Hormonal Modifications Research Articles

In Vivo Effects of 137 Cesium on Steroidogenesis on Rats Chronically Contaminated from Different Ages

More than twenty years after the Chernobyl nuclear power plant explosion, radionuclids are still mainly bound to the organic soil layers. The radiation exposure is dominated by the external exposure to gamma-radiation following the decay of 137 cesium (137Cs) and by soil-to-plant-to-human transfer of 137Cs through the food chain. Because of this persistent contamination with 137Cs, questions regarding public health for people living in contaminated areas were still raised. In territories near Chernobyl, studies report various malfunctions affecting the cardiovascular, nervous, immune or urogenital systems, in addition to a large increase of thyroid cancers among adult populations. Moreover, it has been shown increases in children’s general morbidity and increases in rare illnesses in the Chernobyl polluted territories. More particularly, children present some perturbations of the endocrine system, as well as delay of puberty, or acceleration of sexual development. Despite of these observations no experimental study has been conducted regarding the effects of 137Cs on steroidogenesis metabolism to understand mechanisms responsible for these perturbations. Two rodent models were developed in our laboratory, to mimic exposure of adult and juvenile populations. We contaminated rats via their drinking water for nine months (equivalent to twenty years for human) with a dose that can be found in contaminated territories (6500Bq/L). Adults’ rats were contaminated from the age of three months. Pups were contaminated in a first time via dams’ milk, then directly through their drinking water, until the age of 9 months. Concerning hormonal profiles, a three-fold decrease in estradiol level was noted following adult-contamination. This hormonal modification was not found after post-natal contamination. In addition, no modification in circulating testosterone level was observed for both models. Concerning gene expression of biosynthesis enzymes, no change was noticed for adult-contamination. For post-natal contamination, only aromatase (responsible for estradiol synthesis) is up-regulated (two-fold). Surprisingly aromatase protein expression as well as activity were unmodified. These studies reveal that long term contamination of 137Cs differently affects testicular steroidogenesis metabolism when began at birth or from adulthood. It suggests that this radionuclide dos not have the same effects on testicular metabolism before and after puberty. It could be of great interest to study the effects of 137Cs contamination since in-utero development (to mimic Chernobyl’s children). In addition the effects of contamination on several generations should be studied.

In vivo effects of chronic contamination with 137 cesium on testicular and adrenal steroidogenesis

More than 20 years after Chernobyl nuclear power plant explosion, radionuclides are still mainly bound to the organic soil layers. The radiation exposure is dominated by the external exposure to gamma-radiation following the decay of (137)Cs and by soil-to-plant-to-human transfer of (137)Cs into the food chain. Because of this persistence of contamination with (137)Cs, questions regarding public health for people living in contaminated areas were raised. We investigated the biological effects of chronic exposure to (137)Cs on testicular and adrenal steroidogenesis metabolisms in rat. Animals were exposed to radionuclide in their drinking water for 9 months at a dose of 6,500 Bq/l (610 Bq/kg/day). Cesium contamination decreases the level of circulating 17beta-estradiol, and increases corticosterone level. In testis, several nuclear receptors messenger expression is disrupted; levels of mRNA encoding Liver X receptor alpha (LXRalpha) and LXRbeta are increased, whereas farnesoid X receptor mRNA presents a lower level. Adrenal metabolism presents a paradoxical decrease in cyp11a1 gene expression. In conclusion, our results show for the first time molecular and hormonal modifications in testicular and adrenal steroidogenic metabolism, induced by chronic contamination with low doses of (137)Cs.

Stress and periodontal disease

Stress is an association of physiological and psychological reactions of a person confronted to a change of situation he cannot face. The relationship between stress and any disease is explained by hormonal modifications and behavioural changes induced by the stress. The evidence of such an association between stress and periodontal disease will be evaluated. The purpose of the present review article is to differentiate between old feelings and knowledge, and present findings which show that a lot of prospective studies are still needed for a more defined role of stress and periodontal disease.

