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Journal Article 2003; 24(3-4): 249-254 PubMed PMID: 14523365 Citation  Keywords:  17-alpha-Hydroxyprogesterone:blood, Adolescent, Adrenocorticotropic Hormone:blood, Adult, Female, Hirsutism:blood, Humans, Hydrocortisone:blood, Hyperandrogenism:genetics, Pituitary-Adrenal System:physiopathology, Polycystic Ovary Syndrome:genetics, Stero.   

OBJECTIVES: Impaired adrenal function is common in patients with polycystic ovary syndrome (PCOS). Abnormal regulation of cytochrome P450 17 alpha is believed to cause the exaggerated 17-hydroxyprogesterone (17OHP) response to ACTH stimulation. The aim of the study was to evaluate cortisol and 17OHP response to low dose (1 microg) ACTH test and to compare it with the standard ACTH (250 microg) test in hyperandrogenic women with PCOS.

DESIGN AND MEASUREMENTS: We studied 27 PCOS and 22 control women. All participants were examined for mutations of the CYP21 gene, Cortisol and 17OHP levels before, 30 and 60 minutes after the IV injection of 250 microg ACTH (SDT) and after 1 microg ACTH (LDT). Fasting serum levels of LH, FSH, testosterone, DHEAS were determined in all participants.

RESULTS: Basal and ACTH stimulated Cortisol during the SDT (470+/-138 nmol/L and 761+/-143, respectively) were significantly higher in PCOS vs. controls (232+/-124 and 670+/-130, respectively) (p<0.03, p<0.02, respectively). Basal 17OHP (6.1+/-2.1 nmol/L) and the peak response to SDT (14.2+/-3.6 nmol/L) were significantly higher in PCOS vs. controls (4.2+/-2.1, 10.9+/-3.0, respectively) (p<0.003, p<0.004, respectively). Abnormally elevated 17OHP response to SDT was detected in 6/27 PCOS women (22%). No statistically significant difference between the PCOS and control groups were noted during the LDT in both cortisol and 17OHP levels.

CONCLUSIONS: These data suggest that the exaggerated 17-hydroxyprogesterone (17OHP) response to ACTH stimulation in PCOS is revealed by stimulation at a pharmacological dose (250 microg) but not by a physiological dose (1 microg)....

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Journal Article 2003; 24(3-4): 241-248 PubMed PMID: 14523364 Citation  Keywords:  Adipocytes:drug effects, Adipose Tissue:physiology, Animals, Animals, Newborn:physiology, Blood Glucose:metabolism, Body Weight:drug effects, Cells, Cultured, Corticosterone:blood, Estradiol:blood, Female, Follicle Stimulating Hormone:blood, Glucose:pharm.   

UNLABELLED: It is recognized that there exists a link between hyperandrogenicity and insulin resistance.

OBJECTIVE: By using the neonatally androgenized female rat we explored whether this treatment modifies peripheral insulin sensitivity and visceral fat function at adulthood.

EXPERIMENTAL DESIGNS: On day 5 of age, female Sprague-Dawley pups were injected, sub cutaneous, with either 50 ml of sterile corn oil alone (CT) or containing 1.25 mg of testosterone propionate (TP) and further used for experimentation on day 100 of age. CT and TP rats were killed by decapitation in non-fasting condition and blood samples were kept frozen for measurement of different metabolites. Immediately after sacrifice, freshly dissected visceral fat pads were used for isolation of adipocytes, these cells were then incubated with medium alone or containing different concentrations of insulin in order to determine leptin secreted into the medium. Additionally, in vivo metabolic responses to intravenous high glucose load were performed in, 24 hour-fasting, CT and TP rats.

