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Biomedical subjects

F Petraglia

Publications and source records attributed to F Petraglia.

At least 145 records · Page 8Linked to original sources
PubMed1998

High levels of serum allopregnanolone in women with premature ovarian failure.

The endocrine characteristics of patients with premature ovarian failure (POF) have not been fully elucidated. The aim of the present study was to evaluate whether steroidogenic activity in women with POF is different with respect to fertile and postmenopausal subjects. In particular, circulating levels of allopregnanolone, a neuroactive steroid involved in modulation of reproductive function in rats, have been evaluated and correlated with serum levels of delta 4 precursor (dehydroepiandrosterone sulfate (DHEAS)), delta 5 intermediates (androstenedione, 17-hydroxyprogesterone (17-OHP), progesterone) and final products (estradiol and testosterone) of androgens. Levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and sex hormone binding globulin (SHBG) were also determined. In all cases specific radioimmunological assays were used. Women with POF showed statistically significantly lower concentrations of 17-OHP, androstenedione and testosterone when compared to fertile controls, while no differences were found between women with POF and postmenopausal women. Serum DHEAS levels were similar in POF patients and in fertile controls and higher with respect to postmenopausal women. Serum allopregnanolone levels were significantly higher in women with POF than in postmenopausal and in fertile women. A significant inverse correlation between allopregnanolone levels and menopausal age in patients with POF was observed while no significant correlation was found between allopregnanolone and progesterone, androstenedione, 17-OHP and testosterone levels. In conclusion, allopregnanolone is scarcely influenced by the reduction of ovarian and adrenal activity observed in POF.

Adult↗
PubMed1998

Beta-endorphin response to oral glucose tolerance test in obese and non-obese pre- and postmenopausal women.

Beta-endorphin (beta-EP) is a neuropeptide involved in several brain functions, regulating the reproductive axis and behavioral changes. Estrogens play a modulatory role on circulating levels of beta-EP in women. Previous clinical studies have demonstrated high plasma beta-EP levels in obese subjects and increased beta-EP release after an oral glucose tolerance test (OGTT) in normal or obese women. The aim of the present study was to evaluate plasma beta-endorphin levels in response to an OGTT in pre- and postmenopausal obese and non-obese women, in order to investigate if the decrease in gonadal steroid levels at menopause could modify in a different manner the control of beta-endorphin release in response to glucose administration. A group of 24 normal women (age range 45-55 years) were included in the study. The patients were subdivided in four groups of six subjects each: group A, premenopausal women with body mass index (BMI) < 25 (control); group B, premenopausal women with BMI > 25 (obese); group C, post-menopausal women with BMI < 25 (control); group D, postmenopausal women with BMI > 25 (obese). All women were studied between 8.30 and 9.00 am, after overnight fasting, and underwent an OGTT. In obese premenopausal women, basal plasma beta-EP levels were significantly higher than in non-obese women (p < 0.01). In postmenopausal women, regardless of body weight, low basal plasma beta-EP levels were found. A significant increase in plasma beta-EP levels, at 30 and 60 minutes after oral glucose ingestion, was shown in control premenopausal women. No significant modifications to OGTT were shown in plasma beta-EP levels in the other three groups of women. In conclusion, while in premenopausal women the response of plasma beta-EP levels to OGTT is maintained, in postmenopause there is a lack of response to OGTT. This suggests that beta-EP release is dependent upon gonadal steroids, while it is only in part influenced by body weight.

Adult↗
PubMed1998

Contraception as prevention and therapy: sex steroids and the brain.

