Low testosterone levels in pre-term newborns born small for gestational age.

Previous studies showed that small for gestational age (SGA) newborns have an increased prevalence of hypospadias and other congenital defects of external genitalia. We observed that in the first days of life, SGA male pre-term newborns have reduced testosterone levels compared with adequate for gestational age pre-term newborns, independently from the presence of abnormalities of the external genitalia.

Effects of finasteride, a 5 alpha-reductase inhibitor, on circulating androgens and gonadotropin secretion in hirsute women.

An oral 5-mg dose of finasteride, a 5 alpha-reductase inhibitor, was administered for 3 months to 10 hirsute women to determine the effect on gonadotropin secretion, on basal and stimulated androgen secretion, and on hair growth. Hair growth was assessed by the Ferriman-Gallwey score. All of the above determinations were evaluated before and after 1 and/or 3 months of finasteride treatment. Basal and GnRH-stimulated gonadotropin secretions were not affected. Indeed, finasteride did not modify the pulsatility of LH secretion. No change was seen in estradiol, PRL, free testosterone, androstenedione, dehydroepiandrosterone sulfate, and sex hormone-binding globulin concentrations. Serum concentrations of cortisol (F) were significantly reduced after 1 month of finasteride treatment. The F levels returned to pretreatment levels after 3 months. Plasma levels of dihydrotestosterone and 3 alpha-androstanediol glucuronide significantly decreased during finasteride treatment. A significant increase in testosterone concentrations was observed after 3 months. Finasteride did not modify the responses of testosterone, androstenedione, and dehydroepiandrosterone sulfate to ACTH-(1-24) injection. Conversely, finasteride blunted the F response to corticotropin stimulation. Three months of finasteride treatment significantly decreased the Ferriman-Gallwey score. In conclusion, finasteride significantly decreased dihydrotestosterone and hair growth in hirsute women without negatively affecting gonadotropin secretion.

Central deficiency of beta-endorphin in alcohol addicts.

Alcohol addiction may induce its dependence through a mechanism involving opiate receptors and opioid peptides. For these reasons, we measured ACTH, beta-lipotropin, and beta-endorphin in the plasma and cerebrospinal fluid (CSF) of 29 alcohol addicts and compared these values with those found in 8 normal volunteers. Although no significant differences existed in peripheral concentrations of the 3 peptides, alcohol addicts had beta-endorphin levels in CSF (mean +/- SE, 29.4 +/- 4.5 fmol/ml) that were 3-fold lower than those of the controls (98.4 +/- 10.5 fmol/ml; P less than 0.001) and ACTH levels 4 times higher than control values (30.0 +/- 1.8 vs. 7.4 +/- 1.1 fmol/ml in controls; P less than 0.001), while no difference was found in beta-lipotropin levels. These results suggest that alcohol addiction is associated with a marked alteration in the CSF content of proopiocortin-related peptides which may play a role in the alcohol-seeking behavior typical of the syndrome.

Proopiocortin-related peptide plasma levels throughout prepuberty and puberty.