RESULTS: We found that neonatal androgenization induced adult animals displaying higher visceral adiposity mass, body weight and leptinemia than CT rats. No group differences were found in basal circulating levels of several hormones and metabolic parameters. The results of the high glucose load 90-min test indicated that TP and CT rats developed similar glycemia but this accounted because of an early significantly higher peak values of circulating insulin in TP than in CT rats, regardless of similar enhancement in circulating glucocorticoid concentrations in both groups. While high glucose load significantly increased, over the baseline, circulating leptin concentrations as early as 30 min post-glucose in CT rats, in TP animals, it significantly enhanced leptinemia only by the end of the test. Finally, results of in vitro incubations of isolated visceral adipocytes indicated that cells from androgenized rats spontaneously released more leptin than control cells, although they were less responsive than CT cells to insulin-induced leptin output.

CONCLUSION: Our study strongly supports the hypothesis that development of insulin resistance seems to be dependent on early hyperandrogenicity....

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Clinical Trial 2003; 24(3-4): 233-240 PubMed PMID: 14523363 Citation  Keywords:  Aged, Aged, 80 and over, Aging:pathology, Endocrine Glands:drug effects, Female, Health Status Indicators, Humans, Immunity:drug effects, Male, Metabolism:drug effects, Mortality, Peptides:pharmacology, Pineal Gland:chemistry, Respiratory Tract Diseases:e.   

OBJECTIVES AND DESIGN: Researchers of the St. Petersburg Institute of Bioregulation and Gerontology of the North-Western Branch of the Russian Academy of Medical Sciences and the Institute of Gerontology of the Ukrainian Academy of Medical Sciences (Kiev) clinically assessed the geroprotective effects of thymic (Thymalin) and pineal (Epithalamin) peptide bioregulators in 266 elderly and older persons during 6-8 years. The bioregulators were applied for the first 2-3 years of observation.

RESULTS: The obtained results convincingly showed the ability of the bioregulators to normalize the basic functions of the human organism, i.e. to improve the indices of cardiovascular, endocrine, immune and nervous systems, homeostasis and metabolism. Homeostasis restoration was accompanied by a 2.0-2.4-fold decrease in acute respiratory disease incidence, reduced incidence of the clinical manifestations of ischemic heart disease, hypertension disease, deforming osteoarthrosis and osteoporosis as compared to the control. Such a significant improvement in the health state of the peptide-treated patients correlated with decreased mortality rate during observation: 2.0-2.1-fold in the Thymalin-treated group; 1.6-1.8-fold in the Epithalamin-treated group; 2.5-fold in the patients treated with Thymalin plus Epithalamin as compared to the control. A separate group of patients was treated with Thymalin in combination with Epithalamin annually for 6 years and their mortality rate decreased 4.1 times as compared to the control.

CONCLUSIONS: The obtained data confirmed the high geroprotective efficacy of Thymalin and Epithalamin and the expediency of their application in medicine and social care for health maintenance and age-related pathology prevention in persons over 60 to prolong their active longevity....

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Journal Article 2003; 24(3-4): 227-232 PubMed PMID: 14523362 Citation  Keywords:  Amino Acid Sequence, Animals, Dose-Response Relationship, Drug, Enzyme-Linked Immunosorbent Assay, Hemolymph:metabolism, Leeches:metabolism, Lipopolysaccharides:pharmacology, Molecular Sequence Data, Peptides:metabolism, Radioimmunoassay, Spectrometry, Ma.   

: We demonstrate the presence in leech hemolymph of high levels of a peptide recognized by antiserum directed against bovine chromacin. The purification of the chromacin-like peptide was carried out by an acidic extraction, followed by solid phase and high pressure gel permeation chromatography and reversed-phase HPLC purification. Its sequence (GDFELPSIADPQATFESQRGPSAQQVDK) was established by a combination of techniques, including automated Edman degradation, MALDI-TOF measurement and DOT immunobinding assays with anti-chromogranin A. Mass spectrometry measurement revealed a m/z 3177Da, revealing the fact that the molecule is phosphorylated. ELISA titrations performed at each step of the purification revealed a major increase in the level of the peptide (ca. 125 nmol/microl of coelomic fluid) 15 min after LPS exposure. The increase in chromacin-like peptide levels is both time and concentration dependent. The level of this peptide decreased significantly 4 hours after LPS exposure. This report is the first discovery of a chromogranin derived like peptide in invertebrates....

