Biomedical subjects

F Petraglia

Publications and source records attributed to F Petraglia.

At least 109 records · Page 6Linked to original sources

PubMed2000

Evaluation of circulating activin-A as a serum marker of hepatocellular carcinoma.

Because in experimental hepatocarcinogenesis apoptosis increases from normal to preneoplastic to carcinoma tissue, proapoptotic factors, such as activin-A, may represent useful markers for hepatocellular carcinoma (HCC). In this study, serum activin-A was measured in 99 cirrhotic patients, of whom 55 had HCC. Activin-A concentrations were higher in HCC patients (median, 2.33 ng/ml; range, 0.41-8.12) than in patients with nonmalignant cirrhosis (1.28 ng/ml; range, 0.35-6.25) (P < .05). All 12 patients with activin-A greater than 3 ng/ml and serum alpha-fetoprotein greater than 30 ng/ml had HCC, in comparison to 32 of 41 patients who had only one and to 11 of 46 patients who had both markers below these cutoffs (P < .0001). No correlation was found between activin-A and alpha-fetoprotein in the two groups, whereas in patients with HCC, activin-A was strictly correlated with serum aspartate aminotransferase (P < .001). Activin-A mRNA for inhibin betaA subunit was expressed both in tumor and nontumor liver tissues in a case of HCC superimposed on cirrhosis and was not expressed in a case of HCC without cirrhosis. In conclusion, cirrhotic patients with HCC have high serum activin-A, to the production of which both the cirrhotic liver and the liver tumor are likely to contribute.

Activins↗

PubMed1999

GH, IGFBP-1, and IGFBP-3 response to oral glucose tolerance test in perimenopausal women: no influence of body mass index.

OBJECTIVES: an increasing interest is being focused on the role of the somatotropic axis in the modulation of body weight and fat distribution, particularly in climacteric women. The influence of the glycometabolic state on the somatotropic axis in postmenopausal and in obese subjects has not been investigated. The aim of the present study is to evaluate whether menopause and body mass index (BMI) affect the response of growth hormone (GH), insulin-like growth factor-binding protein-1 (IGFBP-1) and -3 (IGFBP-3) to the oral glucose tolerance test (OGTT). METHODS: the study included 24 women, aged 45-55 years, categorized into 4 groups, premenopausal pre-obese (BMI = 28.5 +/- 0.8 Kg/m2) and normal body weight (BMI = 22.2 +/-1.1 Kg/m2), and postmenopausal pre-obese and normal body weight. All women underwent: (1) a biophysical evaluation with determination of waist/hip ratio; (2) an assessment of fat and lean tissue mass and body fat distribution by total body DEXA; and to (3) an OGTT. RESULTS: in response to OGTT plasma GH levels significantly decreased in all groups, but the relative decrease was more prominent in the lean subjects. A significant decrease of IGFBP-1 levels in response to OGTT was observed in all women, regardless of menopausal age and BMI, while IGFBP-3 levels did not significantly change in either group. CONCLUSIONS: in conclusion, the impact of both BMI and menopausal condition on GH, IGFBP-1, and -3 response to OGTT is limited to a blunted GH response in overweight women compared with normally-weighing ones. These findings appear to rule out the hypothesis that a common glycometabolic derangement may affect both the modifications of body weight and of the somatotropic axis observed in perimenopausal women.

Body Composition↗

PubMed1999

Increased midtrimester amniotic fluid activin A: a risk factor for subsequent fetal death.

