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Biomedical subjects

F Petraglia

Publications and source records attributed to F Petraglia.

At least 271 records · Page 15Linked to original sources
PubMed1989

Opioid control of luteinizing hormone secretion in humans.

The observation that heroin-addicted subjects are amenorrheic and/or hypogonadic suggested a possible role of endogenous opioid peptides (EOP) in the regulation of the hypothalamus-pituitary-gonodal axis. Because EOP are localized all through the axis, they may influence the reproductive function acting at various levels. The injection of morphine decreases plasma LH levels, abolishing the pulsatile pattern of secretion. The evidence that naloxone, an opiate receptor blockade, increases LH levels suggests a tonic inhibitory action of EOP. The naloxone-induced LH increase is not observed before pubertal maturation, in both sexes, and is absent in children with delayed or precocious puberty and in those with Klinefelter's or Turner's syndrome, suggesting a role of gonadal function on the opioid control of LH secretion. In adult women this LH response to naloxone is present during the periovulatory and the luteal phase of the menstrual cycle, suggesting a permissive role of estradiol and mainly of progesterone on the action of EOP on the LH secretion. Indeed, in amenorrheic subjects naloxone lacks to stimulate plasma LH levels and the treatment for the induction of ovulation restores this activity. An increased inhibitory action of EOP on GnRH release may explain the inefficacy of naloxone to stimulate LH secretion in hypogonadotropinic patients, while a decreased action has been hypothesized in postmenopausal women. The clinical implications of EOP in reproductive medicine appear to be promising.

Child↗
PubMed1989

Plasma beta-endorphin levels in obese and non-obese patients with polycystic ovarian disease.

Several reports have shown elevated circulating beta-endorphin (beta-EP) levels in patients with polycystic ovarian disease (PCOD). However, it is not yet clear whether these high beta-EP levels are linked to the etiopathogenesis of PCOD or are secondary to the obesity. In the present study we measured beta-EP plasma concentrations in 19 PCOD patients, 10 with normal weight (Group A) and 9 with excessive weight (Group B), and in 18 normally ovulating women, 10 with normal weight (Group C) and 9 with excessive weight (Group D). beta-EP values were similar in the two groups of non-obese patients and controls. beta-EP concentrations were also similar in the two groups of obese patients and controls, and they were significantly higher (p less than 0.05) than in non-obese patients. Our data indicate that in PCOD, elevated beta-EP values are related to obesity, suggesting that they are not linked to the pathogenesis of PCOD.

Adolescent↗
PubMed1989

Effect of oral contraceptives or dexamethasone on plasma beta-endorphin during the menstrual cycle.

Several studies have showed a significant increase of plasma beta-endorphin levels during the periovulatory days of the menstrual cycle. The aim of the present study was to investigate the origin of the periovulatory changes of plasma beta-endorphin, trying to discriminate between a possible ovarian and/or pituitary origin. Daily plasma beta-endorphin, luteinizing hormone (LH), and cortisol levels were measured from the 8th to the 20th day of the menstrual cycle in healthy normal-cycling women (10 cases) before and during dexamethasone (DEX; 6 cases) or estroprogestinic treatment with monophasic (5 cases) or triphasic (5 cases) pill. In the control menstrual cycle, during the preovulatory days, a significant increase of plasma beta-endorphin was found. While oral contraceptives abolished the midcycle increase of plasma beta-endorphin, the periovulatory plasma beta-endorphin peak was present during DEX treatment. Plasma cortisol levels did not show any significant change throughout the control menstrual cycle, while they were significantly lowered by the DEX administration and significantly increased during estroprogestinic treatment. These results suggest that the increase of plasma beta-endorphin during the periovulatory days is related to the ovulatory function, and suggest a possible ovarian origin.

Adolescent↗
PubMed1989

Inhibin and activin modulate the release of gonadotropin-releasing hormone, human chorionic gonadotropin, and progesterone from cultured human placental cells.

