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Biomedical subjects

M Luisi

Publications and source records attributed to M Luisi.

At least 37 records · Page 2Linked to original sources
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

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↗
PubMed1999

Raloxifene analog LY 117018 effects on central and peripheral beta-endorphin.

Raloxifene is a selective estrogen receptor modulator with a benzothiophene structure, that exerts an estrogen-like action on some target tissues and an anti-estrogenic action on the uterus and breasts. A limited number of data are available on the effect of raloxifene on neuroendocrine function. Since beta-endorphin (beta-EP) is considered a marker of neuroendocrine function, the aim of the present study was to evaluate the effects of a 14 day treatment with a raloxifene analog, LY 117018, on beta-EP content in the hypothalamus, hippocampus, anterior and neuro-intermediate pituitary lobe, and in the plasma of fertile and ovariectomized (ovx) rats. The effect of LY 117018 in ovx rats was compared to that of 17 beta-estradiol. beta-EP contents were measured by a specific radioimmunoassay. While ovariectomy determined a significant decrease in beta-EP levels in the anterior and neurointermediate pituitary lobe and plasma (p < 0.01), no changes of beta-EP content in the hypothalamus and hippocampus were found. The administration of 17 beta-estradiol or LY 117018 in ovx rats significantly increased beta-EP concentration in the anterior and neurointermediate pituitary lobe, in the hypothalamus and plasma (p < 0.01), though they did not significantly modify hippocampal beta-EP content. When LY 117018 was administered together with 17 beta-estradiol in ovx animals, a clear anti-estrogenic effect in all organs and in plasma was observed, resulting in significantly lower beta-EP content with respect to the group treated with 17 beta-estradiol alone (p < 0.01). The chronic administration of LY 117018 in fertile rats significantly decreased beta-EP content in the anterior pituitary, hippocampus and plasma (p < 0.01), while it increased beta-EP hypothalamic content and did not change beta-EP content in the neurointermediate lobe. In conclusion, raloxifene analog LY 117018 has an estrogen-like action on neuroendocrine opiatergic pathways when administered alone in ovx rats, while it exerts an anti-estrogen effect in fertile or in ovx rats treated with 17 beta-estradiol.

Animals↗
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

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

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

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

Adult↗
PubMed1998

The effect of microgravity on testicular androgen secretion.

BACKGROUND: Spaceflight causes a number of physiological changes in the human body. Most would consider space travel to be a stressful event even for well-trained astronauts. Should this be true, pituitary gonadotrophins (mainly LH) and testicular androgens, like testosterone (T), should decrease inflight in male astronauts. We therefore hypothesized that lowered testicular androgen levels might occur in men during spaceflight, due to stress-dependent lowered LH concentrations. METHODS: In order to test this hypothesis, on different day pre-, in- and postflight we assayed wake-time salivary and urinary T in four astronauts, as well as wake-time plasma levels of adrenocorticotropin (ACTH), cortisol (CS), LH, T and its peripherally active metabolite 3-alpha-diol glucuronide (3ADG). In order to compare clinical to subjective data, all 7 male crewmembers anonymously answered a daily questionnaire from pre- to postflight asking them to self-rate sexual drive and potency, muscle strength and mood. RESULTS: Salivary, urinary and plasma T, as well as 3ADG, decreased during flight, while LH unexpectedly increased inflight (p < 0.05). A parallel decrease in sexual drive was observed (p < 0.05). A dramatic recovery of salivary T was found on R + 1. CONCLUSIONS: This was the first time that spaceflight was demonstrated to cause temporary, still dramatic hypoandrogenism which was not due to blunted pituitary gonadotrophin secretion. The cause for hypoandrogenism is unknown but it may depend on fluid shift affecting testicular function or androgen distribution in various body compartments.

Adult↗
PubMed1997

Changes in human adrenal and gonadal function onboard Spacelab.

Astronauts have to face chronic stress during the mission period. This might cause: (i) increased adrenocortico-trophin (ACTH) and cortisol (Cort) secretion; (ii) impaired luteinizing hormone (LH) output with consequent testosterone (T) hyposecretion in men. Moreover, should the subjects prove not to synchronize their inner clocks to the time shift protocols defined by NASA, most results would be questionable. The aim of this study was to verify if plasma testicular androgens were lower than baseline and Cort biorhythm was preserved in male astronauts during a short duration flight.

Adrenocorticotropic Hormone↗
PubMed1995

Prolonged treatment of hirsutism with flutamide alone in patients affected by polycystic ovary syndrome.