OBJECTIVE: The objective of this study was to determine whether concentrations of activin A and corticotropin-releasing factor in amniotic fluid can identify patients at risk of fetal death. STUDY DESIGN: A retrospective case-control study of women who have had a midtrimester amniocentesis was designed. Case subjects consisted of patients who had a spontaneous fetal death after the procedure, whereas the control group consisted of patients who had a normal pregnancy outcome after midtrimester amniocentesis. Dimeric activin A was measured by a specific 2-site enzyme immunoassay, and corticotropin-releasing factor was measured by a specific and sensitive radioimmunoassay after acidic extraction. Statistical analysis was performed with Mann-Whitney U test, Fisher's exact test, and chi2 tests and regression analysis. RESULTS: First, activin A was detectable in all amniotic fluid samples. Second, the concentration of activin A in amniotic fluid increased with advancing gestational age. Third, patients who subsequently had a fetal death had a higher median concentration of activin A than those with a normal pregnancy outcome (P <.01). Fourth, an amniotic fluid concentration of activin A greater than the 95th confidence interval for gestational age was found in 40% of patients who subsequently had a fetal death (odds ratio: 21.6; P <.005). Finally, the median concentration of corticotropin-releasing factor in amniotic fluid was not different in case subjects and control subjects. CONCLUSIONS: An elevated concentration of activin A in amniotic fluid identifies women at risk of fetal death.

Activins↗

PubMed1999

Antagonism by pivagabine of stress-induced changes in GABAA receptor function and corticotropin-releasing factor concentrations in rat brain.

Pivagabine [4-(2.2-dimethyl-l-oxopropylamino) butanoic acid] (PVG) is a hydrophobic 4-aminobutyric acid derivative with neuromodulatory activity. The effects of subchronic treatment with PVG on stress-induced changes both on brain concentrations of corticotropin-releasing factor (CRF) and neurosteroids and on the function of the gamma-aminobutyric acid type A (GABAA) receptor complex were investigated in male rats. Subchronic treatment with PVG (100-200 mg/kg, i.p.) resulted in a dose-dependent inhibition of the foot shock-induced increase in the binding of t-[35S]butylbicyclophosphorothionate to unwashed membranes prepared from the cerebral cortex of rats killed immediately after stress; PVG treatment alone had no effect on this parameter. This antagonistic action of PVG was also shown in adrenalectomized-orchietomized rats. Foot-shock stress decreased by 74% and increased by 125% the CRF concentration in the hypothalamus and cerebral cortex, respectively. PVG prevented these effects of stress on CRF concentration in both brain regions; this drug per se reduced hypothalamic CRF concentration by 52% but had no effect in the cortex. Moreover, intracerebroventricular injection of CRF, like stress, induced a dose-dependent increase of [35S]TBPS binding to cerebral cortical membranes: an effect not prevented by subchronic treatment of PVG. Finally, PVG did not antagonize the stress-induced increases in the concentrations of neuroactive steroids in brain or plasma. These results suggest that the marked antistress action of PVG is mediated by antagonizing the effects of stress on GABA(A) receptor function and CRF concentrations in the brain, but not by altering the stress-induced increase in neurosteroid concentrations.

Adrenalectomy↗

PubMed1999

Inhibin B levels in azoospermic subjects with cytologically characterized testicular pathology.

