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Biomedical subjects

F Petraglia

Publications and source records attributed to F Petraglia.

At least 325 records · Page 18Linked to original sources

Prolactin secretion after surgery or bromocriptine treatment of prolactinoma.

In prolactinoma patients, the unresponsiveness of prolactin (PRL) to dynamic tests with thyrotropin-releasing hormone (TRH) or dopamine agonist or antagonist drugs suggests that the disease is caused by the failure of central dopaminergic inhibition. The absence of PRL secretory response to dopamine or TRH in prolactinoma patients also may be an effect of the disease. Twenty-six women diagnosed by dynamic tests and radiologic examination as having PRL-secreting adenoma were treated surgically (15) or with bromocriptine (11) and their condition was evaluated one to three years later by TRH, nomifensine, and domperidone tests. Basal PRL levels decreased after surgery and bromocriptine treatment. At the time of the follow-up study, PRL levels were elevated in six of the 15 surgically treated patients and in six of the 11 treated with bromocriptine. Thyrotropin-releasing hormone, nomifensine, and domperidone produced standard PRL responses in normoprolactinemic patients but not in hyperprolactinemic patients. These results indicate that the alteration of TRH or dopaminergic receptors in the regulation of PRL secretion in prolactinoma is related to the disease and disappears when the tumor is removed or treated successfully with bromocriptine.

Adenoma↗

Opioid control of LH secretion in humans: menstrual cycle, menopause and aging reduce effect of naloxone but not of morphine.

A number of studies have been made on the role played by endogenous opioid peptides in the secretion of LH in humans. However no previous studies have compared the effects of the most potent pharmacological agonist and antagonist, morphine and naloxone, in the same subjects. The present study examined the acute effects of injections of morphine and naloxone on plasma LH levels in 30 healthy subjects (18 women and 12 men). Fertile women were subdivided into follicular (n = 6) and luteal (n = 6) phase groups; the remaining 6 were postmenopausal women. The 12 men were sub-divided in two groups of 6 subjects according to age (24-33 years, and over 60 years). There was a two day interval between injection studies in the same subjects. Morphine significantly decreased plasma LH levels in all groups examined (P less than 0.01). On the other hand, naloxone caused a significant increase in plasma LH levels in fertile women during the luteal phase of the cycle, but not during the follicular phase or in postmenopausal subjects, and in young but not in aged men (P less than 0.01). These results indicate that in humans there is a change in the activity of the opioids regulating LH secretion during the menstrual cycle, after menopause and in aged men and that these may be studied by the use of naloxone. The inability of naloxone under certain conditions to increase LH levels reflects the decreased activity of the endogenous system, while morphine, being active in all the subjects, seems to be less discriminative, at least in physiological conditions.

Adult↗

Beta-endorphin concentrations in the hypothalamus, pituitary and plasma of streptozotocin-diabetic rats with and without insulin substitution therapy.

The concentrations of beta-endorphin like immunoreactivity (beta-END) in the hypothalamus, pituitary and plasma were studied in rats of either sex, one month after induction of diabetes by single iv injection of streptozotocin. As controls, both normal and undernourished rats, weight-matched with diabetic rats, were used. Diabetic male and female rats had a marked depletion of beta-END stores in the hypothalamus and neurointermediate lobe (NIL) but not in the anterior pituitary. Depletion of beta-END was reversed to normal by insulin replacement therapy. Severe undernourishment was not as effective as diabetes to reduce beta-END stores in the hypothalamus and NIL. A significant reduction of beta-END was observed only in the NIL of undernourished female rats. Plasma beta-END and beta-lipotropin (beta-LPH) concentrations were not significantly altered in diabetic rats. These results indicate that the lack of insulin may affect beta-END synthesis in the hypothalamus and NIL.

Animals↗

Plasma endorphins in Rett syndrome: preliminary data.

Plasma levels of beta-endorphin (beta-EP) and prolactin (PRL) were measured in 5 girls with Rett syndrome and in a control group before and after giving 10 mg metoclopramide i.v. beta-lipotropin (beta-LPH) was only measured in basal conditions. Basal values of beta-EP and beta-LPH were lower than in control individuals. The responses of plasma beta-EP to metoclopramide in Rett syndrome patients were less intense than in control individuals, while the PRL increase in girls with Rett syndrome was significantly higher than in control subjects. These preliminary data suggest a derangement of the dopaminergic system.

Adolescent↗

Dissociation between CSF and plasma B-endorphin in major depressive disorders: evidence for a different regulation.

