The Experts below are selected from a list of 81 Experts worldwide ranked by ideXlab platform
John W. Funder - One of the best experts on this subject based on the ideXlab platform.
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aldosterone and mineralocorticoid receptors physiology and pathophysiology
International Journal of Molecular Sciences, 2017Co-Authors: John W. FunderAbstract:Aldosterone is a uniquely terrestrial Hormone, first appearing in lungfish, which have both gills and lungs. Mineralocorticoid receptors (MRs), on the other hand, evolved much earlier, and are found in cartilaginous and bony fish, presumptive ligand cortisol. MRs have equivalent high affinity for aldosterone, progesterone, and cortisol; in epithelia, despite much higher cortisol circulating levels, aldosterone selectively activates MRs by co-expression of the enzyme 11β-hydroxysteroid dehydrogenase, Type 11. In tissues in which the enzyme is not expressed, MRs are overwhelmingly occupied but not activated by cortisol, which normally thus acts as an MR antagonist; in tissue damage, however, cortisol mimics aldosterone and acts as an MR agonist. The risk profile for primary aldosteronism (PA) is much higher than that in age-, sex-, and blood pressure-matched essential hypertensives. High levels of aldosterone per se are not the problem: in chronic sodium deficiency, as seen in the monsoon season in the highlands of New Guinea, plasma aldosterone levels are extraordinarily high, but cause neither hypertension nor cardiovascular damage. Such damage occurs when aldosterone levels are out of the normal feedback control, and are inappropriately elevated for the salt status of the individual (or experimental animal). The question thus remains of how excess salt can synergize with elevated aldosterone levels to produce deleterious cardiovascular effects. One possible mechanism is through the agency of the elusive ouabain-like factors (OLFs). Such factors are secreted from the adrenal in response to ACTH (adrenalocortical Tropic Hormone), to angiotensin via AT2R, and—the polar opposite of aldosterone—to sodium loading. They act on blood vessels to cause vasoconstriction and thus elevate blood pressure to dump excess sodium through pressure natriuresis. Their levels are chronically elevated in PA in response to the continually elevated sodium status, and they thus act to constrict coronary and systemic arteries. In the context of the elevated blood volume and total body sodium in a PA patient, this raises blood pressure and acts as the proximate cause of cardiovascular damage. If this is the case, it would appear to offer new insights into therapy for PA. One would be the use of digibindin, or its more recent successors as antagonists of OLFs acting on Na/K ATPase at the vessel wall. A second would be to routinely combine a low dose MR antagonist, an ENaC inhibitor, and sodium restriction as first-line therapy for bilateral aldosterone overproduction. Finally, for unilateral cases post-surgery, there is good reason to include low-dose MRs in drug therapy if required, given the ability of cortisol in damaged blood vessels to mimic aldosterone vasoconstrictor action.
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Aldosterone and Mineralocorticoid Receptors—Physiology and Pathophysiology
MDPI AG, 2017Co-Authors: John W. FunderAbstract:Aldosterone is a uniquely terrestrial Hormone, first appearing in lungfish, which have both gills and lungs. Mineralocorticoid receptors (MRs), on the other hand, evolved much earlier, and are found in cartilaginous and bony fish, presumptive ligand cortisol. MRs have equivalent high affinity for aldosterone, progesterone, and cortisol; in epithelia, despite much higher cortisol circulating levels, aldosterone selectively activates MRs by co-expression of the enzyme 11β-hydroxysteroid dehydrogenase, Type 11. In tissues in which the enzyme is not expressed, MRs are overwhelmingly occupied but not activated by cortisol, which normally thus acts as an MR antagonist; in tissue damage, however, cortisol mimics aldosterone and acts as an MR agonist. The risk profile for primary aldosteronism (PA) is much higher than that in age-, sex-, and blood pressure-matched essential hypertensives. High levels of aldosterone per se are not the problem: in chronic sodium deficiency, as seen in the monsoon season in the highlands of New Guinea, plasma aldosterone levels are extraordinarily high, but cause neither hypertension nor cardiovascular damage. Such damage occurs when aldosterone levels are out of the normal feedback control, and are inappropriately elevated for the salt status of the individual (or experimental animal). The question thus remains of how excess salt can synergize with elevated aldosterone levels to produce deleterious cardiovascular effects. One possible mechanism is through the agency of the elusive ouabain-like factors (OLFs). Such factors are secreted from the adrenal in response to ACTH (adrenalocortical Tropic Hormone), to angiotensin via AT2R, and—the polar opposite of aldosterone—to sodium loading. They act on blood vessels to cause vasoconstriction and thus elevate blood pressure to dump excess sodium through pressure natriuresis. Their levels are chronically elevated in PA in response to the continually elevated sodium status, and they thus act to constrict coronary and systemic arteries. In the context of the elevated blood volume and total body sodium in a PA patient, this raises blood pressure and acts as the proximate cause of cardiovascular damage. If this is the case, it would appear to offer new insights into therapy for PA. One would be the use of digibindin, or its more recent successors as antagonists of OLFs acting on Na/K ATPase at the vessel wall. A second would be to routinely combine a low dose MR antagonist, an ENaC inhibitor, and sodium restriction as first-line therapy for bilateral aldosterone overproduction. Finally, for unilateral cases post-surgery, there is good reason to include low-dose MRs in drug therapy if required, given the ability of cortisol in damaged blood vessels to mimic aldosterone vasoconstrictor action
Renato Pasquali - One of the best experts on this subject based on the ideXlab platform.