Pretreatment with a mixture of essential fatty acids protects rats from anxiogenic effects of REM deprivation

Rapid eye movements (REM) deprivation induces complex deteriorating effects, which include brain morphological changes such as reduced neurogenesis processes, brain neurochemical and hormonal modifications, and cognitive decline. One of the major effects of REM deprivation is an increased anxiety level. The aim of this study was to examine the effects of pretreatment with a specific mixture of essential fatty acids on the increased level of anxiety on the behavioral level (elevated plus maze), on the hormonal level (corticosterone level) and on the physiological level (thermoregulation).The results showed that pretreatment with a mixture of essential fatty acids protect the rats from the anxiolytic effects of REM deprivation. The effects of essential fatty acids on sleep mechanisms, on the one hand, and on anxiety levels, on the other hand, may explain the beneficial effects of the pretreatment.

Maternal adaptations to pregnancy in spontaneously hypertensive rats: leptin and ghrelin evaluation

Leptin and/or ghrelin, initially thought to be considered messengers of energy metabolism, are now considered to play a role in normal and complicated pregnancy. In this study, pregnant, spontaneously hypertensive rats (SHR) have been used to evaluate, for the first time, the modification of leptin and ghrelin both at serum and tissue levels. In SHR, we evaluate plasma leptin level and tissue protein expression in both placenta and adipose tissue at the end of gestation (day 20) versus normotensive Wistar-Kyoto (WKY) animals. The expression of functional leptin receptor (Ob-Rb) in peripheral tissues and in the hypothalamus was evaluated. Moreover, we measured plasma ghrelin level and its mRNA expression in the stomach and placenta. SHR strain presented significantly lower plasma leptin levels when compared with those found in pregnant or not WKY controls. Interestingly, in the placenta, leptin gene expression was higher in SHR than normotensive WKY. Moreover, we demonstrated a resistance to the effects of leptin via 'downregulation' of hypothalamic receptors in pregnant SHR. Conversely, SHR presented significantly higher ghrelin plasma levels when compared with those found in pregnant or not WKY. However, we observed that ghrelin level in the stomach of SHR did not change during pregnancy, and on the opposite, mRNA ghrelin in the placenta of SHR was lower than that of normotensive rats, suggesting a different production of this hormone in the fetal-placental unit. These data gain further insight into metabolic hormone modifications observed in a model of pre-existing hypertension associated with pregnancy.

Stress indicators in steers at slaughtering

This work aimed to assess the blood modifications of some slaughtering-linked stress hormones in cattle subject to butcher standardized procedures. The blood samples of 20 Limousine 12-13 months old steers have been collected before slaughtering, during lairage, and after stunning by captive bolt gun, during exsanguination. The plasma level of epinephrine, norepinephrine, cortisol and beta-endorphin have been assayed by EIA. The data indicate that catecholamines, cortisol and beta-endorphin did not significantly increase after stunning in these animals.

Endocrine and inflammatory alterations in post-traumatic stress disorder

Post-traumatic stress disorder has frequently been found associated with alterations in endogenous stress hormone systems, for example the hypothalamus–pituitary–adrenal axis and sympatho–adrenal–medullary system. Hormonal alterations are observed at the central and peripheral level of the central nervous system, and in the periphery for inflammatory disinhibition. Both consequences bear significant hazards for the individual, the former by sustaining or exacerbating the psychiatric condition, the latter by its detrimental effects on somatic health. However, the role of hormonal modifications in the development and maintenance of post-traumatic stress disorder symptoms and in the accompanying cognitive and emotional impairments still remains quite unclear.

Responses of the Steroid Circadian System to Alcohol in Humans: Importance of the Time and Duration of Intake

Reports provide conflicting data about the effects of alcohol consumption on the hormonal system. Any study of these effects must control for a number of variables, including sex, alcohol status (alcoholic addiction vs. non-addiction), medical status (malnutrition, liver disease), and conditions of alcohol exposure, including an acute or continuous pattern of intake. The latter appears to be an especially critical factor in interpreting these effects. The authors therefore conducted a trial with a circadian design in which alcohol was administered repeatedly and regularly over a 26 h period for a total dose of 256 g. Because this protocol involves continuous alcohol administration, it is similar to administration among alcoholics and thus sheds new light on alcohol's effect on hormone secretion. Using healthy volunteers rather than alcoholics, however, prevents any confounding due to liver disorders and nutritional deficiencies, and thus makes it possible to focus on the direct role of alcohol in hormonal modifications. In these conditions, the continuous administration of alcohol did not affect cortisol secretion, but serum testosterone levels were significantly higher at all time points during the alcohol session than at the corresponding time points during the control session. These data are not consistent with previously reported findings for the relation between alcohol and both cortisol and testosterone, because in the current experiment the action of ethanol on steroid secretion should involve the circadian clock more than the hormonal system itself.

