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Biomedical subjects

F Petraglia

Publications and source records attributed to F Petraglia.

At least 343 records · Page 19Linked to original sources
PubMed1986

Opioids act centrally to modulate stress-induced decrease in luteinizing hormone in the rat.

Because endogenous opioid peptides (EOP) and CRF are activated during stress and decrease LH levels when injected centrally, we have explored the roles of these peptides in the stress-induced inhibition of LH secretion. Three opioid peptide systems [i.e. endorphin (END), enkephalin, dynorphin (DYN)], are present in the hypothalamus, acting on different opiate receptor subtypes (i.e. mu, delta, kappa). We first evaluated which EOP might be involved in the stress-induced decrease of LH levels. Immunoneutralization of EOP and pharmacological blockade of opiate receptors were used to reverse the decrease in LH induced by inescapable intermittent footshock in castrated male rats. Anti-beta-END and anti-DYN-A serum (intracerebroventricularly [icv]) or pretreatment with beta-END antagonist, beta-human END-(6-31) (2 and 5 nmol, icv), or with kappa-antagonists, Mr1452 MS and Mr2266 BS (10 mg/kg BW, ip), reversed electroshock-induced decrease in LH concentrations. beta-funaltrexamine (beta-FNA), an irreversible mu 1-opiate receptor antagonist, was partially effective in blocking the inhibitory effect of stress on LH levels. Neither passive immunization with anti-enkephalin nor the pretreatment with the delta-opiate receptor antagonist, ICI 154,129, (10 and 100 nmol, icv) modified the effect of stress. We then evaluated which endogenous opioid ligands and/or receptors might mediate the inhibitory effect on LH levels of 2 nmol ovine CRF injected icv. Anti-beta-END serum and beta-human END-(6-31), reversed the CRF-induced decrease of LH concentrations, whereas beta-FNA was only partially active. Anti-DYN-A and anti-ENK serum, kappa- and delta-antagonists did not prevent the decline of LH levels in rats receiving CRF centrally. These data suggest that stress-induced inhibition of LH secretion involves the stimulation of beta-END and DYN-A systems via mu/epsilon- or kappa-opiate receptors and that the decrease in circulating LH levels induced by centrally administered CRF may be mediated by the activation of beta-END system. Therefore, it is possible that the activation of the central CRF/beta-END pathway may play an important role in the stress-induced inhibition of reproductive functions.

Animals↗
PubMed1986

Hyperendorphinemia in obese children and adolescents.

To study the role of opioid peptides in human obesity, plasma beta-endorphin (beta EP), beta-lipotropin (beta LPH), and cortisol resting values, circadian rhythms, and responses to hypoglycemia were studied in 6 prepubertal and 6 pubertal obese adolescents (at least 40% above ideal body weight) and in 10 normal subjects matched for age, sex, and pubertal development. Baseline plasma beta LPH and beta EP concentrations in both obese children and adolescents were twice as high as those in normal controls, while cortisol levels were not different. Cortisol, beta EP, and beta LPH levels had a clear circadian rhythmicity in all subjects, with the exception of obese pubertal boys whose plasma beta EP concentrations were constant throughout the day. After insulin administration, the fall in blood sugar was similar in all groups. Plasma cortisol and beta EP responses were similar in both obese and normal prepubertal subjects. In obese pubertal adolescents, beta EP did not increase significantly after hypoglycemia, although it did increase in normal weight pubertal subjects. In normal prepubertal subjects, the circadian rhythms of beta EP and beta LPH secretion and release induced by hypoglycemia suggest the presence of a well developed neuroendocrine control of proopiomelanocortin-related peptide secretion. In prepubertal obese children, the increased plasma beta EP and beta LPH levels with the maintenance of their circadian rhythm and responsivity to hypoglycemia suggest overactivity of anterior pituitary secretion. In obese adolescents, in spite of the normal rhythm of beta LPH and cortisol, beta EP levels did not change throughout the day, thus suggesting beta EP secretion from nonpituitary sources in these subjects. The present study indicates a possible direct role for hyperendorphinemia in the induction of overeating in obese children and adolescents.

