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Biomedical subjects

F Petraglia

Publications and source records attributed to F Petraglia.

At least 307 records · Page 17Linked to original sources
PubMed1987

Opioid regulation of luteinizing hormone in amenorrheic patients after therapy for induction of ovulation.

This study evaluated the activity of central opiate receptors modulating luteinizing hormone (LH) secretion before and during treatment with human menopausal gonadotropin (n = 8) or purified human urinary follicle-stimulating hormone (n = 6) in 14 patients with hypogonadotropic hypogonadism (n = 6) or secondary amenorrhea (n = 8). LH response to saline infusion and naloxone administration (4 mg intravenously) was assessed. As control, 6 normal ovulating women were studied. Before therapy, all amenorrheic patients showed no LH increase after naloxone injection. Gonadotropin treatment restored the naloxone-induced LH response at preovulatory and midluteal phases in ovulating patients with secondary amenorrhea. The same response was present in spontaneously ovulating women but was absent in the hypogonadotropic hypogonad patients, despite the gonadotropin therapy's efficiency. In conclusion, when the alteration of gonadotropin-releasing hormone synthesis and/or release is reversible, the opioid system actively participates in the regulation of the hypothalamus-pituitary-gonadal axis.

Adult↗
PubMed1987

Proopiomelanocortin-related peptides in feto-placental structures throughout pregnancy.

This study evaluates the presence of proopiomelanocortin (POMC)-related peptides in four embryos and eight fetal pituitaries starting from 5 to 25 weeks of pregnancy. Moreover, fetal membranes (amnion and chorion) were also investigated. Freshly collected samples were boiled in acetic acid to destroy enzymes, homogenized and submitted to high performance liquid chromatography (linear gradient from 25 to 40% acetonitrile in 0.01 M HCI, in 15', 1.5 ml/min). The collected fractions were tested for the presence of beta-lipotrophin (beta-LPH), beta-endorphin(beta-EP), gamma-endorphin(gamma-EP) through RIAs. beta-EP and beta-LPH were detected from 7 weeks of pregnancy while gamma-EP appeared later. Only the cephalic portion of the embryos contained the peptides where beta-LPH predominates while no immunoreactivity was detected in the rostral one. In the fetal pituitary there is a progressive increase of gamma-EP according to the gestational age and both beta-EP and beta-LPH showed a trend toward constancy in the 15-25 week range. Amnion and chorion contain a significant amount of the three peptides. Their ontogenesis starts earlier than in the embryo; beta-LPH or beta-EP were detected at 5 weeks of pregnancy. In both tissues beta-EP was higher in the first than in the second trimester. These data demonstrate a different pattern of POMC ontogeny and processing between the conceptus and his environment. This suggests that the POMC-related opiod system of the fetus and of fetal adnexes are independent of each other, possibly subserving to different functions.

Amnion↗
PubMed1987

Plasma beta-endorphin in response to oral glucose tolerance test in obese patients.

In order to clarify the possible interaction between endogenous opioids and glucose homeostasis in obesity we studied Beta-Endorphin (B-Ep), ACTH, cortisol and insulin plasma levels in response to an oral glucose tolerance test (OGTT) in 8 females suffering from uncomplicated obesity and in 6 healthy volunteers of normal weight. Results were evaluated in terms of secretion areas subtracted from basal value. Basal glucose, insulin and B-Ep levels were significantly higher in the obese patients compared to controls, cortisol levels and ACTH were not statistically different between obese and normal subjects. During OGTT total areas of insulin secretion were significantly higher in the obese patients; cortisol, ACTH, B-Ep plasma levels did not change in controls, whereas obese patients showed a response to B-Ep which reached a peak at 60 minutes. The area of B-Ep response to OGTT in obese patients was significantly higher than in controls. On the basis of these results we may suggest that the opioid system belongs to the chain of neuroendocrine and metabolic events responsible for the origin and the growth of overweight. But the possibility exists that obesity itself can enhance the B-Ep secretion above all through overeating. In this regard it is to stress that glucose ingestion induces in obese patients, differently from normal subjects, insulin hypersecretion and the B-Ep secretion, possibly from gastro-enteric tract and/or pancreatic isles.

Adrenocorticotropic Hormone↗
PubMed1987

Effects of neuroleptic treatments on peripheral opioid secretion.