Persisting neural and endocrine modifications induced by a single fat meal.

1. High-fat diets, modify the neuroendocrine response and, when prolonged, result in positive energy balance and obesity. Little is known about the effects of fat on the mechanisms operating in the initial steps of the neural and endocrine disturbances. 2. The studies reported here were designed to access the impact of the consumption of a single exclusively animal fat meal (lard), 24 h following its ingestion a) on the response of the hypothalamic serotonergic system to a standard laboratory chow meal and b) on the circulating levels of glucose, insulin, and leptin. The release of serotonin in the extracellular medial hypothalamic space (including the paraventricular-PVN and ventromedian-VMH nuclei) was determined using electrochemical detection following HPLC in samples obtained in vivo by microdialysis, in nonanesthetized adult male Wistar rats. 3. A lard meal resulted in decreased hypothalamic serotonin release postprandially and attenuated (24 h later) the hypothalamic serotonin response that normally follows a balanced meal. 4. In permanently catheterized rats, postprandial glucose and insulin levels measured in samples obtained in vivo, were either not, or only slightly, modified after a lard meal, whereas plasma leptin levels were increased. Interestingly, 24 h after a meal, insulin and leptin levels were increased in those animals eating a fat meal compared with those eating chow. Next-day glucose levels remained identical after the absorption either of a chow, or a lard meal. 5. The changes induced by the fat meal on peripheral and central regulators of energy and glucose homeostasis represent either adaptive mechanisms or early alterations that could render the organism vulnerable to further insults.

Short-term modification of sex hormones is associated with changes in ghrelin circulating levels in healthy normal-weight men

The aim of this study was to evaluate the effect of selective and short-term sex hormone modifications on ghrelin levels in normal-weight eugonadal men undergoing hormonal contraceptive treatments. Seven men received an oral progestin [cyproterone acetate (CPA) or dienogest (DNG)] 10 mg/day for 3 weeks (CPA-DNG group), 7 CPA orally 5 mg/day in association with testosterone enanthate (TE) im 200 mg/week for 8 weeks (CPA-TE group), and 7 placebo (PLAC) for 8 weeks (PLAC group). Anthropometry and blood levels of LH, FSH, testosterone, estradiol, glucose, insulin and total ghrelin were evaluated. At baseline, no parameters differed among the three groups. After treatment, LH and FSH decreased in both CPA-DNG and CPA-TE groups, whereas they did not change in the PLAC group. Testosterone and estradiol decreased in the CPA-DNG group to the hypogonadal range, increased in the CPA-TE group to supraphysiological concentrations and, as expected, remained unchanged in the PLAC group. Total ghrelin levels increased in the CPA-DNG, decreased in the CPA-TE and did not change in the PLAC group. Ns modifications in the other parameters were observed in any group, demonstrating that the short-term changes of circulating sex hormones are able to modify ghrelin levels. These data, therefore, suggest that sex steroids are important regulators of ghrelin in normal-weight healthy men too.

Pharmacologic modifications of hormones to improve their therapeutic potential for diabetes management

Rapid-acting genetically engineered insulin analogues emerging in the last 10 years are now established as more effective prandial insulins than traditional short-acting human insulin. The development of analogues for use as basal insulin, however, has been much slower. Methods of pro-tracting the time-action curve of injected insulin include complexing with proteins, insulin crystal formation, shifting the iso-electric point of the amino acid sequence or attaching a fatty-acid side chain to the molecule. The latter two methods have been more successful in producing physiologic insulin profiles when compared with the former methods. The principle of acylation has also been applied to prolong the action of other hormones, such as glucagon-like peptide 1 (GLP-1), as the native peptide has a very short half-life. Preliminary results with this compound and other GLP-1 analogues show promise in treating patients with type 2 diabetes. In summary, the development of new insulin and other hormone preparations by the manipulation of native peptide structure has recently improved our antidiabetic armamentarium, and further research will continue this fruitful approach.

