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Biomedical subjects

F Petraglia

Publications and source records attributed to F Petraglia.

At least 379 records · Page 21Linked to original sources

Gonadal steroid modulation of naloxone-induced LH secretion in the rat.

The effect of acute administration of the opioid receptor antagonist naloxone hydrochloride (5 mg/kg, s.c.) on plasma LH levels was evaluated in female and male rats 24, 36 and 48 h and 1, 3 and 5 weeks after gonadectomy and in 5-week gonadectomized rats after acute or chronic (2 weeks) administration of oestradiol benzoate (OB, 10 micrograms/rat per day, s.c.), testosterone propionate (TP, 150 micrograms/rat, s.c.) or dihydrotestosterone propionate (DHT, 150 micrograms/rat, s.c.) respectively. Concurrent evaluation of plasma LH after administration of LH releasing hormone (LHRH, 1 microgram/kg, i.p.) was performed in the same experimental groups. In rats of both sexes, a significant rise in plasma LH after naloxone was observed in sham-operated and recently gonadectomized rats (24-48 h); in female rats 36 and 48 h after gonadectomy the rise was higher than in controls. One, 3 and 5 weeks after gonadectomy, naloxone failed to stimulate LH release in both female and male rats. In gonadectomized rats undergoing steroid replacement therapy, OB administered 72 h before testing, TP (16 and 72 h) and DHT (16 h) were the most effective in reinstituting the LH response to naloxone. Chronic administration of gonadal steroids did not restore normal LH responsiveness to naloxone. In most experimental groups, LH responses after naloxone were clearly unrelated to pituitary LH responsiveness to LHRH, which indicates that the opioid antagonist was acting via the central nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of dopaminergic drugs on hypothalamic and pituitary immunoreactive beta-endorphin concentrations in the rat.

Beta-endorphin concentrations have been evaluated in the hypothalamus, pituitary lobes and plasma after 1-and 3-week treatment with 2-Br-alpha-ergocriptine or lisuride, two potent dopaminergic drugs. Hypothalamic beta-endorphin concentrations were significantly decreased after the administration of the dopaminergic agents for 1 or 3 weeks. Similarly, beta-endorphin concentrations decreased in the neurointermediate lobe and plasma. After gel chromatography, it appeared that in the anterior pituitary, beta-lipotropin concentrations were unchanged or lightly increased concomitantly with a decrease of beta-endorphin. Our data indicate that, both in the hypothalamus and the neurointermediate pituitary lobe, beta-endorphin is under an inhibitory dopaminergic tone. The latter may also play a role in inhibiting beta-endorphin cleavage from beta-lipotropin in the anterior pituitary.

Animals↗

Opiates and their antagonists modulate luteinizing hormone acting outside the blood brain barrier.

The effects of morphine methyl-iodide and naloxone methyl-bromide, two quaternary derivatives of morphine and naloxone, were evaluated on the modulation of luteinizing hormone secretion in intact and gonadectomized rats. Quaternary compounds are effective in modulating LH release, indicating a site outside the blood brain barrier for their action. More precisely, the median eminence and not the pituitary seems to be the site of action of opiates in modulating LH secretion, since the effect of the quaternary derivatives is abolished by surgical ablation of the median eminence.

Animals↗

Correlations between plasma levels of opioid peptides and adrenal androgens in prepuberty and puberty.

In 139 prepubertal children and in 38 pubertal adolescents plasma levels of ACTH, cortisol, beta-lipotropin (BLPH), beta-endorphin (BEP) and dehydroepiandrosterone sulphate (DHAS) were determined by specific radioimmunoassays directly (steroids) or after plasma purification (peptides). ACTH and cortisol concentrations remain stable during both prepuberty and puberty, while DHAS levels constantly increased from 5 to 16 years. Both BLPH and BEP increase from early infancy to late prepuberty when they reach adult values. During puberty both opioids remain constantly within the adult range. BLPH and BEP concentrations were significantly correlated to those of DHAS throughout prepuberty. These data suggest a possible role of BLPH and BEP in and/or other proopiocortin-related peptides in the development of adrenarche, while the lack of particular changes in these peptide levels during sexual maturation seems to exclude their role in gonadarche and pubertal development.

Adolescent↗

Beta-endorphin, beta-lipotropin and adrenocorticotropic hormone levels in cerebrospinal fluid, and brain damage in chronic alcoholics.