The effects of short- and long-term neuroleptic therapy on peripheral secretion of beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH) were examined in 25 chronic schizophrenic patients. Haloperidol was given to 8 patients for 10 days (group A: 0.1 mg/kg b.w./day) and to another group of 8 patients for 30 days (group B: 10-18 mg/day). The other 9 patients were given a combination of haloperidol (6-30 mg/day) with either chlorpromazine (25-75 mg/day), clotiapine (40-60 mg/day), or fluphenazine decanoate (25-75 mg/month) for 14-18 months (group C). beta-EP and beta-LPH levels were assayed before and after each treatment. Haloperidol plasma levels were assayed in group B patients at the end of treatment. beta-EP mean basal levels were higher in patients than in controls; however, beta-LPH mean basal levels were higher only for group A patients. After treatment, the mean levels did not differ from those prior to therapy in groups A and B, while beta-LPH levels were significantly higher in group C. Level increases or decreases in single patients did not correlate with drug dose or duration of treatment, with baseline peptide levels or with the clinical effects of the various treatments.

Adult↗
PubMed1987

Beta-endorphin and dynorphin participate in the stress-induced release of prolactin in the rat.

In the rat, exposure to stress increases prolactin (Prl) secretion, and endogenous opioid peptides (EOP) are believed to play a role in this response. The aim of the present study was to evaluate the specific involvement of the different EOP (i.e. beta-endorphin [beta-END], dynorphin A [DYN-A], methionine-enkephalin [Met-ENK], and/or opiate receptors (i.e., mu/epsilon, kappa, delta) in the stress-related increase in circulating Prl. Rats were subjected to inescapable intermittent footshock (60 Hz, 2.5 mA, 1 s duration, 2 h) 2 h after the intracerebroventricular (i.c.v.) injection of specific antisera raised against beta-END, DYN-A or Met-ENK. In addition, selective opiate antagonists (beta h-END-[6-31], a peptide beta-END antagonist [5 nmol, i.c.v.], beta-funaltrexamine [beta-FNA], an mu 1 receptor antagonist [4.8 nmol, i.c.v.], Mr 1,452 MS and Mr 2,266 BS, two kappa-receptor antagonists [10 mg/kg body weight, i.p.], ICI 154, 129, a delta-receptor antagonist [100 nmol, i.c.v.]) were administered prior to footshock stress. Blood samples were collected through an indwelling jugular cannula. Exposure to footshock rapidly and significantly increased plasma Prl levels. This stress-induced release of Prl was reduced by both antisera against beta-END or DYN-A, as well as by pretreatment with beta h-END-(6-31), beta-FNA and kappa-receptor antagonists. Antiserum against Met-ENK and delta-antagonist were inactive. These results suggest that the activation of the two endogenous opioid systems, beta-END and DYN-A, centrally modulate the release of Prl induced by footshock stress.

Animals↗
PubMed1987

Ritanserin, a serotonin-S2 receptor antagonist, does not prevent 5-hydroxytryptophan-induced beta-EP, beta-LPH and cortisol secretion.

Ritanserin, a new serotonin antagonist selective upon S2 receptor subclass is available. Thus, in order to better define the positive control of serotoninergic pathway on proopiomelanocortin (POMC)-related peptide release, a group of 7 healthy male volunteers has been submitted to a 5-hydroxytryptophane (5-OH-TP) test (200 mg p.o.) before and after 4 days Ritanserin pretreatment. Plasma beta-endorphin (beta-EP), beta-lipotropin (beta-LPH) and cortisol levels were measured hourly for 4 h after each 5-OH-TP loading. Hormonal levels were measured by specific RIAs on extracted (cortisol) and chromatographed (beta-EP and beta-LPH) plasma samples. Basal plasma concentrations of the three hormones were unchanged by Ritanserin pretreatment. Similarly, the integrated areas of beta-LPH, beta-EP and cortisol release in response to 5-OH-TP remained unaffected by the receptor blockade. These data confirm that serotonin-acting drugs are able to stimulate POMC-related peptide release and indicate that such interaction is not mediated through S2 receptor subclass.

5-Hydroxytryptophan↗
PubMed1987

Circulating opioids and plasma renin activity in insulin-dependent diabetics with renal haemodynamic alterations.

Circulating opioids were studied in insulin-dependent diabetics with renal haemodynamic alterations. Higher circulating beta-endorphin (beta-EP) and lower beta-lipotropin (beta-LPH) levels were found in patients with glomerular hyperfiltration than in diabetics with normal glomerular filtration rate (GFR) and controls. Moreover, significantly positive correlations between beta-EP and GFR, and between beta-EP and renal plasma flow were demonstrated in these patients. On the contrary, reduced beta-EP levels were observed in diabetics with impaired GFR and overt nephropathy. Plasma renin activity was increased in diabetics with glomerular hyperfiltration and reduced in diabetics with overt nephropathy. Circulating opioids might, therefore, play a role in renal haemodynamic alterations, both in patients with early and advanced glomerular changes.

