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F Strollo

Publications and source records attributed to F Strollo.

At least 19 recordsLinked to original sources
PubMed2005

The pituitary-testicular axis in microgravity: analogies with the aging male syndrome.

Extraterrestrial exploration has gone on for decades before reversible testicular failure was shown to be a consequence of space flight in humans and animals at the end of the XXth century. This phenomenon was initially thought to depend on the psycho-physical stress expected to derive from a decidedly unusual environment, but the lack of consistent data concerning cortisol increase and/or gonadotrophin suppression pointed to the possibility of a primary defect. This was indirectly confirmed by the observation that a continuum of testicular androgen secretion potential exists from microgravity to centrifuge-derived hypergravity. Further experiments using tissue slices and suspended cells confirmed a direct inhibitory effect of microgravity upon testicular androgen production. A parallel deterioration of major physiological parameters, such as bone density, muscle mass/force, red blood cell mass, hydration and cardiopulmonary performance, has been repeatedly described during space missions, which, luckily enough, fully recover within days to weeks after landing, the time lag depending on single organ/system adaptation rates. According to the Authors of the present review, when taking together all reported changes occurring in space, a picture emerges closely resembling the so-called aging male syndrome, which is currently the object of daily screening and clinical care in their endocrine unit, so that microgravity may become a tool for better understanding subtle mechanisms of testicular senescence.

Aging↗
PubMed2005

Morpho-functional alterations in testicular and nervous cells submitted to modelled microgravity.

Humans, as well as other life forms, have developed on earth under the terrestrial gravitational field. Questions concerning the effect of the gravity vector changes on the animal physiology have begun to emerge only in the last decades. Physiological alterations were observed during space flights, but space-born investigations at cellular levels are still very limited. Earth-bound simulations of low gravity obtained with the 3-dimensional Random Positioning Machine are extensively utilized to explore the effects of microgravity on cell function. After only a few minutes, weightlessness affected the cytoskeleton of lymphocytes, astrocytes, neurons and testicular cells, disorganizing microtubules, intermediate filaments and microfilaments. Cell division was impaired, mitochondria were disrupted and apoptotic phenomena occurred. Expression of proteins involved in transmembrane ion and water transport were also affected. In the Leydig cells the key enzymes (3beta- and 17beta-hydroxysteroid dehydrogenases) leading to testosterone synthesis were depressed. However, after 20 h of clinorotation the cells were able to synthesize heat shock proteins that initiated protection and recovery. The cytoskeleton was again well organized, normal mitosis occurred and the percentage of apoptotic cells returned to the range of 5%, similar to the control cultures. Ion and water transmembrane proteins and steroid dehydrogenases returned to normal levels. Long-term experiments showed that low gravity induced only transient alterations in the cultured cells, which were able to adapt to the gravity vector changes and to regain normal activity. These data may explain the physiological adaptation occurring in astronauts during and after space flights.

Animals↗
PubMed2004

Microgravity-induced alterations in cultured testicular cells.

Cultured STe cells (2n karyotype) from swine testis were submitted to simulated microgravity using a 3D Random Positioning Machine for 5 min., 15 min., 30 min., 1 h and 23 h. Sample processing included: histological characterization of cell types, immunohistochemical identification of (i) microtubules (a-tubulin), (ii) alkaline phosphates, (iii) 3 beta-hydroxy-steroid-dehydrogenase (3?-HSDH), and histochemical lipid analyses. After 5 min. simulated microgravity a slight microtubule disorganisation occurred, which increased dramatically with increasing microgravity duration. After 23 h microtubule arrays were completely disrupted. 3 beta-HSDH immunostaining was detectable only in one cell type: under control conditions and 5 min. into microgravity immunoreactivity was strong, but completely disappeared thereafter. Immunostaining intensity for alkaline phosphates, a good marker for myoid cells, decreased after 15 min. in microgravity.

3-Hydroxysteroid Dehydrogenases↗
PubMed2002

Microgravity-induced apoptosis in cultured glial cells.

Apoptosis is a form of naturally occurring cell death that plays fundamental roles during embryonic developement. In adults, it neatly disposes of cells damaged by injuries provoked by external causes such as UV radiation, ionisation and heat shock. Alteration of the gravity vector may be one of the external apoptosis inducers. Neurophysiological impairment signs were seen during space flights in astronauts, but very few studies were carried out on the nervous system and none at the cellular level. In this study, we submitted cultured C6 glioma cells to microgravity (0xg) of varying duration, obtained by clinorotation in a Fokker three-dimensional clinostat for 15 min, 30 min, 1h, 20h or 32h. After 30 min at 0xg, numerous nuclei underwent the classical morphological alterations (chromatin condensation, nuclear fragmentation, apoptotic bodies) that lead to the programmed cell death. After 30 min at 0xg, immunostaining for the enzyme caspase-7 was present in the cytoplasm of many cells concurrently with DNA fragmentation identified by the TUNEL method. At 32h, the number of apoptotic nuclei was much reduced indicating the ability of glial cells to adapt to altered gravity.

