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Biomedical subjects

E Casarosa

Publications and source records attributed to E Casarosa.

At least 19 recordsLinked to original sources
PubMed2006

High basal serum allopregnanolone levels in overweight girls.

OBJECTIVE: Several studies demonstrated that obese subjects have a hyperactive hypothalamic-pituitary-adrenal axis and that sex steroid hormones have been closely related to the regulation of adiposity, either through direct or indirect physiological mechanisms. Allopregnanolone (3alpha-hydroxy-5alpha-pregn-20-one; AP) is a circulating neuroactive steroid hormone involved in the modulation of behavioral functions, stress and neuroendocrine axis. The aim of our study was to evaluate basal serum AP levels in obese children. SUBJECTS AND MEASUREMENTS: We studied 27 normal weight (NW) and 23 overweight (OW) girls. Gonadotropins and steroid hormones were assessed in all patients. RESULTS: Basal AP concentrations in OW girls were significantly higher than in NW controls (P=0.013). There was no difference found between the other gonadal and adrenal hormones. Considering the pubertal stage, we demonstrated that obese pubertal girls presented higher AP concentrations than prepubertal and pubertal NW ones (P=0.020), and higher dehydroepiandrosterone sulfate (DHEAS) levels with respect to prepubertal obese girls, and prepubertal and pubertal NW patients (P=0.025). AP and DHEAS were significantly directly related to weight (r=0.31 and r=0.54, respectively) and body mass index (r=0.29 and r=0.34, respectively). In pubertal OW girls, a significant positive correlation between AP and DHEAS (r=0.60), A (r=0.72) and luteinizing hormone (r=0.64) levels was demonstrated. CONCLUSION: The present study demonstrates that AP is hypersecreted in children and adolescent with OW involving DHEAS concentrations, too. Our data suggest a possible role of AP in the regulation of neuroendocrine axis related to obesity. We can also speculate that in OW girls, who could manifest emotional and behavioral problems, a part of higher levels of this neuroactive steroid might act as gamma-aminobutyric acid agonist producing anxiolytic-sedative effects.

17-alpha-Hydroxyprogesterone↗
PubMed2005

Virtual fetal touch through a haptic interface decreases maternal anxiety and salivary cortisol.

OBJECTIVE: To evaluate whether a virtual reality workstation (Fetouch system) offering three-dimensional (3D) fetal visual and kinesthetic interaction may affect maternal stress. METHODS: Maternal-fetal visual and kinesthetic interaction was obtained through a haptic interface based on 3D reconstruction of sequencial bi-dimensional ultrasound images of the fetus. Maternal stress was assessed before and after visual/kinesthetic interaction with the fetus: 1) by using the State Trait Anxiety Inventory-Form Y (STAI) test, and 2) by measuring salivary cortisol levels. Statistical analysis was performed by paired t test and analysis of variance for repeated measures. RESULTS: After the fetal visual and kinesthetic experiences, a significant reduction was observed in anxiety (low state anxiety group, P < .0034; high state anxiety group, P < .0108), as well as in salivary cortisol concentration (P < .0004). CONCLUSION: Physical interaction with the fetus through a 3D model may reduce maternal stress.

Adult↗
PubMed2005

Tibolone, transdermal estradiol or oral estrogen-progestin therapies: effects on circulating allopregnanolone, cortisol and dehydroepiandrosterone levels.