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sex difference in the relationship between the hypothalamic pituitary adrenal axis and sex Hormones in obesity
Obesity, 2006Co-Authors: Valentina Vicennati, Luana Ceroni, Silvia Genghini, Laura Patton, Uberto Pagotto, Renato PasqualiAbstract:Objective This study was carried out to investigate the role of sex in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis and its relationship with testosterone levels in male and female obesity. Research methods and procedures Twenty-two obese men (OB-M) and 29 obese women (OB-W) participated in the study. Two groups of normal weight men (NW-M) and women (NW-W), respectively, served as controls. In basal conditions, blood concentrations of major androgens, sex Hormone-binding protein, and gonadotropins were assessed, and the free androgen index (testosterone x100/sex Hormone-binding globulin) was calculated. All subjects underwent a combined corticotropin-releasing Hormone plus arginine-vasopressin stimulation test. Results OB-M and NW-M had higher basal adrenal cortical Tropic Hormone (ACTH) and cortisol levels than their female counterparts. In addition, ACTH, but not cortisol basal, levels were significantly higher in obese than in normal weight controls in both sexes. OB-W had a higher response than OB-M to the combined corticotropin-releasing Hormone plus arginine-vasopressin test of both ACTH and cortisol [expressed as incremental percentage of area under the curve (AUC%)]. The same finding was present between NW-W and NW-M. Basal luteinizing Hormone levels were negatively correlated to ACTH(AUC%) in both OB-W and OB-M. In the OB-W, however, a positive correlation was found between cortisol(AUC%) and testosterone (r = 0.48; p = 0.002), whereas a tendency toward a negative correlation was present in OB-M. Discussion In conclusion, we have shown a significant positive relationship between the activity of the HPA axis and testosterone in obese women, which suggests a partial responsibility of increased HPA axis activity in determining testosterone levels. In addition, it clearly seems that, as reported in normal weight subjects, a sex difference in the HPA axis activity still persists even in the presence of obesity.
George W Smith - One of the best experts on this subject based on the ideXlab platform.
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decreased acth secretion during prolonged transportation stress is associated with reduced pituitary responsiveness to Tropic Hormone stimulation in cattle
Domestic Animal Endocrinology, 2007Co-Authors: Marlon Knights, George W SmithAbstract:The present study examined the effect of transportation stress on hypothalamic-pituitary-adrenal axis responsiveness to Tropic Hormone stimulation and on abundance of corticotropin releasing factor (CRF) receptor R1 (CRFR1) and arginine vasopressin (AVP) receptor V3 (V3) mRNAs in the anterior pituitary (AP) of cattle. Holstein steers were transported for 10 h or used as non-transported controls (NTC). Blood samples were collected at start of transportation and every 1-2h thereafter. To test AP responsiveness to Tropic Hormones, animals were challenged (i.v.) with CRF (0.5 microg/kg), AVP (1 microg/kg) or CRF plus AVP immediately after end of transportation and blood samples collected every 30 min for 3h. The AP of animals transported for 0, 4 or 10 h were harvested for mRNA analyses. Plasma ACTH in transported animals increased within 1h and remained elevated for 6 and 8h versus NTC and 0 h values, respectively. Plasma concentrations of cortisol increased in response to transportation and remained elevated throughout the transport period. Injection of CRF or AVP to NTC animals increased plasma ACTH, but ACTH secretion in response to CRF or AVP was dramatically reduced in transported animals. ACTH secretion following co-injection of CRF and AVP tended to be less in transported animals, but was almost 100% greater than when secretagogues were administered separately. Despite decreased AP responsiveness to CRF and AVP, AP CRFR1 and V3 mRNAs were increased after 10 h transportation. Results indicate decreased AP responsiveness to CRF and AVP may regulate duration of ACTH secretion in response to transportation stress in cattle.