BACKGROUND AND OBJECTIVE: Inhibin B, a heterodimeric glycoprotein of gonadal origin, is the most important circulating form of inhibin in human males and an inverse relationship between inhibin B and FSH plasma levels was been recently observed. Azoospermia represents the end-point of different kinds of testicular damage, ranging from a normal spermatogenic pattern (obstructive forms) to the complete absence of germ cells (Sertoli Cell Only Syndrome, SCOS). Furthermore, azoospermia may be related to maturational disturbances at different levels (spermatogonial, spermatocytic, spermatidic). To better define the relationship between testicular damage and inhibin levels and to evaluate the diagnostic value of this hormone in the management of subjects with azoospermia, we performed specific inhibin B assays in a group of azoospermic subjects affected by different kinds of testicular pathology. PATIENTS: Eighty-nine azoospermic men were studied by testicular ultrasound examination, fine needle aspiration of the testes and hormonal parameters (FSH, LH and testosterone, inhibin B). Thirty normozoospermic subjects were considered as controls for seminal and hormonal parameters. DESIGN AND RESULTS: On the basis of cytological analysis five different testicular appearences were identified in azoospermic patients: (i) Sertoli cell only syndrome (SCOS); (ii) Severe hypospermatogenesis; (iii) Spermatogonial and/or spermatocytic arrest; (iv) Spermatidic arrest; (v) Normal germ line (obstructive forms). No difference in LH and testosterone levels was found among the different groups. A significant negative correlation was present between inhibin B and FSH both in azoospermic men (r = - 0.503, P < 0.0001) and normozoospermic controls (r = -0.361, P < 0.05). Groups characterized by obstructive azoospermia and spermatidic arrest showed inhibin B concentrations similar to normozoospermic subjects (130.7 +/- 73.5, 160.3 +/- 35.1 and 148.5 +/- 46.8 ng/l, respectively), while groups characterized by SCOS, severe hypospermatogenesis and spermatogonial and/or spermatocytic arrest showed mean inhibin B concentrations significantly lower than controls (56.5 +/- 56.0, 57.9 +/- 31.2; 48.9 +/- 16.7 ng/l, respectively). In the group of SCOS, 8 out of 42 subjects (19.0%) showed inhibin B concentrations within the normal range despite high FSH levels. CONCLUSIONS: This study demonstrated that, in humans, spermatids play an important role in the mechanism regulating inhibin B secretion by Sertoli cells. The significance of this hormone as a diagnostic parameter in azoospermic patients does not seem to be specific because it does not permit discrimination between obstructive forms or spermatidic arrest. Furthermore, despite an evident clinical, cytological and hormonal pattern for SCOS, inhibin B levels are normal in some of these patients. The significance of this latter result remains to be elucidated.

Adult↗

PubMed1999

Polycystic ovary syndrome: it is always bilateral?

OBJECTIVE: To evaluate whether patients with unilateral polycystic ovary showed different ovarian and uterine blood flow from those with bilateral polycystic ovaries, and to investigate whether there was a correlation between the ultrasonographic aspect and different hormonal parameters. DESIGN: An observational study. SUBJECTS: Sixteen patients with unilateral polycystic ovary and twenty patients with bilateral polycystic ovaries underwent clinical, biochemical, gray-scale and color Doppler ultrasonographic evaluation. METHODS: The following parameters were evaluated: hormonal (luteinizing hormone (LH), follicle stimulating hormone (FSH), LH/FSH concentration ratio, estradiol, prolactin, androstenedione, testosterone), clinical (body mass index, Ferriman-Gallwey score), ultrasonographic (ovarian volume, number and distribution of subcapsular follicles, stromal score) and Doppler (uterine artery and intraparenchymal vessel pulsatility index, ovarian stromal vascularization), in oligomenorrheic patients in the early follicular phase (cycle days 3-5) or in amenorrheic patients at random. RESULTS: Significantly higher androstenedione plasma levels and LH/FSH concentration ratios were observed in bilateral polycystic ovaries. In unilateral polycystic ovaries, gray-scale and color Doppler ultrasonography showed different features in the affected and the unaffected ovary, similar to the appearance of a polycystic and normal ovary, respectively. CONCLUSION: Polycystic ovary syndrome does not predetermine a single ultrasonographic and Doppler pattern.

Adolescent↗

PubMed1999

Endocrine, neuroendocrine and behavioral effects of oral dehydroepiandrosterone sulfate supplementation in postmenopausal women.