The aim of the present study was to evaluate, in healthy postmenopausal women, the impact of tibolone (2.5 mg), transdermal estradiol (50 microg) (TE) and different oral estrogen-progestin regimens, conjugated equine estrogens (0.625 mg) plus medroxyprogesterone acetate (5 mg) (CEE + MPA) and estradiol (2 mg) plus norethisterone acetate (1 mg) (E2 + NETA) on circulating estradiol, progesterone, allopregnanolone, cortisol and dehydroepiandrosterone (DHEA) levels. Blood samples were collected before and after 1, 3, 6 and 9 months of treatment in 85 postmenopausal women. Estradiol levels increased (p < 0.001) in the TE, CEE + MPA and E2 + NETA groups after 1 month of therapy, but did not change in the tibolone group during the entire follow-up period. Both E2 + NETA and tibolone treatments induced an increase in progesterone levels (p < 0.05) after 1 year of therapy. Allopregnanolone levels showed an increase in all estrogen-based groups, being significant after 3 months of treatment (p < 0.01). Patients receiving tibolone showed a significant increase in allopregnanolone levels at 3 months (p < 0.05), but lower than in the other groups. Cortisol levels decreased significantly in the TE and CEE + MPA groups after 6 months and 12 months of treatment, respectively. Neither tibolone nor E2 + NETA treatments modified circulating cortisol levels. DHEA levels significantly (p < 0.05) decreased after 6 months of TE or estrogen-progestin therapies independently of the presence or the type of progestin used. In contrast, DHEA remained stable throughout the 12 months of treatment with tibolone. The increase of allopregnanolone, a steroid with sedative and anxiolytic properties, in response to these different treatments could underlie, at least in part, the central effects that hormone replacement therapy and tibolone have on anxiety, mood and behavior. Unlike estrogen-based therapy, tibolone treatment did not reduce the DHEA milieu in the menopause, and thus did not enhance the androgen deficiency syndrome in postmenopausal women.

Administration, Cutaneous↗
PubMed2004

Adrenal response to adrenocorticotropic hormone stimulation in patients with premenstrual syndrome.

Several studies have been performed during recent years to investigate the existence of a possible endocrine cause for premenstrual syndrome (PMS); the results reported are often discordant. Great interest has been raised around allopregnanolone, which could be involved in the determination of mood disorders reported by PMS patients. During the luteal phase, lower levels of this hormone have been detected in PMS patients. The aim of our study was to evaluate estradiol, progesterone, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), androstenedione, total and free testosterone, cortisol, pregnenolone and allopregnanolone levels in 20 patients suffering from PMS and to compare them with those found in 20 fertile healthy women in the follicular and the luteal phases. Adrenocorticotropic hormone (ACTH) tests after dexamethasone suppression were performed in 10 patients of each group during the follicular and the luteal phases. In the PMS group, significantly lower allopregnolone levels were found in the luteal phase, while progesterone was lower in the PMS group in both phases. In the PMS group, higher free testosterone levels were found during the luteal phase and higher DHEA levels in both the follicular and the luteal phases. The present data confirm reduced allopregnanolone levels in the luteal phase in PMS patients, together with higher levels of DHEA and free testosterone. It is possible to conclude that, in addition to the previously described reduced luteal secretion of allopregnanolone, the adrenal gland production of this steroid in PMS sufferers is also impaired in the luteal phase. Considering the specific actions of these hormones on the control of mood and behavior, this specific hormonal milieu may contribute to the cyclic occurrence of anxiety, aggressiveness and irritability reported by PMS patients.

Adolescent↗
PubMed2003

Adrenal function under long-term raloxifene administration.

The aim of the present study was to evaluate the effect of long-term (12 months) administration of raloxifene hydrochloride (60 mg/day) on the steroid production of the adrenal cortex and on the hypothalamic-pituitary-adrenal axis in postmenopausal women. We performed a basal evaluation, a corticotropin releasing factor (CRF) (100 microg i.v. bolus) test and a dexamethasone (DXM) (0.25 mg) suppression-adrenocorticotropic hormone (ACTH) (10 microg i.v. bolus) stimulation test in 11 postmenopausal women, before and after 3, 6 and 12 months of raloxifene treatment. Raloxifene administration significantly modified circulating levels of adrenal steroids, decreasing cortisol (-24%), dehydroepiandrosterone (DHEA) (-36%), and its sulfate (DHEAS) (-41%), and androstenedione (-29%), and increasing circulating allopregnanolone (+39%) levels. Progesterone and 17OH-progesterone levels remained unmodified, while estradiol and estrone levels showed a significant decrease (-51% for estradiol and -61% for estrone). We also observed an increase in circulating ACTH (+58%) and beta-endorphin (+120%). No modifications in the hormonal responses to CRF were observed during the treatment. DXM significantly suppressed circulating steroids at any time with a lower suppression of cortisol from the third month and a higher suppression of DHEA at 12 months. ACTH administration was associated with a significantly blunted cortisol response from the sixth month and a significantly increased response of allopregnanolone from the third month. The present data exclude a raloxifene effect on pituitary sensitivity to CRF and demonstrate a reduced adrenal sensitivity to ACTH, sustained by the opposite changes in basal cortisol and Delta5 androgens, which were reduced, and in ACTH and beta-endorphin, which were increased, as well by the reduced response of cortisol to the direct ACTH stimulus. The reduction of circulating cortisol levels and cortisol response to the ACTH challenge suggests that raloxifene protects against the neurotoxic effects of endogenous glucocorticoids. Furthermore, the progressive increase in basal allopregnanolone and its increased response to ACTH indicate that chronic raloxifene administration exerts direct effects on the pattern of adrenal enzymes, leading to specific changes in the circulating levels of this anxiolytic progesterone metabolite. The important reduction in the circulating levels of estradiol and estrone under long-term raloxifene administration may represent a further mechanism by which this molecule may exert a protective effect against breast and endometrial malignancies.