The plasma patterns of ACTH, beta-lipotropin (beta LPH) and beta-endorphin (beta EP), in addition to those of cortisol and dehydroepiandrosterone sulfate (DHAS), were studied in 139 prepubertal children (subdivided into different age groups) and 38 adolescents (subdivided according to Tanner's pubertal stages) aged 10-16 yr. The adult control group was composed of 23 females and 12 males aged 17-40 yr. No sex differences were found in ACTH, beta LPH, beta EP, and cortisol plasma levels. ACTH plasma levels were slightly lower in the 1- to 3-yr-old groups than in males at 4-5 yr and females at 8-9 yr. No further significant differences were observed in any of the age or pubertal groups, the concentrations being constantly in the adult range. beta LPH and beta EP plasma levels were lowest at 1-3 yr in both males (beta LPH: 2.1 +/- 0.25, beta EP: 1.85 +/- 0.59 fmol/ml, mean +/- SE) and females (beta LPH: 2.8 +/- 0.31; beta EP: 2.41 +/- 0.41 fmol/ml); plasma levels of both hormones increased progressively in both sexes until Puberty 1 stage of sexual maturation, at which time levels were 7.3 +/- 0.78 and 8.69 +/- 1.0 fmol/ml in males and 7.1 +/- 0.34 and 6.76 +/- 0.13 fmol/ml in females; these levels are similar to adult values. A highly significant linear correlation was found between both beta LPH and beta EP concentrations and the age of the subjects; this was not true for ACTH plasma levels. Cortisol plasma levels were similar in all groups. DHAS plasma levels increased progressively from 1-3 yr to the end of sexual maturation when adult values were reached. During prepuberty, DHAS levels were significantly correlated with both beta LPH and beta EP, but not ACTH. These data indicate that plasma beta LPH and beta EP concentrations, in contrast to ACTH levels, increase progressively throughout prepuberty and suggest that the processing of the parent proopiocortin molecule or secretion of the processed peptides from the anterior pituitary (or other sources) may change from early infancy to adulthood. Furthermore, the correlation between both beta LPH and beta EP with DHAS plasma levels in prepuberty suggests a role of proopiocortin-related peptides in adrenarche.

Fetomaternal opioid levels and parturition.

The present study evaluates the plasma level changes in beta-lipotropin and beta-endorphin in nine women at term throughout spontaneous labor, in ten pregnant women undergoing elective cesarean section in the absence of uterine contractions, and in ten women submitted to emergency cesarean section because of fetal distress occurring during labor. A basal plasma sample was taken before labor in the 39th week of pregnancy. Two subsequent samples were then obtained before and after parturition, together with umbilical cord samples at birth. beta-lipotropin and beta-endorphin were measured by radioimmunoassay after silicic acid plasma extraction and gel filtration. In cases of spontaneous labor, there was a progressive increase in opioid concentrations as labor progressed, the maximal values being observed after delivery. Cord values were similar to those observed in the mother, without showing any relationship to them. Pregnant women undergoing cesarean section in the absence of labor show constant beta-lipotropin and beta-endorphin concentrations both before and after fetal extraction, both values being significantly lower than those found at delivery after spontaneous labor. beta-Endorphin neonatal levels were significantly higher than in the respective mothers and were in the same range as those of infants born through vaginal delivery. In the third group (cesarean section performed at the first stage of labor), presurgical opioid levels were higher than in women at the same stage of spontaneous labor, whereas postextraction values showed a wide range, with mean values similar to those observed after spontaneous delivery.(ABSTRACT TRUNCATED AT 250 WORDS)

Different patterns of central and peripheral beta EP, beta LPH and ACTH throughout life.

The aim of the present study was to evaluate the relationship between central and peripheral concentrations of proopiocortin-related peptides in different periods of life. One hundred and eighty-nine plasma samples from normal subjects (18-87 years) obtained in basal conditions, and 20 cerebrospinal fluid (CSF) samples obtained by lumbar puncture from healthy volunteers (18-75 years) were studied. beta Lipotropin (beta LPH), beta endorphin (beta EP) and ACTH were measured by specific RIA after silicic acid plasma extraction and gel chromatography (beta LPH and beta EP). No sex differences were found in the patterns of the three peptides either in the plasma or in CSF. In the plasma samples, both beta LPH and beta EP concentrations showed a pattern throughout life which was expressed by a paraboloid function with the lowest values found in young and old subjects and with peaks at 51.3 and 48.2 years, respectively. On the contrary, ACTH values failed to be represented by a significant linear or curvilinear regression and presented only a slight decrease in subjects over 75 years of age. CSF levels of beta LPH were significantly lower in 45-76 year old subjects (18.8 +/- 12.6 fmol/ml, M +/- SD) than in 18-44 year old subjects (34.5 +/- 15.8; p less than 0.05), as were those of beta EP (elderly: 41.2 +/- 19.7; young: 94.2 +/- 36.7; p less than 0.05), which showed a significantly linear inverse correlation with age (r = 0.6062, p less than 0.01). These CSF samples did not show any ACTH variations connected with age.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of hirsutism: comparisons between different antiandrogens with central and peripheral effects.