Effects of chronic retinoid administration on pituitary function

It has been reported that retinoids may affect hypothalamic-pituitary-thyroid axis, causing central hypothyroidism. In the present study, we evaluated pituitary function in 11 male psoriatic patients at baseline and after 1 and 3 months of treatment with acitretin (all-trans retinoic acid, 35 mg/day). Serum LH, FSH, testosterone, cortisol, GH and IGF-I levels were not affected by the treatment. By contrast, we observed a significant decrease in TSH levels (from 0.92 +/- 0.3 to 0.80 +/- 0.3 mU/I, p < 0.05) at 1 month, that reverted to baseline after 3 months. No change in free T4 (FT4) levels occurred, while free T3 (FT3) levels were reduced at 1 and 3 months (from 6.7 +/- 0.5 to 6.2 +/- 0.3 and 6.1 +/- 0.6 pmol/l; p < 0.05, respectively). Moreover, acitretin treatment induced a significant reduction of PRL levels after 3 months (from 182 +/- 70 to 150 +/- 56 mU/l, p < 0.05). During treatment, no change in TSH and PRL response either to TRH or dopamine infusion was observed. In conclusion, we demonstrated that treatment with low dose of acitretin induced a series of hormonal modifications that, in addition to a mild and transient reduction of TSH levels, included a persistent reduction of FT3, probably due to changes in thyroid hormone metabolism, and a decrease in PRL levels.

Effects of finasteride on the morphology of polycystic ovaries

Along with clinical and endocrine modifications ovarian morphology continues to be the basis for the diagnosis of polycystic ovaries syndrome (PCOS). Androgenic effects on the ovaries may be caused either by testosterone or by dihydrotestosterone. The enzyme that catalizes the transformation from testosterone to DHT is the 5-a-reductase which is present in the follicles stroma and luteal bodies of women’s ovaries. Treatment with inhibitors of the 5-a-reductase blocks the transformation from testosterone to DHT. The objective of the study was to evaluate ultrasonographic differences in the ovaries of women with this syndrome after treatment with finasteride an inhibitor of 5-a-reductase. (excerpt)

Endocrine modifications and interventions during critical illness.

The ongoing hypermetabolic response in patients with prolonged critical illness leads to the loss of lean tissue mass. Since the cachexia of prolonged illness is usually associated with low concentrations of anabolic hormones, hormonal intervention has been thought to be beneficial. However, most interventions have been shown to be ineffective and their indiscriminate use even causes harm. Before considering endocrine intervention in these frail patients, a detailed understanding of the neuroendocrinology of the stress response is warranted. It is now clear that the acute phase and the later phase of critical illness behave differently from an endocrinological point of view. The acute stress response consists primarily of an actively-secreting pituitary in the presence of low circulating peripheral anabolic hormones, suggesting resistance of the peripheral tissues to the effects of anterior pituitary hormones. However, when the disease process becomes prolonged, there is a uniformly-reduced pulsatile secretion of anterior pituitary hormones with proportionally reduced concentrations of peripheral anabolic hormones. The origin of this suppressed pituitary secretion is located in the hypothalamus, as hypothalamic secretagogues can reactivate the anterior pituitary and restore pulsatile secretion. The reactivated pituitary secretion is accompanied by an increase in peripheral target hormones, indicating at least partial sensitivity of these tissues to anterior pituitary hormones in this chronic phase of illness. Thus, endocrine intervention with a combination of hypothalamic secretagogues that more completely reactivate the anterior pituitary could be a more physiological and effective strategy for inducing anabolism in patients with prolonged critical illness.

Sulfonation and molecular action.

