Human Beta-endorphin Research Articles

Specific binding of .BETA.-endorphin to the isolated renal basolateral membranes in vitro.

Binding of human beta-endorphin (beta-EP) to rat renal basolateral membranes was characterized using [125I]Tyr27-beta-EP ([125I]beta-EP) as a primary ligand. Ten millimolar of ethylenediaminetetra acetic acid (EDTA) completely inhibited the degradation of [125I]beta-EP in the incubation mixture at 4 degrees C, thus making it possible to quantitatively examine the [125I]beta-EP binding. The specific binding of [125I]beta-EP to the basolateral membranes was reversible and saturable, and a nonlinear least-squares regression analysis of a saturation isotherm revealed two different classes of specific binding sites. One class had an apparent dissociation constant (Kd) of 0.68 nM and a lower number of binding sites (33 fmol/mg protein), whereas the other class had a lower affinity (apparent Kd of 210 nM) and a higher number of binding sites (7.3 pmol/mg protein). Inhibition of the [125I]beta-EP binding by naloxone (10 microM) was approximately only 20%, and that by D-Ala2-D-Leu5-enkephalin (10 microM) was null, suggesting the major role of a non-opioid binding component in specific [125I]beta-EP binding to basolateral membranes. Moreover, a 50% inhibition by 10 microM of dynorphin(1-13) suggests that a certain region of the primary structure of beta-EP, excluding at least the NH2-terminal enkephalin sequence, is of particular importance for the [125I]beta-EP binding. These lines of evidence suggest the existence of two different classes of specific binding sites for beta-EP on the renal basolateral membranes, and the high-and low-affinity bindings may be attributed to opioid and non-opioid receptors, respectively, as judged by known characteristics of opioid and non-opioid receptors in other peripheral tissues.

A novel β-endorphin binding protein: Complement S protein (= vitronectin) exhibits specific non-opioid binding sites for β-endorphin upon interaction with heparin or surfaces

Human beta-endorphin (1-31) (beta H-endorphin) was found to specifically interact with purified complement S protein from human plasma. As found by chemical cross-linking beta H-endorphin bound to both, the 65- and 75-kDa molecular mass forms of S protein. The interaction of S protein with heparin as well as the adsorption of S protein to surfaces led to an almost 10-fold increase of specific binding which was due to the exposure of further beta H-endorphin-binding sites. The interaction of beta H-endorphin with S protein bore characteristics of a ligand-receptor interaction, such as time dependence, reversibility, high affinity, saturability, and structural specificity and was mediated through the non-opioid COOH terminus of the beta H-endorphin molecule. beta H-Endorphin binding to S protein was observed at physiological pH or cation concentrations, indicating that the interaction may well occur in vivo. Our results provide conclusive evidence that interactions of S protein with very different effectors led to similar conformational changes which uniformly resulted in exposure of a highly specific beta H-endorphin binding domain on S protein. With S protein as major beta H-endorphin-binding protein in the periphery, the molecular basis of a widespread system of humoral target sites of the neuroendocrine effector appears to be established. In view of S protein involvement in processes of inflammation and wound repair and beta-endorphin effects on immunocompetent cells, the demonstrated S protein-beta H-endorphin interaction appears to be of considerable functional significance.

A Neuroendocrinological Study in Female Migraineurs: Prolactin and Thyroid Stimulating Hormone Responses

To evaluate the change of the neurotransmitter function in migraine, a neuroendocrinological study was performed in eleven female migraineurs and nine female controls. Thyrotropin releasing hormone, luteinizing hormone releasing hormone, and insulin were simultaneously loaded (the Triple test). Before and after loading, serum glucose, prolactin (PRL), thyroid stimulating hormone (TSH), luteinizing hormone, follicle stimulating hormone, adrenocorticotropic hormone, cortisol, human growth hormone and beta-endorphin were measured. The Triple test produced an increase of PRL in both migraine and control groups, but in migraineurs the increase was significantly larger than in controls. TSH also increased in response to the test, but the TSH response in patients was less than in controls, although not significantly so. The responses of other substances showed no significant differences between the two groups. Although dopaminergic hypofunction in migraine has been proposed by some authors, the present findings rather suggest a serotonergic hyperfunction.

