Experimental assessment of major regulatory systems (adrenal, thyroid and gonadal) in liver metastases from s45 sarcoma

Author(s):  
И.В. Каплиева ◽  
Е.М. Франциянц ◽  
Л.К. Трепитаки ◽  
Н.Д. Черярина

Метастазирование в печень - частый признак прогрессирования злокачественного процесса, механизм которого до конца не изучен. Цель - изучение особенностей функционирования основных систем нейрогуморальной регуляции: надпочечниковой (ГГНС), тиреоидной (ГГТС) и гонадной (ГГГС), на этапах метастазирования саркомы 45 (С45) в печень. Методика. Работа выполнена на 43 белых крысах-самцах. Через 1, 2, 5, 7 нед. от момента введения клеток саркомы 45 в дислоцированную под кожу селезенку. Органы взвешивались, в сыворотке крови (СК) методом РИА исследовали уровни фолликулостимулирующего гормона, лютеинизирующего гормона (ЛГ), тиреотропного гормона, адренокортикотропного гормона, кортизола, альдостерона, общей формы тестостерона, свободной и общей форм тироксина и трийодтиронина (Тсв и Т); методом ИФА - эстрона, эстрадиола, свободного тестостерона. Результаты. Метастазирование в печень сопровождалось активацией с последующим истощением ГГНС со снижением в 1,8 раза уровней кортизола и альдостерона в крови; значительной активацией ГГГС (пятикратное увеличение ЛГ в крови и уменьшение в 1,7 раза массы семенников) вследствие гипотестостеронемии (в 9,7 раза) на фоне гиперэстрадиолемии (в 2,3 раза); активацией ГГТС с формированием «low T» синдрома (в 4,6 раза). Заключение. Процесс метастазирования в печень - системная патология, в основе которой лежат глубокие нарушения работы основных систем регуляции организма. Aim: To evaluate functioning of three major systems of neurohumoral regulation, adrenal (HPA), thyroid (HPT), and gonadal (HPG) axes, in liver metastasis based on weights of organs and blood levels of hormones. Methods: The study included 34 white male rats. Organs were weighted at 1, 2, 5, and 7 weeks after S45 sarcoma cell injections into the subcutaneously transferred spleen; blood serum levels of FSH, LH, TSH, ACTH, cortisol, aldosterone, total testosterone, free and total thyroxine, and triiodothyronine were measured by RIA; estrone, estradiol, and free testosterone concentrations were measured by ELISA. Results. The process of liver metastasis was accompanied by activation and following exhaustion of the HPA axis with 1.8 time decreases in blood levels of cortisol and aldosterone , significant activation of the HPG axis (5-fold increased LH level and 59% decreased testicular weight) due to hypotestosteronemia (9.7 times) and hyperestradiolemia (2.3 times), and activation of the HPT axis with the low T3 syndrome (4.6 times). Conclusion. Liver metastasis is a systemic pathology based on profound dysfunction of the major regulatory systems.

2017 ◽  
Vol 22 (2) ◽  
pp. 93-100 ◽  
Author(s):  
I. V Kaplieva ◽  
E. M Frantsiyants ◽  
L. K Trepitaki ◽  
N. D Cheryarina ◽  
Yu. A Pogorelova

The aim of the study was to reveal characteristics of steroid metabolism in tumor, metastases, adrenal glands (AG) and blood serum (BS) in male rats in the course of liver metastasis, as well as diagnostic signs of metastases. Material and methods. The study included 44 white male rats weighing 180-250 g. S-45 sarcoma was transplanted intrasplenically. Estrone, estradiol, free testosterone, 17-OHP, cholesterol, cortisol (in tissues and BS), DHEAS (in tissues), DHEA and ACTH (in BS) were studied by the using standard test kits for ELISA and RIA. Results. We found that the pituitary gland does not participate in liver metastatic process (low ACTH in BS). AG are assumed to play a regulatory role of steroidogenesis in tissues. Characteristics of liver metastases that not re-metastasize - non-active metastases (NAM) are: decreased cortisol in the perifocal zone (PZ) and the less estrone increase in metastases. Characteristics of metastases that re-matastasize to lungs - active metastases (AM) are: increased cortisol in PZ and the greater estrone gain in metastases. Hypo-estradiolemia and hyper-testosteronemia were diagnostic criteria for the upcoming liver metastasis; hyper-estradiolemia along with the decline of free testosterone - signs of liver metastases; hyper-cortisolemia and hypercholesterolemia are for AM in experimental liver metastasis, hypo-cortisolemia and hypocholesterolemia are signs of NAM in the liver of male rats. Conclusion. Consequently, one of the detected pathogenetic mechanisms of liver metastasis is presented by deactivation of the central pituitary regulation of steroidogenesis with regulating function passed to AG which results in steroid imbalance with accumulation of estrone in metastases and multidirectional changes in cortisol levels in PZ and BS, depending on the activity of metastases.