Although it is clear that human chorionic gonadotropin (hCG) and progesterone play fundamental roles in pregnancy, the regulation of placental production of these hormones remains to be defined. Recent evidence suggests that the human placenta expresses proteins related to inhibin (alpha beta subunits) or activin (beta beta subunits). Inhibin and activin (follicle-stimulating hormone-releasing protein) possess opposing activities in several biological systems including pituitary follicle-stimulating hormone (follitropin) secretion, erythroid differentiation, and gonadal sex-steroid production. The actions of purified inhibin and activin on hormonogenesis by primary cultures of human placental cells were studied. The addition of activin increased gonadotropin-releasing hormone (GnRH) and progesterone production and potentiated the GnRH-induced release of hCG. Inhibin by itself did not modify placental immunoreactive GnRH, hCG, and progesterone secretion but reversed the activin-induced changes. Neither inhibin nor activin influenced the release of human placental lactogen. Furthermore, transforming growth factor beta, structurally related to inhibin/activin, did not significantly influence hormone release from cultured placental cells. These results support the hypothesis that inhibin and activin may play a role in regulating the release of GnRH, hCG, and progesterone from placenta and implicate inhibin-related proteins in the endocrine physiology of human pregnancy.

Activins↗
PubMed1989

Impairment of dopaminergic and opioidergic activity in patients with polycystic ovarian disease is restored by treatment for the induction of ovulation.

The luteinizing hormone (LH) response to metoclopramide (MCP), a dopamine receptor antagonist, and naloxone (NAL), an opioid receptor antagonist, was evaluated in 7 patients with polycystic ovarian disease (PCOD) before and during treatment with purified human urinary follicle-stimulating hormone (hFSH), and in 6 control women during spontaneously ovulating cycles. Before treatment, in all patients both MCP and NAL administration did not increase plasma LH levels. In the 6 subjects ovulating following hFSH treatment the LH response to MCP and NAL at preovulatory and midluteal phases was restored, as it occurred in control women. Our results suggest that in PCOD the dopamine and opioid activity in the hypothalamus are decreased. The reversal of peripheral ovarian response induced by treatment for the induction of ovulation may restore these impaired neuroendocrine activities.

Adult↗
PubMed1989

Different dopaminergic control of plasma luteinizing hormone, follicle-stimulating hormone and prolactin in ovulatory and postmenopausal women: effect of ovariectomy.

The main aim of this study was to evaluate the effect of dopamine infusion on plasma luteinizing hormone (LH), follicle-stimulating hormone, (FSH) and prolactin (PRL) after acute (1 week postovariectomy) and chronic (postmenopausal women) estrogen withdrawal. We also studied the same group of postmenopausal women after ovariectomy to evaluate the possible influence of other gonadal factors on the endocrine effects of dopamine. In order to have a further indication of neuroendocrine dopamine activity on pituitary secretions, we measured the change in plasma LH, FSH and PRL after the administration of metoclopramide, a dopamine receptor antagonist. Our findings confirm that in fertile women dopamine infusion inhibits plasma LH and FSH levels and show that 1 week after ovariectomy the LH decrease during dopamine administration is still present whereas the FSH decrease is not. In all groups of patients, dopamine significantly inhibited plasma PRL levels. Metoclopramide increased plasma LH levels in reproductive-age women before ovariectomy, but not in postmenopausal women. Plasma FSH levels did not change in any group and PRL levels increased after metoclopramide administration in all subjects. The present findings show that dopamine regulation of LH is impaired in long-term menopause, but not shortly after ovariectomy. These changes in LH control are not followed by similar changes in PRL secretion, which remains under tonic inhibitory regulation by dopamine. The different behavior of LH and FSH after ovariectomy and in postmenopause shows the independence of LH and FSH regulation.

Adult↗
PubMed1989

Presence of acetylated and shortened endorphins in human fetal pituitary gland.