Adult↗
PubMed1987

Prostaglandin-induced mid-pregnancy abortion increases plasma and amniotic fluid levels of beta-lipotropin and beta-endorphin.

The continuous and progressive rise of beta-endorphin (B-EP), beta-lipotropin (B-LPH) and cortisol plasma levels during labor in term-pregnant women represents one of the most relevant maternal hormonal responses to the stress of parturition. The aim of the present study was to evaluate the changes of these hormones, both in plasma and amniotic fluid (except cortisol), in a group of pregnant women undergoing prostaglandin-induced therapeutic abortion at the 2nd trimester of pregnancy. B-EP, B-LPH and cortisol were measured by radioimmunoassay. Both plasma and amniotic fluid samples were purified through extraction and chromatography (Sephadex G-75 columns). The prostaglandin derivative, 16-phenoxy-PGE2-methylsulfonylamide (sulprostone, Schering, Berlin) (500 micrograms, i.m., every 4 h), caused a rapid and significant rise of plasma B-EP, B-LPH and cortisol levels in all subjects. The relative increase of the 3 hormones was less relevant after the 2nd and absent after the 3rd injection of PGE2. The amniotic fluid concentrations of B-EP and B-LPH were also raised 2 h after the 1st injection. These data indicate that sulprostone-induced abortion activates both maternal and fetoplacental release of opioids independently of the trend of uterine contractions. The pattern of pro-opiomelanocortin-related labor differs from spontaneous labor and can probably be linked to a direct effect of the drug.

Abortifacient Agents↗
PubMed1987

Prolactin changes after administration of agonist and antagonist dopaminergic drugs in puerperal women.

Prolactin (PRL) is an anterior pituitary hormone which plays a large part in the reproductive function of mammals. Its only well-documented effect in humans is that of initiating and maintaining lactation. Among hypothalamic neurotransmitters regulating the anterior pituitary function, dopamine (DA) is currently considered to correspond to the PRL-inhibiting factor. The central control mechanisms which induce high PRL levels in puerperal women are not well understood. To study DA tonus in puerperium we tested plasma PRL levels in different groups of puerperal subjects (6 per group) after acute administration of direct or indirect DA agonists or placebo: DA, L-dopa (a DA precursor), L-dopa plus carbidopa (a peripheral dopa-decarboxylase inhibitor), nomifensine (a DA-releasing and blocking or reuptake agent) and amphetamine (a DA releaser). The same tests with the same drug doses were performed on groups of healthy volunteers. A consistent reduction in plasma PRL levels after both direct and indirect DA agonist drugs compared to placebo was evident in puerperal and in control women. A different trend was only observed with the use of DA and amphetamine in puerperal subjects, who, unlike controls, failed to show a rebound in plasma PRL levels after the termination of drug infusion. These findings support the view that the inhibitory control of tuberoinfundibular neurons over PRL secretion is maintained in puerperium and changes in the affinity of DA receptors are related to the endocrine milieu which occurs during gestation.

Amphetamine↗
PubMed1987

Opioid control of luteinizing hormone secretion in patients with hirsutism and hyperandrogenemia.

The present study was designed to evaluate the influence of hyperandrogenemia on the activity of the opioid system regulating LH secretion in menstruating women. Ten subjects presenting with hirsutism and hyperandrogenemia and 9 healthy normally cyclic subjects participated in the study. Naloxone or saline was administered on 2 different days both during the follicular (6-8 days after menstrual bleeding) and during the luteal phase of the menstrual cycle. Naloxone significantly increased plasma LH levels in the luteal, but not during the follicular phase of the cycle in both subject groups. It may be inferred from these observations that opioid-mediated inhibition of LH secretion is not altered in menstruating hyperandrogenic patients, suggesting that the circulating androgens are not an important determinant of the functional neuroendocrine activity of the opioid system.

Adult↗
PubMed1987

Corticotropin-releasing factor decreases plasma luteinizing hormone levels in female rats by inhibiting gonadotropin-releasing hormone release into hypophysial-portal circulation.

