Serum allopregnanolone levels in pregnant women: changes during pregnancy, at delivery, and in hypertensive patients.

Allopregnanolone is a neuroactive steroid measurable in peripheral circulation. The aim of the present study was to investigate the presence and the possible changes in serum allopregnanolone and progesterone levels in pregnant women during gestation, at delivery, and in patients with chronic hypertension, with or without superimposed preeclampsia. We also evaluated allopregnanolone in cord blood. Three groups of pregnant women were studied: 1) healthy controls followed longitudinally throughout gestation (n = 14); 2) at vaginal or cesarean delivery (n = 66); and 3) with chronic hypertension (n = 12), with (n = 7) or without (n = 5) superimposed preeclampsia. Allopregnanolone and progesterone levels were measured in maternal and cord serum by RIA. In healthy pregnant women, serum allopregnanolone and progesterone levels progressively increased throughout gestation. Whereas no changes were found at vaginal delivery, serum allopregnanolone and progesterone levels were significantly lower at delivery by emergency cesarean section (P < 0.01). Umbilical cord serum allopregnanolone and progesterone levels in emergency cesarean were significantly lower than those found at vaginal delivery (P < 0.01). Patients with chronic hypertension, with or without superimposed severe preeclampsia, showed serum allopregnanolone levels significantly higher than those of healthy women at the same gestational age (P < 0.01). In conclusion, maternal serum allopregnanolone levels increased during normal gestation were lower in women who underwent emergency cesarean and higher in patients with chronic hypertension, with or without preeclampsia. Because allopregnanolone is active on the central nervous system and in the control of systemic blood pressure, an involvement of this neurosteroid in the adaptive processes induced by pregnancy is suggested.

Placental corticotropin-releasing factor. An update.

Corticotropin-releasing factor (CRF) produced in placenta has paracrine effects within placenta, decidua, and myometrium and endocrine effects on mother and fetus. CRF is a potent local regulator of myometrial contractility and of prostaglandin release, Recently, urocortin, a new member of the CRF family, has been localized in human placenta and membranes. Urocortin mimics some of the local effects of CRF in intrauterine tissues, that is, increase of adrenocorticotrophic hormone (ACTH) and prostagiandin release and myometrial contractility. A local CRF-BP modulates the paracrine effects of CRF and urocortin. The various CRF receptor subtypes are well distributed in placenta and membranes. CRH also acts on placental blood vasculature and has an action on fetal adrenal gland to stimulate the production of the steroid DHEA-S. In nonpregnant women, plasma CRF levels are low; they become higher during the first and second trimesters of pregnancy. A clear increase is evident at term and when CRF-BP levels decrease. Women with preterm labor show high CRF and low CRF-BP levels, supporting an involvement of this pathway in mechanism of parturition.

Putative role of placental corticotropin-releasing factor in the mechanisms of human parturition.