The sulfonation of endogenous molecules is a pervasive biological phenomenon that is not always easily understood, and although it is increasingly recognized as a function of fundamental importance, there remain areas in which significant cognizance is still lacking or at most minimal. This is particularly true in the field of endocrinology, in which the sulfoconjugation of hormones is a widespread occurrence that is only partially, if at all, appreciated. In the realm of steroid/sterol sulfoconjugation, the discovery of a novel gene that utilizes an alternative exon 1 to encode for two sulfotransferase isoforms, one of which sulfonates cholesterol and the other pregnenolone, has been an important advance. This is significant because cholesterol sulfate plays a crucial role in physiological systems such as keratinocyte differentiation and development of the skin barrier, and pregnenolone sulfate is now acknowledged as an important neurosteroid. The sulfonation of thyroglobulin and thyroid hormones has been extensively investigated and, although this transformation is better understood, there remain areas of incomplete comprehension. The sulfonation of catecholamines is a prevalent modification that has been extensively studied but, unfortunately, remains poorly understood. The sulfonation of pituitary glycoprotein hormones, especially LH and TSH, does not affect binding to their cognate receptors; however, sulfonation does play an important role in their plasma clearance, which indirectly has a significant effect on biological activity. On the other hand, the sulfonation of distinct neuroendocrine peptides does have a profound influence on receptor binding and, thus, a direct effect on biological activity. The sulfonation of specific extracellular structures plays an essential role in the binding and signaling of a large family of extracellular growth factors. In summary, sulfonation is a ubiquitous posttranslational modification of hormones and extracellular components that can lead to dramatic structural changes in affected molecules, the biological significance of which is now beginning to be appreciated.

Evaluation of the pituitary-testicular function during experimental nephrosis

To investigate the pituitary-testicular function in nephrotic rats, a sequence of experiments was undertaken in adult male rats after a single dose of puromycin aminonucleoside (PAN). Endocrine modifications were evaluated chronologically throughout the experimental disease in order to determine the appearance of hormone alterations which lead to the axis dysfunction. Serum concentration of LH, FSH, androstenedione, total and free testosterone, estradiol as well as urine testosterone were measured by specific RIAs on days 3, 7 and 10 after treatment on nephrotic and control groups. Prolactin was also evaluated on day 10. Likewise, total weight of various androgen responsive tissues from both groups was recorded, and the number of androgen receptor (AR) binding sites were determined. To know the functional status of the hipophyseal-testicular unit, groups of nephrotic and control rats were stimulated with LHRH (300 ng/100 g b.w.) or with one or four doses of hCG (8 UI), respectively. Additionally, the relative in vitro biological activity of FSH from nephrotic and control rats before and after LHRH stimulus was determined. The results from the hormonal profile revealed clear endocrine disorders characterized by a progressive diminution of all serum hormones except prolactin and urine testosterone, which remained unmodified. The weight of the main androgen responsive tissues, the ventral prostate and the seminal vesicle, decreased parallelly to androgen diminution. The binding analysis of AR shows a significant elevation of the available androgen sites in all analyzed tissues except kidney and hypothalamus. The secretion of LH and FSH from nephrotic animals after LHRH administration was lower than that from intact animals at the registered times. Interestingly, the biological activity of FSH from nephrotic rats was not detectable at both, before and after LHRH administration. Testicular response to hCG stimuli, in terms of testosterone synthesis was not significantly different in the two groups analyzed with respect to the intact animals. By contrast, no response was observed in terms of estradiol production at either one or four doses of hCG. On the whole, the results presented herein allow us to conclude that experimental nephrosis has a harmful effect on the pituitary-testicular axis, and strongly suggests that the endocrine dysfunction is initiated at the hypophyseal level; even though a specific testicular damage is also present.

Vomissements incoercibles du premier trimestre de la grossesse : rôle de l’hyperthyroïdie biologique et du sexe fœtal

Objectives. Our objectives were to link hyperemesis gravidarum with biochemical hyperthyroidism and hormonal modification (HCG and estradiol) and to test the hypothesis that biological abnormalities (ionogram and liver enzyme) are more often report in hyperemesis gravidarum with biochemical hyperthyroidism. Study design. Thirty three patients admitted in « Hôpital Jeanne de Flandre » with hyperemesis gravidarum were studied prospectively. Results. Twenty-two patients (66.7%) had biochemical hyperthyroïdsm (suppressed thyroid stimulating hormone or increased triiodothyronin index or tetraiodothyronin index). Hyperthyroid patients were more likely than euthyroid patients to have abnormal electrolyte levels (16/22 [72.7%] vs 3/1 [27.3%], P<0.02) or increased liver enzyme levels (8/22 [36.4%] vs 3/11 [27.3%]). The severity of hyperemesis was found to vary directly with the degree of hyperthyroidism. We report a female predominance among the offspring of mothers with hyperemesis gravidarum. Conclusion. Our results are suggestive of the involvement of hyperthyroidism and fetal sex in the pathogenesis of hyperemesis gravidarum. Also these hypothesis are not clearly understood, human chorionic gonadotrophin occur in the two mechanisms.