In 34 chronic alcoholics, subdivided into two groups according to the state of the blood-brain barrier (BBB), beta-lipotropin (beta-LPH), beta-endorphin (beta-EP), ACTH and cortisol levels were determined in basal conditions in the plasma and cerebrospinal fluid (CSF). Hormonal concentrations were correlated with brain damage and mnesic function. The results indicate the reduced CSF beta-EP content in chronic alcoholics and suggest that peripheral beta-EP may penetrate into the CSF compartment when there is BBB damage. They also sustain the different origins of central and peripheral pro-opiocortin-related peptides, and support the concept that beta-EP, beta-LPH and ACTH may be autonomously regulated at the central level. Moreover, both morphological brain damage and mnesic impairment in chronic alcoholics are unrelated to CSF peptide levels. The role of opioid peptides in the nature of alcohol-seeking behavior is supported.

Adrenocorticotropic Hormone↗

Simultaneous circadian variations of plasma ACTH, beta-lipotropin, beta-endorphin and cortisol.

The major objective of this study was to investigate the analogy existing between the typical circadian periodicity of ACTH and that recently described of beta-lipotropin (beta-LPH) and beta-endorphin (beta-EP) plasma levels. The determination of their concentrations, plus cortisol, has been performed on the same plasma samples of 6 healthy volunteers. All hormones were measured by radioimmunoassay. Those of beta-LPH and beta-EP were preceded by a purification of plasma through silicic acid extraction and Sephadex G-75 gel filtration. The highest values (mean +/- SEM) were found in the morning (ACTH: 10.3 +/- 0.9; beta-LPH; 6.3 +/- 0.7; beta-EP: 6.5 +/- 0.5 fmol/ml; cortisol: 378 +/- 30 pmol/ml) and the lowest values in the evening (ACTH: 6:1 +/- 0.7; beta-LPH: 3.3 +/- 0.4; beta-EP: 3.7 +/- 0.6 fmol/ml; cortisol: 130 +/- 23 pmol/ml). Statistical analysis using the Fourier method led to the evidence of a concomitant circadian secretory pattern of the three proopiocortin-related peptides. These results strongly suggest that the phasic secretion of ACTH, beta-LPH and beta-EP underlies a common central control.

Adrenocorticotropic Hormone↗

Circulating beta-endorphin levels at various stages of life: possible connections with migraine pathogenesis.

Recently, the existence of a circulating peptide, beta-endorphin (B-EP) with potent analgesic properties has been revealed. Our group has evaluated B-EP plasma levels in several physiological and pathological models. The life span pattern of this newly identified hormone was characterized by a progressive increase during prepuberal development, by stable levels in adults with typical circadian and monthly variations, and by a decrease in aging subjects. Cerebrospinal fluid B-EP contents inversely showed a declining linear trend throughout life, which suggests an independent source of B-EP in this compartment. The concomitant changes in the reproductive system suggested the possible influence of gonads on B-EP plasma levels, as confirmed by decreasing B-EP levels in gonadectomized humans and rats. Headache, which is likely to occur concomitantly with hormonal milieu variations, appeared to be associated with a deficiency in the B-EP system, centrally and peripherally, the lowest values being found in the protracted forms of headache.

Adolescent↗

Circadian variations of proopiocortin-related peptides in children with migraine.

Basal and throughout-the-day variations of B-lipotropin (BLPH), B-endorphin (BEP), ACTH and cortisol plasma levels were studied in seven prepubertal children who had been affected by common migraine for periods of 6-26 months and in six healthy volunteers. Despite normal cortisol concentrations, children with migraine show higher BLPH (15.1 +/- 2.7 fmol/ml, M +/- SE), ACTH (25 +/- 2.7) and BEP (9.1 +/- 1.1) levels than controls. In both groups of children, evening values (8 p.m.) were significantly lower than morning values, but in migraineurs the decrease of the three peptides was less. The raised proopiocortin-related peptide plasma levels found in children suffering from migraine cannot be explained at present, although the discomfort experienced by the patients may create a situation of chronic stress which could explain such a finding. Whatever the explanation is, these findings differentiate prepubertal migraine from the most severe forms of headache occurring in adult life where lower than normal opioid levels have been demonstrated.

Adrenocorticotropic Hormone↗

Evaluation of central opioid tonus in menstrual migraine.

The aim of this study is to make an evaluation of the activity of endogenous opioid tonus in patients affected by menstrual migraine. We tested the LH response to naloxone injection, an opiate receptor antagonist, in 18 migraineurs in the early and late luteal periods going towards the attacks. The lack of any response in the latter group demonstrates an opioid disregulation in this kind of pathology.

Adult↗

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.

Adolescent↗

Fetomaternal opioid levels and parturition.

