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Biomedical subjects

F Petraglia

Publications and source records attributed to F Petraglia.

At least 199 records · Page 11Linked to original sources

Corticotropin-releasing hormone increases prostaglandin F2 alpha activity on human myometrium in vitro.

OBJECTIVE: Our purpose was to study the capability of synthetic corticotropin-releasing hormone to directly stimulate human myometrium and to modulate the activity of prostaglandins F2 alpha and E2. STUDY DESIGN: Strips from human myometrium were obtained from 127 elective cesarean sections at term. The in vitro effect of human rat corticotropin-releasing hormone on myometrial contractility has been studied in resting myometrial strips mounted in a two-chamber bath for isolated organs. Stimuli (corticotropin-releasing hormone, prostaglandins F2 alpha and E2, and oxytocin) were administered as one single dose in the perfusion chamber. In each experiment one myometrial strip was used as a control. RESULTS: Corticotropin-releasing hormone significantly increases (p < 0.01) the myometrial response to prostaglandin F2 alpha. The hormone neither has a direct inotropic effect nor is it able to enhance the effect of prostaglandin E2 and oxytocin on myometrial strips. CONCLUSION: The positive effect of corticotropin-releasing hormone on the myometrial response to prostaglandin F2 alpha adds new support to the theory that placental corticotropins may modulate the onset of labor.

Corticotropin-Releasing Hormone↗

Effect of activin-A on progesterone synthesis in human luteal cells.

OBJECTIVE: To examine the effect of activin-A on basal and hCG-stimulated P production by human luteal cells. DESIGN: Mixed luteal cell cultures and distinct cultures of two luteal cell types: small and large luteal cells from early and midluteal phase. SETTING: Corpora lutea (CL) were obtained from the Obstetrics and Gynecology Department of the Catholic University, Rome, Italy. PATIENTS: Fifteen nonpregnant women between 30 and 45 years of age underwent surgery for nonendocrine gynecological diseases. INTERVENTIONS: Corpora lutea were obtained at the time of hysterectomy. The luteal cells were dispersed in Ham's F-12 medium containing collagenase at 37 degrees C in shaking water bath for 2 hours, filtered, centrifuged, and resuspended in fresh medium. MAIN OUTCOME MEASURES: The cells diluted to a final concentration of 60,000 to 100,000 cells/mL of medium. After 24 hours, the cells attached to the wells and were incubated with or without hCG and/or activin-A at different concentrations. RESULTS: Activin-A starting from 25 micrograms/L significantly decreased basal and hCG (250 mIU/mL [conversion to SI unit, 1.00])-induced P production by mixed luteal cells. The small luteal cells responded to hCG (250 mIU/mL), and the treatment with activin-A (from 25 to 100 micrograms/L) reduced their basal and hCG-induced P production. Activin-A addition did not change the amount of P release by large luteal cells at any concentration. CONCLUSIONS: These results imply that activin-A plays a role in the local regulation of human CL.

Activins↗

Evidence suggesting an additional control mechanism regulating episodic secretion of luteinizing hormone and follicle stimulating hormone in pre-pubertal children and post-menopausal women.

The possible differential regulation of pulsatile follicle stimulating hormone (FSH) and luteinizing hormone (LH) secretion in pre-pubertal children and in post-menopausal women was investigated. Children were studied for 4 h and post-menopausal women for 6 h; blood samples were taken every 10 min. Post-menopausal women were studied before and 21 days after administration of a single i.m. dose of gonadotrophin-releasing hormone (GnRH) analogue. Eight post-menopausal women and 18 children (nine boys and nine girls) were enrolled. The children were divided into two groups: A, at Tanner stages 0-1 (four boys and three girls); B, at Tanner stage 2-3 (five boys and six girls). Plasma LH and FSH concentrations were determined using an immunofluorimetric assay. Time series were analysed and the specific concordance (SC) index was computed to determine the degree of concordance between episodes of LH and FSH secretion. While children of group A had LH concentrations below the minimal detectable dose of 0.1 IU/l, group B showed measurable LH plasma concentrations (1.4 +/- 0.3 IU/l, mean +/- SEM). Plasma FSH concentrations were detectable in both groups. Group A showed FSH plasma concentrations significantly lower than those of group B (0.75 +/- 0.2 and 1.95 +/- 0.4 IU/l respectively; P < 0.05), but FSH pulse frequency was higher in group A (P < 0.05). Children of group B showed significant concomitance of LH and FSH secretory events at time 0 (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Episodic changes of serum procollagen type I carboxy-terminal propeptide levels in fertile and postmenopausal women.