Animals↗
PubMed2002

Microgravity-induced programmed cell death in astrocytes.

Cultured astrocytes were submitted to simulated microgravity using a Fokker clinostat under continuous rotation (60 rpm) for 15', 30', 1h, 20h and 32h. Samples processing included (i) nuclear stainings using Propidium Iodide and 4,6-diamidino-2-phenilindole, dihydro chloride, (ii) immunohistochemical identification of Caspase-7, (iii) identification of DNA fragmentation using the terminal dUTP nick end labelling and (iv) Scanning Electron Microscope analysis. After 30' at simulated microgravity the glial cells showed morphological evidence of apoptosis: cell shrinkage, chromatin condensation, nuclear blebs and fragmentation. The enzyme caspase-7 was present and DNA fragmentation was evident. After 32h the density of the cell population was much lower than that observed in controls.

Journal Article↗
PubMed2001

Leptin levels in diabetic and nondiabetic subjects.

The role of leptin in human pathophysiology elicits considerable interest in view of its potential role as a treatment tool for obesity and other insulin resistant states, like type 2 diabetes mellitus (T2DM). Leptin has been extensively studied in obese humans, and much less so in other pathologic conditions. Leptin level has been reported to correlate with percent body fat mass (%FM), fasting serum insulin (FPI), insulin sensitivity and blood pressure. The aim of this study was to compare the leptin concentration, and its relationship with some anthropometric and biochemical parameters related to insulin resistance in 140 moderately obese type 2 diabetics (T2DM) and 160 age and weight matched non-diabetic controls in order to get a better insight into the possible role of leptin in the metabolic abnormalities of diabetes. The leptin levels were lower in the diabetic population only when both sexes were combined (p < 0.05) and were higher in the females of both groups. Among the nondiabetics, the leptin levels appeared to be related to BMI, %FM, HDL and FPI, while this was not the case in the diabetics. After correction for BMI, leptin appeared to be correlated with the FPI levels only in the non-diabetic females. When plasma leptin was included in a multiple linear regression model with plasma leptin as a dependent variable, BMI, W:Hr and FPI levels were significantly related to leptin in the non diabetic population, while no relationship reached the level of statistical significance among the diabetics, with the exception of the borderline value for the FPI (p = .052). In conclusion, leptin levels were independent of any of the parameters examined in our diabetic population, possibly due to the progressive loss of the normal mechanisms of leptin regulation with advancing disease. Conclusive data can only be obtained from the longitudinal study of a cohort of newly diagnosed diabetic subjects.

Aged↗
PubMed2001

Simulated microgravity induces alteration in the central nervous system.

To investigate whether the signs of neurophysiological impairment observed in flight may be traced back to cytomorphology, we undertook a ground-based study focusing upon the architecture of cultured glial cells under simulated microgravity obtained by three-dimensional clinorotation.

Actin Cytoskeleton↗
PubMed2000

Adaptation of the human endocrine system to microgravity in the context of integrative physiology and ageing.

This review deals with changes occurring in space in different endocrine systems. Sections are dedicated to hormones involved in bone remodelling, the hypothalamic-pituitary-adrenal axis, the hypothalamic-pituitary-thyroid axis, pancreatic hormones, the hypothalamic-pituitary-gonadal axis and the hypothalamic-pituitary-somato-mammotropic system. In space, most systems - especially those regulating bone/muscle metabolism and reproduction - undergo changes resembling those observed during senescence, but recover within weeks or months after return. This suggests space as a possible experimental model for the study of "reversible ageing processes". Studying ageing through space technology might give us the opportunity to combine the holistic view of integrative physiology with the most ambitious goal of the present scientific community, i.e. to yield successful ageing by promoting chronic disease prevention studies and by optimizing safe, anti-ageing therapeutic protocols.

Adaptation, Physiological↗
PubMed2000

Leptin and aging: correlation with endocrine changes in male and female healthy adult populations of different body weights.