Plasma and cerebrospinal fluid (CSF) levels of ACTH, B-lipotropin (B-LPH) and B-endorphin (B-EP) were simultaneously measured in 10 patients with major depression (35-57 yr) with a disease history of 10-34 yr, 7 of them with recurrent episodes, and in 13 age-matched healthy controls. In patients, lumbar puncture was performed after a 10 days drug-free period. Plasma B-EP and B-LPH levels were measured by RIA after silicic acid plasma extraction and Sephadex G-75 column chromatography. Plasma ACTH concentrations were measured by IRMA. For CSF assays the extraction step was avoided. In depressed patients, plasma ACTH (16.2 +/- 6.9 fmol/ml, mean +/- SD), B-LPH (19.8 +/- 8.5) and B-EP (17.8 +/- 7.0) levels were significantly higher (p less than 0.01) than in controls. On the contrary, CSF levels of the three peptides were similar in the two groups. No correlations were found between plasma or CSF concentrations and duration of the disease or severity of the actual episode. These data add further evidence to the independent regulation between central and peripheral POMC-related peptides. They also reduce the possibility that peptides of pituitary origin, directly from the gland or through the peripheral circulation, could penetrate the CSF.

Adrenocorticotropic Hormone↗

Reduced estriol and dehydroepiandrosterone sulphate plasma levels in methadone-addicted pregnant women.

The plasma levels of human chorionic somatomammotropin (hCS), estriol (E3), dehydroepiandrosterone sulphate (DHA-S), cortisol and the circadian changes of the two last adrenal hormones were studied in 25 pregnant methadone-addicted women (MA) and 21 pregnant drug-naive controls (C) at different periods of gestation and in 13 non-pregnant women (7 MA and 6 drug-naive). MA pregnant women showed normal plasma levels of hCS both at the second (6.9 +/- 0.1 vs. 7.2 +/- 0.1 micrograms/ml) and third (9.6 +/- 0.2 vs. 9.3 +/- 0.2) trimester, while plasma concentrations of E3 at term were lower than normal (MA: 4.4 +/- 0.8; C: 8.2 +/- 1.0 ng/ml, P less than 0.05). DHA-S plasma levels of MA pregnant women were half the normal values in three trimesters of gestation, while there were no differences in non-pregnant subjects. Circadian variations of cortisol and DHA-S plasma levels were present in both MA and C. The blunted DHA-S but normal cortisol plasma levels found in MA pregnant women indicate that opiate abuse interferes with adrenal function, mainly of the fetus. Due to the scarce availability of adrenal precursors, these data suggest that E3 measurements should not be considered as a useful index of fetal well-being in the presence of opiate addiction.

Adult↗

Hyperendorphinemia in obesity and relationships to affective state.

Eight obese patients (exceeding ideal body weight by 50% or more) with no endocrinological or metabolic disorders and 8 healthy, age-matched, normal-weight volunteers were submitted to an overnight short dexamethasone (DXM) suppression test and to a psychological assessment through various psychometric scales. Plasma B-Endorphin (B-EP), B-Lipotropin (B-LPH), ACTH and cortisol concentrations were evaluated in basal conditions, as well as 9 and 17 hours after late night administration of 1 mg DXM in both groups. All hormones were measured by radioimmunoassay, either directly in the plasma (ACTH and cortisol) or after silicic acid extraction and Sephadex G-75 column chromatography (B-LPH and B-EP). In obese patients, plasma B-EP levels in basal conditions were three times higher than in normal weight controls and remained unaltered by DXM suppression. ACTH and B-LPH, in contrast, were within the normal range and were significantly reduced by DXM. In 3 of the 8 patients, plasma cortisol concentrations at 17 hours post-DXM were greater than 50 ng/ml indicating an early escape from the suppression. Psychometric evaluations revealed a prevalence of depressive personality in obese patients. These data indicate an hypersecretion of B-EP in obese patients, which is only partially dependent on hypothalamic control.

Adrenocorticotropic Hormone↗

Changes in immunoreactive beta-endorphin, methionine-enkephalin and ACTH in bone marrow cells and fluid from leukemic children.

The present study demonstrates the presence of the endogenous opioid peptides, beta-endorphin (beta-EP) and methionine-enkephalin (MET-ENK), and of ACTH in cell homogenates and interstitial fluid from sternal biopsy of leukemic children. The peptides were identified by chromatography and radioimmunoassay. In leukemic children with lymphoblastic cells present in the sternal sample, concentrations of immunoreactive (ir) beta-EP in the cell homogenate, but not in the fluid, were significantly higher than in leukemic children with normal bone marrow. In contrast, ir MET-ENK and ir ACTH did not differ between the two study groups either in the cell homogenate or in the fluid. These data suggest the presence of a complex system of opioid peptides in the cells and interstitial fluid of bone marrow of leukemic children with the highest concentrations of ir beta-EP appearing in samples collected during the active phase of the disease, and may suggest a possible role of opioid peptides as immunomodulatory substances.