Aging in women and men is characterized by a progressive decline of circulating dehydroepiandrosterone (DHEA) levels and its sulfate ester (DHEAS). The improvement of wellbeing described in postmenopausal women treated with DHEA suggests that this steroid may exert specific actions on the central nervous system (CNS). The postmenopausal period is associated with several neuroendocrine modifications. The decrease of circulating levels of beta-endorphin is considered a hormonal marker of those changes. The aim of the present study was to investigate neuroendocrine and behavioral effects of three months of DHEAS supplementation in postmenopausal women. Postmenopausal women (n = 22) were divided in three groups: the first group was treated with oral DHEAS (n = 8) (50 mg/day), the second treated with the same dose of oral DHEAS + transdermal estradiol (n = 8) (DHEAS) 50 mg/day, estradiol 50 micrograms/patch) and the third with transdermal estradiol alone (n = 6) (50 micrograms/day). Before and after 1, 2 and 3 months of therapy, the following circulating steroid and protein hormone levels were evaluated: DHEA, DHEAS, androstenedione, testosterone, estrone, estradiol, 17-hydroxyprogesterone, sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH), luteinizing hormone (LH), beta-endorphin, growth hormone (GH) and cortisol, and a Kupperman score was performed. Before and after treatments, plasma beta-endorphin levels were evaluated in response to three neuroendocrine tests: (a) clonidine, an alpha 2-presynaptic adrenergic agonist (1.25 mg i.v.) (b) naloxone, an opioid receptor antagonist (4 mg i.v.) and (c) fluoxetine, a serotonin selective reuptake inhibitor (30 mg p.o.). In both groups of women treated with DHEAS, mean basal serum DHEA, DHEAS, androstenedione, and testosterone levels significantly increased after treatment, while no changes were shown in the group receiving estradiol alone. Serum estradiol, estrone, GH and plasma beta-endorphin levels significantly increased progressively for the three months of treatment, with higher levels for estrone and estradiol in subjects receiving estradiol alone or plus DHEAS. Serum SHBG, cortisol, and 17-hydroxyprogesterone did not show significant variations under any treatment. Serum LH and FSH levels showed a significant decrease in groups treated with estradiol alone or plus DHEAS at the second and third months. The Kupperman score showed that all treatments were associated with similar and progressive improvement. Before therapy clonidine, naloxone and fluoxetine stimuli failed to modify circulating beta-endorphin levels. After each of the treatments, the beta-endorphin response was completely restored and was similar, independent of the kind of therapy. Restoration of the beta-endorphin response to specific stimuli suggests that DHEAS and/or its active metabolites modulates the neuroendocrine control of pituitary beta-endorphin secretion, which may support the therapeutic efficacy of the DHEAS on behavioral symptoms.

Administration, Oral↗

PubMed1999

Adjuvant L-arginine treatment for in-vitro fertilization in poor responder patients.

The objective of the present study was prospectively and randomly to evaluate the role of L-arginine in improving uterine and follicular Doppler flow and in improving ovarian response to gonadotrophin in poor responder women. A total of 34 patients undergoing assisted reproduction was divided in two groups according to different ovarian stimulation protocols: (i) flare-up gonadotrophin-releasing hormone analogue (GnRHa) plus elevated pure follicle stimulating hormone (pFSH) (n = 17); and (ii) flare-up GnRHa plus elevated pFSH plus oral L-arginine (n = 17). During the ovarian stimulation regimen, the patients were submitted to hormonal (oestradiol and growth hormone), ultrasonographic (follicular number and diameter, endometrial thickness) and Doppler (uterine and perifollicular arteries) evaluations. Furthermore, the plasma and follicular fluid concentrations of arginine, citrulline, nitrite/nitrate (NO2-/NO3-), and insulin-like growth factor-1 (IGF-1) were assayed. All 34 patients completed the study. In the L-arginine treated group a lower cancellation rate, an increased number of oocytes collected, and embryos transferred were observed. In the same group, increased plasma and follicular fluid concentrations of arginine, citrulline, NO2-/NO3-, and IGF-1 was observed. Significant Doppler flow improvement was obtained in the L-arginine supplemented group. Three pregnancies were registered in these patients. No pregnancies were observed in the other group. It was concluded that oral L-arginine supplementation in poor responder patients may improve ovarian response, endometrial receptivity and pregnancy rate.

Adult↗

PubMed1999

Inhibins: paracrine and endocrine effects in female reproductive function.

A great deal of new information has arisen in the past 2 years concerning the physiology of inhibins and their clinical relevance in reproductive medicine. It is now recognized that the two inhibin isoforms, inhibin A and inhibin B, are produced by the gonads in the course of gamete maturation and have different patterns of secretion during the menstrual cycle. Inhibins are also produced by the placenta and fetal membranes and may be involved in physiological adaptation of pregnancy. Clinically, inhibins may serve as sensitive tumor markers in postmenopausal women, or as useful tools for evaluating ovarian reserve in infertile women; they may also be used in the diagnosis of materno-fetal disorders.