Hirsutism is a common symptom of women affected by polycystic ovary syndrome (PCOS). The effectiveness of the antiandrogen flutamide alone was studied in 25 patients affected by PCOS with severe hirsutism for a period of 24 months. Seventeen of these patients had not been treated before and eight had had previous but unsatisfactory therapy. Nineteen patients showed a normal body weight (BMI < 25 kg/m2) whereas six were obese (BMI > 35 kg/m2). A chemical and endocrinological evaluation and an assessment of the degree of hirsutism, assigned by Ferriman-Gallwey score (mean 22 +/- 3.038), was performed under baseline conditions. Patients started treatment with flutamide (Eulexin, Schering-Plough, Kenilworth, USA) at the dose of 500 mg daily. A chronobiological assessment of gonadotropin episodic secretion and of gonadotropin response to GnRH challenge (10 micrograms in bolus) was done before and on day 7 of flutamide administration. During treatment, our patients showed a marked and significant reduction of hirsutism starting from a score of 6 and reaching the maximum (9.6 + 2.1) at 24 months of therapy. No relevant hormonal changes or side-effects were observed during therapy. Our data demonstrate that hirsutism in PCOS can rapidly and markedly respond to treatment with flutamide alone without important side-effects even if administered for a long period.

Adult↗
PubMed1995

[Tolerance of long-term protirelin tartrate treatment].

Synthetic TRH (TRH-T) has recently been used for the treatment of chronic and acute neurologic disorders. We studied the effects of long-term (30 days) refracted daily intramuscular administration of 4 mg TRH-T on neuroendocrine and cardiovascular system and on glucose and fat metabolism in 22 patients (mean age 62.7 +/- 10.9) with chronic cerebrovascular disease. All subjects were submitted to ECG and arterial blood pressure determination and were assayed for TSH, thyroid hormone, PRL, glucose, creatinine, nitrogen, glutamine transaminase, cholesterol and triglycerides plasma levels before therapy (T0), after 30 treatment days (T30) and after a 15 days washout (T45). Thyroid hormone, TSH and PRL serum levels were detected also after 15 days of TRH-T therapy (T15). In addition, TSH and PRL response to 200 micrograms iv TRH was assessed at T0, T30 and T45. TRH-T administration did not cause significant alterations of neuroendocrine balance. Furthermore, we observed no changes in lipid metabolism, renal and liver function, arterial blood pressure, and ECG. In conclusion, TRH-T may be safely used in elderly patients with chronic cerebrovascular disease, independently to cardiovascular disorders.

Aged↗
PubMed1993

Subclinical hypothyroidism: neurobehavioral features and beneficial effect of L-thyroxine treatment.

Frank hypothyroidism is known to induce neurological and mental dysfunction. The aim of this study was to assess selected neuropsychological and behavioral features by means of standardized tests in a group of 14 patients with subclinical hypothyroidism who were free from neuropsychological complaints and to evaluate the possible effects of L-thyroxine treatment on their performance. Patients were submitted to the Crown and Crisp Experiential Index and to the Wechsler Memory Scale; their ratings on the neurobehavioral tests and their thyroid hormone profile were compared to those of a control group of 50 age- and sex-matched subjects. Comparison was also carried out between pretreatment ratings and those obtained following a 6-month L-thyroxine course (0.1-0.15 mg/day). The Wechsler Memory Scale ratings showed a significant impairment in patients' memory-related abilities [memory quotient (MQ) = 89.1 +/- 2.9; P = 0.002 (patients versus controls)]; the Crown and Crisp Experiential Index ratings demonstrated moderate differences between untreated patients and controls with respect to hysteria (P = 0.03), anxiety (P = 0.05), somatic complaints (P = 0.0005), and depressive features (P = 0.002) scales; the total score was also significantly higher (42.0 +/- 3.8; P = 0.005). After L-thyroxine treatment the patients' performances showed an improvement in memory skills, as evaluated by the Wechsler Memory Scale [MQ = 99.9 +/- 4.0; P = 0.002 (treated versus untreated)]; somatic complaints (P = 0.02) and obsessionality (P = 0.04) ratings and the Crown and Crisp Experiential Index total score (P = 0.04) significantly decreased with respect to untreated patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Relevance of oestrone presentation to the specificity of the elicited antisera, as revealed by affinity separation.

Polyclonal antisera raised against two different azobenzoyl-oestrone derivatives were analysed to investigate both the latency/intensity relationship of the immune response and the influence of antigen presentation on the specificity of the antisera elicited. Elongation of the azo-bridge of the hapten ([p(carboxyphenyl)-azo]-1,3,5[10]- oestratrien-3 ol-17 one) with a short aliphatic chain (4-amino-n-butyric acid) resulted in a marginal increase in the antibody yield, without affecting the time required to attain the maximum titre. The increased flexibility and mobility of the extended azo-bridge was shown to result in the appearance of antisera which cross-reacted with oestrogens with D ring structures different to that of oestrone. Antiserum fractionation by affinity chromatography through a stationary phase exposing the carrier protein determinants, as modified by the addition of the coupling bridge and the phenol ring, resulted in a reduction in its specificity. These findings are discussed with regard to the phenomena underlying the specificity of a polyclonal antiserum.