The aim of the present study was to optimize the use of serum procollagen type I carboxy-terminal propeptide (PICP) as a possible marker of postmenopausal-376lted changes of bone metabolism. Postmenopausal (n = 20) and healthy fertile young (n = 4) women were studied after informed consent. The postmenopausal women were subdivided in 4 groups: (1) nontreated; (2) treated with estrogen-progestogen replacement therapy; (3) treated with calcitonin, or (4) with kidney or liver diseases. Blood samples were collected at 15-min time intervals for 4, 6 or 8 h. Serum concentration of PICP was measured by radioimmunoassay, in duplicate at two different dilutions. In postmenopausal women mean +/- SEM serum PICP levels were slightly but nonsignificantly higher than in fertile women. Serum PICP levels in estrogen-progestogen or calcitonin-treated women were significantly lower than in non-treated postmenopausal women. Episodic changes of circulating PICP level were observed in fertile and postmenopausal women. The pulses of serum PICP levels did not show significant differences among the groups of women studied. The present study showed that the measurement of serum PICP levels is a useful marker for investigating the changes of bone metabolism. In particular, low PICP levels in postmenopausal women under steroid hormone or calcitonin treatment in part reflect the changes of bone turnover. The pulses of serum PICP levels during a time interval suggest that collagen metabolism in women undergoes a rapid turnover.

Adult↗

Local production and action of follistatin in human placenta.

The aim of the present study was to investigate the possible production, localization, and action of follistatin in human placenta, fetal membranes (amnion, chorion), and maternal decidua. Four different experimental approaches were used: 1) Southern blot analysis following reverse polymerase chain reaction to identify follistatin messenger RNA (mRNA) in tissue homogenates; 2) immunohistochemistry to localize immunoreactive (ir-) follistatin in the various intrauterine tissues; 3) measurement by RIA of ir-follistatin levels in culture medium of placental cells; and 4) possible action of follistatin on human CG (hCG) and progesterone release from cultured placental cells. Placental and decidual cells collected during first trimester or at term gestation express follistatin mRNA; fetal membranes (amnion, chorion) at term also express follistatin mRNA. Immunoreactive follistatin is localized in syncytial cells of placental villi at term as well as in large decidual cells, in amnion epithelium, and in chorionic cells. The placental secretion of follistatin has been confirmed by the evidence of measurable levels of ir-follistatin in the medium of cultured placental cells at term; the release is time dependent and is not modified by the addition of forskolin or progesterone. The addition of increasing doses of recombinant human follistatin does not significantly influence the release of hCG or progesterone from cultured placental cells, whereas the activin A-induced hCG and progesterone release are completely reversed. The present data showed that 1) human placenta, fetal membranes, and decidua express follistatin mRNA; 2) ir-follistatin is localized and released from placental cells at term; and 3) follistatin has a functional role in the local control system regulating placental hormone production.

Base Sequence↗

Intrinsic secretory characteristics of luteinizing hormone and prolactin episodic release during pubertal development.