Beta-endorphin and islet hormone release in humans: evidence for interference with cAMP

The present studies were undertaken to characterize further the influence of synthetic human beta-endorphin (0.5 mg/h) on insulin and glucagon responses to intravenous glucose in humans. Infusion of beta-endorphin in 10 normal volunteers caused a clear-cut inhibition of the overall insulin responses to a glucose pulse (0.33 g/kg iv) with values of glucose disappearance rates in the diabetic range [0.89 +/- 0.09 (P less than 0.01) vs. saline 1.82 +/- 0.15%/min]. Glucose-induced glucagon suppression was significantly lower during beta-endorphin, a fact that could have contributed to the reduced glucose utilization rates. The infusion of theophylline (150 mg + 350 mg/h) to increase the intracellular cAMP activity by inhibiting phosphodiesterase completely reversed the inhibitory effect of beta-endorphin on glucose-induced insulin secretion. As a consequence, glucose disappearance rates rose to 1.77 +/- 0.18%/min. Theophylline did not influence significantly the glucagon-releasing effect of beta-endorphin as well as the reduced glucagon suppression. An infusion of exogenous calcium (100 mg as iv bolus + 5 mg/min) to raise serum calcium in the hypercalcemic range (15 mg/dl) and lysine acetylsalicylate (72 mg/min) to block the synthesis of endogenous prostaglandin E did not interfere with the inhibiting effect of beta-endorphin on insulin secretion. These data confirm that beta-endorphin stimulates glucagon and inhibits basal and glucose-stimulated insulin secretion and suggest that the opioid influences the intraislet adenylate cyclase activity.

Catalysis of Slow C‐Terminal Processing Reactions by Carboxypeptidase H

A hypothesis was examined that carboxypeptidase H (CpAse H), which is known to catalyse the release of lysine and arginine from the C-terminus of peptides, can also release histidine, tyrosine, and phenylalanine. Synthetic peptides terminating in -His-Lys or -Tyr-Lys were used as model substrates for the enzyme and amino acid analysis was employed to detect release of the terminal amino acids. With N-acetyl-beta-Ala-Asn-Ala-His-Lys and N-acetyl-beta-Ala-Asn-Ala-Tyr-Lys, which correspond to intermediates in the processing of porcine and human beta-endorphin, lysine was removed rapidly and quantitatively but no release of histidine or tyrosine could be detected. To allow more sensitive analysis, radiolabelled substrates were employed and the amounts of the products formed on incubation with CpAse H were determined after separation by ion-exchange chromatography. With 125I-D-Tyr-Ala-His-Lys-Lys as substrate at pH 5.7, very small amounts of D-Tyr-Ala were released; the main product was D-Tyr-Ala-His. At pH 5.0 the release of histidine from 125I-D-Tyr-Ala-His took place 6,000 times more slowly than the release of lysine from 125I-D-Tyr-Ala-Lys. When the tripeptides were incubated at pH 5 with porcine pituitary secretory granules, the lysine was released rapidly but no release of histidine could be detected. The results demonstrate that CpAse H catalyses the release of C-terminal histidine with great difficulty.(ABSTRACT TRUNCATED AT 250 WORDS)

Beta-endorphin in the brainstem and the cerebellum of the human infant: Regional levels' profile assessed with immunoaffinity chromatography and solid phase radioimmunoassay

The regional levels' profile of human beta-endorphin (beta h-EP) was studied in the brainstem and the cerebellum of 16 infant victims of “Sudden Infant Death Syndrome” and other death causes. An immunoaffinity chromatography procedure based on a monoclonal antibody directed specifically against the N-terminus of beta-EP was used to extract this peptide from the tissue samples. Beta-EP was then assessed quantitatively by means of a very sensitive solid phase radioimmunoassay (using a polyclonal antibody specific for the C-terminus of beta-EP) developed especially for the study presented here.

Purification and characterization of an N alpha-acetyltransferase from Saccharomyces cerevisiae.