To evaluate whether the hypothalamus is the site of action of CRF in inhibiting LH levels in female rats, we measured hypophysial-portal blood concentrations of immunoreactive GnRH (irGnRH) after the central injection of CRF. Ovine CRF (0.1, 1.0, 2.0, and 5.0 nmol) was injected intracerebroventricularly to intact rats on the afternoon of proestrus and in long term ovariectomized (OVX) rats in the presence or in absence of estradiol benzoate (OVX + EB). CRF injection decreased the amplitude of the proestrous irGnRH surge without affecting presurge levels. CRF (0.1 nmol) attenuated the afternoon irGnRH surge in OVX + EB rats; higher doses of CRF blocked this surge and decreased nonsurge irGnRH levels. No dose-related alterations of irGnRH levels were observed in OVX rats; only the highest dose of CRF was active. For comparison, plasma LH concentrations were measured after a single dose of CRF (2 nmol) in rats under the same experimental conditions. While CRF decreased LH concentrations in anesthetized proestrous and OVX + EB rats, it was inactive in OVX rats. In contrast, CRF injection in awake rats did decrease LH concentrations in all experimental conditions, suggesting that in OVX rats, the anesthetic (Saffan) used during portal blood collection affected CRF action on LH secretion. Indeed, the observation that the LH response to opiate receptor blockade with naloxone (2.5 mg/kg) in anesthetized OVX rats was different compared to that in awake rats suggested that the ineffectiveness of CRF to decrease irGnRH and LH in OVX anesthetized rats was related to the action of the anesthetic on the opioid system. The existence of a putative CRF-opioid interaction in the inhibitory control of LH secretion was supported by the effectiveness of naloxone to reverse the CRF-induced decrease in LH levels in EB-treated and untreated OVX rats. These results indicate that CRF attenuates LH secretion by a central action to inhibit irGnRH release into the hypophysial-portal circulation and that this action is independent of basal concentrations of irGnRH and/or LH. Moreover, the present results support the involvement of endogenous opioids in mediating the effect of CRF on LH secretion.

Animals↗
PubMed1987

Differences in the opioid control of luteinizing hormone secretion between pathological and iatrogenic hyperprolactinemic states.

The cause of the amenorrhea that occurs in patients with hyperprolactinemia is unknown. The involvement of endogenous opioid peptides in the inhibition of GnRH release as a central factor leading to the hypogonadotropic state has been recently described. This study analyzed the LH response to opiate receptor blockade by naloxone (4 mg, iv) in groups of subjects with amenorrhea due to hyperprolactinemia of different etiologies. Patients presenting with a PRL-secreting pituitary adenoma (n = 7), idiopathic hyperprolactinemia (n = 9), or hyperprolactinemia during pharmacological treatment for schizophrenia (n = 5) were studied. Furthermore, to evaluate whether high circulating PRL levels influence the activity of the opioid system after the menopause, a group of seven postmenopausal subjects was tested before and 1 week after the administration of metoclopramide (10 mg, three times a day), a dopamine receptor antagonist. Normal premenopausal women (n = 6) served as controls. Naloxone significantly increased plasma LH levels in both prolactinoma and idiopathic hyperprolactinemic patients (P less than 0.01 vs. basal and placebo). In neither of those groups was a significant correlation found between the plasma LH response to naloxone and basal plasma PRL levels. In contrast to pathological hyperprolactinemia, blockade of opiate receptors did not significantly change LH secretion in either amenorrheic women with pharmacologically induced hyperprolactinemia or postmenopausal women. These results suggest that the effect of hyperprolactinemia on opioid modulation of LH secretion is related to the nature of the hyperprolactinemic state, supporting the existence of increased opioid inhibition of LH levels in pathological hyperprolactinemia.

Adenoma↗
PubMed1987

Adenosine 3',5'-monophosphate, prostaglandins, and epinephrine stimulate the secretion of immunoreactive gonadotropin-releasing hormone from cultured human placental cells.

Cell culture and biochemical procedures were used to identify and study the possible mechanisms regulating the secretion of GnRH-like immunoreactivity (GnRH-LI) from human placenta. Monolayer primary cultures of trophoblasts were established after mechanical and enzymatic dispersion of normal human term placenta. The cultured cells stained immunocytochemically positive with anti-GnRH serum, and GnRH-LI extracted from the cells eluted from high performance liquid chromatography with the same retention time as authentic GnRH. One week after plating, exposure to high concentrations of K+ or to various doses of veratridine, a Na+ ionophore, increased GnRH-LI release into the culture medium. This effect was reversed by Ca2+ antagonists (cobalt, EGTA, and verapamil). Dibutyrylcyclic AMP, forskolin, theophylline, and theobromine also increased GnRH-LI concentrations in the medium of cultured placental cells in a dose-related manner, as did prostaglandins E2 and F2 alpha and epinephrine. The effect of epinephrine on GnRH-LI concentrations was mimicked by isoproterenol and reversed by propranolol, suggesting an effect mediated by beta-adrenergic receptors. These results indicate that GnRH-LI release from cultured human placental cells is stimulated by the opening of ionic channels and activation of the adenylate cyclase/cAMP system, and that prostaglandins and epinephrine may be involved in the regulation of GnRH-LI release from human placenta.