The brain is one of the specific target tissues for sex steroid hormones. Estrogens, progestins and androgens are able to induce several effects in brain areas of the central nervous system (CNS), through the binding with specific receptors. Specific receptors for gonadal steroids have been identified in the amygdala, hippocampus, basal forebrain cortex, cerebellum, locus ceruleus, midbrain rafe nuclei, glial cells, pituitary gland, hypothalamus and central gray matter. At the hypothalamic level, the principal target for sex steroids is those neurons producing the pulsatile release of the gonadotropin releasing hormone (GnRH), localized in the mediobasal hypothalamus and the arcuate nucleus. The GnRH release depends on the complex and co-ordinated interrelationships among gonadal steroids, pituitary gonadotropins and neuroactive transmitters, such as the noradrenaline, dopamine, opioid peptides (beta-endorphin), acetylcholine, serotonin, gamma-aminobutyrric acid, corticotropin releasing hormone and neuropeptide Y. The interplay of these control mechanisms is governed by peripheral feedback signals; as well as the input from higher brain centers they may modify the GnRH secretion. The anterior pituitary lobe is the best known target tissue for endogenous or exogenous sex steroid hormones, because it is possible to detect luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in blood, as the expression of the pituitary cells' activity. The synthesis and release of FSH and LH by the gonadotropic cells depend upon the peripheral control of gonadal hormones and the GnRH hypothalamic release. In summary, during a woman's reproductive life, the interaction between neurotransmitters, neuropeptides and gonadal hormones modulates the hypothalamo-pituitary-gonadal axis by acting selectively on the synthesis and release of GnRH and of pituitary gonadotropic hormones. The increased use of oral contraceptives in the last 30 years and, in general, of sex steroid hormone derivative therapies, has led to the study of the biochemical and metabolic properties of the different progestin molecules available in hormonal therapies by focusing attention on the interactions between estrogens and progestins in the modulation of the hypothalamo-pituitary-gonadal axis. The different kinds of estrogen and progestin molecules used in oral contraceptives inhibit the ovulatory process and may interfere with other sex steroid hormone receptors, thus exerting multiple effects in each target tissue.

Androgens↗
PubMed1997

Neuroendocrine effects of different estradiol-progestin regimens in postmenopausal women.

OBJECTIVE: New regimens and routes of administration of hormonal replacement therapy (HRT) in climateric women are becoming available. Since there is no information on the neuroendocrine effects of sequential combined treatment with 17 beta-estradiol and a progestin, the present study evaluated the neuroendocrine, clinical vasomotor and psychological changes before and after different sequential combined HRT regimens (17 beta-estradiol plus nomegestrol acetate, or cyproterone acetate, or vaginal progesterone). Vasomotor and behavioral effects were evaluated by using the Kupperman score, while changes in plasma endorphin (beta-END) levels were used as marker of neuroendocrine effects. METHODS: Postmenopausal women (n = 30) were randomly divided into three groups (ten women for each group); all women received continuous 17 beta-estradiol (50 mg, transdermal) and each group was sequentially treated with different progestins for 12 days/month: group A, cyproterone acetate (5 mg p.o.); group B, nomegestrol acetate (5 mg p.o.); and group C, progesterone (100 mg, vaginal cream). A group of healthy fertile women (n = 8) served as control. Before and after 6 months of HRT, postmenopausal women underwent an evaluation of subjective Kupperman score and two neuroendocrine tests: (a) naloxone (4 mg i.v.) and (b) clonidine (1.25 mg i.v.). Plasma beta-END levels were measured before and at 15, 30, 45, 60 and 90 min after drug injection. Control women were studied by administering the two neuroendocrine tests only once. RESULTS: Postmenopausal women before HRT showed a pathological Kupperman and no changes of plasma beta-END levels in response to the clonidine and naloxone tests score. On the contrary the increase was significant in healthy women. In each of the three groups of treated women both naloxone and clonidine tests induced a significant increase in plasma beta-END levels (P < 0.01). After 6 months of HRT, an improvement of vasomotor and psychological symptoms was shown by a decrease of Kupperman score. CONCLUSIONS: The present study indicates that sequential treatment with transdermal 17 beta-estradiol and progestin, no matter which progestin was used, restores the beta-END release, improves vasomotor and psychological symptoms.

Administration, Cutaneous↗
PubMed1997

A long-term treatment with gonadotropin-releasing hormone agonist plus a low-dose oral contraceptive improves the recovery of the ovulatory function in patients with polycystic ovary syndrome.

OBJECTIVE: To evaluate the hormonal and clinical follow-up after the suspension of a longterm therapy with GnRH-agonist (GnRH-a) plus oral contraceptive (OC) in comparison to OC alone in patients with polycystic ovary syndrome (PCOS). DESIGN: Hormonal (plasma LH, FSH, sex steroid levels) and clinical (Ferriman-Gallwey score and ultrasound) parameters were monitored at various moments during the 6 months of treatment and during the 6 months after treatment suspension. SETTING: Physiopathology of Human Reproduction, University of Modena, Italy. PATIENT(S): Thirty patients with PCOS were enrolled and randomly subdivided in two groups of 15 each. INTERVENTION(S): Group A was treated with 3.75 mg IM GnRH-a plus OC. Group B was treated only with OC. RESULT(S): Both therapeutical regimens were effective in reducing androgenic milieu, Ferriman-Gallwey score, and ovarian volume within the 6th month of treatment. However, only patients treated with GnRH-a + OC showed a normal LH:FSH ratio, adequate plasma E2 and P levels, and ovulatory cycles during the 6 months of the after treatment follow-up. Patients treated with OC alone showed no beneficial effect after the 3rd month of the follow-up. CONCLUSION(S): These data support the evidence of a higher efficacy of the combined regimen (GnRH-a + OC) than OC alone in the treatment of patients with PCOS. In addition, the former regimen is associated with recovery of normal ovulatory cycles.