OBJECTIVE: To compare the clinical and endocrinologic effects of cyproterone acetate (CPA), an antiandrogen with progestational activity; flutamide, a nonsteroidal antiandrogen, and finasteride, an inhibitor of 5alpha-reductase. DESIGN: Randomized, open, controlled clinical study. SETTING: Department of Obstetrics and Gynecology, University of Pisa, Pisa, Italy. PATIENT(S): Forty-five hirsute women were enrolled in the study: 29 were hyperandrogenic and 16 had idiopathic hirsutism. Three women dropped out of the study. INTERVENTION(S): Women were randomly treated with finasteride (5 mg/d; n = 14), CPA (25 mg plus ethinyl E2 (EE); n = 13), or flutamide (500 mg/d; n = 15) for 1 year. MAIN OUTCOME MEASURE(S): Hirsutism was assessed using the Ferriman-Gallwey method. Levels of total and free T, androstenedione (A), DHEAS, sex hormone-binding globulin, dihydrotestosterone, and 3alpha-androstanediol glucuronide were evaluated at the beginning of the study and every 3 months. RESULT(S): Treatment with finasteride, flutamide, and CPA significantly decreased the Ferriman-Gallwey score. The percent decreases in the hirsutism score induced by the different treatments were similar. Treatment with CPA plus EE significantly decreased levels of total and free T, A, dihydrotestosterone, and 3alpha-androstanediol glucuronide. These parameters were unchanged with flutamide therapy. Finasteride significantly increased total T levels but reduced dihydrotestosterone and 3alpha-androstanediol glucuronide concentrations. CONCLUSION(S): Finasteride, CPA, and flutamide are equally effective in decreasing hirsutism, despite different mechanisms of action.

Effect of epimestrol on gonadotropin and prolactin plasma levels and response to luteinizing hormone-releasing hormone/thyrotropin-releasing hormone in secondary amenorrhea and oligomenorrhea.

The effects of epimestrol (5 mg every 6 hours for 5 days) on basal levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (Prl), estradiol, progesterone, and dehydroepiandrosterone sulfate, and on the response to LH-releasing hormone (LH-RH) and thyrotropin-releasing hormone (TRH) stimulation, were studied in 18 cases of secondary amenorrhea and oligomenorrhea of hypothalamic-pituitary origin, in three cases of anorexia nervosa, in two cases of long-lasting progestin-induced amenorrhea, and in one case of precocious menopause. The results in the first 18 patients indicate that epimestrol treatment induces a significant increase in LH and Prl levels after 24 hours, while the FSH increase becomes significant only after 4 days of therapy. Twelve hours after discontinuation of treatment, all three hormone levels decreased significantly to values similar to the basal levels, while the pituitary response to LH-RH indicated a much more marked LH secretion than before treatment. A second test, performed 36 hours after the last drug administration, again showed a significantly higher LH response than that found under basal conditions. No significant variations were observed in the FSH response to LH-RH, nor in the Prl response to TRH. These data suggest that epimestrol interferes at the level of the centers responsible for Prl and gonadotropin secretion in the manner of a weak estrogen.

Body composition and metabolic profile in women with complete androgen insensitivity syndrome.

Clinical and experimental data suggest that androgen receptor (AR) signaling plays a role on body composition, glucose homeostasis and lipid metabolism. The effect of AR disruption on such parameters was not extensively investigated in human people. A group of young to middle-age adult women with complete androgen insensitivity syndrome (CAIS, n = 18, age 32.2 +/- 9.3 years; women with testes removed n = 14) was investigated for body mass index (BMI), body composition (dual energy X-ray absorptiometry), serum glucose levels, insulin sensitivity (HOMA-IR) and lipid profile. Mean BMI (24.2 +/- 7.4 kg/m(2)) was not significantly increased (T-score 1.0 +/- 2.5, p = NS vs Italian female reference values), but prevalence of obesity was higher in women with CAIS than that reported in age-related Italian females (16.7% vs 3.6%, respectively). The majority of obese individuals with CAIS was in the subgroup with intact testes (3/4). DXA assessment (n = 15) demonstrated values of total free fat mass similar to that of 46,XX female controls. Increased body fat was found in CAIS women in comparison with both female and male controls. Abnormal values of cholesterol (total and LDL) and HOMA-IR were present in a large subset of patients. Our data suggest that in women with CAIS disruption of AR signaling may increase body fat and affect some metabolic parameters. Assessment of body composition, metabolic profile and, likely, cardiovascular risk seems to be advisable with ageing in these individuals.

