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Biomedical subjects

F Petraglia

Publications and source records attributed to F Petraglia.

At least 181 records · Page 10Linked to original sources
PubMed1995

Activin beta A subunit is expressed in bovine oviduct.

It is evident that members of several growth factor families are actively involved in embryogenesis from its earliest phases. Several reports also indicate the oviduct as a possible source of growth factors, suggesting an active role of this organ in mammalian embryonic development. The aim of this study was to investigate the presence of activin/inhibin subunits in bovine oviduct since activin is a well-characterised morphogen in amphibian development. The presence of transcripts for alpha, beta A, and beta B subunits was investigated by analysing oviduct epithelial cells mRNA with reverse transcription-polymerase chain reaction (RT-PCR). Moreover, antisera specific for the three subunits were used for the Western blot analysis of the proteins secreted by oviduct epithelial cells in vitro and for their immunohistochemical localisation in different oviductal regions. Oviduct epithelial cells expressed only the beta A-subunit gene. Immunoreactive material was present among in vitro secreted proteins, indicating that the transcript is translated into a polypeptide that has been localised in the epithelium of both the ampullary and isthmic tract of the organ. Consistent with these results, the antisera for the alpha and beta B subunits did not recognise any specific antigen either among secreted proteins or in the sections. These results indicate that beta A subunit gene is expressed in bovine oviduct epithelial cells, and the protein is secreted in vitro and can be found along the whole extension of the organ. In the absence of alpha or beta B subunits, this suggests that activin A is present in bovine oviduct.(ABSTRACT TRUNCATED AT 250 WORDS)

Activins↗
PubMed1995

Involvement of mu-opioid receptors in the modulation of pituitary-adrenal axis in normal and stressed rats.

The availability of the most selective, high-affinity, natural opioid agonists for mu-receptors (dermorphin-DM) and delta-receptors (deltorphin-DT) has provided the possibility for in vivo studying of the role of acute and chronic activation of mu- and delta-opioid receptors on the functional activity of the hypothalamus-pituitary-adrenocortical (HPA) axis, both in basal conditions and in response to an acute stress in adult male rats. Plasma corticosterone (CS) and beta-endorphin-like-immunoreactivity (beta-EP-LI) levels were measured by specific radioimmunoassays before and after 5 and 30 minutes from the exposure to cold (3 +/- 0.5 C) water and forcing them to swim for 10 minutes (acute cold swimming stress). Acute administration of DM, the specific mu-receptor agonist, enhanced basal and stress induced plasma levels of CS and beta-EP-LI. These effects were antagonized by pretreatment with naloxone, specific mu-opioid receptor antagonist, but not by naltrindole, a delta-opioid receptor antagonist. Long-term administration of DM did not alter resting plasma levels of CS and beta-EP-LI, but significantly reduced stress-induced increase of these hormones. Both the acute and chronic administration of the DT, highly selective delta-opioid receptors agonist, failed to modify resting and stress induced hormone levels. Our present data show that DM throughout mu-opioid receptors, but not DT, modulates the response of HPA axis to acute stress in rats, increasing or decreasing the release of CS and beta-EP-LI when acutely or chronically administered, respectively.

Adrenal Glands↗
PubMed1995

Allopregnanolone concentration in hippocampus of prepubertal rats and female rats throughout estrous cycle.

Hippocampus plays an important role in cognition, neuroendocrine function and sexual behaviour. Changes of hippocampal neuropeptide and neurotransmitter concentrations are associated to behavioural changes occurring throughout reproductive life. The present study focused the attention on the presence of a neurosteroid, 5 alpha-pregnan-3 alpha-ol-20-one (termed allopregnanolone) in hippocampus. In particular, hippocampal allopregnanolone concentration in male and female prepubertal rats and in female rats throughout estrous cycle were evaluated. Hippocampal extracts were eluted on high pressure liquid chromatography and allopregnanolone concentration was measured by radioimmunoassay. Prepubertal male and female rats (15 days old) showed highest values which significantly decreased with advancing age (25 and 60 days) (p < 0.01); the lowest hippocampal concentration of allopregnanolone was found in adult rats. Female rats on proestrus morning and afternoon showed an hippocampal allopregnanolone concentration significantly higher than on diestrus or on estrus (p < 0.01), while rats on estrus showed hippocampal allopregnanolone concentration significantly lower than during other days of estrus cycle (p < 0.01). These data indicate differences in hippocampal concentration of allopregnanolone between prepubertal and adult rats and throughout estrous cycle in female rats. This finding suggest a putative role of neurosteroids in the modulation of behavioral changes occurring throughout reproductive life.