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Journal Article 2003; 24(3-4): 215-223 PubMed PMID: 14523360 Citation  Keywords:  Aging:metabolism, Animals, Autoradiography, Cell Division:drug effects, DNA:biosynthesis, Male, Melatonin:pharmacology, Microscopy, Electron, Rats, Rats, Sprague-Dawley, Spleen:cytology, T-Lymphocytes:drug effects, Thymus Gland:drug effects,.   

OBJECTIVES: In this study we investigated the effect of melatonin treatment on the proliferative activity, the rate of DNA synthesis and the histopathological changes of splenic and thymic lymphocytes in old rats.

METHODS: Two subgroups of old rats (25-months-old) were used in this study. One subgroup was given melatonin in the drinking water (250-300 mg/day/rat) for 3 months while the second subgroup was given water containing diluent. A third group consisted of young rats (3-months-old) which served as an additional control.

RESULTS: A (3)H-thymidine autoradiographic investigation showed a reduction in both the proliferative activity and the rate of DNA synthesis in splenic and thymic lymphocytes in old rats. In addition, light and electron microscopy showed severe histopathological changes in these cells from diluent-treated old rats. Melatonin administration increased the proliferative activity and the rate of DNA synthesis in the lymphocytes of both the spleen and thymus of the old animals. Also, histopathological changes were partially reversed by melatonin treatment with the tissues appearing similar to those in the young rats.

CONCLUSION: The stimulation of the lymphocyte activity by melatonin is a beneficial response, especially in old rats, since aging results in an inhibition in lymphocytic functions....

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Journal Article 2003; 24(3-4): 209-214 PubMed PMID: 14523359 Citation  Keywords:  Animals, Immunohistochemistry, Leydig Cells:physiology, Luminescent Measurements, Male, Organ Size:physiology, Photoperiod, Rats, Rats, Wistar, Seminiferous Tubules:anatomy & histology, Testis:anatomy & histology, Testosterone:blood,.   

OBJECTIVE: The aim of this study was to examine the effects of photoperiod on testes in rat.

DESIGN: For this purpose 21 male Wistar rats were used. Animals were divided into three groups. Control rats in group I were kept under 12 hrs light: 12 hrs dark conditions (12L: 12D) for 10 weeks. Animals in group II were exposed to long photoperiods (18L: 6D), while rats in group III were exposed to short photoperiods (6L: 18D) for 10 weeks. At the end of the experiment, all animals were killed by decapitation and blood samples were obtained. Serum testosterone levels were determined with the use of a chemiluminescent enzyme immunoassay. The testes of all rats were removed and weighed. Testicular tissue was processed semiquantitative evaluation of immunohistochemical testosterone staining. Intensity of immunostaining was determined on a scale between 0 (no staining) and 5 (heavy staining). For morphometric comparison, diameters of seminiferous tubules in each group were measured.

RESULTS: In rats exposed to long photoperiods, testicular weights, diameters of seminiferous tubules and serum testosterone levels were significantly increased as compared to those in control rats. Whereas, exposure of rats to short photoperiods resulted in significantly decrease of testicular weights, diameters of seminiferous tubules and serum testosterone levels as compared to those in control rats and rats maintained in long photoperiods. Immunostaining of testosterone was moderate (3+) in control rats, heavy (5+) in rats exposed to long photoperiods and minimal (1+) in rats exposed to short photoperiods.

CONCLUSIONS: The results of our study indicate that testicular functions increase after exposure to long photoperiods and decrease after exposure to short photoperiods....

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Journal Article 2003; 24(3-4): 203-208 PubMed PMID: 14523358 Citation  Keywords:  Aged, Aged, 80 and over, Alzheimer Disease:blood, Cohort Studies, Dementia:blood, Follicle Stimulating Hormone:blood, Gonadotropins:blood, Humans, Hypogonadism:blood, Immunoenzyme Techniques, Luteinizing Hormone:blood, Male, Sex Hormone-Binding Globulin:m.   