Androgens↗
PubMed1997

Inhibin, activin and follistatin in the human placenta--a new family of regulatory proteins.

The family of inhibin-related proteins has been investigated extensively in the last decade. It is composed of three members: inhibin, activin and follistatin. Inhibin and activin are chemically related, while follistatin acts as an activin-binding protein. Initially identified as regulators of pituitary follice stimulating hormone (FSH) secretion, inhibin, activin and follistatin have more recently been characterized as growth factors, embryo modulators and immune factors. Human placenta, amnion, chorion and maternal decidua express mRNAs for inhibin, activin and follistatin, and the presence of both immunoreactive and bioactive proteins has been demonstrated. The proteins are present in maternal and fetal circulation, and are measurable in amniotic fluid with changes related to gestational age and to the occurrence of gestational diseases. Various biological actions have been described in embryo and intrauterine tissues, which suggest a role for these proteins in the development of the gestational unit. However, several questions remain to be elucidated. The chemical forms of inhibin, activin and follistatin produced by human placenta and the mechanisms involved in the regulation of their secretion are largely unknown. The nature of the receptors for these proteins and the physiological implications of receptor activation have not yet been elucidated and this will require further investigation.

Activins↗
PubMed1997

Difference of LH and FSH secretory characteristics and degree of concordance between postmenopausal and aging women.

OBJECTIVE: Several neuroendocrine changes occur at menopause and the present study aimed to verify whether the episodic release and the degree of concordance of LH and FSH differs between early and late postmenopausal women. METHODS: Postmenopausal (n = 32) women were enrolled and subdivided in two groups according to the menopausal age: group A (n = 22), patients with more than 2 but less than 5 years from the occurrence of menopause; group B (n = 10), patients with more than 15 years from the occurrence of menopause. All subjects underwent a pulsatility study (4 h, sampling every 10 min) to assess LH and FSH secretory characteristics and their degree of concordance. RESULTS: Mean +/- S.E.M. LH and FSH plasma levels were lower in older women than in postmenopausal women (P < 0.01). The secretory pattern was pulsatile for both LH and FSH and their pulse amplitudes were lower in aged women (P < 0.01). No significant difference was observed in terms of pulse frequency between the two groups. LH and FSH pulses were co-secreted in early postmenopausal women while such a concordance was lost in older women. CONCLUSIONS: Late postmenopause is characterized by the reduction of the amplitude of gonadotropin pulses in comparison to women in early postmenopause, reflecting changes of both GnRH secretion and/or pituitary responsiveness to GnRH. The age-related loss of concordance between LH and FSH pulses discloses the existence of a hidden FSH stimulating system, which drives FSH episodic release independently and more promptly than GnRH.

Aging↗
PubMed1997

Modulatory effects of a synthetic steroid (tibolone) and estradiol on spontaneous and GH-RH-induced GH secretion in postmenopausal women.

OBJECTIVE: Since hormonal replacement therapy (HRT) affects plasma GH levels, the present study aimed to verify the effect of tibolone, a synthetic steroid, on modulating spontaneous and growth hormone releasing hormone (GH-RH) induced GH secretion. METHODS: Postmenopausal women (n = 30) were enrolled and randomly subdivided in three groups (n = 10 each group): (1) treated with transdermal estradiol (50 micrograms) (Dermestrill, Rottapharm, Monza, Italy) biweekly; (2) treated with transdermal estradiol (100 micrograms) (Dermestrill, Rottapharm, Monza, Italy) biweekly; (3) treated with tibolone 2.5 mg/day (Livial, Organon Italia, Rome, Italy). Patients underwent a GH-RH test (1 microgram/kg) and 15 of them underwent to a pulsatility study before and 5 weeks after treatment. RESULTS: Mean (+ S.E.M.) GH plasma levels increased in all patients after any type of HRT. GH response to GH-RH stimulation (expressed as maximal response to GH-RH or as delta value) was similar in the three groups while significant changes occurred in spontaneous pulsatile GH release. Tibolone and both dosages of transdermal estradiol significantly reduced GH pulse frequency and increased pulse amplitude. CONCLUSIONS: The reduced plasma GH levels observed during postmenopause are probably related to a reduced endogenous GH-RH and not to a reduced pituitary ability to respond to GH-RH. In addition tibolone, as well as transdermal estradiol, are effective in restoring the spontaneous GH episodic release.