Animals↗
PubMed1995

Maternal plasma and placental immunoreactive corticotrophin-releasing factor concentrations in infection-associated term and pre-term delivery.

The present study aimed to investigate whether microbial invasion of the amniotic cavity affects maternal plasma or placental immunoreactive corticotrophin releasing factor (ir-CRF) concentrations in pregnant women with pre-term or term labour. A cross-sectional study was conducted collecting blood samples in: (1) women with pre-term labour and intact membranes (25-36 weeks), with or without microbial invasion of the amniotic cavity (subdivided into three groups: 1A, no microbial invasion of the amniotic cavity, delivery at term, n = 54; group 1B, delivery < 48 h, no microbial invasion of the amniotic cavity, n = 10; group 1C, delivery < 48 h, microbial invasion of the amniotic cavity, n = 8); (2) women at term, not in labour and without microbial invasion of the amniotic cavity (n = 15); (3) women in spontaneous active labour at term without (A) (n = 55) or with (B) (n = 16) microbial invasion of the amniotic cavity; and (4) healthy women not in labour at 25-36 weeks of gestation (n = 25). Specimens of trophoblast tissue were collected from pregnant women with pre-term labour (no microbial invasion of the amniotic cavity, n = 6; microbial invasion of the amniotic cavity, n = 4) or delivering at term (no microbial invasion of the amniotic cavity, n = 8; microbial invasion of the amniotic cavity, n = 4). A specific radioimmunoassay on acidic extracts of plasma or placental specimens was used.(ABSTRACT TRUNCATED AT 250 WORDS)

Amnion↗
PubMed1995

Hypertension in pregnancy: changes in activin A maternal serum concentration.

Human placenta is the major source of activin A in maternal circulation. The aim of the present study was to evaluate maternal activin A serum concentration in pregnant women with chronic hypertension (n = 14), pregnancy-induced hypertension (n = 10) or pre-eclampsia (n = 16). In the group of pregnant women with chronic hypertension and of healthy pregnant women (n = 10) activin A was measured in samples collected longitudinally throughout gestation. Using a specific two-site enzyme-linked immunosorbent assay, it has been possible to measure maternal serum activin A concentration. In addition, the effect of recombinant human activin A administration on mean arterial pressure and heart rate in female rats have been also investigated. Mean +/- SEM of maternal serum activin A concentration in pre-eclamptic women (57.4 +/- 28.3 ng/ml), was significantly higher than in women with pregnancy-induced hypertension (14.8 +/- 10.5 ng/ml), chronic hypertension (10.3 +/- 5.4 ng/ml) or healthy control women (9.2 +/- 9.4 ng/ml) (P < 0.01). Serum activin A levels evaluated 2 weeks after anti-hypertensive treatment were not significantly different in pre-eclamptic women. Moreover, when exogenous recombinant human activin A was administered in female rats arterial pressure or frequency of heart rate did not change. The present study showed that maternal serum activin A concentration is abnormally high in patients with pre-eclampsia. Thus, since the patients with chronic hypertension or pregnancy-induced hypertension have activin A concentration in the normal range of values, activin A may be a prognostic marker of hypertension in pregnancy.

Activins↗
PubMed1995

Steroid-protein interaction in human placenta.