The intrinsic characteristics of LH and prolactin (PRL) episodic secretion were evaluated in a group of 18 children (8M and 10F). The children were divided into two groups according to the Tanner stage: Group A (Tanner < or = 1, N = 7, 3M and 4F, 6-10 years of age) and group B (Tanner 2-3, N = 11, 5M and 6F, 9-11 years of age). A pulsatility study of 4 h, sampling every 10 min, was carried out in all children. LH and PRL plasma levels were assayed by IFMA and RIA respectively. LH and PRL secretory episodes were then identified on plasma determinations using the program DETECT. Instantaneous secretory rates (ISR) were then computed for both LH and PRL using the specific algorithm within the DETECT program. Plasma LH levels were different between the two groups of children. Group A children showed undetectable LH plasma levels (below the minimal detectable dose of 0.1 mIU/ml), while group B demonstrated LH plasma levels in the normal range of values for age and sexual development (1.5 +/- 0.3 mIU/ml, mean +/- SEM). LH pulse frequency for group B was 3.2 +/- 0.4 peaks/4 h. No significant differences in mean plasma PRL levels, pulse frequency and pulse amplitude were observed between the two groups of children. Computation of ISR for LH (group B only) and PRL (both groups) identified the intrinsic episodic characteristics of the two hormones. No significant differences in LH and PRL pulse frequencies were observed when comparing the results estimated on ISR with those estimated on plasma concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Acute stress- or lipopolysaccharide-induced corticosterone secretion in female rats is independent of the oestrous cycle.

The aim of the present study was to test whether oestrous cycle is associated with the hypothalamus-pituitary-adrenal (HPA) axis function. Thus, corticosterone secretion in rats was investigated following lipopolysaccharide (LPS), acute cold-swimming or ether stress or synthetic corticotrophin-releasing factor (CRF) administration throughout the oestrous cycle. Moreover, plasma corticosterone response to cold-swimming stress or LPS administration also was studied at different times of day on pro-oestrus of di-oestrus-I. The following observations were obtained: the morning plasma corticosterone levels in control rats did not differ with the stage of the oestrous cycle; plasma corticosterone levels increased significantly following LPS administration (2 mg/kg, ip) or following acute exposure to cold (4 degrees C)-swimming or ether stress. However, this increase in plasma corticosterone levels was not related to the stage of the oestrous cycle; synthetic CRF injection induced an increase in plasma corticosterone levels constant on di-oestrus-I and pro-oestrus; plasma corticosterone response to LPS administration or acute cold-swimming stress showed diurnal changes, with the lowest values at 18.00 h, which was independent of the oestrous cycle. By showing the unchanged corticosterone response to LPS, to acute stress and to exogenous CRF throughout the oestrous cycle, and the independence of the diurnal pattern of stress response on the oestrous cycle, the present study suggests that the oestrous cycle has no influence on the HPA activity under the present experimental conditions in rats.

Animals↗

Pulsatile fluctuations of plasma-gonadotropin-releasing hormone and corticotropin-releasing factor levels in healthy pregnant women.

Several data emphasize the neuroendocrine aspects of human placenta. Classical hypophyseotropic neurohormones are produced and secreted by the human placenta. Indeed, in contrast with non pregnant subjects, gonadotropin-releasing hormone (GnRH) and corticotropin-releasing factor (CRF) are measurable in maternal plasma during pregnancy. The aim of the present study was to investigate the characteristics of the secretory pattern of maternal plasma GnRH and CRF levels. A total of 25 healthy pregnant women participated in the present cross-sectional study. Plasma levels of the two neurohormones were measured according to three different time-intervals: 1) every five minutes for eight hours (n = 4), 2) every ten minutes for four hours (n = 15), 3) every four hours for 24 hours (n = 7). Following an acidic extraction plasma GnRH and CRF levels were measured by specific radioimmunoassay. Using two different algorithms (Detect and Cluster) a pulsatile pattern for both plasma GnRH and CRF levels was observed. Specific pulse frequency, amplitude, and duration were found. In the groups of women studied with a longer sampling interval, pulse frequency of GnRH or CRF levels did not differ between first and third trimester of gestation. However, amplitude of CRF pulses were significantly higher at term than at early stages of pregnancy (p < 0.01), while GnRH pulse amplitude was highest in women at first trimester of gestation. Evaluating the degree of concordance in all subjects, GnRH pulses significantly correlated with CRF pulses at 30 min. lag (p < 0.01). No significant circadian changes were found for any circulating neurohormone measured.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗

Pituitary and ovarian interleukin-1 alpha content changes according to estrous cycle and acute stress exposure.