Adolescent↗
PubMed1986

Naloxone-induced luteinizing hormone secretion in normal, precocious, and delayed puberty.

The aim of the present study was to evaluate the activity of opiate receptors involved in the control of LH secretion during pubertal development, as determined by the LH response to naloxone. Normal children (n = 28) of both sexes, subdivided according to breast (girls) or testicular (boys) development, and patients with idiopathic precocious puberty (n = 7), delayed puberty (n = 8), or hypergonadotropic hypogonadism (n = 4) were studied. Plasma LH levels were measured after the administration of naloxone (NLX; 0.08 mg/kg BW, iv), GnRH (50 micrograms, iv) or placebo. In healthy subjects, NLX significantly increased plasma LH levels only in girls and boys at the most advanced stage of gonadal maturation. NLX was ineffective in prepubertal and early pubertal children, and it did not significantly alter LH levels in children with delayed puberty or hypogonadism or in most of the children with precocious puberty. GnRH injection consistently increased plasma LH levels in healthy subjects as well as in the children with pubertal disturbances. These results indicate that the LH response to NLX occurs only at the most advanced stages of pubertal maturation when normal or precocious and is absent in early puberty or in children with pubertal disturbances. Furthermore, the results suggest that opioid regulation of LH secretion in humans changes during puberty, reaching an adult-like functional state with maturation of the hypothalamus-pituitary-gonadal axis.

Adolescent↗
PubMed1986

Met-enkephalin enhances follicle-stimulating hormone-dependent progesterone production from cultured granulosa cells.

beta-Endorphin (beta-EP) and methionine-enkephalin (Met-Enk) have been detected in human follicular fluid in concentrations several times higher than those in plasma. These data stimulated us to study the possible physiological role of ovarian opioids. We, therefore, determined the effects of both beta-EP and Met-Enk, alone or in combination with naloxone, on FSH-induced progesterone (P) secretion by cultured granulosa cells. Granulosa cells were collected from follicular fluid recovered at laparoscopy in seven superovulated women. The cells were preincubated with RPMI-1640 medium containing 20% fetal calf serum in 5% CO2 for 48 h, followed by the addition of 100 mU purified FSH and the various test substances for 48 more h. beta-EP (10 nM to 1 pM) had no effect on P secretion either alone or in combination with FSH and/or naloxone. Micro- to picomolar amounts of Met-Enk increased FSH-induced P secretion up to 186.9 +/- 35.1% (+/- SEM). Met-Enk had no affect in the absence of FSH, and its action was significantly blunted by the concomitant addition of 10(-5) M naloxone. These data provide evidence for a dose-dependent naloxone-reversible synergistic action of Met-Enk and FSH on P secretion by cultured granulosa cells. This finding supports the hypothesis of the existence of an ovarian opioid system.

Cells, Cultured↗
PubMed1986

Dysregulation of plasma pro-opiomelanocortin-related peptides in neurotic depression.

In order to assess whether a central hypothalamic impairment could account for the pro-opiomelanocortin (POMC)-related peptide over-secretion in depressive disorders, plasma B-lipotropin (B-LPH), B-endorphin (B-EP) and cortisol concentrations were measured in 9 patients affected by neurotic depression: every 4 h over a 24-h period; in response to insulin-induced hypoglycaemia (0.1 IU/kg body weight), and during dexamethasone (DXM) administration (0.5 mg X 4/day for 2 days). Eight age-matched healthy volunteers (controls) were also studied. B-EP and B-LPH were determined by specific radioimmunoassays after plasma extraction and gel chromatography. Compared with the controls, the patients showed a 3 times higher plasma B-EP, twice the normal B-LPH levels, and a 20% cortisol increase. The neurotic depressed patients showed and evening-related decrease in the levels of the 3 hormones, expressed as mean values, similar to that in the controls, whereas the single cosinor analysis revealed a significant circadian rhythm of B-LPH and B-EP only in 3 and 2 patients, respectively. Insulin-induced hypoglycaemia (ITT) stimulated the release of B-LPH and cortisol in both groups, whereas the B-EP increase was absent in the patients. DXM reduced plasma cortisol and B-LPH levels in controls and patients, but in the latter it failed to reduce the B-EP concentrations. The present data indicate that neurotic depressed patients are characterized by increased activity of the hypothalamic-pituitary-adrenal axis, with maintained circadian rhythmicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Abnormal beta-endorphin and beta-lipotropin responses to TRH and LRH administration in primary and secondary affective disorders.