Animals↗
PubMed1991

Highly specific polyclonal antisera against estriol: cross-reactivity restriction following affinity chromatography.

An immunosorbent technique was developed to attenuate cross-reactivity of a polyclonal antiserum against a 4(2) (rho-carboxyphenylazo)-1,3,5[10]-estratrien-3,16 alpha,17 beta-triol-bovine serum albumin conjugate. The chromatographic separation of antiserum through stationary phases having either rho(carboxymethyl)phenylazo-phenol or rho(carboxymethyl)-phenylazo-2-naphthol side residues reduced the antiserum avidity, while increasing the apparent antiserum affinity and decreasing the residual cross-reactivities against heterologous ligands. The highly specific antiserum obtained allowed the development of a competitive binding assay over an extended analytical range, which opens up the possibility of direct measurement of estriol from the early pregnancy to delivery. The significance of the attenuation of antiserum cross-reactions after affinity chromatography is discussed with reference to epitope-paratope interaction in the case of small endogenous molecules like estrogens.

Animals↗
PubMed1990

Effect of fenfluramine on prolactin and thyroid-stimulating-hormone response to thyrotropin-releasing-hormone in obese and normal women.

In order to demonstrate the suggested failure of the serotoninergic system in human obesity and to evaluate the role of central serotoninergic activity in prolactin (PRL) and thyroid stimulating hormone (TSH) release in this condition, 13 euthyroid obese and 9 healthy women of normal weight were studied. A TRH test (200 micrograms i.v.) was performed before and after administration of fenfluramine (FF) 60 mg b.d. for 14 days. In the controls, FF did not modify the expected significant increase in PRL induced by TRH. In obese patients, however, the PRL levels was significantly increased after TRH, but the increase was less than in the controls. After FF, the PRL response to TRH was larger than in the pretreatment phase, with values similar to those observed in normal subjects. In neither group FF did change the TSH-stimulating effect of TRH, but the hormonal response in obese patients was greater than in the controls. The restoration of the responsiveness of PRL to TRH after central serotoninergic stimulation confirms the hypothesis that a failure of the serotoninergic system may occur in human obesity. Since FF does not interfere with the secretory pattern of basal and stimulated TSH in normal or obese subjects, the serotoninergic system does not seem to play a major role in the control of TSH secretion.

Adult↗
PubMed1990

Impaired growth hormone response to insulin-induced hypoglycaemia in obese patients: restoration blocked by ritanserin after fenfluramine administration.

The aim of the present study was to test whether the serotoninergic system may be involved in the well known reduced growth hormone (GH) response to insulin-induced hypoglycaemia (IIH) in obese patients. Ten obese women and 10 normal-weight control women underwent three IIH tests, at 14-day intervals: the first in basal conditions, the other two after randomized administration of a serotoninergic drug, fenfluramine (FF, 120 mg/day for 7 days) and FF plus ritanserin (RIT, 30 mg/day for the first 2 days and 20 mg/day on the following days). Ritanserin is a new selective 5-HT2 blocker receptor agent. Both controls and obese patients showed similar normal basal GH levels before each test and insulin administration always effectively reduced glucose levels to values lower than 2.2 mmol/l. In the controls, the expected GH increase to IIH (peak value 56 +/- 13.4 mU/l, AUC 234.4 +/- 55 mU/min/ml) was unaffected by FF administration (peak value 43 +/- 11.4; AUC 216.8 +/- 34.8). In response to the first IIH, the obese patients showed a significantly lower GH increase than in the case of the controls (peak value 21.4 +/- 4.6 mU/l, P less than 0.02; AUC 93.2 +/- 18.6, P less than 0.02). However, in comparison with the basal test, FF administration significantly (P less than 0.001) enhanced GH response to insulin hypoglycaemia (peak value 33.4 +/- 4; AUC 150 +/- 14.6), reaching values not significantly different from those of the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Treatment of complicated benign prostatic hyperplasia with LHRH-analogues in aged patients.

The effect of administration of an LHRH-analogue (LHRH-a) was evaluated in 11 patients with benign prostatic hyperplasia (BPH) in whom there were contraindications for surgery. These patients, who already had impaired potency due to age or serious illness, were given 1500 micrograms LHRH-a in the first week and 1200 micrograms from the eighth day onwards. They all improved significantly (P less than 0.001) with regard to their urological symptoms on day 60 of treatment. Our results demonstrate the influence of androgen in maintaining established BPH, the effectiveness of LHRH-a therapy in selected patients with BPH and the usefulness of a salivary testosterone assay for the follow-up of treatments expected to lower the bioavailability of androgen to target tissues.

Aged↗