Aging is associated with changes in plasma levels of several hormones. There are conflicting reports on whether circulating leptin levels change during aging, the possible explanation for which is that alterations in adiposity and body mass index (BMI) also occur. In this study we measured plasma leptin and other hormonal parameters known to influence leptin in 150 men and 320 women of a wide age (18-77 yr) and BMI (18.5-61.1 kg/m2) range. Subjects of each gender were separated into 2 groups of similar BMI, i.e. nonobese (BMI, <30) and obese (BMI, >30), and treated separately. Statistical analysis was performed, treating each group of subjects as a whole population or divided into age groups (<30, 30-50, and >50 yr). BMI-adjusted leptin levels were progressively lower with increasing age in women, with a consistent fall after menopause (-21%; P < 0.001); in men, leptin levels also tended to be lower in subjects more than 50 yr of age, but the reduction was not significant. Multiple linear regression analysis, performed on subjects treated either as a whole population or divided into obese and nonobese, showed that in both genders BMI and age were independent contributors of leptin levels, and there was an inverse relationship between leptin and age in both obese (standardized coefficient beta = -0.25 in women and -0.23 in men; P < 0.01) and nonobese (-0.22 in women and -0.20 in men; P < 0.05) subjects. The correlation of leptin and age with plasma levels of sex and thyroid hormones, GH, insulin-like growth factor I, PRL, and insulin was also evaluated. The variables that correlated with leptin were included in a multiple regression model that included BMI and age. Testosterone in men (-0.43 in nonobese and -0.19 in obese; P < 0.05) and estradiol in women (0.22 in nonobese and 0.24 in obese; P < 0.05) were important contributors to leptin levels; also, dehydroepiandrosterone sulfate in obese women (-0.16) and sex hormone-binding globulin in obese subjects of both genders (0.15 in women and 0.19 in men) were significant determinants in the model. However, none of the hormonal parameters abolished the negative correlation between leptin and age or the gender difference in leptin levels. In conclusion, our data show that in adult humans of different body weight, serum leptin gradually declines during aging; leptin reduction is higher in women than in men, but it is independent from BMI and other age-related endocrine changes.

Adolescent↗
PubMed2000

Testosterone urinary excretion rate increases during hypergravity in male monkeys.

Real and simulated microgravity impairs T secretion both in animals and in the human. To verify whether hypergravity might enhance T secretion as a consequence of an opposite mechanical effect, 6 male monkeys were centrifuged at 2 G for 3 weeks after a 1 G stabilization period lasting 3 weeks and then taken back to 1 G for 1 week and urine were collected daily for T excretion measurement. Significantly higher level were observed during the initial 2 G phase as compared to pre- and post centrifugation periods and the trend was the same during the remaining 2 G period. This may reflect changes in testicular perfusion rather than endocrine adaptation per se.

Animals↗
PubMed1999

Hormonal changes in humans during spaceflight.

Readers of this review may feel that there is much more that we do not know about space endocrinology than what we know. Several reasons for this state of affairs have been given: 1. the complexity of the field of endocrinology with its still increasing number of known hormones, releasing factors and precursors, and of the interactions between them through various feedback mechanisms 2. the difficulty in separating the microgravity effects from the effects of stress from launch, isolation and confinement during flight, reentry, and postflight re-adaptation 3. the experimental limitations during flight, such as limited number of subjects, limited number of samples, impossibility of collecting triple samples for pulsatile hormones like growth hormone 4. the disturbing effects of countermeasures used by astronauts 5. the inadequacy of postflight samples for conclusions about inflight values 6. limitations of conclusions from animal experiments and space simulation studies The endocrinology field is divided in to nine systems or axes, which are successively reviewed: 1. Rapid bone demineralization in the early phase of spaceflight that, when unopposed, leads to catastrophic effects after three months but that slows down later. The endocrine mechanism, apart from the effect of exercise as a countermeasure, is not yet understood. 2. The hypothalamic-pituitary-adrenal axis is involved in stress reactions, which complicate our understanding and makes postflight analysis dubious. 3. In the hypothalamic-pituitary-gonadal axis, pulsatility poses a problem for obtaining representative values (e.g., for luteinizing hormone). Reproduction of rats in space is possible, but much more needs to be known about this aspect, particularly in women, before the advent of space colonies, but also in males because some evidence for reversible testicular dysfunction in space has been found. 4. The hypothalamic-pituitary-somato-mammotrophic axis involves prolactin and growth hormone. The latter also acts as a stress hormone and its secretion is greatly decreased in spaceflown rats, but not in astronauts, which may be due to differences in the regulation of growth hormone secretion between rats and humans. 5. The hypothalamic-pituitary-thyroid axis involves the thyroid hormones thyroxine and triiodothyronine, which are lowered in space, suggesting mild hypothyroidism. 6. The renin-angiotensin-aldosterone axis, which regulates water and electrolytes, involves antidiuretic hormone and two natriuretic peptides and shows paradoxical behavior in space. 7. Erythrocyte mass regulation involves erythropoietin, and space anemia is still not explained. 8. The endocrine pancreas involves insulin and glucagon, with loss of insulin sensitivity in space due to lack of exercise, which phenomenon requires more study before the advent of space colonies. 9. The sympathetic system acts through epinephrine, norepinephrine and dopamine and seems to have an increased activity in space in contrast to what had been widely believed. From the foregoing conclusions, it is clear that much further study is needed in all fields of space endocrinology. On the other hand, future studies will allow us to understand what happens in a given endocrine subsystem in the absence of the "gravity factor", the perturbing factor to which the human race has become adapted through thousands of years of evolution. This should provide us with a fuller understanding of the internal homeostatic mechanisms. An important point is that some endocrine systems seem to undergo changes in space that resemble those observed during senescence, but after spaceflight, recovery always occurs within weeks or months after return. This is particularly true for the systems regulating bone and muscle metabolism and reproduction, exactly as happens with the immune, neurosensory, and cardiovascular systems. Further space research may help us find new insights in the pathophysiology of aging and hopefully define novel prev