Anomalous anterior pituitary hormone responses to acute administration of TRH and LRH have previously been observed in patients with primary affective disorders (PAD), with TRH eliciting GH, FSH and LH rises, and LRH eliciting GH and Prl rises. We examined whether the same unusual responses were present also for beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH) in 15 PAD patients, in 9 patients with secondary affective disorders (SAD), and in 7 controls. TRH (500 micrograms iv) elicited rises of beta-EP plasma levels in 5 PAD and 2 SAD patients, and of beta-LPH in 4 PAD and 3 SAD patients. LRH (150 micrograms iv) elicited rises of plasma beta-EP levels in 2 PAD and 2 SAD patients, and of beta-LPH in 5 PAD and 2 SAD patients. No rises of beta-EP and beta-LPH plasma levels were observed in PAD patients after saline administration, nor in the controls after TRH, LRH or saline administration.

Adult↗
PubMed1986

Endogenous opioid inhibitory tone on LH secretion in normal puberty and in several pubertal disturbances.

To further evaluate the role exerted by endogenous opioids on LH secretion a naloxone challenge (0.08 mg/Kg b.w. i.v.) was performed in 23 healthy children at different stages of puberty, in 5 adolescents in different period of menstrual cycle, in 3 case of idiopathic precocious puberty (PP), in 7 cases of delayed puberty (DP), in 4 females affected by hypogonadotropic hypogonadism (HH) and in 6 patients affected by polycystic ovary disease (PCOD). Naloxone does not induce any significant change on LH plasma levels in prepubertal healthy children and in all the cases of PP and DP. Similarly there was no LH response in healthy adolescents neither in HH nor in PCOD, the response to naloxone appears only in preovulatory and luteal phases. These data indicate that the central opioid system regulating LH secretion in humans is active only at more advanced stages of puberty and it does not seem to play a role in the beginning of sexual maturation. Moreover gonadal steroids seem to play a fundamental modulatory role on opioid-controlled LH secretion.

Adolescent↗
PubMed1986

Oestrous cycle-related LH responsiveness to naloxone: effect of high oestrogen levels on the activity of opioid receptors.

Endogenous opioid peptides have a tonic inhibitory control on LH secretion, participating in the functional changes of the hypothalamic-pituitary-ovarian axis. To evaluate the activity of the endogenous opioid systems during the oestrous cycle, we measured plasma LH levels after naloxone administration (5 mg/kg, s.c.) at 09.00 and 16.00 h on all days of the cycle (two further measurements were taken at 14.00 and 18.00 h on the day of pro-oestrus) and after one dose or one week's treatment with oestradiol benzoate (OB; 0.2 micrograms/rat). Concentrations of LH were measured in the same experimental models after injection of LH-releasing hormone (LHRH; 1 microgram/kg, i.p.) or saline. Naloxone induced a significant rise in LH levels on the day of oestrus, dioestrus day-1 and dioestrus day-2; this response was blunted on the morning of pro-oestrus and absent in the afternoon and after acute and chronic OB treatment. Conversely LHRH was most effective in increasing LH levels on the day of pro-oestrus and in OB-treated rats. These results indicate that opioid mechanisms, independently of the time of day and the pituitary responsiveness, exhibit a reduced activity when preovulatory changes occur, probably as a result of increased oestrogen levels.

Animals↗
PubMed1986

beta-Endorphin modulates the inhibitory action of corticotropin-releasing factor on luteinizing hormone secretion.