N alpha-Acetyltransferase, which catalyzes the transfer of an acetyl group from acetyl coenzyme A to the alpha-NH2 group of proteins and peptides, was isolated from Saccharomyces cerevisiae and demonstrated by protein sequence analysis to be NH2-terminally blocked. The enzyme was purified 4,600-fold to apparent homogeneity by successive purification steps using DEAE-Sepharose, hydroxylapatite, DE52 cellulose, and Affi-Gel blue. The Mr of the native enzyme was estimated to be 180,000 +/- 10,000 by gel filtration chromatography, and the Mr of each subunit was estimated to be 95,000 +/- 2,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme has a pH optimum near 9.0, and its pI is 4.3 as determined by chromatofocusing on Mono-P. The enzyme catalyzed the transfer of an acetyl group to various synthetic peptides, including human adrenocorticotropic hormone (ACTH) (1-24) and its [Phe2] analogue, yeast alcohol dehydrogenase I (1-24), yeast alcohol dehydrogenase II (1-24), and human superoxide dismutase (1-24). These peptides contain either Ser or Ala as NH2-terminal residues which together with Met are the most commonly acetylated NH2-terminal residues (Persson, B., Flinta, C., von Heijne, G., and Jornvall, H. (1985) Eur. J. Biochem. 152, 523-527). Yeast enolase, containing a free NH2-terminal Ala residue, is known not to be N alpha-acetylated in vivo (Chin, C. C. Q., Brewer, J. M., and Wold, F. (1981) J. Biol. Chem. 256, 1377-1384), and enolase (1-24), a synthetic peptide mimicking the protein's NH2 terminus, was not acetylated in vitro by yeast acetyltransferase. The enzyme did not catalyze the N alpha-acetylation of other synthetic peptides including ACTH(11-24), ACTH(7-38), ACTH(18-39), human beta-endorphin, yeast superoxide dismutase (1-24). Each of these peptides has an NH2-terminal residue which is rarely acetylated in proteins (Lys, Phe, Arg, Tyr, Val, respectively). Among a series of divalent cations, Cu2+ and Zn2+ were demonstrated to be the most potent inhibitors. The enzyme was inactivated by chemical modification with diethyl pyrocarbonate and N-bromosuccinimide.

Effects of bile salts on plasma concentration of beta-endorphin-like immunoreactivity in men.

The effects of bile salts on the release of beta-endorphin-like immunoreactivity (beta-END-LI) were investigated in men using a specific radioimmunoassay developed by the authors. Plasma beta-END-LI was determined after extraction by the acid-acetone method (recovery: 73 +/- 5%). Oral administration of 400 mg of sodium taurocholate caused a rise in plasma beta-END-LI from 9.9 +/- 0.5 pmol/liter to 21.3 +/- 1.2 pmol/liter after 30 min and 18.1 +/- 0.5 pmol/liter after 60 min, with return to the initial value after 90 min. Oral administration of chenodeoxycholic acid (CDCA) also increased plasma beta-END-LI from a basal level of 8.4 +/- 0.7 pmol/liter to 18.7 +/- 0.8 pmol/liter after 30 min. Oral administration of ursodeoxycholic acid (UDCA) increased plasma beta-END-LI from 7.3 +/- 0.3 pmol/liter to 30.6 +/- 0.2 pmol/liter after 30 min. In gel chromatography, the beta-END-LI released after UDCA administration separated into two components, which eluted in the same positions as human beta-lipotropin and human beta-endorphin, respectively. These results suggested that bile salts may participate the release of beta-END-LI.

The effects of corticotropin, opioid peptides and crude pituitary extract on the production of dehydroepiandrosterone and corticosterone by mature rat adrenal cells in tissue culture

In order to study the steroidogenic response to pituitary factors, a technique of monolayer tissue culture of mature female rat adrenal cells was used. During the first 24 h, rat adrenal cells produced dehydroepiandrosterone (DHEA) and small amount of corticosterone but in the absence of corticotropin (ACTH), the release of these two steriods were reduced to very low levels. The addition of synthetic α-ACTH-(1–24)[0.01–100ng/ml] elicited a marked increase in the production of both steriods. This stimulating effect was not observed when synthetic methionine and leucine-enkephalins (1–100 ng/ml), human beta-endorphin (1–100 ng/ml) or human betalipotropin (1 ng/ml), were added to the culture medium. When these peptides were added concomitantly with α-ACTH (1–24) at half of the maximum response dose (1 ng/ml), no synergistic effect upon DHEA and corticosterone production was shown. The addition of crude extract from rat pituitary gland (1–100 ng/ml) with or without α-ACTH-(1–24) definitely showed both a stimulatory and synergistic effect upon the production of these two steroids. Furthermore, the ratio between DHEA production and corticosterone production was significantly higher when crude extract of the pituitary gland was given alone or concomitantly with α-ACTH(1–24) than when α-ACTH(1–24) was given alone. These data suggest the existence of a still undefined pituitary adrenal adrogen stimulating which may preferentially stimulate DHEA production over corticosterone production.

Characterization and identification of heparin-induced nonopioid-binding sites for beta-endorphin in human plasma.