Adrenal Cortex↗
PubMed2001

Circulating levels of allopregnanolone, an anticonvulsant metabolite of progesterone, in women with partial epilepsy in the postcritical phase.

PURPOSE: Several lines of evidence indicate that there exists a relation between ovarian hormones and epilepsy. Estrogens decrease seizure threshold and increase brain excitability, whereas progesterone has an inhibitory effect and reduces epileptiform activity. Recently considerable interest has turned to neuroactive steroids, a group of progesterone metabolites, as endogenous modulators of excitability of the central nervous system (CNS). Their ability to alter neuronal firing rapidly occurs through interaction with gamma-aminobutyric acid (GABA) A receptor complex. In a previous experience, serum allopregnanolone (3alpha-OH-5alpha-pregnan-20-one) levels were measured in 15 women with partial epilepsy in the intercritical phase, and no significant differences were found between patients and control subjects. METHODS: To find out if there are changes in serum allopregnanolone levels after epileptic seizure, blood samples were drawn immediately, 15 min, and 6 h after a seizure in seven fertile females with partial epilepsy. RESULTS: The most interesting finding is that allopregnanolone increases in serum during the first 15 min after partial seizures (p < 0.05) and decreases after 6 h. CONCLUSIONS: These data are consistent with a role for allopregnanolone in the control of neuronal excitability and seizures.

Adult↗
PubMed2001

Neuroendocrine effects of raloxifene hydrochloride in postmenopausal women.

Raloxifene is a selective estrogen modulator able to exert an estrogen-like action on some target tissues and a specific antiestrogenic action on the uterus and breast. In ovariectomized rats, it has been shown to stimulate the beta-endorphin and allopregnanolone concentrations of the anterior and neurointermediate pituitary lobes, the hypothalamus and the hippocampus. The present study aimed to evaluate, in 12 healthy postmenopausal women, the effect of 60 mg/day raloxifene hydrochloride administration for 6 months on plasma beta-endorphin and allopregnanolone levels, and on the dynamic changes of both beta-endorphin and allopregnanolone secretion after the administration of: (1) clonidine, an alpha 2-presynaptic adrenergic agonist; (2) naloxone, an opioid receptor antagonist; and (3) fluoxetine, a serotonin selective reuptake inhibitor. The administration of raloxifene significantly increased both circulating beta-endorphin and allopregnanolone concentrations, at both the third and sixth months of treatment (p < 0.01). Clonidine, fluoxetine and naloxone administration before therapy was not able to stimulate the release of beta-endorphin, but the response was completely restored after raloxifene administration. Before therapy, clonidine and naloxone tests were accompanied by a significant rise in allopregnanolone secretion; the same changes were observed after raloxifene administration, but with significantly higher allopregnanolone concentrations at each time considered. While the fluoxetine test before therapy failed to increase the release of allopregnanolone, the same test after 6 months of raloxifene administration was characterized by a significant release of allopregnanolone at 60 and 90 minutes. The present data indicate that raloxifene has an estrogen-like effect on neuroendocrine pathways in postmenopausal women.

Adrenergic alpha-Agonists↗
PubMed2000

Progesterone, progestagens and the central nervous system.