Early diagnosis of 5alpha-reductase deficiency in newborns.

5Alpha-reductase-2 deficiency is a rare autosomal recessive form of 46,XY disorders of sex differentiation (DSD), caused by mutations in the steroid 5alpha-reductase type 2 gene (SRD5A2), presenting at birth with variable degrees of undervirilization. We report on three Italian newborns with 46,XY DSD in whom the evaluation of testosterone, dihydrotestosterone, testosterone/dihydrotestosterone (T/DHT) ratio and molecular analysis of the 5alpha-reductase type 2 gene was made in their first month of life. Baseline T/DHT ratio suggested 5alpha-reductase-2 deficiency; the diagnosis was confirmed by molecular genetics (homozygous mutation in exon 4 [G196S], heterozygous mutation in exon 1 and 5 [W35X/Y235F], heterozygous mutation plus polymorphism in exon 1 [G34W/A49T]). Proper investigation permitted early reassignment to male sex in two babies, assigned to female sex just after birth. In infancy, the T/DHT ratio, assessed by suitable assay methods and evaluated by age-appropriate reference values, seems to be able to select newborns affected by 5alpha-reductase-2 deficiency. Molecular analysis of the SRD5A2 gene should be warranted in newborns with abnormal ratio before sex assignment.

[Effect of cold stress on the concentrations in the hypothalamus, pituitary, and blood of beta-lipotropin and beta-endorphin in the rabbit]. / Effetto dello stress da freddo nel coniglio sulle concentrazioni ipotalamiche, ipofisarie e plasmatiche di beta lipotropina e beta endorfina.

To evaluate the rabbit availability in beta-Lipotrophin studies we have investigated their brain, pituitary and plasmatic concentrations in basal conditions and after cold-stress. Previous silicic Acid extract and Sephadex G-75 column chromatography, the two peptides were measured through two specific and sensitive RIAs. The results reveal the presence of beta LPH and beta EP and their increase after cold-stress in hypothalamus, pituitary and peripheral plasma concentrations while not in midbrain.

beta-lipotrophin and beta-endorphin plasma levels during pregnancy.

beta-lipotrophin (beta-LPH) and beta-endorphin (beta-EP) plasma levels were measured by radioimmunoassay after glass powder extraction and Sephadex G-75 column chromatography in plasma samples from controls (ten healthy males and twenty-six young women in early follicular phase), from eighty-two pregnant women in weeks 9-40 after their last menstrual period, from nine women just after delivery and the cord blood of their neonates, in fifteen mixed cord blood samples and in seven amniotic fluid samples obtained by amniocentesis. No sex differences were found in beta-LPH (120.6 +/- 8.5 pg/ml) or beta-EP (31.1 +/- 2.4 pg/ml) plasma levels or in their molar ratio (1.34 +/- 0.09) (MR). beta-LPH plasma levels increased in early pregnancy (13-16 weeks) (185.0 +/- 27.1 pg/ml) and remained high until weeks 21-24, then declining to levels similar to those of controls. beta-EP plasma levels were significantly depressed in weeks 9-12 (20.7 +/- 5.3 pg/ml), subsequently increasing to a maximum at weeks 36-37 (42.7 +/- 6.8 pg/ml). beta-LPH/beta-EP molar ratio was about double normal in early pregnancy and decreased to normal in the second half. The present data indicate that beta-LPH and beta-EP present different patterns throughout pregnancy and that beta-EP levels increase progressively, reaching the highest concentrations at term. At delivery, both beta-LPH and beta-EP showed maximum values (beta-LPH: 230.2 +/- 20.4 pg/ml; beta-EP: 78.0 +/- 7.4 pg/ml) and a MR of 1.02 +/- 0.10 indicating that stressful situations, such as labour, stimulate a simultaneous rise in beta-LPH and beta-EP plasma levels. Cord blood specimens showed a wide range of values (beta-LPH:75-347 pg/ml; beta-EP: 16-287 pg/ml) with a MR of 1.21 +/- 0.14. Amniotic fluid samples obtained late in the third trimester of pregnancy were characterized by beta-LPH levels of 119.4 +/- 26.4 pg/ml and beta-EP levels of 29.6 +/- 7.5 pg/ml.