A complex interaction between the immune and neuroendocrine systems has been established. In particular, cytokines are known to be one of the mediators of the stress response, and modulate hormone secretion by acting in the brain, pituitary and gonads. The aim of the present study is to investigate whether pituitary and ovarian interleukin-1 alpha (IL-1 alpha) content changes according to the estrous cycle. In addition, the possible pituitary and ovarian IL-1 alpha changes in rats exposed to acute (5 min) or chronic intermittent (twice a day for 4 days) cold swimming stress were studied. The IL-1 alpha content of ovarian and pituitary homogenates was measured by a sensitive and specific radioimmunoassay. Immunoreactive IL-1 alpha (irIL-1 alpha) was detectable only in ovaries collected in rats at proestrus and estrus while not in those collected at diestrus I and II. The highest values were found at proestrus. No significant changes were found in ovarian irIL-1 alpha content in rats exposed to acute or chronic intermittent stress in comparison to control rats. In the pituitary, no difference in IL-1 alpha content was found throughout the estrous cycle. Acute stress induced a significant increase in pituitary irIL-1 alpha content only at proestrus (p < 0.01), however, no significant differences were found in comparison to control rats after chronic intermittent stress. The proestrus-related changes of ovarian IL-1 alpha may constitute a hormone-dependent signal within the ovary that is involved in the ovulatory process.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Episodic release of prolactin in women with weight loss-related amenorrhea.

Amenorrhea associated with weight loss is characterized by several neuroendocrine aberrations. The aim of the present study was to define the characteristics of episodic secretion of prolactin in women with weight loss-related amenorrhea. To evaluate whether hypoestrogenism was responsible for the changes in prolactin secretion in amenorrheic women, the pulsatile secretory pattern was also studied during hormone replacement therapy (HRT). Fifteen patients were studied by blood sampling every 10 min for 8 h. Four normally cycling women were studied as a reference group, during both the midfollicular and midluteal phases. Mean plasma prolactin levels and pulse amplitude were lower in amenorrheic patients than in controls. The prolactin pulse frequency was higher than that in controls during the follicular phase, but lower than controls during the luteal phase of the menstrual cycle. During HRT, mean plasma prolactin levels significantly increased, pulse frequency decreased and pulse amplitude significantly increased both during estradiol and estradiol plus medroxyprogesterone acetate administration. In conclusion, in amenorrhea associated with weight loss the chronobiological organization of prolactin secretion is deranged, both as a result of a neuroendocrine alteration and as a result of low plasma levels of gonadal steroids.

Amenorrhea↗

Activin at parturition: changes of maternal serum levels and evidence for binding sites in placenta and fetal membranes.

OBJECTIVE: To evaluate maternal serum activin A levels in pregnant women at parturition, correlated to the mode of delivery, and to localize activin receptor messenger RNA in human placenta and fetal membranes. METHODS: A specific two-site enzyme-linked immunosorbent assay (ELISA) was used to measure maternal activin A levels. Activin receptor mRNA was localized in placenta and fetal membranes by in situ hybridization, using ActRII or ActRIIB antisense riboprobes. RESULTS: Serum activin A levels increased significantly in pregnant women during vaginal or cesarean delivery after spontaneous labor. No significant changes of serum activin A were found in patients undergoing elective cesarean delivery. Syncytiotrophoblast and amnion cells hybridized to radiolabeled ActRIIB probe, whereas few cells within the structure of the villi and decidual cells hybridized to radiolabeled ActRII probe. CONCLUSION: The present studies indicate that vaginal or cesarean delivery following spontaneous labor is characterized by increased activin A levels and that activin receptors are present on trophoblast and fetal membranes.

Activin Receptors↗

Exposure to low frequency pulsed electromagnetic fields increases interleukin-1 and interleukin-6 production by human peripheral blood mononuclear cells.