Human placenta produces a large variety of bioactive substances with endocrine and neural competence: pituitary and gonadal hormones, hypothalamic-like releasing or inhibiting hormones, growth factors, cytokines and neuropeptides. The most recent findings indicate that locally produced hormones regulate the secretion of other placental hormones supporting a paracrine/autocrine regulation. In placental endocrinology, a particular relevance is played by steroid hormones. In fact, a specific gonadotropin-releasing hormone (GnRH)-human chorionic gonadotropin (hCG) regulation of placental steroidogenesis has been proposed as a placental internal regulatory system acting on steroids production from human placenta. In addition, activin and inhibin have been proposed as further regulatory substances of the synthesis and secretion of steroids; the addition of activin A to placental culture augments GnRH, hCG and progesterone, and this effect can be significantly reduced by the addition of inhibins. Finally, a steroid-steroid interaction is suggested by the evidence that placental estrogen has a positive role in the regulation of progesterone biosynthesis. Other steroid-protein interactions have been observed in human placenta. In fact, recent data indicate that progesterone inhibits placental corticotropin-releasing factor (CRF) and estrogens act on placental conversion of cortisol to cortisone, activating cortisol secretion by the fetal adrenal and enhancing fetal adrenal function with advancing gestation.

Animals↗
PubMed1995

Corticotropin releasing factor decidualizes human endometrial stromal cells in vitro. Interaction with progestin.

Decidualization of endometrial cells is a hormone-dependent process of differentiation which occurs during the menstrual cycle and pregnancy. Recent in vitro studies have revealed that cAMP and its generators induce decidualization of stromal cells isolated from proliferative endometrium and that progestins enhance the effect of cAMP. Since corticotropin releasing factor (CRF) generates cAMP and prostaglandins in other organs, in the present study the effect of CRF, a hypothalamic factor also produced by decidua and fetal membranes, on in vitro decidualization of endometrial stromal cells was evaluated. The addition of CRF to a culture medium of stromal cells induced in vitro decidualization, as indicated by morphologic changes from elongated fibroblast-like cells into larger and round cells and by the release of prolactin in the medium. The effect of CRF on stromal cells and on prolactin release was significantly augmented by the coincubation in the presence of medroxyprogesterone acetate. This observation indicates CRF as a novel factor of decidualization and confirms that progestins act as enhancers of the expression of decidual products.

Cell Differentiation↗
PubMed1995

Corticotropin-releasing hormone induces an exaggerated response of adrenocorticotropic hormone and cortisol in polycystic ovary syndrome.

OBJECTIVE: To evaluate pituitary-adrenal responsive to corticotropin-releasing hormone (CRH) stimulus in polycystic ovary syndrome (PCOS). DESIGN: Controlled clinical study. PATIENTS: Twelve women aged 17 to 32 years, who had been diagnosed as having PCOS, were studied. Fifteen appropriately age- and weight-matched ovulatory patients served as the control. INTERVENTION: In the early follicular phase or after progestin-induced menses, human CRH was injected at 8:00 A.M. and blood samples were collected at 0, 15, 30, 60, and 90 minutes after stimulus. Plasma levels of ACTH and cortisol were measured. RESULTS: Baseline levels of ACTH and cortisol were similar in PCOS and control patients. Both ACTH and cortisol response to CRH were markedly greater in the PCOS population as compared with controls. Moreover, ACTH- and cortisol-stimulated secretion was prolonged for the whole period of the study in hyperandrogenic patients with respect to controls, where baseline levels were attained 60 minutes after the stimulus. CONCLUSIONS: Our results are consistent with the hypothesis that women with PCOS may demonstrate hyperfunction of the hypothalamic-pituitary-adrenal axis, which may be involved in the physiopathologic events leading to the complexity of the syndrome.

Adolescent↗
PubMed1995

Naltrexone treatment restores menstrual cycles in patients with weight loss-related amenorrhea.