Oestrogen, progestagens and androgens are able to modulate several brain functions. Receptors for gonadal steroids have been identified in several brain areas: amygdala, hippocampus, cortex, basal forebrain, cerebellum, locus coeruleus, midbrain rafe nuclei, glial cells, pituitary gland, hypothalamus and central grey matter. The mechanism of action of sex steroids at this level is similar to that observed in the peripheral target organs, including both genomic and non-genomic effects. The increased use of sex steroid hormone derivative therapies has lead to study of the biochemical and metabolic properties of the different progestin molecules available in hormonal therapies. In particular, experimental and clinical studies focused the attention of researchers on interactions between oestrogens and progestins in the neuroendocrine control of the brain functions and its clinical implications. Moreover, steroids are also synthesized de novo in the brain or may be derived from the conversion of blood-borne precursors, suggesting that the brain is also a source of steroids, named neurosteroids. Neurosteroids exert non-classical rapid actions as allosteric agonists of gamma-aminobutyric acid receptor A (GABA(A)) and also modulate classic neurotransmitters in the brain. In addition, progesterone derivatives, e.g. pregnanolone, and 3alpha 5alpha-OH THP (allopregnanolone) are synthesized de novo by astrocytes and oligodendrocites starting from cholesterol. Physiological or pathological modifications of the synthesis and release of neurosteroids play a relevant role in the control of brain function.

Animals↗
PubMed2000

Effects of estradiol and raloxifene analog on brain, adrenal and serum allopregnanolone content in fertile and ovariectomized female rats.

Allopregnanolone is a neuroactive steroid synthesized in rat gonads, adrenal cortex, and central nervous system. It has been suggested that sex steroid hormones might influence allopregnanolone concentrations but no clear data have ever been reported. The aim of the present study was to investigate the effects of administration of 17beta-estradiol (17beta-E2), the raloxifene analog LY-117018 or their combination on allopregnanolone levels in fertile and ovariectomized (OVX) rats. Thirteen groups of 12 Wistar female rats each received either 17beta-E2 (0.1 or 1 microg/day) or LY-117018 (25, 250, and 1,250 microg/day), or 17beta-E2 1 microg/day plus LY-117018: 25, 250, and 1,250 microg/day for 14 days. The rats were then sacrificed and allopregnanolone content was assessed in the hypothalamus, hippocampus, pituitary, adrenals, and serum. Ovariectomy determined a significant decrease in allopregnanolone content in the hypothalamus, hippocampus, pituitary, and serum, while increasing it in the adrenals (p<0.01). In OVX rats, the administration of either 17beta-E2 or LY- 117018 restored ovariectomy-induced allopregnanolone changes. The administration of LY-117018 in addition to 17beta-E2 to OVX animals suppressed the increase in allopregnanolone levels determined by 17beta-E2 in the hippocampus, hypothalamus, and pituitary, but not in the adrenals and serum. In fertile rats, the administration of LY-117018 reproduced the effects of ovariectomy. This study shows that the raloxifene analog LY-117018 has an estrogen-like action on the central nervous system of OVX rats when administered alone, while it acts as an antiestrogen in the presence of 17beta-E2, both in OVX animals treated with 17beta-E2 and in fertile rats. A different effect was observed in the adrenal glands. The mechanism of action of this compound has still to be clarified.

Adrenal Glands↗
PubMed2000

Ovarian follicular fluid contains immunoreactive estriol: lack of correlation with estradiol concentrations.