Women's health issues and their relationship to periodontitis

The emergence of sex-specific associations between periodontitis and certain systemic disorders has prompted researchers to investigate the possibility of associations between periodontitis and specific women's health issues. The authors review the potential relationships between periodontitis and hormonal changes and their ramifications in regard to pregnancy outcomes, cardiovascular disease, or CVD, and osteoporosis. Changes in hormone levels, such as those that occur during puberty, pregnancy, menstruation and menopause, as well as those that occur with the use of hormonal supplements, have long been associated with the development of gingivitis. Furthermore, bacterial anaerobes have been found to change during the normal hormonal cycle. In periodontitis, the inflammatory response results in ulceration of the gingivae and the subsequent entry of bacterial cells, bacterial products, peptidoglycan fragments and hydrolytic enzymes into the systemic circulation. The result is a systemic response of increased cytokines and biological mediators, as well as increased levels of serum antibodies. Some researchers have found that pregnant women with periodontitis were 7.5 times more likely to have a preterm low-birth-weight infant than were control subjects. Other researchers reported that the risk of preterm birth was directly related to the severity of periodontitis. Similarly, researchers have linked periodontitis to CVD. Many studies have indicated that estrogen exerts a protective effect against CVD development, and much evidence suggests that when hormone replacement therapy is administered to postmenopausal women, this effect continues. A relationship between periodontitis and osteoporosis has been established, such that more clinical attachment loss has been noted in osteoporotic people. The literature suggests that more sex-specific research is essential to determine the strategies needed to prevent and treat adverse pregnancy outcomes, CVD and osteoporosis through hormone modification and periodontitis control. Dentists must assume greater responsibility for the overall health of their patients, and acquire knowledge of relevant systemic conditions to interact meaningfully with medical colleagues.

Endocrinological and ultrasonographic variations after immature oocyte retrieval in a natural cycle.

In-vitro oocyte maturation is an appealing alternative in reproductive medicine but the results obtained are still poor. The aim of our prospective and observational investigation was to study the hormonal modifications that immature follicular aspiration might induce in a natural cycle as well as the implications that these alterations may have in the endometrium. Eleven patients (13 cycles) were included in our in-vitro oocyte maturation programme. Ovaries were scanned with transvaginal probes every day and follicular aspiration was performed when a follicle of 9 mm was visualized. Blood was also drawn for hormonal analysis. Endometrial thickness was recorded every day after oocyte retrieval. Two endometrial biopsies were taken on days 6 and 8 after oocyte retrieval. We observed a significant drop in serum oestradiol concentrations after immature oocyte retrieval previous to follicle dominance. Immediately after, rises in both FSH and LH were detected. Also, a new dominant follicle started to grow 3-4 days later. Steroid hormones secreted by this newly recruited follicle were significantly lower than in controls, inducing inadequate endometrial thickness. These studies show that exogenous hormonal administration might be necessary to achieve a correct endometrial growth when in-vitro oocyte maturation is employed in IVF.

Circadian rhythmicity of whole-blood glutathione in healthy subjects

Objectives: Physiologic rhythms of antioxidants have been the subject of considerable interest in recent years. Physiologically, it is known that 24-h variability in whole-blood glutathione (GSH) could depend on various factors, such as meal composition, protein dietary content, meal-related hormonal modifications, and stress. Experiments were conducted to determine if the circadian variations previously observed in hepatic concentrations of reduced glutathione in animals also occurred in healthy volunteers.Methods: The circadian periodicity of whole-blood glutathione was explored. All parameters were measured enzymatically at 4-h intervals over a 24-h period.Results: Circadian rhythms were not found. The rhythms peak for glutathione content occurred at 9 h with a small peak at 21 h. The nadir occurred at 17 h and 1 h.Conclusion: These data show that despite this wide distribution of glutathione throughout the day we could not find any significant intertime variability.