OBJECTIVE: To evaluate whether the efficacy of naltrexone administration in patients with hypothalamic amenorrhea correlates to the response to an acute naloxone test. DESIGN: Thirty patients with hypothalamic amenorrhea associated with weight loss were studied. After naloxone test (4 mg in bolus IV) patients were divided into two groups: group A, nonresponsive (n = 15) and group B, responsive (n = 15). Group A underwent two cycles of hormonal replacement therapy with E2 patches and medroxyprogesterone acetate. Then all patients were administered naltrexone at the dosage 50 mg/d orally for 6 months. A third group of 10 amenorrheic patients were treated with oral placebo with the same schedule. RESULTS: Plasma gonadal steroid levels increased in all patients and in 24 of 30 patients the menstrual bleeding occurred within 90 days from the beginning of treatment. After 6 months from naltrexone discontinuation, 18 of 24 patients still showed the occurrence of menstrual cycles. Luteinizing hormone plasma levels and LH pulse amplitude increased after 3 months of treatment and remained unchanged 6 months after naltrexone suspension. Plasma FSH levels did not show any change in any patient. The body mass index increased after 3 months in all patients who menstruated. Patients treated with placebo did not show any significant change in gonadotropins and gonadal steroid plasma levels. CONCLUSIONS: The present study supports the efficacy of naltrexone therapy for patients with hypothalamic amenorrhea either responsive or nonresponsive to naloxone test.

Administration, Oral↗
PubMed1995

Naltrexone administration modulates the neuroendocrine control of luteinizing hormone secretion in hypothalamic amenorrhoea.

Because endogenous opioids have been considered to be deeply involved as a causal factor of hypothalamic amenorrhoea, this study was designed to evaluate the efficacy of the administration of naltrexone, an antagonist of opioid receptors, on luteinizing hormone (LH) secretion in patients with hypothalamic amenorrhoea. A total of 30 patients with hypothalamic amenorrhoea were studied. Patients were divided into two groups: group A, hypogonadotrophic (n = 15), and group B, normogonadotrophic (n = 15). All patients were administered naltrexone at a dose of 50 mg/ day per os for 6 months. A third group of 10 amenorrhoeic patients was treated with placebo per os with the same schedule. All patients were evaluated for LH spontaneous pulsatile release in baseline conditions and after 3 and 6 months of treatment. Plasma gonadal steroid concentrations increased significantly in all patients after 3 months of naltrexone therapy, but only hypogonadotrophic patients showed a sharp increase in both LH plasma concentrations and LH pulse amplitude within the first 3 months of treatment which remained unchanged until the sixth month of treatment. Plasma follicle stimulating hormone concentrations did not change significantly in any patient. Menstrual bleeding occurred within 90 days of the beginning of treatment in 24 out of the 30 patients. Patients treated with placebo did not show a significant change in gonadotrophin and gonadal steroid plasma concentrations. The results of our study support the efficacy of naltrexone administration on neuroendocrine pathways controlling LH secretion in patients with hypothalamic amenorrhoea.

Amenorrhea↗
PubMed1995

Effect of corticotropin-releasing factor-binding protein on prostaglandin release from cultured maternal decidua and on contractile activity of human myometrium in vitro.

Human placenta and uterine tissues are sites of production and local action of corticotropin-releasing factor (CRF). The recent evidence that CRF-binding protein (CRF-BP), a protein that blocks CRF-induced pituitary ACTH release, is produced by placental tissues suggested the present study to investigate the effects of CRF-BP on prostaglandin release and contractile activity of myometrial strips. Primary cultures of decidual cells were prepared using tissue collected from healthy women undergoing cesarean delivery at term. Mechanical and enzymatic cell dispersions were carried out, and experiments were performed 24-28 h after cell plating. The prostaglandin E2 (PGE2) concentration in cultured medium was measured by RIA. Myometrial strips were obtained from the upper edge of the uterine incision during elective cesarean section at term. Dissected free of connective tissue, strips were mounted in a 30-mL two-chamber organ bath containing oxygenated Tyrode's buffer (37 C) and connected to a two-channel isometric smooth muscle transducer. Cultured decidual cells collected at term significantly increased the release of PGE2 in the presence of CRF (P < 0.01). The addition of CRF-BP did not significantly modify PGE2 release, but completely reversed the effect of CRF. When human myometrial strips were incubated in the presence of CRF and PGF2 alpha, a significant increase in contractile activity was observed (P < 0.01); preincubation with CRF-BP prevented the increased contractile activity induced by CRF. The present data show that CRF-BP is able to counteract the biological effect of CRF on human pregnancy endometrium and myometrium and suggest that CRF-BP may be a regulatory protein that plays a role in the local function of uterine tissues during pregnancy.

Animals↗
PubMed1995

Abnormal concentration of maternal serum activin-A in gestational diseases.