Estradiol and estrone concentrations in ovarian follicular fluid change according to the ovulatory cycle, but no studies on the possible presence and/or changes of estriol are available. The aim of the present study was to evaluate whether estriol is measurable in follicular fluid and how its concentration changes according to the volume of ovarian follicles and to the maturational stage of oocytes. A group of women (n = 39) undergoing a program of induction of ovulation was included in this study and divided into three groups according to the causes of infertility: those with unexplained infertility (n = 11); those with endocrine disturbances (n = 5); and normal ovulatory women (n = 23) (controls). The follicles recruited (n = 116) on the basis of morphology and the appearance of the oocyte cumulus-corona complex were divided into: mature (n = 22); intermediate (n = 75); immature (n = 11); and atretic (n = 8). Ovarian follicles were also divided according to the diameter of each: < 1.5 cm (n = 38); 1.6-2.4 cm (n = 66); and > 2.5 cm (n = 12). Ovarian follicular fluids were aspirated under ultrasound guidance and a blood specimen was collected from each subject. Estriol and estradiol concentrations were evaluated by radioimmunoassay in serum and follicular fluid following an ether extraction. Estriol was found in high concentration in each sample of follicular fluid, significantly higher than in the respective serum sample (p < 0.01). Although the estradiol concentration was significantly lower in follicles containing immature and atretic oocytes than in intermediate or mature follicles (p < 0.01), the estriol concentration did not depend upon the maturational stage. In addition, the follicular fluid estriol concentration did not differ according to the causes of infertility. Follicular fluid and serum estradiol concentrations showed significant correlation (p < 0.01), whereas no significant correlation was observed between serum and follicular estriol concentrations. The present data show that follicular fluid contains a high concentration of estriol and that its changes are independent of the ovulatory cycle and estradiol concentrations, supporting an independent origin and suggesting a different function for estriol.

Estradiol↗
PubMed2000

Six-month oral dehydroepiandrosterone supplementation in early and late postmenopause.

The adrenal production of the delta 5-androgens, dehydroepiandrosterone (DHEA) and its sulfate ester dehydroepiandrosterone sulfate (DHEAS), declines linearly with aging. The evidence that DHEA or DHEAS administration may alleviate some of the problems related to aging has opened new perspectives for clinical research. The present study aims to investigate the effects of a 6-month DHEA supplementation in early and late postmenopausal women, with normal or overweight body mass index (BMI), on the level of circulating steroids, sex hormone binding globulin (SHBG), beta-endorphin and gonadotropins, and on the adrenal gland response to dexamethasone suppression and adrenocorticotropic hormone (ACTH) stimulation. Early postmenopausal women (50-55 years) both normal weight (BMI 20-24, n = 9) and overweight (BMI 26-30, n = 9) and late postmenopausal women (60-65 years) both of normal weight and overweight, were treated with oral DHEA (50 mg/day). Circulating DHEA, DHEAS, 17-OH pregnenolone, progesterone, 17-OH progesterone, allopregnenolone, androstenedione, testosterone, dihydrotestosterone, estrone, estradiol, SHBG, cortisol, luteinizing hormone, follicle stimulating hormone and beta-endorphin levels were evaluated monthly and a Kupperman score was performed. The product/precursor ratios of adrenal steroid levels were used to assess the relative activities of the adrenal cortex enzymes. Before and after 3 and 6 months of therapy, each women underwent an ACTH stimulating test (10 micrograms i.v. in bolus) after dexamethasone administration (0.5 mg p.o.) to evaluate the response of cortisol, DHEA, DHEAS, androstenedione, 17-OH pregnenolone, allopregnanolone, progesterone and 17-OH progesterone. The between-group differences observed before treatment disappeared during DHEA administration. Levels of 17-OH pregnenolone remained constant during the 6 months. Levels of DHEA, DHEAS, androstenedione, testosterone and dihydrotestosterone increased progressively from the first month of treatment. Levels of estradiol and estrone significantly increased after the first/second month of treatment. Levels of SHBG significantly decreased from the second month of treatment only in overweight late postmenopausal women, while the other groups showed constant levels. Progesterone levels remained constant in all groups, while 17-OH progesterone levels showed a slight but significant increase in all groups. Allopregnanolone and plasma beta-endorphin levels increased progressively and significantly in the four groups, reaching values three times higher than baseline. Levels of cortisol and gonadotropins progressively decreased in all groups. The product/precursor ratios of adrenal steroid levels at the sixth month were used to assess the relative activities of the adrenal cortex enzymes and were compared to those found before therapy. The 17,20-desmolase, sulfatase and/or sulfotransferase, 17,20-lyase and 5 alpha-reductase activities significantly increased, while the 3 beta-hydroxysteroid-oxidoreductase activity did not vary. On the contrary, the 11-hydroxylase and/or 21-hydroxylase activities showed a significant decrease after 6 months of treatment. In basal conditions, dexamethasone significantly suppressed all the adrenal steroids and this suppression was greater after 3 and 6 months of treatment for DHEA, DHEAS and allopregnanolone, while it remained unchanged for other steroids. Before treatment, ACTH stimulus induced a significant response in all parameters; after the treatment, it prompted a greater response in delta 5- and delta 4-androgens, progesterone and 17-OH progesterone, while cortisol responded less in both younger and older normal-weight women. The endometrial thickness did not show significant modifications in any of the groups of postmenopausal women during the 6 months of treatment. Treatment with DHEA was associated with a progressive improvement of the Kupperman score in all groups, with major effects on the vasomotor symptoms in