2020 ◽  
Vol 18 (5) ◽  
pp. 381-386
Author(s):  
Yusuke Yoshino ◽  
Ichiro Koga ◽  
Yoshitaka Wakabayashi ◽  
Takatoshi Kitazawa ◽  
Yasuo Ota

Background: The change in the prevalence of hypogonadism with age in men with human immunodeficiency virus (HIV) infection is subject to debate. Objective: To address this issue, we diagnosed hypogonadism based on serum levels of free testosterone (fTST) rather than total testosterone which is thought to be an inaccurate indicator. We also determined the relationship between age and fTST levels and identified risk factors for hypogonadism in men with HIV infection. Method: We retrospectively reviewed fTST levels and associated clinical factors in 71 wellcontrolled HIV-infected men who were treated at Teikyo University Hospital between April 2015 and March 2016 and who had data available on serum fTST levels, measured >6 months after starting antiretroviral therapy. fTST was measured using radioimmunoassay on blood samples collected in the morning. Risk factors for hypogonadism were identified using Welch’s t-test and multiple regression analysis. Results: The men had a mean (± standard deviation) age of 47.4 ± 13.6 years, and mean (± standard deviation) serum fTST level of 13.0 ± 6.1 pg/mL. Fifteen (21.1%) men had hypogonadism based on a fTST <8.5 pg/mL. Serum fTST levels significantly decreased with age (−0.216 pg/mL/year). Older age and low hemoglobin levels were identified as risk factors for hypogonadism. Conclusion: The men in the study experienced a more rapid decline in fTST levels with age than men in the general population (−0.161 pg/mL/year). Serum fTST levels in men with HIV infection should be monitored, especially in older men and those with low hemoglobin levels.


1994 ◽  
Vol 62 (1) ◽  
pp. 76-80 ◽  
Author(s):  
Marcos Y. Khoury ◽  
Edmund C. Baracat ◽  
Dolores P. Pardini ◽  
José Gilberto H. Vieira ◽  
Geraldo R. de Lima

Author(s):  
Katarzyna Grzesiak ◽  
Aleksandra Rył ◽  
Ewa Stachowska ◽  
Marcin Słojewski ◽  
Iwona Rotter ◽  
...  

Background: The purpose of our investigation was to analyze the relationship between the serum levels of inflammatory mediators (HETE, HODE) and the levels of selected metabolic and hormonal parameters in patients with benign prostatic hyperplasia (BPH) with regard to concomitant metabolic syndrome (MetS). Methods: The study involved 151 men with BPH. Blood samples were taken for laboratory analysis of the serum levels of metabolic and hormonal parameters. Gas chromatography was performed using an Agilent Technologies 7890A GC System. Results: We found that waist circumference was the only parameter related to the levels of fatty acids, namely: 13(S)-HODE, 9(S)-HODE, 15(S)-HETE, 12(S)-HETE, and 5-HETE. In the patients with BPH and MetS, triglycerides correlated with 9(S)-HODE, 15(S)-HETE, 12(S)-HETE, and 5-HETE, which was not observed in the patients without MetS. Similarly, total cholesterol correlated with 9(S)-HODE, and 15(S)-HETE in the patients with BPH and MetS, but not in those without MetS. In the group of BPH patients with MetS, total testosterone positively correlated with 13(S)-HODE, and free testosterone with 9(S)-HODE. Conclusions: Based on this study, it can be concluded that lipid mediators of inflammation can influence the levels of biochemical and hormonal parameters, depending on the presence of MetS in BPH patients.


2008 ◽  
Vol 158 (3) ◽  
pp. 393-399 ◽  
Author(s):  
Els Elaut ◽  
Griet De Cuypere ◽  
Petra De Sutter ◽  
Luk Gijs ◽  
Michael Van Trotsenburg ◽  
...  

ObjectiveAn unknown proportion of transsexual women (defined as post-operative male-to-female transsexuals on oestrogen replacement) experience hypoactive sexual desire disorder (HSDD). It has been suggested that the absence of ovarian androgen production together with oestrogen treatment-related increase in sex hormone-binding globulin (SHBG) levels could be leading to HSDD, due to low levels of biologically available testosterone. This study wishes to document the HSDD prevalence among transsexual women and the possible association to androgen levels.DesignCross-sectional study.MethodsTranssexual women (n=62) and a control group of ovulating women (n=30) participated in this study. Questionnaires measuring sexual desire (sexual desire inventory) and relationship and sexual satisfaction (Maudsley Marital Questionnaire) were completed. Serum levels of total testosterone, LH and SHBG were measured in blood samples obtained at random in transsexual women and in the early follicular phase in ovulating women.ResultsThe transsexual group had lower levels of total and calculated free testosterone (both P<0.001) than the ovulating women. HSDD was reported in 34% of the transsexual and 23% of the ovulating women (P=0.30). Both groups reported similar levels of sexual desire (P=0.97). For transsexual women, no significant correlation was found between sexual desire and total (P=0.64) or free testosterone (P=0.82). In ovulating women, these correlations were significant (P=0.006, resp. P=0.003).ConclusionsHSDD is reported in one-third of transsexual women. This prevalence is not substantially different from controls, despite markedly lower (free) testosterone levels, which argues against a major role of testosterone in this specific group.