Adenosine Monophosphate↗
PubMed1987

Dexamethasone fails to suppress hyperendorphinaemia of obese children.

In order to evaluate the origin of hyperendorphinaemia in obese patients, plasma B-endorphin (B-EP), B-lipotropin (B-LPH) and cortisol levels were measured in basal conditions and after overnight treatment with 1 mg of dexamethasone. Thirteen obese children (weight excess ranging from 44 to 100%) and 10 normal weight controls were studied. Weight gain started in prepuberty and could not be explained by concurrent diseases. Hormone levels were measured by RIA, either directly in the plasma (cortisol) or after silicic acid extraction and Sephadex G-75 column chromatography (B-EP and B-LPH). Basal B-EP levels in the obese children (19.4 +/- 4.9 pmol/l, mean +/- SEM) were significantly higher than in the controls (7.8 +/- 1.2, P less than 0.01), whereas B-LPH and cortisol was within normal range. In the controls, post-dexamethasone morning and afternoon hormone levels were significantly suppressed. In the obese children, B-EP concentrations remained unaffected by the treatment (14.6 +/- 5.3 and 14.9 +/- 5.2 at 08.00 and 16.00 h, respectively), whereas both B-LPH and cortisol values were significantly decreased. These data demonstrate that a short-term dexamethasone treatment is unable to correct the increased B-EP levels which characterize obese children, whereas it is effective on B-LPH and cortisol concentrations. It can be concluded that circulating B-EP in this condition loses the control of CRH. However, the origin of hyperendorphinaemia in obese patients still remains to be investigated.

Adolescent↗
PubMed1987

Progesterone and progestins modulate beta-endorphin concentrations in the hypothalamus and in the pituitary of castrated female rats.

Hypothalamic and pituitary beta-endorphin (B-EP) concentrations are modified by ovariectomy and estrogen treatments, supporting a direct interaction between this peptidergic system and gonadal steroids. Because the use of progestins is becoming even more diffuse in clinical practice, we evaluated the effect of progesterone and of the synthetic progestins medroxyprogesterone acetate (MPA), norethisterone acetate (NET) and desogestrel on the concentration of B-EP in the medial-basal hypothalamus and the anterior and neurointermediate pituitary lobes in ovariectomized rats (OVX), treated or untreated with estradiol benzoate (EB). B-EP concentrations were significantly increased by desogestrel in the anterior lobe and by progesterone, desogestrel and medroxyprogesterone acetate in the neurointermediate lobe. Progesterone and progestins significantly reduced B-EP increase induced by estradiol benzoate in the anterior lobe. Estradiol benzoate treatment did not modify the effect of progesterone and desogestrel on B-EP in the neuro-intermediate pituitary lobe. Norethisterone acetate and progesterone increased B-EP concentrations in the medial-basal hypothalamus, while the other steroids were inactive. In contrast, in the hypothalamus all progestins attenuated the increase of B-EP induced by estradiol benzoate (p less than 0.01). These data indicate that progesterone and progestins modulate the hypothalamic and pituitary B-EP concentrations in concert with estrogens. The capacity of progestins to modify the hypothalamic contents of B-EP may represent one of the mechanisms of action of these steroids in influencing brain function.

Animals↗
PubMed1987

Adrenal steroid responses to naloxone in polycystic ovarian disease.

In order to investigate the role of the adrenal gland in the pathogenesis of polycystic ovarian disease (PCOD), we evaluated the adrenal steroid response to an opiate receptor blockade. Six healthy menstruating volunteers and 6 patients with PCOD were given a saline or naloxone (4 mg i.v.) injection in the early follicular phase. Blood samples were taken prior to the injections and every 15-30 minutes in the following 2 hours. Cortisol, androstenedione (A) and dehydroepiandrosterone (DHA) plasma levels were determined by RIA after extraction (cortisol) and celite chromatography (A and DHA). While in controls naloxone increased only cortisol concentrations, in PCOD patients DHA plasma levels also were stimulated by the opiate receptor antagonist. In PCOD patients the increase of cortisol (p less than 0.05) and of DHA (p less than 0.001) levels resulted significantly higher than in controls. In both groups A plasma levels remained unchanged after naloxone administration. These data confirm that endogenous opioids exert an inhibitory control on the pituitary-adrenal axis. In PCOD patients the response to naloxone led to a hypersecretion of adrenal delta 5-androgens, which could account for the development of the syndrome.

Adrenal Glands↗