The present study investigates the possible role of endogenous opioid peptides in mediating the inhibitory effect of corticotropin-releasing factor (CRF) on circulating luteinizing hormone (LH). The central injection of an antiserum against beta-endorphin (beta-END) reversed CRF-induced LH decrease in castrated male rats, while antisera raised against DYN-A or M-Enk were inactive. beta-END-(6-31) (2 nmole, icv), a beta-END antagonist, and beta-funaltrexamine (4.8 nmole, icv), a mu 1 opiate receptor antagonist, also reversed the effect of CRF on LH. Either kappa (Mr 1456 and Mr 2266) (10 mg/kg, ip), or delta (ICI 154,129) (10 nmole, icv) opiate receptor antagonists did not significantly modify the inhibitory effect of CRF on circulating LH levels. These results suggest that central beta-END participates in the inhibitory action of CRF on LH secretion.

Animals↗
PubMed1986

Reduction of beta-endorphin levels in the amniotic fluid of heroin addicts.

Plasma levels of beta-endorphin and beta-lipotropin in 18 heroin addicts were found to be similar to those in pregnant control subjects at all stages of gestation. In contrast, amniotic fluid levels of beta-endorphin were significantly lower in heroin abusers than in controls in both the first and second trimesters. Amniotic fluid levels of beta-lipotropin were reduced only in the second trimester. At term, when the patients were almost drug free, the amniotic fluid levels of both peptides were in the control range. These data support the existence of a specific control mechanism for amniotic fluid levels of beta-endorphin and beta-lipotropin, independent of the maternal pituitary, and show that exogenous opiates interfere with it negatively.

Amniotic Fluid↗
PubMed1986

Central and peripheral beta-endorphin response to transcutaneous electrical nerve stimulation.

The effects of transcutaneous electrical nerve stimulation on plasma and cerebrospinal fluid (CSF) levels of beta-Endorphin (beta-EP) were studied in 6 groups of pain-free patients. Different modes of TENS were applied for 20 minutes. Regardless of mode and/or frequency of the stimulation plasma and/or CSF beta-EP levels were significantly increased. Plasma and CSF responses were not correlated suggesting that TENS activates different opiatergic pathways at central and peripheral level.

Aged↗
PubMed1985

Short-term effects of ovariectomy: the opioid control of LH secretion in fertile climacteric and postmenopausal women.

The aim of this study was to evaluate the activity of opiate receptors involved in the regulation of LH secretion in relationship to ovariectomy. Menstruating fertile (n = 5) and climacteric (n = 7) patients and postmenopausal (n = 5) women who underwent therapeutical bilateral ovariectomy were studied in the first week postsurgery and LH plasma levels were evaluated after naloxone (4 mg in bolus plus 4 mg infusion/90 min), LHRH (10 micrograms + 10 micrograms iv) and saline administration. Two groups of fertile (n = 6) and postmenopausal (n = 6) subjects were studied as controls. Since the LH responsiveness to naloxone was impaired in climacteric patients after ovariectomy, the test was repeated in 5 of them after 1 and 6 months of estrogen-gestagen treatment (conjugated estradiol + noretisterone acetate), showing a significant increase in all patients in both cases. In four subjects treated with only gestagen, naloxone was still unable to significantly modify LH plasma levels. These results indicate that ovariectomy affects the activity of opiate receptors, resulting in the first week postsurgery LH rise inversely related to basal LH levels. Furthermore, these results indicate that one or six cycles of estrogen-gestagen treatment in ovariectomized patients similarly induces a restoration of the opiate receptors neuroendocrine activity.

Adult↗
PubMed1985

Domperidone in defective and insufficient lactation.

The clinical use of anti-dopaminergic drugs to stimulate plasma PRL levels, to induce lactogenesis and maintain an adequate lactation has been widely suggested, taking into consideration the main inhibitory role of hypothalamic dopamine on PRL secretion. We therefore studied the effects of domperidone (DOM), a direct anti-dopaminergic drug with a low tendency to be secreted in the milk and which does not cross the blood-brain barrier, on inducing lactogenesis in 8 puerperal women with a history of defective lactogenesis (group A) and inducing galactopoiesis in 9 puerperal women who showed 2 weeks after delivery an insufficient lactation (group B). A placebo treatment was performed in 7 and 8 puerperal women with the same characteristics of group A and B, respectively. PRL plasma levels were assayed in basal conditions and after suckling from the 2nd to the 5th day of puerperium in group A and through a 10-day treatment in group B. In both groups domperidone-treated subjects always showed baseline PRL levels and daily milk yield significantly higher than those of the placebo group (P less than 0.01). The lack of any side-effects and the positive results suggest a high usefulness of such a drug in inducing and/or maintaining successful breast feeding, which is at present considered so important for a healthy development of infants.

