control subjects and were positively correlated with body weight (p less than .025). Based on these data and indirect evidence in the literature, we propose a role may exist for beta-END and/or beta-LPH in human obesity and in adrenal androgen secretion.