The present study evaluates the plasma level changes in beta-lipotropin and beta-endorphin in nine women at term throughout spontaneous labor, in ten pregnant women undergoing elective cesarean section in the absence of uterine contractions, and in ten women submitted to emergency cesarean section because of fetal distress occurring during labor. A basal plasma sample was taken before labor in the 39th week of pregnancy. Two subsequent samples were then obtained before and after parturition, together with umbilical cord samples at birth. beta-lipotropin and beta-endorphin were measured by radioimmunoassay after silicic acid plasma extraction and gel filtration. In cases of spontaneous labor, there was a progressive increase in opioid concentrations as labor progressed, the maximal values being observed after delivery. Cord values were similar to those observed in the mother, without showing any relationship to them. Pregnant women undergoing cesarean section in the absence of labor show constant beta-lipotropin and beta-endorphin concentrations both before and after fetal extraction, both values being significantly lower than those found at delivery after spontaneous labor. beta-Endorphin neonatal levels were significantly higher than in the respective mothers and were in the same range as those of infants born through vaginal delivery. In the third group (cesarean section performed at the first stage of labor), presurgical opioid levels were higher than in women at the same stage of spontaneous labor, whereas postextraction values showed a wide range, with mean values similar to those observed after spontaneous delivery.(ABSTRACT TRUNCATED AT 250 WORDS)

Apgar Score↗

[Circulating opioid peptides in chronic renal failure: acute effect of dialysis treatment].

In 14 patients affected by chronic renal failure (7 males and 7 females) it has been evaluated the secretion of beta LPH, beta EP, ACTH and Cortisol in basal conditions and immediately after a dialytic treatment. For beta LPH and beta EP measurements on each thawed plasma a silic acid extraction and a successive peptides separation by a Sephadex G-75 column chromatography preceeded the two specific RIAs. Basal beta LPH plasma levels resulted significantly higher than in normal controls, while that of beta EP, ACTH and Cortisol were in the normal range. The dialytic treatment was able to increase ACTH and Cortisol plasma levels, without to modified beta LPH and beta EP plasma levels.

Adrenocorticotropic Hormone↗

Opioid plasma levels during labour.

6 healthy pregnant women, monitored with external cardiotocography, were studied. Blood samples were collected hourly throughout labour until delivery of the fetus and placenta, and again on the 5th day of puerperium. beta-Lipotropin (beta LPH) and beta-endorphin (beta EP) were determined by specific radioimmunoassays in each sample, after silicic acid plasma extraction and G-75 column chromatography. Both opioid plasma levels rise progressively during labour, reaching their highest values 1 h before delivery (beta LPH: 296.0 +/- 60.2 pg/ml; beta EP 106.2 +/- 40.6 pg/ml) as compared with values of 157.0 +/- 35.4 (beta LPH) and 57.0 +/- 7.3 pg/ml (beta EP) (mean +/- SE) at the beginning of labour. With the exception of 1 case, a significant correlation was observed between beta LPH and beta EP plasma levels. The two opioid plasma levels decrease after delivery of the placenta (272.5 +/- 59.6 and 118.2 +/- 68.4 pg/ml) and subsequently decrease further to levels of 105.6 +/- 46.4 (beta LPH) and 33.7 +/- 16.5 (beta RP) on the 5th day of puerperium. beta LPH and beta EP plasma levels showed a significant correlation throughout labour with the 'uterine contractility force/hour', which was calculated by the addition of tocographic areas of each uterine contraction at 1-hour intervals. These data demonstrate that the increase in plasma opioid concentrations during labor is directly related to the number and intensity of uterine contractions.

Endorphins↗

Central deficiency of beta-endorphin in alcohol addicts.

Alcohol addiction may induce its dependence through a mechanism involving opiate receptors and opioid peptides. For these reasons, we measured ACTH, beta-lipotropin, and beta-endorphin in the plasma and cerebrospinal fluid (CSF) of 29 alcohol addicts and compared these values with those found in 8 normal volunteers. Although no significant differences existed in peripheral concentrations of the 3 peptides, alcohol addicts had beta-endorphin levels in CSF (mean +/- SE, 29.4 +/- 4.5 fmol/ml) that were 3-fold lower than those of the controls (98.4 +/- 10.5 fmol/ml; P less than 0.001) and ACTH levels 4 times higher than control values (30.0 +/- 1.8 vs. 7.4 +/- 1.1 fmol/ml in controls; P less than 0.001), while no difference was found in beta-lipotropin levels. These results suggest that alcohol addiction is associated with a marked alteration in the CSF content of proopiocortin-related peptides which may play a role in the alcohol-seeking behavior typical of the syndrome.

Adrenocorticotropic Hormone↗