Adult↗
PubMed1985

Hypothalamus-pituitary-adrenal axis of heroin addicts.

The hypothalamus-pituitary-adrenal axis of heroin addicts was investigated by evaluating plasma cortisol levels throughout the day in 37 heroin abusers (HA), 17 of whom showed detectable morphine levels, indicating heroin administration in the previous hours and in 12 controls. All HA showed lower cortisol levels in basal condition (100.7 +/- 61.7 ng/ml, M +/- S.D.) compared to the control group (159.7 +/- 40.6, P less than 0.05). Moreover all HA (65.1 +/- 28.9%), and in particular those taking heroin during the study (39.1 +/- 41.4%), show a reduced cortisol decrease in the evening, which was significantly lower than in controls (85.3 +/- 10.1%; P less than 0.01). As far as the acute effects of opiates are concerned morphine (0.1 mg/kg) significantly reduced plasma cortisol levels within 60 min in a group of 8 healthy subjects. The same pattern was displayed by only 3/8 HA whose morphine levels were higher than 1 ng/ml, i.e. in those reaching the highest plasma morphine concentrations. These data indicate that chronic opiate abuse leads to a hypoadrenalism which could be the result of morphine-induced changes at the hypothalamic level.

Adolescent↗
PubMed1985

Impairment of opioid control of luteinizing hormone secretion in menstrual disorders.

With the aim of examining central opioid influences on the control of luteinizing hormone (LH) secretion, we evaluated the LH response to naloxone, an opioid receptor antagonist, in patients affected by normo-, hyper-, and hypogonadotropic amenorrhea, polycystic ovarian disease and hyperprolactinemia. The results indicate that opioid influences are altered in well-defined pathologic conditions (hyperprolactinemia, obesity), in addition to being modified by gonadal steroids.

Adenoma↗
PubMed1985

Beta-endorphin and met-enkephalin in peritoneal and ovarian follicular fluids of fertile and postmenopausal women.

Immunoreactive (IR) beta-endorphin (beta-EP) and met-enkephalin (MET-ENK) have been found in peritoneal fluid (PF) and ovarian follicular fluid (FF). Gel chromatography also revealed the presence of coeluting IR beta-lipotropin and gamma-lipotropin. IR beta-EP and IR MET-ENK levels in healthy menstruating women were from 10 to 40 times higher than those present in circulating plasma, which indicated a possible local production. The highest concentrations of IR beta-EP in FF were found in the largest follicles, whereas in the PF they correlated with the luteal period of the menstrual cycle and with progesterone concentrations. No relevant changes in IR MET-ENK were detected in the FF or in the PF in relation to the phase of the menstrual cycle. In postmenopausal women, the concentrations of the two IR opioid peptides were undetectable in both fluids.

Adult↗
PubMed1985

CSF beta-EP in headache and depression.

Cerebrospinal fluid (CSF) levels of beta-endorphin (beta-EP) were measured in 9 migraineurs with interparoxysmal headache (MIH), in 13 patients with major depression in an active phase (5 suffered from MIH), and in 16 age-matched controls. beta-EP was measured by specific RIA after gel-chromatography. While beta-EP levels of depressed patients (58.5 +/- 21.0 fmol/ml, M +/- SD) were similar to those of controls (65.8 +/- 26.6), those of migraineurs (15.0 +/- 11.1) were significantly reduced (p less than 0.01). In depressed patients also suffering from MIH, beta-EP concentrations (22.8 +/- 7.2, p less than 0.05) were half those reported in depressed patients without pain problems. The reduced CSF beta-EP levels in patients whose headache and depression coexist support the notion that this neuropeptide is concerned with chronic pain, independently of the affective state.

Adult↗