Corticotropin-releasing factor is a 41-amino-acid neuropeptide synthesized in the paraventricular nucleus of the hypothalamus and released in response to stress. Its major role is the regulation of the hypothalamus-pituitary-adrenal axis by stimulation of ACTH release from the anterior pituitary gland. In addition, corticotropin-releasing factor modulates behavioral, vascular, and immune responses to stress. Corticotropin-releasing factor was first detected in the extracts of human placentas obtained at full term from spontaneous deliveries. Placental corticotropin-releasing factor content and messenger RNA expression progressively increase during normal pregnancy, and corticotropin-releasing factor levels in maternal plasma have a similar time course. The addition of corticotropin-releasing factor to primary trophoblast cell cultures stimulates ACTH secretion in a dose-dependent manner, and its action is mediated by cyclic adenosine monophosphate as second messenger. In addition, corticotropin-releasing factor is a potent local regulator of myometrial contractility and of membrane prostaglandin release. The effects of corticotropin-releasing factor in these various tissues are mediated by specific receptors. Placental corticotropin-releasing factor is also secreted into the fetal circulation and the stimulation of fetal pituitary ACTH and fetal adrenal gland dehydroepiandrosterone sulfate release in vitro has been shown. Recently, urocortin, a new peptide related to corticotropin-releasing factor, has been found in human placenta. Corticotropin-releasing factor and urocortin share some of their biologic effects, acting on the same receptors. A large-molecular-weight corticotropin-releasing factor-binding protein modulates the activity of both these peptides. Plasma corticotropin-releasing factor levels are low in nonpregnant women and become higher during the second trimester of pregnancy, rising steadily until about 35 weeks, and then increasing more rapidly until term. Vaginal delivery is a condition associated with the highest values of maternal corticotropin-releasing factor levels. Corticotropin-releasing factor is also measurable in fetal plasma (20-fold lower than in maternal circulation) and in amniotic fluid. Increased maternal plasma corticotropin-releasing factor levels characterize some gestational diseases. Women with chronic hypertension and preeclampsia have high corticotropin-releasing factor levels, and intrauterine growth retardation is associated with an activation of the hypothalamus-pituitary-adrenal axis, reflected by increased fetal plasma concentrations of ACTH, cortisol, and corticotropin-releasing factor. The role of corticotropin-releasing factor in preterm labor is uncertain, but midgestational plasma corticotropin-releasing factor levels may be higher in women delivering preterm. In these various pathologic states, maternal plasma corticotropin-releasing factor-binding protein levels undergo opposite changes, decreasing to very low levels. The endocrine-paracrine corticotropin-releasing factor/corticotropin-releasing factor-binding protein pathways may play a major role in the mechanism of human parturition.

Eligibility criteria for labor induction with prostaglandins.

Particular conditions exist at the end of some pregnancies which cause an increase in maternal and fetal risk. A valid alternative for these pregnancies is represented by the administration of prostaglandins, in order to obtain labor induction. The goal of our study was to define the eligibility criteria and the epidemiological characteristics that correlate most with a favorable obstetrical outcome. The study was conducted on 133 informed, consenting patients subjected to labor-induced delivery with prostaglandins E2. The mode of delivery in relationship to parity demonstrated that the pluriparous patients had fewer difficulties in labor and in its induction: of the 43 pluriparous cases, none had a cesarean section for failed induction and 95.3% delivered vaginally. One hundred percent of the patients with a Bishop score of more than 4 went into labor, as opposed to 81% of the patients with a score of less than 4. Therefore, taking into consideration the cost of the method, we retain that choosing an active position is valid, respecting the eligibility criteria for the induction of labor described above.

[Chronic tonsillitis in childhood: a bacteriological study in connection with benzathine penicillin treatment and the role of bacterial flora in tonsillar hypertrophy]. / Tonsillite cronica dell'età pediatrica: studio batteriologico in rapporto al trattamento con benzatin-penicillina e ruolo della flora batterica nell'ipertrofia tonsillare.

In this study the authors evaluated the importance of bacteriological study in the diagnostics of chronic tonsillitis in children and investigated the eventuality of modification in superficial as well as parenchymal tonsillar microflora brought about by preventive treatment with benzylpenicillin G. The study further aimed at revealing an eventual relationship between microflora and classic laboratory parameters (haemochromocytometric examination, leukocytic formula, VES, ASLO and urine analysis) as well as at evaluating the possibility of a correlation between the degree of tonsillar hypertrophy and microflora. The 100 patients studied had chronic tonsillitis, were between the ages of 4 and 12 and were all candidates for tonsillectomy. The subjects were divided into two groups of 50 patients each; one group had not had any antibiotic treatment for at least 30 days prior to the study, while the second group had undergone antibiotic treatment during the days or weeks immediately before the study and was administered benzylpenicillin G 24 hours prior to sampling. The superficial and intraparenchymal tonsillar tampon samples taken in both groups underwent bacteriological studies. The most frequently isolated bacteria was Haemophilus Influenzae (40% of the cases). A clear-cut prevalence of this bacteria was observed in those patients treated with benzylpenicillin G as opposed to those not treated. Haemolytic Group A Streptococcus was found almost exclusively in the tonsils of those patients not treated with antibiotics (14 out of 15 cases). Various degrees of tonsillar hypertrophy were observed although no sure correlation between the presence of the pathology and the bacteria found, either superficially or in the parenchyma, was established. Furthermore, no significant was revealed between the presence of superficial or intraparenchymal bacteria.