Endocrine Glands↗

PubMed1999

Activin A, inhibin A, inhibin B and parturition: changes of maternal and cord serum levels according to the mode of delivery.

OBJECTIVE: To evaluate whether activin A, inhibin A, and inhibin B levels in maternal and umbilical artery serum change according to the mode of delivery. DESIGN: Maternal and cord blood specimens were collected at term after spontaneous labour and vaginal delivery, or elective caesarean section. SETTING: Universities of Pisa, Turin, Naples and Udine. POPULATION: Forty-two healthy pregnant women, at 3940 weeks of gestation, divided into two subgroups: group 1 vaginal delivery (n = 21), were delivered of 10 female and 11 male infants; group 2 elective caesarean section (n = 21), were delivered of 11 female and 10 male infants. MAIN OUTCOME MEASURES: Serum activin A, inhibin A, inhibin B concentrations in maternal and umbilical cord blood. RESULTS: At vaginal delivery, maternal serum inhibin A and inhibin B levels were lower and activin A levels higher than at elective caesarean section. Maternal levels of activin A, inhibin A and inhibin B were constantly higher than in umbilical arterial blood, independent of the mode of delivery. No significant difference was observed in umbilical arterial serum levels of the three proteins between the two modes of delivery. Umbilical arterial serum activin A and inhibin A concentrations did not show a significant difference between male and female infants in either vaginal or caesarean section, but male infants showed inhibin B levels significantly higher than female, independent of the mode of delivery. CONCLUSIONS: In the presence of active labour, the human placenta secretes larger amounts of activin A and lesser amounts of inhibin A and inhibin B into the maternal circulation. Inhibin-related proteins in the fetal circulation do not show differences according to the mode of delivery, suggesting that they have a different method of production or metabolic rate compared with maternal activin and inhibins.

Activins↗

PubMed1999

Changes of serum allopregnanolone levels in the first 2 years of life and during pubertal development.

Allopregnanolone is the best characterized among neurosteroids, and its role in the control of neuroendocrine axes has attracted increasing interest recently. However, there is no available information about circulating levels of allopregnanolone during infancy, childhood and puberty. We studied two groups of children: 1) those aged between 0 and 2 y (n = 72), and 2) those aged between 6 and 18 y, at different Tanner's stages (n = 82). In each of these patients, serum allopregnanolone, progesterone, cortisol, and dehydroepiandrosterone levels were evaluated after informed consent; allopregnanolone was measured by RIA after acid extraction on cartridge. There was no significant variation of serum allopregnanolone levels either in male and female children during the first 2 y of life. Furthermore, although serum dehydroepiandrosterone levels showed a significant decrease, inversely correlated with age of the children (p < 0.01), serum cortisol and progesterone levels showed a significant age-related increase during the first 2 y of life. Cortisol and allopregnanolone levels were positively correlated (p < 0.01). During puberty, we observed a progressive increase in serum allopregnanolone levels in both boys and in girls, which were higher at Tanner' s stage IV-V (0.7+/-0.01 nM; mean +/- SEM) than at stages I-II (0.32+/-0.02 nM; p < 0.01); mean levels were significantly higher at puberty than in the first 2 y of life (p < 0.01). Furthermore, during puberty, serum progesterone and dehydroepiandrosterone levels also increased progressively with age in both boys and girls. Allopregnanolone and dehydroepiandrosterone levels were positively correlated throughout puberty. The present results indicate that serum allopregnanolone levels do not change during the first 2 y of life but increase during pubertal development, suggesting that this steroid may be involved in the adaptive neuroendocrine mechanisms related to puberty.

Adolescent↗

PubMed1999

Urocortin stimulates placental adrenocorticotropin and prostaglandin release and myometrial contractility in vitro.