A total of 21 human fetal pituitaries was collected from spontaneous abortions (11 cases) or prostaglandin (PG)-induced abortions at the second trimester. Pituitaries were homogenized, fractionated by HPLC, and the fractions were tested by specific RIA for alpha-endorphin (EP) (beta-EP 1-16), gamma-EP (beta-EP 1-17), beta-EP (beta-EP 1-31), and their alpha-N-acetylated derivatives. In the fetal pituitaries collected after spontaneous abortion, the contents of alpha-EP (23.4 +/- 7.5 pmol/mg protein, mean +/- SE) and gamma-EP (28.9 +/- 9.7) were similar to those of beta-EP (28.6 +/- 7.4). Both beta-EP/alpha-EP (1.2 +/- 0.3) and beta-EP/gamma-EP (1.1 +/- 0.3) ratios approached unity. Although 35.7 and 30.2% of alpha-EP and gamma-EP were acetylated, acetyl-beta-EP was only 8.4% of the total beta-EP immunoreactivity. In the five cases of PG-induced abortion that were more than 20 wk of pregnancy, the pituitary content of beta-EP (75.9 +/- 21.2) and gamma-EP (26.2 +/- 7.5) were significantly higher than in samples collected after spontaneous abortion (13.3 +/- 8.2 and 5.9 +/- 1.8, respectively, p less than 0.01). On the contrary, neither alpha-EP (31.3 +/- 5.2), acetyl-alpha-EP (0.94 +/- 0.28), acetyl-gamma-EP (0.65 +/- 0.07), acetyl-beta-EP (0.35 +/- 0.05) pituitary contents in PG-induced abortions differed from those measured after spontaneous abortion (alpha-EP: 25.6 +/- 6.6; acetyl-alpha-EP: 0.92 +/- 0.41; acetyl-gamma-EP: 0.82 +/- 0.30; acetyl-beta-EP: 0.96 +/- 0.44).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylation↗
PubMed1989

Identification of immunoreactive neuropeptide-gamma in human placenta: localization, secretion, and binding sites.

The aim of the present study was to evaluate the possible presence of immunoreactive neuropeptide-gamma (irNPY) in human placenta. Acidic extracts of human placental tissue collected at term pregnancy contained high irNPY concentrations. The extracted irNPY eluted from HPLC with the same retention time as synthetic NPY. The presence of the peptide in placental cells was confirmed by immunohistochemical findings showing numerous cells of the cytotrophoblast layer positively staining for NPY. Further supporting local production of the peptide, primary cultures of human placental cells released irNPY into the culture medium and the addition of high K+ concentrations increased the release of the peptide. The finding of irNPY in human placenta stimulated the characterization of binding sites of NPY in the same tissue. Using autoradiographic techniques we showed specific binding of [125I]NPY in human placental tissue. The binding of [125I]NPY to the placental receptors was saturable and widely distributed within the placental tissue. Finally, the addition of NPY to the medium of cultured placental cells increased the release of immunoreactive CRF, suggesting a possible role of NPY in placental hormone production. The effect of NPY was dose related and augmented by the addition of norepinephrine (10 nM). These results showed that human placenta produces and secretes irNPY and that NPY receptors are present in placental tissue. Moreover, the evidence that NPY stimulated the release of immunoreactive CRF from cultured placental cells suggests an action of NPY in placental hormonogenesis.

Autoradiography↗
PubMed1989

Plasma and amniotic fluid immunoreactive neuropeptide-Y level changes during pregnancy, labor, and at parturition.

This study was designed to determine the presence of and possible changes in plasma and amniotic fluid immunoreactive neuropeptide-Y (irNPY) levels in pregnant women during gestation and at parturition. We studied 127 healthy pregnant and 12 nonpregnant women. The peptide was extracted from plasma or amniotic fluid with a propanolformic acid mixture and measured by RIA. The mean plasma irNPY concentration in 15 pregnant women during the first trimester of gestation was 129 +/- 12 (+/- SE) pmol/L, compared to 40 +/- 8 pmol/L in nonpregnant women (p less than 0.01). The mean values were 144 +/- 13 and 156 +/- 24 pmol/L, respectively, in 15 pregnant women during the second trimester and 33 women during the third trimester. These values did not differ from that during the first trimester. Amniotic fluid irNPY levels were similar to those in plasma and did not vary among the 3 groups of women studied during the various trimesters of gestation. During labor, plasma irNPY levels progressively increased, reaching the highest levels at the most advanced stages of cervical dilatation (greater than 8 cm, 351 +/- 38 pmol/L) and at the time of vaginal delivery (416 +/- 73 pmol/L). Plasma irNPY levels then decreased significantly 2 h after vaginal delivery. The amniotic fluid irNPY levels in women during the early or late stages of labor were similar. Moreover, plasma and amniotic fluid irNPY levels at the time of elective cesarean section also were similar. These results indicate that pregnant women have high plasma and amniotic fluid irNPY levels and that the stress of labor results in a further increase in plasma levels, suggesting a possible role of NPY in human pregnancy and parturition.