Adolescent↗

Abnormal dexamethasone suppression test in daily chronic headache sufferers.

The dexamethasone suppression test (DST) was administered in 48 daily chronic headache (DCH) sufferers, 37 of whom also suffered from mild to severe depression. In 14 of 48 subjects (29.2%), cortisol values at 1600h were greater than 50 ng/ml, despite normal suppression at 0800h. The escapers showed basal cortisol values and (Depression scale) scores on the Minnesota Multiphasic Personality Inventory higher than suppressors. Thus, a group of DCH sufferers appeared to share a biochemical defect often seen in endogenous depression. The escape from dexamethasone suppression could be a psychobiological indicator of vulnerability to develop depressive disorder and/or chronic pain complaints.

Adult↗

Benefits and risks of different hormonal replacement therapies in post-menopausal women.

A total of 113 women who presented with climacteric symptoms participated in the study. They were randomly allocated to seven groups of 10-27 subjects, who received for 6 mth the following therapies, respectively: conjugated oestrogens (CE) 0.625 mg/day for 21 days + norethisterone (NET) 5 mg/day from day 12 to day 21; CE + cyproterone acetate (CPA) 12.5 mg/day from day 1 to day 10; oestradiol valerate (EV) 2 mg/day for 21 days + NET; EV + CPA; oestriol (E3) 2-4 mg/day; tibolone (ORG OD14) 2.5 mg/day; and placebo, one tablet/day. Hot flushes decreased significantly over the treatment period in all seven groups. However, E3 was less effective at the dose used than CE, EV or ORG OD 14. At the end of the 6 month treatment period histological examination revealed no changes in endometrial morphology in any of the patients treated. Indeed, the addition of a progestogen even induced regression of endometrial hyperplasia in 8 cases. No significant variation in the plasma levels of triglycerides, total cholesterol, high-density lipoprotein (HDL) or low-density lipoprotein (LDL) was observed after the second and sixth months of treatment with E3 or ORG OD 14. After 6 months, treatment with CE/EV + CPA produced a significant increase in HDL, while treatment with CE/EV + NET brought about a reduction in total cholesterol and HDL and an increase in LDL.

Adult↗

Plasma beta-endorphin levels in anovulatory states: changes after treatments for the induction of ovulation.

The goal of this study was to evaluate the effects of menstrual cyclicity on plasma beta-endorphin (beta-EP) levels. For this purpose, beta-EP and cortisol plasma concentrations were measured during the menstrual cycle in healthy control subjects (n = 12), in patients affected by anovulatory syndrome (n = 6), and in amenorrheic patients (n = 8). In the same patients, beta-EP and cortisol were also measured under treatment for the induction of ovulation with pulsatile luteinizing hormone-releasing hormone or human menopausal gonadotropin plus human chorionic gonadotropin administration. In spontaneous and pharmacologically induced ovulatory cycles, a significant preovulatory rise of plasma beta-EP levels was always evident. Constant levels were found in the other periods of ovulatory cycles and in the patients affected by anovulatory syndrome and primary amenorrhea. Cortisol levels did not show any significant change throughout the cycle, either in controls or in patients before or after treatment. This result suggests that when ovulation occurs, plasma beta-EP levels show a relevant rise, the physiologic significance of which remains to be elucidated.

Adult↗

Endogenous opioid peptides in uterine fluid.

The present study demonstrates the presence of the endogenous opioid peptides beta-endorphin (beta-EP) and methionine-enkephalin (MET-ENK), in the uterine fluid of fertile women and normally cycling and superovulated cows. The two peptides are undetectable in the uterine fluid of untreated postmenopausal women, whereas they are present following estrogen-progesterone treatment. Immunoreactive (IR) MET-ENK concentrations were higher in the secretory than in the proliferative phase of the menstrual cycle. IR beta-EP and IR MET-ENK are present also in the follicular, oviductal, and uterine fluid of cows, and in the uterine fluid, concentrations of IR MET-ENK are higher in the superovulated than in the control animals. Because opioids play important roles on endocrine and immune functions, the present data support the potential physiologic role of endometrial secretions.

Adult↗

Somatostatin and oxytocin infusion inhibits the rise of plasma beta-endorphin, beta-lipotrophin and cortisol induced by insulin hypoglycaemia.