OBJECTIVES: Sex steroids such as testosterone and estradiol might protect the brain against Alzheimer's disease (AD). We previously found lower levels of testosterone in men with AD compared with controls. We wanted to assess levels of pituitary gonadotropins that regulate sex steroid levels, to determine whether primary or secondary hypogonadism was responsible for low levels of testosterone in cases.

METHOD: We included 45 men with AD (McKhann, 1987), 15 men with other types of dementia and 133 elderly controls from the Oxford Project to Investigate Memory and Ageing. Gonadotropins (follicle stimulating hormone or FSH and luteinizing hormone or LH), sex hormone binding globulin (SHBG, which determines the amount of free testosterone) and testosterone were measured using enzyme immunoassays.

RESULTS: We found no difference in average LH (8.7 +/- 9 UI/L), FSH (13 +/- 17 UI/L) or SHBG (44 +/- 18 nmol/L) levels between AD cases and controls. Similar to our earlier findings, testosterone levels were significantly lower in men with AD (13 +/- 6 nmol/L) compared with controls (17 +/- 8, O.R. = 0.92, 95% C.I. = 0.87 to 0.97, p<0.005). Results were unchanged when controlled for age, SHBG and gonadotropin levels.

CONCLUSION: Although normal, the levels of gonadotropins were inappropriately low for the levels of testosterone. Our results support a preliminary conclusion that secondary hypogonadism occurs in men with AD. This could be a consequence of brain degeneration. This is contrary to an earlier study (Bowen, 1999) that found raised levels of gonadotropins in cases with AD, suggesting primary hypogonadism. Our cohort was younger than theirs and gonadotropin levels increase with age. We are enlarging our data set to investigate whether primary hypogonadism occurs in older cases with AD or whether secondary hypogonadism precedes cognitive dysfunction in men at risk for AD. If this is true, testosterone replacement therapy for hypogonadal men at risk for dementia may be indicated....

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Clinical Trial 2003; 24(3-4): 197-202 PubMed PMID: 14523357 Citation  Keywords:  Adrenocorticotropic Hormone:blood, Adult, Anxiety:physiopathology, Blood Pressure:physiology, Conflict (Psychology), Heart Rate:physiology, Hemodynamics:physiology, Hormones:blood, Human Growth Hormone:blood, Humans, Hydrocortisone:blood, MMPI, Military P.   

OBJECTIVES: Pilots are exposed to the "stress of flight" and the chronically activated stress response may play an important role in circulatory system disease progression. We studied the effect of an experimental mental stress on cardiovascular and neuroendocrine activity, in Air Force Academy cadets, before and after one month intensive course.

DESIGN: Nine cadets were submitted to a psychometric evaluation before Stroop test (ST), including Minnesota Multiphasic Personality Inventory, State and Trait Anxiety Inventory (STAI X1 and X2 form) and Reaction Scheme Test. After ST, subjects completed a STAI X1 form. Heart rate (HR), systolic and diastolic blood pressure (SBP and DBP) were monitored and serum prolactin (PRL), growth hormone (GH), adrenocorticotropin (ACTH) and cortisol levels were determined, during ST. The protocol was repeated at the end of the course.

RESULTS: No significant differences were evident in PRL, GH and ACTH levels. Cortisol concentrations were significantly higher before the course. ST did not modify hormone secretion. ST induced a significant and reproducible elevation of HR and SBP. Basal HR, SBP and DBP values were significantly elevated after the course. Two subjects presented a particular psychometric profile, a different cardiovascular response to ST and did not pass the course.

CONCLUSIONS: acute mental stress significantly activated cardiovascular response without modifying endocrine responses, in relation to the psychological profiles. A significant increase of cardiovascular parameters was present after the course, with enhanced dichotomy between the endocrine and sympathetic system, suggesting a careful evaluation and follow-up for circulatory system diseases in cadets....

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