2008 ◽  
Vol 159 (5) ◽  
pp. 641-647 ◽  
Author(s):  
Catarina B d'Alva ◽  
Gwenaelle Abiven-Lepage ◽  
Vivian Viallon ◽  
Lionel Groussin ◽  
Marie Annick Dugue ◽  
...  

ObjectiveAdrenocortical tumors (ACT) account for no more than 0.2% of the causes of androgen excess (AE). Conversely, these rare tumors have a very poor prognosis. It is difficult and important to exclude this diagnosis whenever there is AE.DesignRetrospective investigation of androgen profiles in a large consecutive series of androgen-secreting (AS) ACT to assess their relative diagnostic value.MethodsA total of 44 consecutive female patients with ACT-AS and a comparison group of 102 women with non-tumor causes of AE (NTAE).ResultsPatients with ACT-AS were older than the ones with NTAE (37.7 vs 24.8 years; P<0.001) and the prevalence of hirsutism, acne, and oligo/amenorrhea were not different. Free testosterone was the most commonly elevated androgen in ACT-AS (94%), followed by androstenedione (90%), DHEAS (82%), and total testosterone (76%), and all three androgens were simultaneously elevated in 56% of the cases. Androgen serum levels became subnormal in all ACT-AS patients after complete tumor removal. In NTAE, the most commonly elevated androgen was androstenedione (93%), while all three androgens were elevated in only 22% of the cases. Free testosterone values above 6.85 pg/ml (23.6 pmol/l) had the best diagnostic value for ACT-AS (sensitivity 82%, confidence interval (CI): 57–96%; specificity 97%, CI: 91–100%). Basal LH and FSH levels were significantly lower in the ACT-AS group.ConclusionFree testosterone was the most reliable marker of ACT-AS. However, the large overlap of androgen levels between ACT-AS and NTAE groups suggests that additional hormonal and/or imaging investigations are required to rule out ACT-AS in case of increased androgens.


2020 ◽  
pp. 60-61
Author(s):  
A.O. Ocheretnyuk ◽  
B.O. Kondratsky ◽  
O.V. Palamarchuk ◽  
V.A. Vashchuk

Objective. Experimentally justify the use of colloidal-hyperosmolar solution based on hydroxyethyl starch HAES-LX-5 % and protein-salt solution based on albumin Lactoprotein with sorbitol (LPS) in burn shock (BS). Materials and methods. The experiments were performed on an experimental model of OS in white male rats. HAES-LX-5 %, LPS solution and control 0.9 % NaCl solution at a dose of 10 ml/kg/day for 7 days were used for infusion therapy. The blood leukocyte intoxication index (LII), medium weight molecules (MWM), C-reactive protein (CRP) were studied. Results and discussion. In the conditions of experimental BS with the introduction of 0.9 % NaCl, the LII on the 7th day significantly increased by 5.37 times (p<0.01) compared with intact animals (0.887±0.108 and 0.165±0.098, respectively). This indicates the development of destructive processes and intoxication of rats in BS. When HAES-LX-5 % and LPS were administered, LII increased only 2.33 times (p<0.01) and 2.41 times (p <0.05) and was significantly lower compared to 0.9 % NaCl. In animals from the group of control pathology there was an increase in blood levels of MWM, on the 1st day by 75.6 %, on the 3rd day – by 159.5 %, and on the 7th day – by 128.0 %, respectively, compared with intact animals. A systemic inflammatory reaction was also formed, which was manifested by an increase in the level of CRP. Pharmacological correction of BS with HAES-LX-5 % and LPS solutions equally inhibited the development of endotoxicosis from the 3rd to the 7th day, which was accompanied by significant (p<0.05) decrease in the level of MWM by 36.2 % and 42.5 %, respectively, after administration of HAES-LX-5 % and by 32.9 % and 38.8 % after administration of LPS relative to control pathology. The use of solutions of HAES-LX-5 % and LPS inhibited the development of inflammation from the 3rd to the 7th day, which was accompanied by a significant (p<0.05) decrease in the level of CRP by 30.7 % and 35.0 % for HAES-LX-5 %, by 29.4 % and 32.9 % for LPS compared to control. Conclusions. It has been experimentally shown in the model of BS that solutions HAES-LX-5 % and LPS show anti-inflammatory activity and reduce the level of endogenous intoxication, inhibiting the development of systemic stress.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23010-e23010
Author(s):  
Irina V. Kaplieva ◽  
Elena Mikhaylovna Frantsiyants ◽  
Lidia K. Trepitaki ◽  
Yulia A. Pogorelova ◽  
Valeria Bandovkina ◽  
...  

