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Biomedical subjects

I Lombardi

Publications and source records attributed to I Lombardi.

6 recordsLinked to original sources

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↗

Long-term low-dose dehydroepiandrosterone replacement therapy in aging males with partial androgen deficiency.

Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) age-related withdrawal is very likely to be involved in the aging process and the onset of age-related diseases, giving rise to the question of whether preventing or compensating the decline of these steroids may have endocrine and clinical benefits. The aim of the present trial was to evaluate the endocrine, neuroendocrine and clinical consequences of a long-term (1 year), low-dose (25 mg/day) replacement therapy in a group of aging men who presented the clinical characteristics of partial androgen deficiency (PADAM). Circulating DHEA, DHEAS, androstenedione, total testosterone and free testosterone, dihydrotestosterone (DHT), progesterone, 17-hydroxyprogesterone, allopregnanolone, estrone, estradiol, sex hormone binding globulin (SHBG), cortisol, follicle stimulating hormone (FSH), luteinizing hormone (LH), growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels were evaluated monthly to assess the endocrine effects of the therapy, while beta-endorphin values were used as a marker of the neuroendocrine effects. A Kupperman questionnaire was performed to evaluate the subjective symptoms before and after treatment. The results showed a great modification of the endocrine profile; with the exception of cortisol levels, which remained unchanged, DHEA, DHEAS, androstenedione, total and free testosterone, DHT, progesterone, 17-hydroxyprogesterone, estrone, estradiol, GH, IGF-1 and beta-endorphin levels increased significantly with respect to baseline values, while FSH, LH and SHBG levels showed a significant decrease. The Kupperman score indicated a progressive improvement in mood, fatigue and joint pain. In conclusion, the present study demonstrates that 25 mg/day of DHEA is able to cause significant changes in the hormonal profile and clinical symptoms and can counteract the age-related decline of endocrine and neuroendocrine functions. Restoring DHEA levels to young adult values seems to benefit the age-related decline in physiological functions but, however promising, placebo-controlled trials are required to confirm these preliminary results.

Aged↗

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↗

Serum activin A levels in males and females during pubertal development.

Activin A is a dimeric protein composed of two beta A-subunits protein of the transforming growth factor-beta (TGF-beta) family. This protein is synthesized by a variety of organs. A sensitive and specific assay for bioactive dimeric activin A has recently been developed, to measure circulating levels in adult women and men, giving a new insights into the possible physiological role of this protein in the reproductive axis and/or in other functions. The aim of the present study was to evaluate serum dimeric activin A levels in boys and girls during pubertal development. The study was performed on a group of children (n = 54) aged between 6 and 18 years at different Tanner stages. Serum levels of activin A were measured using a specific and sensitive two-site ELISA. Serum activin A levels were not significantly different at various Tanner stages (Tanner I, 0.36 +/- 0.02 ng/ml; Tanner II, 0.33 +/- 0.02 ng/ml; Tanner III, 0.35 +/- 0.03 ng/ml; Tanner IV, 0.41 +/- 0.04 ng/ml; Tanner V, 0.35 +/- 0.05 ng/ml; p > 0.01). No difference between male and female children was observed. In conclusion, the lack of significant differences in activin A serum levels according to the Tanner stages or to gender demonstrates that this protein is not involved in the endocrine modifications during pubertal development and that its measurement may not provide a sensitive new tool for determining gonadal maturity at puberty.

Activins↗

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↗

17-beta-estradiol and progesterone serum levels in temporomandibular disorder patients.

AIM: Considering the hypothesis that some temporomandibular joint (TMJ) tissues could be a potential target for sexual hormones, the aim of the study was to evaluate estrogen (17-beta-estradiol) and progesterone serum levels in a young adult population affected by articular forms of temporomandibular disorders (TMD) versus a control group of healthy subjects. METHODS: A total of 35 patients with Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) Axis I Group II diagnosis of disk displacement and/or Group III diagnosis of arthralgia, osteoarthritis or osteoarthrosis, were recruited at the Section of Prosthetic Dentistry, Department of Neurosciences, University of Pisa, Italy, along with a sex- and age-matched group of 24 healthy controls. In all patients, 17-beta-estradiol, progesterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) serum levels were determined using a radioimmunoassay. A T-test was performed to compare mean 17-beta-estradiol and progesterone serum levels in the TMD groups with mean serum levels of their respective control groups. Significance was set at p<0.05. RESULTS: Significant differences between patients affected by TMJ disorders and healthy controls were found for serum concentration of 17-beta-estradiol, both in males (p<001) and in the luteal phase of the menstrual cycle in females (p<0.05). No difference was found for progesterone serum levels in the different experimental samples. CONCLUSIONS: The results of this study suggest that high serum estrogens levels might be implicated in the physiopathology of temporomandibular joint disorders, since subjects with these pathologies showed significantly higher serum levels with respect to a group of healthy controls.

Adult↗