[Neonatal adaptive phenomenon: secretion of beta-lipotropin, and beta-endorphin in the first week of life]. / Fenomeni di adattamento neonatale: secrezione di beta lipotropina (beta LPH) e beta endorfina (beta EP) nella prima settimana di vita.

beta Lipotrophin and beta Endorphin plasma levels have been measured in 35 newborns subdivided in 5 groups of 12, 24, 48, 72 and 168 hours of life, 10 umbilical mixed blood samples were also evaluated. After plasma extraction (3 ml) and G-75 Sephadex column chromatography, the peptides were measured by two specific RIAs. beta LPH and beta EP levels were high in umbilical cord plasma (241.0 +/- 43.3 and 70.0 +/- 8.5 pg/ml respectively). A progressive decrement was then observed until the 72th hour of life (28.1 +/- 13.2 and 8.7 +/- 4.8 pg/ml respectively) but the elevated levels found at 24th hour demonstrate an active synthesis and release from fetal and neonatal pituitary. After a slight and transient decreased activity during the first week of life, the statistically significant increase of both beta LPH and beta EP observed at seven day indicate that at this moment pituitary function is restored.

Impaired circadian rhythmicity of beta-lipotrophin, beta-endorphin and ACTH in heroin addicts.

The circadian rhythm of plasma proopiocortin-related peptides was studied in 15 heroin addicts and in 6 sex- and age-matched controls. ACTH, beta-lipotrophin, (beta-LPH), beta-endorphin (beta-EP) and cortisol were measured by RIA either directly (cortisol), or after plasma extraction (ACTH) and Sephadex G-75 gel chromatography (beta-LPH and beta-EP) every 4 h from 8 a.m. to 8 p.m. and again at 8 a.m. the next morning. The means of the two 8 a.m. measurements of beta-LPH (2.67 +/- 0.34 fmol/ml, mean +/- SE), ACTH (2.74 +/- 0.71) and cortisol (218 +/- 31 pmol/ml) levels in heroin addicts were significantly lower than those in controls (6.28 +/- 0.61, 10.1 +/- 0.74 and 364 +/- 27, respectively, P less than 0.01) while beta-EP concentrations in heroin addicts (5.1 +/- 0.6) were similar to those of healthy volunteers (6.44 +/- 0.56). In controls, all three peptides and cortisol show a circadian rhythm of secretion, the lowest values being in the evening and the highest ones in the morning. Heroin addicts partially lack this phenomenon showing constant levels of the three proopiocortin-related peptides throughout the day, with a slight but significant decrease of plasma cortisol. In the 7 subjects who took heroin throughout the study, no systematic changes were observed in the three proopiocortin-related peptides, while it seems that this group of addicts shows a cortisol decrease in the evening to a lesser extent than subjects receiving methadone maintenance only.(ABSTRACT TRUNCATED AT 250 WORDS)

Simultaneous circadian variations of plasma ACTH, beta-lipotropin, beta-endorphin and cortisol.