We have characterized the specific binding of human beta-endorphin (1-31) to novel binding sites which are formed in human plasma or serum in the presence of heparin. The formation of the binding sites is temperature-dependent and does not occur in the presence of other anticoagulants, such as sodium-EDTA, sodium-oxalate, or sodium-citrate. The specific binding of 125I-beta H-endorphin to heparin-induced binding sites in human plasma is saturable and reversible. It is not inhibited by morphine or naloxone or by various opioid peptides which share their NH2-terminal opioid-active sequence with beta H-endorphin. In contrast, binding is inhibited by the COOH-terminal beta H-endorphin fragment Gly-Glu indicating that binding is to nonopioid sites. Electroimmunoprecipitation techniques revealed that these binding sites are identical with S protein/vitronectin or derivatives thereof. S protein is a plasma alpha 1-glycoprotein involved in attachment and spreading of cells and also in blood coagulation and complement activation. It is possible that the interaction of beta-endorphin with S protein is of physiological significance.

Biotinylated human beta-endorphins as probes for the opioid receptor.

The reaction of human beta-endorphin and biotinyl N-hydroxysuccinimide with or without spacer arm, afforded a series of products that were separated by high performance liquid chromatography (HPLC). Liquid secondary ion mass spectrometry of the biotinylated products and their tryptic digests produced abundant protonated molecular ions (MH+), which specified the number and location of biotinylation. Between 1 and 4 biotinyl residues were incorporated per human beta-endorphin molecule, at Lys-9, -19, -24, -28, and -29, but not at the amino-terminal Tyr-1. Three HPLC fractions were isolated for receptor binding studies with monobiotinylation of Lys-9 (B1 beta and B1X beta; X = C6 spacer arm), Lys-19 (B1 gamma), and a mixture of Lys-24, Lys-28, and Lys-29 derivatives (B1 alpha, BX1 alpha). All derivatives displayed tight binding to avidin, and no dissociation from avidin was detectable over several hours at 0 degrees C for the derivatives (BX1 alpha) tested. IC50 values for binding to mu and delta opioid receptor sites were 3-8 times higher for monobiotinylated derivatives than for the parent human beta-endorphin (IC50,mu = 1.5 nM, IC50,delta = 1.3 nM). Association with avidin decreased opioid receptor affinities for the C6 spacer derivative biotinylated at position Lys-9, which is close to the (1-5) enkephalin receptor region. In contrast, avidin did not affect or even increased apparent affinities to mu and delta sites for derivatives biotinylated at the alpha-helical part of the molecule (Lys-19, -24, -28, and -29). Thus, when bound to avidin, the biotinylated human beta-endorphin derivatives with spacer arm (BX1 alpha), substituted near the carboxyl terminal (Lys-24, -28, and -29), displayed mu binding affinities equal to and delta binding affinities only four times lower than underivatized human beta-endorphin. Biotinylated human beta-endorphins also bound to low affinity nonopioid binding sites on NG-108-15 cells; however, affinities to these sites were considerably reduced when derivatives were bound to avidin. The ability of biotinylated human beta-endorphin to cross-link the mu and delta opioid receptors to avidin allows application of the biotin-avidin system as a molecular probe of the opioid receptor.

Secondary structure determination of human beta-endorphin by 1H NMR spectroscopy.

The 1H NMR spectra of human beta-endorphin indicate that the peptide exists in random-coil form in aqueous solution but becomes helical in mixed solvent. Thermal denaturation NMR experiments show that in water there is no transition between 24 and 75 degrees C, while a slow noncooperative thermal unfolding is observed in a 60% methanol-40% water mixed solvent in the same temperature range. These findings are consistent with circular dichroism studies by other workers concluding that beta-endorphin is a random coil in water but that it forms 50% alpha-helix or more in mixed solvents. The peptide in the mixed water-methanol solvent was further studied by correlated spectroscopy (COSY) and nuclear Overhauser effect spectroscopy (NOESY) experiments. These allow a complete set of assignments to be made and establish two distinct stretches over which the solvent induces formation of alpha-helices: the first occurs between Tyr-1 and Thr-12 and the second between Leu-14 and extending to Lys-28. There is evidence that the latter is capped by a turn occurring between Lys-28 and Glu-31. These helices form at the enkephalin receptor binding site, which is at the amino terminus, and at the morphine receptor binding site, located at the carboxyl terminus [Li, C. H. (1982) Cell (Cambridge, Mass.) 31, 504-505]. Our findings suggest that these two receptors may specifically recognize alpha-helices.