Serum plasma activin-A is measurable in the maternal circulation of healthy pregnant women, increases in specimens collected during the third trimester of gestation, and is highest at parturition. Hormone abnormalities are known to be associated with preterm labor or diabetes in pregnancy. Therefore, in the present study serum activin-A levels in normal controls were compared to those in pregnant women with preterm labor or gestational diabetes. In some cases, values were obtained before and after insulin therapy. In other controls and patients with preterm labor, the activin-A concentration in cord serum was also studied. A newly developed two-site immunotest was used to determine activin-A levels. Subjects included normal controls (n = 7), who were sampled throughout gestation every 5 weeks; pregnant women at term (38-40 weeks) not in labor (n = 22); pregnant women at term in spontaneous labor (< 3.0 cm dilated; n = 42); women in preterm labor (25-35 weeks; n = 38); and women with gestational diabetes (20-39 weeks; n = 9). In control women, serum activin-A levels increased from 4.8 +/- 5.5 micrograms/L (mean +/- SD) at 20 weeks to 25.4 +/- 27.8 micrograms/L at 40 weeks (P < 0.01), and values correlated with gestational age. Pregnant women in preterm labor had serum activin-A concentrations (89.04 +/- 173.31 micrograms/L) higher than those in normal controls (P < 0.01), and no significant correlation to gestational age was found in this group of pregnant women. Healthy women in labor showed serum activin-A concentrations higher than those in women at term but not in labor (P < 0.01). Diabetic patients had serum activin-A concentrations (52.39 +/- 23.32 micrograms/L) significantly higher than those in normal controls. In these patients, maternal serum activin-A concentrations significantly decreased to the range in healthy controls at the same gestational age after insulin therapy (9.48 +/- 3.82 micrograms/L). The present study shows that preterm labor is associated with increased concentrations of activin-A in the maternal circulation and cord serum. Hypersecretion of activin-A is also shown in same patients with gestation diabetes; this reverts to normal after insulin treatment.

Activins↗
PubMed1995

Evidence for a role for the neurosteroid allopregnanolone in the modulation of reproductive function in female rats.

The present study investigated the effect of allopregnanolone (5 alpha-pregnan-3 alpha-ol-20-one) or of passive immunoneutralization of brain allopregnanolone, the most potent steroid produced by neurons, on ovulation rate and sexual behavior in female rats. Allopregnanolone was injected intracerebroventricularly in rats on diestrus and proestrus and tests were done on estrus. The intracerebroventricular injection of allopregnanolone significantly decreased the number of oocytes collected on estrus (p < 0.01). To support a physiological involvement, antiserum to allopregnanolone was injected centrally to block the activity of the endogenous neurosteroid. When administered on diestrus and proestrus or only on proestrus, the antiserum was shown to be correlated with a significant increase (p < 0.01) in oocytes retrieved on estrus. In female rats treated with antiserum to allopregnanolone, the lordosis intensity was augmented significantly as compared to controls. Finally, the possible changes of medial basal hypothalamus concentration of allopregnanolone throughout the estrous cycle and at the time of ovulation were investigated. Hypothalamic extracts were eluted on high-pressure liquid chromatography and allopregnanolone concentration was measured by radioimmunoassay. Brain cortex was used as control tissue. Hypothalamic allopregnanolone concentration on proestrus morning and afternoon was found to be significantly lower than in the remaining phases of the estrous cycle (p < 0.01), while no significant changes were observed in brain cortex concentration of allopregnanolone. The present results suggest that hypothalamic allopregnanolone may be involved in the mechanism of ovulation, affecting hormonal and behavioral events.

Animals↗
PubMed1995

Evidence for a role of neurosteroids in modulation of diurnal changes and acute stress-induced corticosterone secretion in rats.