Animals↗
PubMed1999

Leptin and androgens in male obesity: evidence for leptin contribution to reduced androgen levels.

Leptin circulates in plasma at concentrations that parallel the amount of fat reserves. In obese males, androgen levels decline in proportion to the degree of obesity. Recently, we have shown that in rodent Leydig cells leptin inhibits hCG-stimulated testosterone (T) production via a functional leptin receptor isoform; others have found that leptin inhibits basal and hCG-induced T secretion by testis from adult rats. In this study, we further investigated the relationship linking leptin and androgens in men. Basal and hCG-stimulated leptin and sex hormone levels were studied in a large group of men ranging from normal weight to very obese (body mass index, 21.8-55.7). Initial cross-sectional studies showed that circulating leptin and fat mass (FM) were inversely related with total and free T (r = -0.51 and r = -0.38, P < 0.01 and P < 0.05, respectively). Multiple regression analysis indicated that the correlation between leptin or FM and T was not lost after controlling for SHBG and/or LH and/or estradiol (E2) levels and that leptin was the best hormonal predictor of the lower androgen levels in obesity. Dynamic studies showed that in obese men the area under the curve of T and free T to LH/hCG stimulation (5000 IU i.m.) was 30-40% lower than in controls and inversely correlated with leptin levels (r = -0.45 and r = -0.40, P < 0.01 and P < 0.05, respectively). Also, LH/hCG-stimulation caused higher increases in 17-OH-progesterone to T ratio in obese men than in controls, whereas no differences were observed between groups either in stimulated E2 levels or in the E2/T ratio. In all subjects, the percentage increases from baseline in the 17-OH-progesterone to T ratio were directly correlated with leptin levels or FM (r = 0.40 and r = 0.45, P < 0.01), but not with E2 or other hormonal variables. In conclusion, our studies, together with previous in vitro findings, indicate that excess of circulating leptin may be an important contributor to the development of reduced androgens in male obesity.

17-alpha-Hydroxyprogesterone↗
PubMed1999

The endocrinology of aging and its relationship to space physiology.

During the last century the number of people over 65 years of age has increased more than four-fold in the industrialized countries and by the year 2030 might account for 20% of the population. Life expectancy at birth is now about 75 (vs. 47 in 1900) and at 75 is 86 years. The scientific community is thus getting more and more interested in understanding the behavioral and clinical features of centenarians. During aging many endocrine systems undergo anatomic and functional changes at different times and with variable intensities, depending on individual genotypes and phenotypes. The most common finding is impaired anabolism, rather than increased catabolism, so that the hypothesis has been put forward that aging itself stems from the functional deterioration of the endocrine system. From a practical point of view, two main questions arise: (i) to which extent the endocrine glands accelerate physical decay?; (ii) may hormonal replacement ensure health at least longer than nowadays?

Aging↗
PubMed1999

Gender affects the pattern of neuroendocrine response to head-up tilt.

One of the major concerns in space medicine is post-mission postural hypotension. Since the beginning, most of the studies have been aimed at the identification of mechanical and neuroautonomic mechanisms within the cardiovascular system potentially involved in this phenomenon. Some gender differences in the cardiovascular reactivity to changing posture have been described so far, which still need better clarification. Moreover, the neuroendocrine contribution to postflight readaptation deserves more indepth studies. Sudden passive head-up tilting is considered to be a good simulation method for hemodynamic changes occurring during transition from 0xg to 1xg. The aim of this study was to verify whether cardiovascular or neuroendocrine changes occurring after sudden passive +70 degrees head-up tilt (HUT) became already evident within 10 min and were similar in healthy young-adult men and women.

Adaptation, Physiological↗