The major objective of this study was to investigate the analogy existing between the typical circadian periodicity of ACTH and that recently described of beta-lipotropin (beta-LPH) and beta-endorphin (beta-EP) plasma levels. The determination of their concentrations, plus cortisol, has been performed on the same plasma samples of 6 healthy volunteers. All hormones were measured by radioimmunoassay. Those of beta-LPH and beta-EP were preceded by a purification of plasma through silicic acid extraction and Sephadex G-75 gel filtration. The highest values (mean +/- SEM) were found in the morning (ACTH: 10.3 +/- 0.9; beta-LPH; 6.3 +/- 0.7; beta-EP: 6.5 +/- 0.5 fmol/ml; cortisol: 378 +/- 30 pmol/ml) and the lowest values in the evening (ACTH: 6:1 +/- 0.7; beta-LPH: 3.3 +/- 0.4; beta-EP: 3.7 +/- 0.6 fmol/ml; cortisol: 130 +/- 23 pmol/ml). Statistical analysis using the Fourier method led to the evidence of a concomitant circadian secretory pattern of the three proopiocortin-related peptides. These results strongly suggest that the phasic secretion of ACTH, beta-LPH and beta-EP underlies a common central control.

[Correlation between presence of estradiol receptors and epidemiological and clinical data on breast cancer]. / Correlazione fra presenza di recettori per l'estradiolo e dati epidemiologici e clinici nel cancro della mammella.

The aim of the study is to find an eventual correlation between the presence of Er receptors and epidemiologic (age, domestic anamnesis, weight, menarca) and clinicist factors (cancerous diameter, linfonodes, first symptoms). The presence of receptors is very important for the start of endocrine therapy. In conclusion we can affirm the absence of correlation between the presence of receptors and the factors we considered. The only exception is about the age of patients; very probably because too little number of patients was considered. On the contrary a correlation was observed between receptors and severity of cancerous receptors in neoplastic tissues was obtained with Poffanelli method using an Ultra-Turrax homogenization followed by a centrifugation at 3800 rpm; the separation was achieved with carbon-dextran.

Lack of correlation between amniotic fluid and maternal plasma contents of beta-endorphin, beta-lipotropin, and adrenocorticotropic hormone in normal and pathologic pregnancies.

Reported are the concentrations of beta-endorphin, beta-lipotropin, and adrenocorticotropic hormone (ACTH) in the amniotic fluid and plasma of 40 healthy pregnant women at different stages of gestation. Moreover, the amniotic fluid levels of the three peptides were evaluated in 20 other pregnant women affected by different pathologic conditions (Cooley's disease, gestosis, diabetes, placental insufficiency, etc.). A silicic acid extraction procedure was performed on the samples. Each extract was subjected to Sephadex G-75 column chromatography, and the two fractions corresponding to beta-lipotropin and beta-endorphin were collected, freeze-dried, and assayed by two specific radioimmunoassays. Levels of ACTH were measured by radioimmunoassay directly on the extracts. Levels of beta-endorphin in amniotic fluid showed the highest values in the first trimester (173 +/- 30 fmol/ml, mean +/- SEM) but were significantly decreased in the second (75.2 +/- 14) and third trimesters (14.3 +/- 1.8). An inverse trend characterized plasma levels of beta-endorphin, which showed a progressive increase from the first trimester to term (10.4 +/- 11.1). Amniotic fluid levels of beta-lipotropin remained stable during the first (48.6 +/- 6.3) and second (54.6 +/- 11.1) trimesters, but decreased significantly in the third trimester (17.9 +/- 2.3). The plasma concentrations of beta-lipotropin showed the highest levels in the first trimester (10.9 +/- 0.9), and decreased significantly at term (8.9 +/- 1.3). Last, amniotic fluid levels of ACTH decreased from 55.3 +/- 4.75 fmol/ml in the first trimester to 12.5 +/- 1.16 in the second trimester, and rose again in the third trimester to 34.4 +/- 6.6 fmol/ml. Plasma levels of ACTH were characterized in the first two trimesters by values twice those recorded for nonpregnant women, and decreased at term to 8.9 +/- 1.4 fmol/ml. In the pregnant patients with fetuses affected by Cooley's disease (second trimester) and in those with edema-proteinuria-hypertension (EPH) gestosis (third trimester), amniotic fluid levels of beta-endorphin, beta-lipotropin, and ACTH were in the same range as those in healthy pregnant women.