Hyperglycemia and obesity as determinants of glucose, insulin, and glucagon responses to beta-endorphin in human diabetes mellitus.

The effect of human beta-endorphin on plasma glucose, insulin, and glucagon concentrations was studied in patients with noninsulin-dependent diabetes mellitus and in normal subjects. The subjects were divided according to their body weight into lean (body mass index, less than 25) and obese (body mass index, greater than 29.5) groups. In lean subjects, infusion of 0.5 mg/h beta-endorphin caused significant increases in peripheral plasma glucose and glucagon levels, but no change in plasma insulin. In obese subjects, there was an immediate marked increase in both plasma insulin and glucagon concentrations during the beta-endorphin infusion, but the plasma glucose response was lower than that of lean subjects. In lean diabetic patients, beta-endorphin produced significant simultaneous increments in both insulin and glucagon concentrations and significantly decreased plasma glucose levels. These hormonal responses to beta-endorphin were amplified in the obese diabetic patients. There was a significant correlation (r = 0.61; P less than 0.01) between fasting plasma glucose levels and the integrated insulin area in response to beta-endorphin. The infusion of a lower dose of beta-endorphin (0.05 mg/h) in diabetic patients produced similar increments in both insulin and glucagon levels and also decreased plasma glucose concentration. These results indicate that beta-endorphin may have important glucoregulatory effects in man depending on the dose administered, the presence of obesity, and the prevailing plasma glucose concentration.

Primary role of glucagon release in the effect of beta-endorphin on glucose homeostasis in normal man.

The present study aimed at evaluating the effect of human beta-endorphin on pancreatic hormone levels and on glucose metabolism in normal subjects. Infusion of 143 nmol/h beta-endorphin in 7 subjects caused a significant rise in plasma glucose concentrations (+ 1.7 +/- 0.3 mmol/l) which was preceded by a significant increase in peripheral plasma glucagon levels (+ 44 +/- 13 ng/l). No changes occurred in the plasma concentrations of insulin and catecholamines (adrenaline and noradrenaline). The influence of beta-endorphin per se on glucose homeostasis was studied in 7 other subjects using the euglycaemic clamp technique in which the endocrine pancreatic function was fixed at its basal level with somatostatin together with replacement of basal insulin and glucagon by the exogenous infusion of these hormones. In this new metabolic conditions, beta-endorphin failed to have significant influences on the various parameters of tracer-estimated glucose metabolism (production, utilization, and clearance) and on the plasma levels of the gluconeogenic precursors (glycerol and alanine). Moreover, the levels of pancreatic and counterregulatory hormones (cortisol and catecholamines) were not different between beta-endorphin and control studies. We conclude that the naturally occurring opioid peptide beta-endorphin produced an hyperglycaemic effect in man which appears to be mediated by glucagon. The opioid seems to have no direct effect on glucose metabolism. These results suggest that the metabolic effects of beta-endorphin in normal man are secondary to its impact on pancreatic hormone secretion and not a consequence of a direct modulation of glucose metabolism.

Beta-endorphin infusion fails to modulate the hormonal and metabolic response to surgery.

The effects of an i.v. infusion of synthetic human beta-endorphin on the hormonal, metabolic and cardiovascular responses to surgery were investigated in female patients undergoing pelvic surgery. A beta-endorphin infusion (2 micrograms/kg as a bolus at induction of anaesthesia + 10 micrograms/kg/h for the first hour of surgery) increased plasma beta-endorphin immunoreactivity to values at least 100-fold greater than those seen during surgery in a control group of patients. In spite of this massive increase the only significant findings were a transient augmentation of the expected hyperglycaemic response and increased plasma glucagon values. There were no significant changes in ACTH, GH, insulin and cortisol secretion, in blood concentrations of lactate or glycerol, or in cardiovascular variables. Complete dissociation between plasma and cerebrospinal fluid concentrations of beta-endorphin was found even when plasma values exceeded 10,000 pmol/l in the presence of anaesthesia and surgery. These results show that the increase in circulating beta-endorphin immunoreactivity associated with clinical stress states are unlikely to modulate the associated hormonal, metabolic and cardiovascular changes.