Urocortin is a new member of the CRF family. Multiple biological effects for urocortin have been shown in rats and in some in vitro models, showing a modulatory role in hormonal and behavioral functions. Human placenta expresses urocortin, but no information is available on the possible local biological actions. The aim of the present study was to evaluate the effect of urocortin on placental ACTH and prostaglandin (PG) secretion, as well as on myometrial contractility. Various in vitro models were used. For investigating the effect of urocortin on ACTH release, primary cultures of human trophoblast cells were used. Culture media, collected before and after 3 h exposure to different doses of urocortin and ACTH, were measured by RIA. Trophoblast tissue explants were incubated for 24 h in the presence of increasing doses of urocortin, and prostaglandin E2 (PGE2) levels were measured by RIA. Strips of myometrial tissue were incubated in an organ bath and connected to an isometric smooth-muscle transducer in the presence of urocortin, with or without prostaglandin F2alpha (PGF2a). In all these experiments, the effect of astressin (a CRF receptor antagonist) on urocortin-induced actions and the effect of equimolar doses of CRF were evaluated. A dose-related increase of trophoblast ACTH or PGE2 was induced by urocortin, whereas astressin inhibited urocortin-stimulated ACTH or PGE2 release. Equimolar doses of CRF showed a similar effect on both ACTH and PGE2. Urocortin increased PGF2alpha-induced myometrial contractility, and this effect was completely abolished by the addition of astressin. The present study showed that human urocortin stimulates placental secretion of ACTH and PGE2, and modulates myometrial contractility, suggesting a role for this peptide in placental and intrauterine CRF pathways.

Adrenocorticotropic Hormone↗

PubMed1999

Human umbilical vein endothelial cells: a new source and potential target for corticotropin-releasing factor.

Corticotropin-releasing factor (CRF) plays a key role in the modulation of fetal-placental unit function during human pregnancy. CRF has a potent vasoactive action on fetal-placental circulation. As products secreted from endothelial cells affect vascular wall reactivity, we investigated whether cultured human umbilical vein endothelial cells (HUVEC) may represent a source and a target for CRF. With RT-PCR we showed that HUVEC express CRF and CRF receptor type 2 messenger ribonucleic acids. Cultured HUVEC also released CRF peptide in a time-dependent way, and the CRF release was differently regulated by various molecules. Dexamethasone decreased CRF release, whereas progesterone and 17beta-estradiol markedly increased it. Forskolin and PGF2alpha were potent stimulators of CRF release from HUVEC. Among the peptides, CRF secretion was stimulated by interleukin-1beta and by endothelin-1. Our study shows for the first time that HUVEC express CRF messenger ribonucleic acid and peptide as well as the CRF R2 gene, and that CRF release is differentially regulated by several distinct molecules. We here propose that CRF has a role in the regulation of the fetal-placental circulation.

Cells, Cultured↗

PubMed1999

Human mammary gland and breast carcinoma contain immunoreactive inhibin/activin subunits: evidence for a secretion into cystic fluid.

OBJECTIVE: Inhibins and activins are members of the transforming growth factor beta superfamily and are known to modulate the growth and differentiation of several cell types. The present study investigated the localization of inhibin and activin subunits in human normal and pathological breast tissues. DESIGN: A cross-sectional study comparing the expression of inhibin/activin subunits alpha, betaA and betaB in surgical specimens from women undergoing reductive mammoplasty (classified, according to the phase of the menstrual cycle, as follicular, luteal, or postmenopausal), and patients submitted to lumpectomy for fibrocystic disease, benign (intraductal papilloma, adenomyoepithelioma, and hamartoma) or malignant breast neoplams (intraductal, intralobular, and invasive carcinoma). METHODS: Immunohistochemistry was used to localize inhibin alpha and activin betaA and betaB subunits in the cytoplasm of epithelial cells of mammary glands. Dimeric activin A, inhibin A and inhibin B were measured by specific two-site enzyme immunoassay in the cystic fluid collected from patients with fibrocystic disease. RESULTS: An intense staining for the alpha inhibin subunit and a mild staining for betaA and betaB subunits were present in samples obtained from normal breast tissue regardless of menstrual cycle phase, and in fibrocystic disease and benign neoplasms. Carcinoma cells stained weakly to moderately for alpha subunit and were negative for betaA and betaB subunits. Fibrocystic disease was associated with absence of betaA subunit expression in normal epithelial cells and intense staining for all subunits in the apocrine cells. Immunoreactive inhibin A, inhibin B, and activin A were also present in cystic fluid, suggesting a local secretion of these proteins. CONCLUSION: These data suggest a local expression and secretion of inhibin and activin in human normal, fibrocystic disease and neoplastic breast tissues. The low expression of these proteins may facilitate abnormal cell proliferation in breast carcinoma.