The neurosteroid allopregnanolone has been shown to be a potent ligand of gamma-aminobutyric acid (GABA)-A receptors and enhances its receptor-mediated inhibitory events. Since central GABA plays a major inhibitory role, via GABA-A receptors, in hypothalamic-pituitary-adrenal (HPA) function in rats, the present study has evaluated the effect of passive immunoneutralization of allopregnanolone on diurnal changes in corticosterone secretion and acute stress-induced corticosterone secretion in rats. In the first protocol, four groups of male rats (prepubertal, fertile, castrated adult and aged) and three groups of female rats (prepubertal, fertile at different phases of the estrous cycle and aged) were studied. Rats were injected intracerebroventricularly (i.c.v.) with 10 microliters anti-allopregnanolone serum or 10 microliters normal rabbit serum (control) 24 h before exposure to an acute cold swimming stress, and sacrificed either before stress or after 5 min stress. In the second protocol, fertile male or female rats at diestrus II were injected i.c.v. with anti-allopregnanolone serum or normal rabbit serum and sacrificed on the following day at 10.00 or 18.00. Truncal blood samples were collected for measuring plasma corticosterone. Our results showed that there was no significant difference in basal plasma corticosterone levels between antiserum-treated and control rats of both sexes. However, in male rats, central injection of antiserum to allopregnanolone significantly potentiated plasma corticosterone response to stress in prepubertal and adult fertile rats as well as in castrated rats. Likewise, in female rats, the stress response of plasma corticosterone was enhanced by passive immunoneutralization of allopregnanolone in prepubertal and fertile rats throughout the estrous cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

The duration of prolactin secretory bursts from the pituitary is independent from both prolactin and gonadal steroid plasma levels in women and in men.

The intrinsic secretory characteristics of prolactin (PRL) have been investigated using newly developed algorhythms for instantaneous secretory rate (ISR) computation. PRL secretory rate, its intrinsic pulsatile characteristics and their possible dependance from gonadal steroids were investigated in five groups of subjects: a) 11 women during the follicular and luteal phase of the same menstrual cycle; b) 5 healthy postmenopausal women; c) 6 women affected by functional hyperprolactinemia; d) 5 normal men; e) 4 agonadal subjects before and during testosterone replacement therapy. All subjects underwent a 6 hours pulsatility study, from 08:00 to 14:00, sampling every 10 minutes. PRL plasma concentrations were determined using a RIA system and the presence of PRL secretory pulses was evaluated with program DETECT, both on plasma time series and after ISR computation. A distinct PRL episodic release was observed in all groups (follicular phase: 5.5 +/- 0.5, luteal phase: 6.5 +/- 0.6, postmenopause: 5 +/- 1, hyperprolactinemic women: 4.2 +/- 0.8, men: 4.8 +/- 0.4, agonadal before testosterone: 6 +/- 1, agonadal during testosterone administration: 5.3 +/- 0.3 peaks/6h), but mainly the computation of ISR allowed to demonstrate that the duration of the lactotropes secretory events was constant in all groups studied. PRL secretory bursts duration ranged between 23.1 +/- 1.8 and 25.4 +/- 2.5 minutes independently both on PRL or on sex steroid plasma levels. In conclusion, the present report shows that in different physiological conditions the intrinsic secretory bursts from lactotropes are constant in duration independently from the functional state, sex and the steroid hormone levels.

Adult↗
PubMed1994

Ontogeny of the circadian rhythm in medial basal hypothalamic beta-endorphin content in female rat.

The present study evaluated the possible role of estrogens in generating the circadian rhythm of medial basal hypothalamus content at the time of puberty in female rats. Accordingly, changes in medial basal hypothalamus beta-endorphin (beta-EP) content were investigated in female rats, before and at puberty. Groups of intact or ovariectomized rats were studied after estradiol-benzoate or placebo treatment. The results showed that circadian rhythm of beta-EP content of medial basal hypothalamus is absent in prepubertal rats, while it appears at puberty, associated to a significant increase of beta-EP concentration. The primary involvement of steroids in generating this circadian rhythm was supported by the finding that estradiol-benzoate treatment caused a precocious appearance of beta-EP hypothalamic diurnal changes in prepubertal rats. Moreover, estradiol-benzoate replacement restored the loss of beta-EP nocturnal increase induced by ovariectomy in pubertal animals. Therefore, these data support the significant role of estrogen in inducing the circadian rhythm of beta-EP content in medial basal hypothalamus at the time of puberty in female rats.

Aging↗