The exposure of human peripheral blood mononuclear cells to extremely low frequency pulsed electromagnetic fields (PEMFs) increased both the spontaneous and the PHA- and TPA-induced production of interleukin-1 (IL-1) and IL-6. Our results suggest that cells of the monocytic lineage, which are good producers of both IL-1 and IL-6, can be important cellular targets for PEMFs. Taking into account that these cytokines are among the most pleiotropic ones, these data can help us understand the previous reported effects of PEMFs on the proliferation of human lymphocytes and the effects exerted by such fields on cartilage and bone cells, whose physiological activity is highly dependent on IL-1 and IL-6.

Adult↗

Maternal decidua and fetal membranes contain immunoreactive neuropeptide Y.

The aim of the present study was to evaluate whether the various intrauterine tissues contain immunoreactive neuropeptide Y (NPY). Previous observations showed that human placenta produces NPY and that it may play a local role. Using a polyclonal NPY antiserum and an immunofluorescent technique, sections of maternal decidua, amnion and chorion collected from a pregnant women at parturition were studied. An intense positive staining for NPY was observed in epithelial amnion cells and in chorionic cytotrophoblast. Some of the maternal decidual cells showed a weaker signal of immunoreactive NPY. In evaluating whether NPY may coexist with other hormones in these tissues, adjacent slices of decidua, amnion and chorion were stained with activin beta B subunit antiserum. In the various tissues a relevant number of cells showed positive signals for both NPY and activin. The present findings showed that the various intrauterine tissues contain NPY and that in a large number of cells of amnion, chorion and decidua the neuropeptide is colocalized with immunoreactive activin. In view of the physiological implications of NPY in the regulation of uterine contractility and of placental hormonogenesis, the present findings indicate a large distribution of NPY in the various intrauterine tissues.

Activins↗

Corticotropin-releasing hormone modulates cytokines release in cultured human peripheral blood mononuclear cells.

Immune and neuroendocrine systems interact at various levels. In particular, either cytokines activate the hypothalamus-pituitary-adrenal axis (HPA) or corticotropin-releasing hormone (CRH) induces the release of beta-endorphin from peripheral human mononuclear cells. The aim of the present study was to investigate whether CRH may affect cytokine production and activity in human peripheral blood mononuclear cells (PBMC). Primary cultures of human PBMC and monocytes were used. They were incubated in presence of different doses of synthetic human CRH. Media were collected and interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) levels were measured by ELISA, while interferon-gamma (IFN-gamma) levels were measured by bioassay. In addition, phytohemoagglutinin-induced lymphocyte proliferation was evaluated by testing [3H]thymidine incorporation in the presence of various doses of CRH. CRH significantly increased IL-6 release from PBMC (p < 0.01). The addition of CRH to PBMC significantly decreased IFN-gamma levels, in a dose dependent manner (p < 0.01). No significant effect of CRH was observed on lymphocyte proliferation or IL-1 beta production. The present results suggest a role for CRH as a paracrine mediator for human immune cells, increasing the evidence of a clear correlation between immune and neuroendocrine system.

Adult↗

Effect of chronic intermittent stress on rat pregnancy and postnatal development.

The present study evaluates the effect of chronic intermittent cold-swimming stress on body weight gain of pregnant rats and subsequent development of the offsprings after birth, till peripubertal stage. When stress was administered during the first half (1-11 days) of gestation, weight gain of pregnant rats was significantly lower at the 9th and 11th days (P < 0.05 vs. control, respectively). No differences of weight gain in comparison with control rats were found at term gestation in pregnant rats exposed to stress continuously. Similarly, stress administered, starting from 12th day till term gestation, had no effect on weight gain. Even though weight gain of pregnant rats during the second half of pregnancy in group stress 1-11 was restored to normal values, a high mortality rate of neonates 1, 2 and 3 weeks after birth was found in this group (P < 0.02, 0.01 and 0.001 vs. controls). There was no significant difference between stressed and control groups with respect to the number or body weight of litters, as well as weight gain of neonates during the first 21 days of life. In addition, in offsprings from all stressed groups, a high number of small for date animals was found after 14 days of life, and 74.4% of these small for date animals died during the peripubertal period. The present data demonstrate that the exposure to stress in utero may induce damaging effects on postnatal development.