The present study investigated the possible effect of somatostatin and oxytocin on the basal and stress-induced rise of beta-endorphin (beta-END), beta-lipotrophin (beta-LPH) and cortisol in the human. For this purpose somatostatin (4.1 micrograms/min for 120 min or oxytocin (0.4 micrograms/min for 120 min) was infused into two different groups of seven healthy subjects; 30 min after the start of the infusion, placebo or insulin (0.1 IU/kg body weight, B.W.) was injected on two different days. In a third experimental step, an insulin tolerance test was performed during saline infusion to evaluate stress-related effects on the different hormonal secretions under basal conditions. Plasma levels of beta-END, beta-LPH and cortisol were measured by radioimmunoassay. Extraction and chromatographic procedures preceded the assay for beta-END and beta-LPH. Neither somatostatin nor oxytocin significantly modified basal plasma levels of beta-END, beta-LPH and cortisol. However these treatments blunted the rise of the three hormones seen at 45 and 60 min during insulin-induced hypoglycaemia (P less than 0.01). These results indicate that somatostatin and oxytocin may influence the beta-END, beta-LPH and cortisol increase induced by stress in humans, without affecting their basal secretion.

Adult↗

CSF and plasma levels of pro-opiomelanocortin-related peptides in reversible ischaemic attacks and strokes.

Plasma and CSF beta-endorphin (beta-EP), beta-lipotropin (beta-LPH) and ACTH levels were studied in a group of 25 patients who underwent reversible ischaemic attacks or completed strokes. CSF beta-EP and beta-LPH in ischaemic patients were higher than those of the control population, independently of both clinical reversibility of the cerebral damage, and the time lapse sampling and the acute event. The presence of a CT demonstrable lesion was related to the highest CSF beta-EP levels. These data confirm an involvement of central opioid substances in the phenomena related to brain ischaemia. ACTH levels in the CSF did not differ from the controls; this finding further supports the concept of an independent central secretion of the different pro-opiomelanocortin-related peptides. The peripheral plasma concentrations of beta-EP, beta-LPH and ACTH, were, in contrast, within the normal range, confirming that CSF and plasma contents of pro-opiomelanocortin-related peptides are differently controlled and originate from different sources.

Adrenocorticotropic Hormone↗

Effects of sodium valproate and diazepam on beta-endorphin, beta-lipotropin and cortisol secretion induced by hypoglycemic stress in humans.

Evidence that gamma-aminobutyric acid (GABA) and benzodiazepine receptors play a role in the inhibition of ACTH-cortisol secretion in humans has until now been drawn only from data indicating that sodium valproate, a GABA mimetic, and diazepam, a benzodiazepine, decrease hypothalamus-pituitary-adrenal (HPA) axis secretion in patients affected by pathological hypersecretion of the axis. Therefore, the present study investigated the effects, in the same healthy subjects, of sodium valproate or diazepam, on both basal and stress-stimulated concentrations of beta-endorphin (beta-EP), beta-lipotropin (beta-LPH) and cortisol. A single maximal dose of sodium valproate (400 mg) or diazepam (10 mg) did not significantly modify basal concentrations of beta-EP, beta-LPH and cortisol. On the other hand, in the same subjects, pretreatment with sodium valproate (20 mg X 3) or diazepam (10 mg X 2) blocked the increases in these hormones produced by hypoglycemic stress in all patients tested (p less than 0.01 vs. placebo at 45, 60 and 90 min after insulin injection), without affecting the decrease in blood glucose levels. The present data show that sodium valproate and diazepam inhibit stress-induced beta-EP, beta-LPH and cortisol secretion in humans, suggesting that endogenous GABA and benzodiazepine receptors participate in physiological mechanisms regulating the activity of the HPA axis.

Adult↗

Plasma opioids in the newborn in relation to the mode of delivery.

Elevated plasma concentrations of beta-lipotropin (beta-LPH) and beta-endorphin (beta-EP) are present in vaginally delivered babies in the first 24 h of life. To establish if fetal distress or different types of delivery influence the secretion of these peptides in the neonatal period, we studied 16 vaginally delivered newborns (VD), 11 neonates extracted through elective cesarean section (CS) and 8 babies suffering from acute intralabor fetal distress (FD). In all groups of newborns the plasma levels of beta-LPH and beta-EP were measured in arterial and venous cord blood, at 1 and 24 h from delivery. beta-LPH and beta-EP were determined by specific radioimmunoassays after silicic acid extraction and Sephadex G-75 column chromatography. In cord plasma, there were no differences between arterial and venous concentrations of either beta-LPH or beta-EP in any of the groups. In the 1st h after delivery the plasma levels of VD newborns were similar to umbilical cord values (beta-LPH: 19.9 +/- 5.2; beta-EP: 18.1 +/- 2.4), while those of CS (beta-LPH: 30.6 +/- 4.5; beta-EP: 30.1 +/- 5.8) and FD (beta-LPH: 64.9 +/- 11.8; beta-EP: 65.7 +/- 24.4) showed a significant increase. At the 24th h of life the plasma concentrations of both peptides decreased significantly in the three groups, but CS and FD babies showed significantly higher plasma values than VD newborns (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗

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

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

Animals↗