Adult↗
PubMed1989

Glucocorticoids but not vasopressin or oxytocin inhibit luteinizing hormone secretion in patients with psychogenic amenorrhea.

Activation of the hypothalamus-pituitary-adrenal (HPA) axis is suggested to play a role in the stress-related inhibition of LH secretion. The aim of our study was to investigate the effects of vasopressin and oxytocin, which are increased in pituitary portal plasma in response to stress, and of glucocorticoids, the final product of HPA activation during stress, on basal plasma LH levels and on pituitary LH response to the GnRH test in amenorrheic (n = 33) and fertile (n = 13) women. Plasma LH levels were evaluated by radioimmunoassay in 2 different experimental conditions: 1. Basal secretion; 2. The GnRH test (10 micrograms + 10 micrograms after a 120-minute interval). These 2 evaluations were done in the presence of both placebo and a pharmacological dose of desmopressin (an analogue of vasopressin) (16.6 ngr/minute), oxytocin (0.2 ngr/minute) or hydrocortisone (4.1 mg/minute). None of these drugs modified basal plasma LH levels either in amenorrheic patients or in controls. Hydrocortisone inhibited the GnRH-induced LH increase in amenorrheic women. These data suggest that the glucocorticoids might play a role in LH secretion and indicate a possible participation of the HPA axis in the impairment of the hypothalamus-pituitary-gonadal axis in women with psychogenic amenorrhea.

Adult↗
PubMed1988

Lack of clinical-EEG effects of naloxone injection on infantile spasms.

In a previous study we found depressed ACTH and normal beta-endorphin values in the cerebrospinal fluid of patients with West's syndrome, whereas normal peptide levels were present in infants with secondary Infantile spasms. This prompted us to study the effects of naloxone administration in children with West's syndrome. After informed consent was obtained from the parents, the effects of naloxone administration on clinical and EEG findings were evaluated in five infants 5-9 months old (3 males, 2 females) with cryptogenic infantile spasms and hypsarrhythmia. The infants were studied at the onset of symptomatology before therapy. An average of 5-10 groups of spasms were present per day. Naloxone (12 micrograms/kg body weight) was administered as an intravenous bolus in two cases, as a slow venous drip in another two cases, and intramuscularly in the last case. EEG and polygraphic monitoring were performed for 2 h. Naloxone did not induce any acute behavioral changes and the number of seizures remained unchanged after treatment. These data reject the possibility that endogenous opioids tonically modulate infantile spasms. Further studies are required to ascertain the involvement of POMC peptides in West's syndrome.

Adult↗
PubMed1988

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.

Adrenocorticotropic Hormone↗
PubMed1988

Plasma B-endorphin resistance to dexamethasone suppression in obese patients.

Patients with simple exogenous obesity are characterized by increased B-endorphin (B-EP) plasma levels, despite normal ACTH and B-Lipotropin (B-LPH). To evaluate the origin of such an hyperendorphinemia, 42 obese patients were submitted to a short overnight dexamethasone suppression test (DST: 1 mg at 23:00 h). Blood samples were taken in basal conditions and 9, and 17 h after DST. The same procedure was applied in 12 healthy, normal weight volunteers. In further five patients, 0.5 mg per 4/die were given. B-EP was measured by radioimmunoassay (RIA) after silicic acid extraction and Sephadex G-75 column chromatography. ACTH and Cortisol were measured by direct IRMA and RIA, respectively. Basal B-EP levels of patients (24.2 +/- 16.5, fmol/ml, M +/- SD) were double than in normal weight controls (10.8 +/- 4.6), while ACTH and cortisol fell in the normal range. ACTH and cortisol were significantly reduced by DST in both patients and controls, while B-EP in patients did not. Cortisol, however, was not suppressed in 7 patients (16%). At 08:00, the suppression of B-EP in controls was 49.0 +/- 18.4%, while in obese patients it was only 21.2 +/- 38.8% (p less than 0.01). However, patients with weight excess below 50% normally suppressed B-EP (41.6 +/- 15.3%), while those with weight excess over 75% did not (11.3 +/- 47.5%). The doubling of dexamethasone intake does not lead to a suppression of plasma B-EP in these last patients. These data indicate the existence of neuroendocrine abnormalities in the hypothalamus-pituitary-adrenal axis of obese patients and suggest that their hyperendorphinemia originates outside the anterior pituitary.