Administration, Cutaneous↗
PubMed1997

Effects of sex steroid hormones on the neuroendocrine system.

Estrogen and progesterone are the most important ovarian steroid hormones regulating female fertility. They have a profound effect on the central nervous system. Target functions of sex steroids in the brain are: pituitary and hypothalamic hormone release, thermoregulatory and cardiocirculatory activities and behavior and mood changes. Furthermore, several studies have shown a correlation between brain neurotransmitters, neuropeptides and sex steroid hormones: they influence synthesis and release of norepinephrine, dopamine, serotonin, gonadotropin releasing hormone, beta-endorphin, corticotropin releasing factor and prolactin. Thus, oral hormone contraceptives inhibit the ovulatory process by blocking the activity of the hypothalamus-pituitary-gonadal axis. This inhibitory effect seems to be due to the action of both estrogens and progestins.

Contraceptives, Oral↗
PubMed1997

Colour Doppler changes and thromboxane production after ovarian stimulation with gonadotrophin-releasing hormone agonist.

The objective of this study was to evaluate the Doppler flow variations which occur following the use of different protocols of ovarian stimulation in an IVF programme, and to investigate the thromboxane production by cultured endometrial cells and its influence on embryo implantation. A total of 60 patients underwent three different ovarian stimulation protocols: long gonadotrophin-releasing hormone agonist (GnRH-a), short GnRH-a and no GnRH-a. Transvaginal ultrasonography and colour Doppler analysis were performed before and during the treatment. On the day that the Doppler examination took place, luteinizing hormone, follicle stimulating hormone, plasma oestradiol and thromboxane concentrations were assayed. On the day of oocyte retrieval, endometrial cells were collected and cultured, and their thromboxane production evaluated. No significant differences in hormonal, ultrasonographic or Doppler parameters were observed between the three groups. Ten out of 56 patients who had a successful embryo transfer became pregnant. In the group of pregnant women the pulsatility index values of both uterine and spiral arteries was lower than in non-pregnant patients, and was associated with significantly lower thromboxane concentrations from cultured endometrial cells. It is concluded that thromboxane plays a role in embryo implantation, and that Doppler flow analysis of uterine and spiral arteries in infertile patients may be important in the management of ovarian stimulation.

Adult↗
PubMed1997

Basic fibroblast growth factor messenger ribonucleic acid levels in human placentas from normal and pathological pregnancies.

This study was designed to determine whether basic fibroblast growth factor (bFGF) gene expression in human placenta varies as a function of gestational age and to evaluate whether bFGF synthesis might be altered in pathological pregnancies. Moreover, we also investigated whether human placental cells express the bFGF receptor gene. The presence of mRNA for bFGF and its receptor was demonstrated by reverse transcriptase-polymerase chain reaction (RT-PCR) performed on total RNA derived from human placental cells at different times of culture. Levels of bFGF mRNA were determined by competitive RT-PCR in human placental tissues collected at the beginning and at the end of pregnancy. Competitive RT-PCR was also employed to evaluate bFGF synthesis in term placentas derived from pregnancies complicated by diabetes. mRNA for both bFGF and its receptor were demonstrated in human placenta starting as early as 8 weeks of pregnancy. Values of bFGF mRNA were significantly higher in first trimester compared with term placentas. Term placentas derived from pregnancies associated with type I diabetes expressed levels of bFGF mRNA higher than those present in normal term placentas. These data demonstrate that bFGF and its receptor are synthesized in human placental cells throughout gestation. Moreover, bFGF gene expression is developmentally regulated. Finally, bFGF might also be partially responsible for the placental alterations observed in pregnancies complicated by diabetes.

Adrenal Cortex↗
PubMed1997

Endogenous estrogen and acetylcholine-induced vasodilation in normotensive women.