e23010 Background: Numerous clinical studies have shown an association between changing thyroid gland (TG) function and the development of tumors. The purpose of the study was to analyze the dynamics of thyroid hormones in the pituitary gland, TG and blood serum (BS) during liver metastasis in order to create thyroid profile of metastasis and to detect thyroid markers of metastasis in BS. Methods: The experiment included 44 white male rats weighing 180-250 g. Sarcoma 45 was transplanted intrasplenically. Levels of thyroid stimulating hormone (TSH) were studied in the pituitary gland, TG, BS; the amount of free (fT4) and total (T4) thyroxine and free (fT3) and total (T3) triiodothyronine in TG and BS were determined by radioimmunoassay (Immunotech, Czech Republic; Arian analyzer, Russia). Results: Exertion of the pituitary gland and overproduction of TSH were observed since the early days of the tumor development, later accompanied by TG hypofunction. Quantitative changes of thyroid hormones in organs did not coincide with their dynamics in BS. The first diagnostic signs of experimental liver metastasis, in the absence of formed metastases in the body, were hyperthyrotropinemia and a tendency to fT3 decrease in BS. Already formed liver metastases were characterized by a marked low T3 syndrome which transformed into a more severe lowT3/lowT4 syndrome during the secondary metastasis. Conclusions: The development of liver metastases is accompanied by the exertion and imbalance of the thyroid system function. Analysis of dynamics of the thyroid axis hormones in BS allows predicting the appearance of liver metastasis and identification of “the point of no return” in the development of the pathology that leads to secondary metastasis and irreversible progression of the disease.


2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Patchaya Boonchaya-anant ◽  
Nitchakarn Laichuthai ◽  
Preaw Suwannasrisuk ◽  
Natnicha Houngngam ◽  
Suthep Udomsawaengsup ◽  
...  

Objective.Obesity is a risk factor for hypogonadotropic hypogonadism in men. Weight loss has been shown to improve hypogonadism in obese men. This study evaluated the early changes in sex hormones profile after bariatric surgery.Methods.This is a prospective study including 29 morbidly obese men. Main outcomes were changes in serum levels of total testosterone (TT), free testosterone (cFT), SHBG, estradiol, adiponectin, and leptin at 1 and 6 months after surgery.Results.The mean age of patients was 31 ± 8 years and the mean BMI was 56.8 ± 11.7 kg/m2. Fifteen patients underwent Roux-en-Y gastric bypass and 14 patients underwent sleeve gastrectomy. At baseline, 22 patients (75.9%) had either low TT levels (<10.4 nmol/L) or low cFT levels (<225 pmol/L). Total testosterone and SHBG levels increased significantly at 1 month after surgery (p≤0.001). At 6 months after surgery, TT and cFT increased significantly (p≤0.001) and 22 patients (75.9%) had normalized TT and cFT levels. There were no changes in estradiol levels at either 1 month or 6 months after surgery.Conclusions. Increases in TT and SHBG levels occurred early at 1 month after bariatric surgery while improvements in cFT levels were observed at 6 months after bariatric surgery.


2011 ◽  
Vol 26 (S2) ◽  
pp. 1874-1874
Author(s):  
M. Flores-Ramos ◽  
I. Méndez Ramírez

ObjectiveTo determine if serum levels of Follicle Stimulating Hormone, Luteinizing Hormone, estradiol, progesterone, Free Testosterone and Total Testosterone differ between perimenopausal women with first depressive episode, recurrent depression and without depression.MethodsDemographic and clinical characteristics were evaluated in 63 perimenopausal women with first depressive episode (N = 20), recurrent depression (N = 23) or non-depressed (N = 20). Hormonal measurements were evaluated at follicular and luteal menstrual phases and mid-cycle, around one menstrual cycle.ResultsWhen compared depressed and non-depressed women we observed lower levels of luteal progesterone, higher levels of total testosterone and an increasing level of FSH in depressed patients. Differences between the three groups were observed in luteal progesterone levels, luteal FT, and luteal TT. Independently of current diagnosis, women with and without pmdd antecedent, differed in progesterone and testosterone levels. We did not find association of perimenopausal depression and history of post partum depression.ConclusionsHormonal profiles differed between groups. Patients with antecedent of pmdd had a similar progesterone and testosterone profile to perimenopausal depressed women.


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