Stimulation of insulin secretion by beta-endorphins (I-27 & I-31)

Synthetic human beta-endorphin potentiates insulin secretion by the isolated perfused rat pancreas when glucose is present in the perfusate at concentrations of either 125 or 200 mg/dl, whereas it fails to exert any effect on insulin secretion in the presence of a substimulatory concentration of 100 mg/dl. Similar potentiation of insulin secretion occurred in response to the 1–27 fragment (beta-endorphin I-27) of beta-endorphin. This transient potentiation lasts only 3 to 4 minutes, whereupon secretion returns toward control levels. Thus beta-endorphin produces only a transient spike-like secretory profile similar to the first phase of glucose-induced insulin secretion and it fails to produce any chronic insulin secretory response comparable to the second phase of insulin secretion. The insulinotropic effect of beta-endorphins occurred at concentrations varying from 0.1 to 5.0 ug/ml. These data suggest that beta-endorphin and beta-endorphin I-27 potentiate insulin secretion via a common beta cell opioid receptor, and that beta-endorphin may exert a paracrine control of insulin secretion. However, any such regulation appears to be via short-term alterations in the secretory process per se .

Beta-endorphin infusion restores acute insulin responses to glucose in type-2 diabetes mellitus.

To address the possibility that an abnormality in pancreatic beta-endorphin activity might contribute to abnormal insulin secretion in diabetes mellitus, we studied the effects of beta-endorphin infusion on islet function in diabetic patients. The iv infusion of human beta-endorphin at a dose of 0.5 mg/h for 2 h in type-2 non-insulin-dependent diabetic patients (n = 12) raised plasma insulin and glucagon levels and slightly but significantly lowered plasma glucose concentrations. beta-Endorphin infusion also resulted in reappearance of a clear-cut acute insulin response to glucose, while second phase insulin release was increased and glucose disposal accelerated. Acute insulin and glucagon responses to arginine were not increased by beta-endorphin, suggesting that the effect of the opioid on the B cells of the diabetic patients is specific for glucose. An intraislet abnormality of opioid peptides action and/or secretion may play a role in the disturbances of insulin secretion in patients with type-2 diabetes mellitus.

Aromatase activity in a rat Leydig cell tumor.

Male Wistar-Furth rats bearing the transplantable LTW(m) Leydig cell tumor have elevated serum estradiol (E2) concentrations. We measured the ability of these tumors to aromatize testosterone (T) to E2 by two methods. First, tumor minces were incubated with [7-3H]T, and the resultant [3H]E2 and [3H]estrone were purified and measured. In addition, tumor cell cultures were incubated with [1 beta-3H]T, and the resultant [3H]H2O was determined as a measure of aromatization. Tumor minces aromatized more actively than normal rat testicular tissue (3.30 +/- 0.15% of the T added was converted to E2 by the tumor vs. 0.30 +/- 0.25% by normal testis). Most of the aromatizing actitivity was localized to the microsomes. Using cell cultures the maximum velocity was 6.1 pmol/h X 5 X 10(5) cells, and the Km was 98 nM. In neither minces nor cell cultures were we able to show stimulation of aromatization with hCG, (Bu)2cAMP, or phorbol esters, although we could show stimulation by these agents in normal testicular cells. We were unable to inhibit the aromatase activity with human beta-endorphin or stimulate it with naloxone. However, we were able to inhibit the aromatase activity with 4-hydroxy-4-androstene-3,17-dione. We conclude that the LTW(m) rat Leydig cell tumor has an active autonomous aromatase system that is not responsive to compounds affecting the adenylate cyclase-cAMP system. It can be inhibited by 4-hydroxy-4-androstene-3,17-dione, a competitive-suicide inhibitor of the aromatase enzyme(s).

β‐Endorphin: intranasal administration increases the serum prolactin level in monkey

Human beta-endorphin has been administered by nasal spray technique at a dose of 0.02 mg per kg in female bonnet monkeys. A significant increase of serum prolactin levels was observed within 30 min and maintained up to 60 min. In the same dose, intravenous injections of the hormone caused a marginal increase of prolactin levels only after 60 min. It was concluded that administration of beta-endorphin by nasal spray is more effective than the intravenous injection.

Anti-beta-endorphin immunoglobulin G in humans.

Human IgG specific for beta-endorphin was identified by enzyme-linked immunoabsorbent assay and isolated by affinity chromatography. From a sample of 27 subjects, three individuals with major depression demonstrated plasma IgG highly reactive with human beta-endorphin, while four other subjects (two with depression and two randomly selected blood donors) had intermediate reactivity. The recognition site for beta-endorphin was retained by F(ab')2 fragments.