Acute exogenous estrogen administration enhances endothelial function in postmenopausal women. To evaluate the effect of endogenous estrogen on endothelium-dependent vasodilation, in 10 fertile normotensive women (age range 45 to 51 years) we studied the changes in forearm blood flow (strain-gauge plethysmography) induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, 1.5 micrograms.100 mL-1.min-1), an endothelium-dependent vasodilator, or sodium nitroprusside (1, 2, 4 micrograms.100 mL-1.min-1), an endothelium-independent vasodilator, in basal conditions and within 1 month after ovariectomy. As control subjects, 10 matched healthy women were also evaluated. In basal condition, vasodilation to acetylcholine and sodium nitroprusside was similar in patients and control subjects. Ovariectomy was followed by endogenous estrogen deprivation (from 71.6 +/- 31.3 to < 12 pg/mL) and was associated with a significant (P < .01) reduction in acetylcholine-induced vasodilation compared with baseline (maximum percent increase in forearm blood flow: baseline 568.2 +/- 47.1%; ovariectomy 309.5 +/- 37.4%); the response to sodium nitroprusside was unaffected by ovariectomy (maximum percent increase in forearm blood flow: baseline 526.4 +/- 36.5%; ovariectomy 454.7 +/- 47.2%; P = NS). In 6 of 10 patients, the study was repeated after 3 months of estrogen replacement therapy (17 beta-estradiol, 50 micrograms/d by transdermal patches). Exogenous estrogen restored acetylcholine-induced vasodilation (maximum percent increase in forearm blood flow: 548.9 +/- 43.1%; P < .01 versus ovariectomy), which was no longer different from baseline, whereas the response to sodium nitroprusside was not affected (maximum percent increase in forearm blood flow: 480.2 +/- 39.3%; P = NS). These results suggest a protective role of endogenous estrogen on endothelium-dependent vasodilation in the forearm vascular bed of normotensive women.

Acetylcholine↗
PubMed1997

Changes in amniotic fluid immunoreactive corticotropin-releasing factor (CRF) and CRF-binding protein levels in pregnant women at term and during labor.

Corticotropin-releasing factor (CRF)-binding protein (CRF-BP) modulates the activity of the hypothalamus-pituitary-adrenal axis during pregnancy, counteracting the actions of circulating or locally produced CRF. The aim of the present study was to evaluate CRF and CRF-BP levels in amniotic fluid of healthy pregnant women during the last 4 weeks of gestation and during spontaneous labor at term. A cross-sectional study was conducted on amniotic fluid collected from pregnant women (n = 68), subdivided into two groups: 1) not in labor (n = 31), and 2) in labor (n = 37). CRF-BP was measurable in all specimens of amniotic fluid, but at 37 weeks of pregnancy the concentration in amniotic fluid was lower (10-fold) than that in maternal plasma (P < 0.01). Pregnant women at 39 and 40 weeks gestation had amniotic fluid CRF-BP levels significantly lower than those at 37 weeks (P < 0.01), and pregnant in women in labor had significantly lower levels than women at term but not in labor (P < 0.01). CRF levels in amniotic fluid and plasma collected in women at 40 weeks gestation not in labor or in labor were significantly higher than those at 37 weeks (P < 0.01). During the last 4 weeks of gestation, amniotic fluid CRF levels in women not in labor did not significantly differ from those obtained at term labor. During the last weeks of pregnancy, amniotic fluid CRF-BP levels decrease and are inversely correlated to CRF levels. The decrease in amniotic fluid CRF-BP at term, augmenting the amount of free CRF, supports the hypothesis that labor is associated with significant changes in local autocrine and paracrine factors that may affect PG release and myometrial contractility, contributing to the mechanism of parturition.

Adult↗
PubMed1997

Expression of corticotropin-releasing hormone and its R1 receptor in human endometrial stromal cells.

Corticotropin-releasing hormone (CRH) is a hypothalamic neuropeptide that has been identified also in several peripheral tissues, including organs of the reproductive system. In man, CRH is synthesized and released by the gonads, the placenta, maternal decidua, and the epithelial endometrium. So far, CRH has been demonstrated in endometrial stromal cells only after decidualization. The aim of this study was to seek evidence of the production and secretion of CRH by endometrial stromal cells in different phases of the menstrual cycle and to look for gene expression of the recently identified CRH receptor R1. Total RNA was extracted from stromal cells monolayers established from endometrial samples collected during both proliferative and secretive phases. After reverse transcription, polymerase chain reaction (PCR) amplification was carried out using primers specific to CRH and to CRH receptor R1, resulting in the expected bands, respectively 233 bp for CRH and 274 bp for CRH-R1. The identity of the obtained CRH PCR product was confirmed by restriction enzyme analysis and by Southern blotting. Purification by high performance liquid chromatography (HPLC) of stromal cell culture medium revealed a major peak of CRH immunoreactivity coeluting with the standard CRH(1-41), thus indicating the secretion of the mature peptide. Our study demonstrates the synthesis and secretion of CRH by endometrial stromal cells at all phases of the menstrual cycle. We also demonstrate the expression of the CRH receptor R1 gene. It can be hypothesized that CRH contributes via autocrine/paracrine mechanisms to endometrial physiology.

Blotting, Southern↗