Adolescent↗
PubMed1988

Neuroendocrine evaluation of central opiate activity in primary headache disorders.

The evaluation of central opiate activity could be of clinical value in the diagnosis and treatment of pain syndromes. The current approach via direct measurement of endogenous opioid peptides in cerebrospinal fluid (CSF) is not devoid of side effects and cannot be used in every-day practice. As an alternative to this method, we have studied the neuroendocrine response of plasma LH to an i.v. naloxone injection in 39 headache sufferers from different diagnostic subgroups, and in 12 age- and sex-matched healthy volunteers. Patients (19 females and 20 males) were affected by common migraine (CM, 11 cases), migraine with interparoxysmal headache (MIH, 9), classical migraine (CIM, 9), and chronic cluster headache (CH, 10). Headache lasted 3-36 years. Prior to naloxone challenge (4 mg i.v.), LH pulsatility was evaluated for 1 h. The next morning, the pituitary response to LH-RH (10 micrograms i.v.) was tested in 20 patients. Plasma LH was measured by RIA in every sample. The response to the tests was evaluated as secretion area of plasma LH minus the mean basal value. Controls (497.5 +/- 85.5 mIU/ml x 120 min), ClM (357.8 +/- 78.9) and CH (450.5 +/- 70.4) patients showed similar results, while in cases of CM (155.3 +/- 71.7, P less than 0.05) and MIH (104.1 +/- 53.7, P less than 0.01) the LH secretion after naloxone injection was significantly blunted. On the contrary, the response of LH to LH-RH was similar in controls and patient groups, thus excluding pituitary dysfunctions in this response.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Absent B-endorphin response to clonidine in obese children.

Plasma B-Endorphin (B-EP), Growth Hormone (GH) and cortisol response to 100 mcg/m2 b.s., i.v. clonidine (an alpha 2-adrenergic agonist) were evaluated in 17 normal weight children (8 prepubertal and 9 pubertal) and in 15 children with simple exogenous obesity (7 prepubertal and 8 pubertal, weight excess ranging from 29% to 97%). All the hormones were measured by radioimmunoassay either directly in the plasma (GH and cortisol) or after extraction and chromatography (B-EP). Obese prepubertal and pubertal children showed basal B-EP levels significantly higher than in controls and no differences were found in GH and cortisol levels. While in controls clonidine stimulated a significant release of plasma GH and B-EP in obese patients, irrespective of pubertal development, no changes were found. Cortisol levels decreased in both groups. These data suggest an impaired adrenergic control of GH and B-EP secretion in children with simple exogenous obesity.

Child↗
PubMed1988

N-terminal ACTH fragments increase the CSF beta-EP content in Alzheimer type dementia.

Eleven patients with presenile Alzheimer type dementia (ATD) were treated with N-terminal ACTH fragments for 14 days. No change in cognitive functions was observed during the treatment. A significant increase in CSF beta-endorphin (beta-EP) levels was found, while ACTH and beta-lipoprotein remain unaffected. The possibility that ACTH and its moieties could interfere with beta-EP activities in CNS is discussed.

Adrenocorticotropic Hormone↗
PubMed1988

Aging brain and dementias: changes in central opioids.

We evaluated the CSF levels of beta-lipotropin (beta-LPH), beta-endorphin (beta-EP) and ACTH, which are three neuropeptides expressed by the same gene encoding for pro-opiomelanocortin, in various groups of demented patients including degenerative (presenile and senile Alzheimer-type dementia, ATD) and vascular (MID) forms. Twelve sex- and age-matched subjects were taken as controls. Our data indicate that ACTH levels are significantly reduced both in ATD and MID patients, while beta-EP and beta-LPH are significantly reduced only in ATD. The low CSF ACTH levels can be considered typical of all demented processes (both degenerative and vascular), while the reduction of beta-EP and beta-LPH in CSF could be due to a degenerative process of CNS.

Adrenocorticotropic Hormone↗