Animals↗

Hormonal treatments modulate pulsatile plasma growth hormone, gonadotrophin and osteocalcin levels in postmenopausal women.

Oestrogen plays a role in modulating growth hormone (GH), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and osteocalcin secretion in women. Indeed, the postmenopausal period is characterized by changes in plasma GH, LH, FSH and osteocalcin levels. The aim of the present study was to investigate the changes in the secretory patterns of these hormones in postmenopausal women under different therapeutic regimens. A total of 20 subjects took part in the study. They were subdivided into four groups comprising 5 untreated postmenopausal women (time since menopause 1-5 years), 5 postmenopausal women receiving steroid hormone replacement therapy, 5 postmenopausal women receiving salmon calcitonin and 5 fertile women with regular menstrual cycles. Blood samples were collected every 15 min for 4 h and hormone levels were measured by radioimmunoassay. Plasma GH levels fell in the postmenopausal women, but were restored under oestrogen-progestogen treatment. The pulsatile patterns of plasma LH and FSH did not show significant differences in the treated and untreated women. Plasma osteocalcin levels showed episodic fluctuations and mean levels decreased under steroid hormone or calcitonin treatment. No significant correlation was observed between plasma GH and osteocalcin or gonadotrophin levels or body mass index.

Calcitonin↗

Modulatory role of estrogens and progestins on growth hormone episodic release in women with hypothalamic amenorrhea.

OBJECTIVE: To define the characteristics of spontaneous GH episodic secretion and the modulatory role of gonadal steroids in patients with hypothalamic amenorrhea associated with weight loss. DESIGN: Women were studied for 8 hours, sampling every 10 minutes, and plasma GH levels were measured by RIA. SUBJECTS: Fifteen patients with weight-loss-related amenorrhea were studied in baseline conditions. Five out of 15 patients underwent two cycles of hormonal replacement therapy with E2 patches (100 micrograms every 3 days for 24 days) and medroxyprogesterone acetate (MPA) (10 mg/d, from day 12 to day 24). On the second cycle of therapy, the pulsatility study was repeated twice: after only estrogen (day 11) and after E2 plus progestin (day 22). Four normally cycling women were studied as a reference group during midfollicular and midluteal phases. RESULTS: Amenorrheic patients showed mean plasma GH levels similar to healthy women during the follicular phase but significantly lower than those observed during the luteal phase. GH pulse frequency was higher in patients than in controls, whereas pulse amplitude was comparable with the follicular phase but lower during the luteal phase. During the hormonal replacement therapy, when only E2 was administered, GH pulse frequency decreased, whereas GH integrated plasma concentrations and GH pulse amplitude increased significantly. After MPA and E2 administration, GH pulse amplitude and GH plasma levels decreased, which was similar to pretreatment condition. CONCLUSIONS: The present study demonstrated that in amenorrhea associated with weight loss the frequency of GH episodic release is significantly higher than in normally cycling women. Moreover, a different modulatory role of estrogen (increased amplitude) and P (decreased amplitude) on the episodic release of GH in amenorrheic women undergoing a replacement treatment was shown by the present data.

Amenorrhea↗

Opioid control of gonadotrophin secretion in humans.

Hypothalamus-pituitary-axis (HPA) is constantly under the modulatory effect of many substances, such as neurotransmitters, neuromodulators and steroid hormones. Recently, the involvement of endogenous opioid peptides (EOP) in the control of the neuroendocrine mechanism modulating gonadotrophin secretion has been supported by several authors. It has been demonstrated that acute morphine administration decreases luteinizing hormone (LH) plasma levels and this is due to an inhibitory modulation on gonadotrophin releasing hormone discharge from the hypothalamic neurons. EOP are usually increased by stressful situations. In stress-induced amenorrhoea, the presence of low LH plasma levels and an abnormal LH pulsatile secretion has been related to an increased opioid activity, thus supporting the integrative role of opioids between hormonal and neuronal afferences of brain.

Endorphins↗