Activins↗

PubMed1999

Raloxifene analog LY 117018 effects on central and peripheral beta-endorphin.

Raloxifene is a selective estrogen receptor modulator with a benzothiophene structure, that exerts an estrogen-like action on some target tissues and an anti-estrogenic action on the uterus and breasts. A limited number of data are available on the effect of raloxifene on neuroendocrine function. Since beta-endorphin (beta-EP) is considered a marker of neuroendocrine function, the aim of the present study was to evaluate the effects of a 14 day treatment with a raloxifene analog, LY 117018, on beta-EP content in the hypothalamus, hippocampus, anterior and neuro-intermediate pituitary lobe, and in the plasma of fertile and ovariectomized (ovx) rats. The effect of LY 117018 in ovx rats was compared to that of 17 beta-estradiol. beta-EP contents were measured by a specific radioimmunoassay. While ovariectomy determined a significant decrease in beta-EP levels in the anterior and neurointermediate pituitary lobe and plasma (p < 0.01), no changes of beta-EP content in the hypothalamus and hippocampus were found. The administration of 17 beta-estradiol or LY 117018 in ovx rats significantly increased beta-EP concentration in the anterior and neurointermediate pituitary lobe, in the hypothalamus and plasma (p < 0.01), though they did not significantly modify hippocampal beta-EP content. When LY 117018 was administered together with 17 beta-estradiol in ovx animals, a clear anti-estrogenic effect in all organs and in plasma was observed, resulting in significantly lower beta-EP content with respect to the group treated with 17 beta-estradiol alone (p < 0.01). The chronic administration of LY 117018 in fertile rats significantly decreased beta-EP content in the anterior pituitary, hippocampus and plasma (p < 0.01), while it increased beta-EP hypothalamic content and did not change beta-EP content in the neurointermediate lobe. In conclusion, raloxifene analog LY 117018 has an estrogen-like action on neuroendocrine opiatergic pathways when administered alone in ovx rats, while it exerts an anti-estrogen effect in fertile or in ovx rats treated with 17 beta-estradiol.

Animals↗

PubMed1998

Neuroendocrine effect of a short-term treatment with DHEA in postmenopausal women.

OBJECTIVES: A progressive decline of plasma dehydroepiandrosterone (DHEA) levels occurs in women during aging related to the reduction of adrenocortical secretion. A specific action of DHEA on the central nervous system (CNS) is suggested by the improvement of psychological and physical well-being in postmenopausal women after DHEA supplementation. The aim of the present study was to investigate the neuroendocrine effects of short-term DHEA supplementation in postmenopausal women, evaluating changes of plasma beta-endorphin (beta-EP) and growth hormone (GH) before and after oral DHEA (100 mg/day) for 7 days in postmenopausal women (n = 6). METHODS: Before and after 7 days of DHEA supplementation, postmenopausal women underwent a neuroendocrine test with clonidine, an alpha 2 presinaptic agonist for adrenergic system (1.25 mg i.v.). Basal plasma DHEA, androstenedione (A), testosterone (T), estrone (E1) and estradiol (E2) levels were evaluated before and after treatment, while plasma beta-EP and GH levels were measured before and 15, 30, 45, 60 and 90 min after clonidine injection. RESULTS: Basal plasma beta-EP and GH levels did not show a significant difference before and after short-term DHEA administration, while circulating A, T, E1 and E2 significantly increased after treatment. The clonidine test induced a significant increase of plasma beta-EP levels in women after receiving DHEA supplementation but not before; conversely, plasma GM levels increased both before and after treatment. CONCLUSIONS: The present study indicates that short-term DHEA supplementation in postmenopausal women is able to restore the impaired response of pituitary beta-EP to clonidine, an alpha 2 presinaptic agonist. According to these data it is possible to hypothesize that DHEA could play a role in the psychological and physical well-being of postmenopausal women acting via a restoration of neuroendocrine control of antero-pituitary beta-EP secretion.