Administration, Oral↗
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

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↗
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

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↗
PubMed1998

Circulating levels of allopregnanolone in humans: gender, age, and endocrine influences.

Allopregnanolone is a neuroactive steroid involved in modulating behavioral functions, stress, and neuroendocrine axes in rats. Changes in plasma allopregnanolone levels throughout the menstrual cycle have been reported in healthy women, but there exists no information on the possible gender or age-related changes or on the source(s) of circulating allopregnanolone. The aim of the present study was to assess serum allopregnanolone concentrations according to gender, menstrual cycle, age, and menopause in normal men and women; serum progesterone (P) and dehydroepiandrosterone (DHEA) levels were evaluated in the same specimens. In addition, the possible source of circulating allopregnanolone in fertile women was investigated by using stimulatory and inhibitory endocrine tests acting on the ovary and/or adrenal cortex. The present study included 189 fertile women, 112 postmenopausal women, and 46 men. Serum steroid levels were determined after extraction, using specific RIAs. Allopregnanolone levels in fertile women in the follicular phase were similar to those in age-matched men; no significant difference was found between fertile women in the follicular phase and postmenopausal women. The highest levels were found in fertile women during the luteal phase (P < 0.01). An age-related decrease was observed in men (P < 0.01), but not in women. P and DHEA levels were significantly higher in women than in men and were higher in fertile women than in postmenopausal women (P < 0.01). Both P and DHEA showed an age-related decrease in men and women (P < 0.01). Serum allopregnanolone and P, but not DHEA, significantly increased in response to a GnRH test, whereas corticotropin-releasing factor and ACTH tests elicited a significant increase in allopregnanolone, P, and DHEA levels (P < 0.01). The suppression of adrenal steroidogenesis by dexamethasone markedly reduced both allopregnanolone and DHEA serum levels (P < 0.01). In conclusion, the present study demonstrated that although men show an age-related decrease, serum allopregnanolone levels in women do not change with age and correlate with P levels during the menstrual cycle and in response to endocrine tests. Ovary and adrenal cortex may be major sources of circulating allopregnanolone in fertile women.

Adrenal Cortex↗
PubMed1998

Aging is associated with changes in allopregnanolone concentrations in brain, endocrine glands and serum in male rats.

OBJECTIVE: Allopregnanolone is a potent neuroactive steroid hormone produced in the brain and in peripheral endocrine glands. The present study investigated possible age-related variations in allopregnanolone content in brain areas, endocrine glands and serum of male rats. DESIGN: Wistar male rats were categorized into 5 groups (6 rats in each) according to age: 6, 12, 16, 18 and 20 months respectively. METHODS: Allopregnanolone content in acidic homogenates of brain cortex, hypothalamus, pituitary, adrenals and gonads was measured by a specific radioimmunoassay. Serum allopregnanolone, corticosterone and testosterone were also assayed by radioimmunoassay. RESULTS: Brain cortex allopregnanolone content decreased significantly with age, while hypothalamic allopregnanolone content remained constant until 18 months and increased significantly at 20 months. Pituitary content showed a significant age-related reduction. Adrenal allopregnanolone content remained constant until 18 months, and was significantly higher at 20 months. Testis and serum allopregnanolone contents showed significant age-related increases. Serum testosterone levels showed an age-related decrease, while no age-related variation in serum corticosterone was found. CONCLUSIONS: The present study showed a significant impact of aging on allopregnanolone contents in brain, endocrine glands and serum, showing an age-related decrease in brain cortex and pituitary, and an age-related increase in testes, adrenals and serum.

Adrenal Glands↗