Prediction of successful induction of labor at term: role of clinical history, digital examination, ultrasound assessment of the cervix, and fetal fibronectin assay.

OBJECTIVE: The purpose of this study was to evaluate whether biochemical (fetal fibronectin assay) or biophysical (cervical assessment by transvaginal ultrasound) tests may have more value than digital examination in predicting successful induction of labor at term. STUDY DESIGN: The study enrolled prospectively 134 women undergoing labor induction at term caused by several obstetric conditions. All participants submitted to digital examination, fetal fibronectin assay, and transvaginal ultrasound for measurement of the cervical length and detection of funneling. The performance of each test in predicting delivery within 24 hours of labor induction was evaluated. Cox multiple regression analysis was performed to identify, among clinical and laboratory tests, which variables were independently associated with the duration of the latent phase and with the total duration of induced labor. RESULTS: The likelihood ratios for positive results (predicting that delivery would occur within 24 hours) were 6.61 (95% CI, 1.7-25.8) for a positive obstetric history (previous vaginal delivery), 2.61 (95% CI, 1.6-4.3) for a "favorable" digital examination, 1.41 (95% CI, 0.9-2.2) for a positive fetal fibronectin test, 1.61 (95% CI, 0.9-3.0) for cervical length, and 2.20 (95% CI, 1.1-4.4) for the presence of funneling at transvaginal ultrasound. The likelihood ratios for negative results were 1.81 (1.3-2.5) for obstetric history, 4.34 (2.5-7.7) for digital examination, 1.41 (0.9-2.1) for fetal fibronectin, 1.29 (1.0-1.7) for cervical length, and 1.48 (1.1-2.0) for funneling. On multiple regression, the only variables independently associated with the duration of the latent phase and with the total duration of induced labor were obstetric history and digital examination. CONCLUSION: Only obstetric history and digital examination predicted accurately vaginal delivery within 24 hours and were independently associated with labor duration. Fetal fibronectin and ultrasound measurements failed to predict accurately the outcome of induced labor.

Healthy women and patients with endometriosis show high concentrations of inhibin A, inhibin B, and activin A in peritoneal fluid throughout the menstrual cycle.

Inhibin A, inhibin B, and activin A are growth factors which play local autocrine/paracrine roles in reproductive tissues. Since peritoneal fluid hormone content may reflect in part ovarian and endometrial secretory activities, the present study aimed to evaluate: (i) whether inhibin alpha-, activin betaA- and betaB-subunits, and activin receptor type II and type IIB mRNA are expressed in peritoneal tissues; (ii) expression and secretion of inhibin A and B, and activin A in cultured endometriotic cells; and (iii) concentrations of inhibin A and B, and activin A in serum and in peritoneal fluid in healthy women and in patients with endometriosis throughout the menstrual cycle. A group of women (n = 72) was recruited at laparoscopy for infertility investigation and divided into two groups: (i) control healthy women (n = 35), (ii) women with endometriosis (n = 37). Both groups were subdivided according to the follicular and luteal phase of the menstrual cycle. At the time of laparoscopy, specimens of peritoneal tissues were collected from three healthy women, while endometriotic tissue samples were collected and cultured from three women with endometriosis. Peritoneal tissues and cultured endometriotic cells expressed inhibin alpha-, activin betaA-, and betaB-subunits, and activin receptors mRNAs; in addition, inhibin-related proteins were measurable in culture medium. In healthy women, inhibin A and B, and activin A concentrations in peritoneal fluid were significantly higher than in serum (P < 0.001), at both phases of the menstrual cycle. Peritoneal inhibin A and B, and activin A concentrations were not significantly different between healthy women and patients with endometriosis, either when evaluated according to the degree of the disease and/or to the phase of the menstrual cycle. In conclusion, the findings that high concentrations are present in peritoneal fluid and that menstrual cycle-related changes occur suggest that reproductive organs may contribute to inhibin-related proteins in peritoneal fluid.

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.

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.