Administration, Oral↗

PubMed1998

Peritoneal fluid levels of immunoreactive corticotropin-releasing factor (CRF) and CRF-binding protein (CRF-BP) in healthy and endometriosic women.

Corticotropin-releasing factor (CRF) is a 41-amino acid neurohormone involved in the neuroendocrine response to stress, also playing a role in cell-mediated immune functions and in inflammation. In the light of recent evidence showing an association between endometriosis and altered cellular immunity factors, the present study investigates immunoreactive (ir) CRF in the peritoneal fluid of healthy women, and in patients with pelvic adhesions and endometriosis. In addition, peritoneal fluid concentrations of CRF-binding protein (CRF-BP), a 37-kDA protein of 322 amino acids able to modulate central and peripheral CRF functions, were evaluated. Peritoneal fluid samples (n = 35) were collected from healthy women (n = 12), from patients with intrapelvic adhesions (n = 8), and from women with endometriosis (n = 15). In the control group a specimen of blood was collected. Peritoneal fluid and plasma CRF levels were measured by a two-site immunoradiometric assay (IRMA), and CRF-BP levels were measured by a specific radioimmunoassay (RIA). CRF and CRF-BP levels in peritoneal fluid were lower than plasma values, and independent of the phase of the menstrual cycle: in particular, in healthy women there was no significant difference between peritoneal fluid and plasma CRF-BP levels during two phases of the menstrual cycle. Peritoneal fluid levels of CRF and CRF-BP were similar in healthy patients and women with pelvic adhesions or with endometriosis, and when patients with adhesions or with endometriosis were considered as single group, no difference in CRF and CRF-BP levels was noted in comparison to the control group. In patients with endometriosis, no significant differences in peritoneal fluid CRF or CRF-BP levels were recorded, although in patients with stage 2 and stage 3 of the disease peritoneal fluid CRF-BP levels were higher than in healthy patients or in those with a lower grade of the disease. These results suggest that the peritoneal concentration of these hormones may reflect the circulating levels: the absence of any significative variations in peritoneal fluid CRF levels according to the degree of the endometriosis, suggests a limited role of CRF in the immunological changes related to the disease

Adult↗

PubMed1998

Serum levels of dimeric activin A are not a marker of placental tumors in the course of chemotherapy.

The aim of the present study was to evaluate whether serum activin A levels may represent, in addition to intact human chorionic gonadotrophin, a marker of placental tumors in the course of chemotherapy. Serial determinations of serum levels of activin A were performed in women with hydatidiform mole (n = 2) or choriocarcinoma (n = 3). Serum activin A levels were measured by using a new specific two-site enzyme immunoassay (EIA) able to detect the dimeric, bioactive, form of the protein. Serum hCG concentrations in samples taken after evacuation before starting chemotherapy were greater than in healthy non-pregnant women (p < 0.001) and decreased following chemotherapy. Activin A serum levels in women with trophoblastic disease after evacuation were significantly higher than in healthy non-pregnant women, but chemotherapy did not significantly affect circulating levels. No correlation was found between changes of activin A and total hCG serum concentrations. Measurement of activin A by ELISA in presence of persistent molar tumor does not seem to be of clinical interest in the follow-up of disease, resulting activin A concentrations after chemotherapy in the range of values occurring throughout menstrual cycle. These evidences suggest that hCG determination is still the most valid for follow-up, because only intact hCG could detect the persistence of trophoblast tissue.

Activins↗