Sugata Dasgupta - One of the best experts on this subject based on the ideXlab platform.
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pre emptive oral dexmethorphan reduces fentanyl induced cough as well as immediate postoperative adrenocortico Tropic Hormone and growth Hormone level
Journal of Anaesthesiology Clinical Pharmacology, 2011Co-Authors: Avik Mukherjee, A Kundu, Sudipta Ghosh, Rajat Choudhuri, Bijoy Kumar Bandopadhyay, Sugata DasguptaAbstract:Background : Fentanyl-induced cough is not always benign and brief and can be remarkably troublesome, spasmodic, and explosive. Dextromethorphan, an opioid derivative with an antitussive action, may be effective in reducing the fentanyl-induced cough. Dextromethorphan, a N-methyl D aspartate receptor antagonist, may have some effect on diminishing the stress response to surgery. This study was undertaken to determine whether preoperative dextromethorphan could effectively attenuate its incidence, severity, and effect on postoperative stress Hormone levels. Materials and Methods : Three hundred and twenty patients of American society of anesthesiologists I-II, aged 18-60 years, undergoing elective laparoscopic cholecystectomy or appendicectomy were randomly allocated into two groups (Group C, control; Group D, dextromethorphan) consisting of 160 patients each. Patients in Group D received dextromethorphan 40 mg orally and in Group C received placebo tablets 60 minutes before induction of anesthesia. The incidence of cough was recorded for 1 minute after fentanyl injection and graded as none (0), mild (1-2), moderate (3-5), and severe (>5 cough). Blood samples were collected for estimation of stress Hormone levels before surgery and again at 1 hour and 24 hours postoperatively and compared. The appearance of adverse reactions was recorded. Results : The incidence of reflex fentanyl cough was lower in dextromethorphan group (3.9%) in comparison to placebo (59.8%). Five patients developed mild and one moderate cough in the dextromethorphan group. In the control group, 31 patients developed mild, 29 moderate, and 32 severe cough. The stress Hormones were significantly higher at 1 hour and 24 hours postoperatively in both groups in comparison to its preoperative values. However, at 1 hour postoperatively, adrenocorticoTropic Hormone, epinephrine, and growth Hormone values were significantly low in the dextromethorphan group (61.5 ± 21.1 pg/ ml, 142.1 ± 11.2 pg/ml, and 3.8 ± 0.7 ng/ml) relative to the control group (73.4 ± 21.9 pg/ml, 158.9 ± 17.9 pg/ml, and 4.2 ± 1.3 ng/ml), but changes became insignificant at 24 hours postoperatively. Conclusion : Preoperative oral dextromethorphan 40 mg decreased the incidence and severity of fentanyl induced cough and reduced the rise in stress Hormones at 1 hour postoperatively.
Shin Yong Moon - One of the best experts on this subject based on the ideXlab platform.
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sex steroid and Tropic Hormone levels may be associated with postoperative prognosis of vitrectomy in korean postmenopausal women a pilot study
Menopause, 2010Co-Authors: Jin Choi, Hoon Kim, Chang Suk Suh, Seok Hyun Kim, Young Min Choi, Jung Gu Kim, Shin Yong MoonAbstract:Objective: The aim of this study was to evaluate the postoperative prognostic value of sex Hormones and related biochemical markers for vitrectomy in postmenopausal Korean women. Methods: Twenty-three postmenopausal women undergoing vitrectomy who had not received Hormone therapy were recruited. Before vitrectomy, hormonal profile such as follicle-stimulating Hormone, estradiol, testosterone, tumor markers, and biochemical markers including homocysteine, glycosylated hemoglobin, protein, albumin, and lipid panel was measured. These parameters were correlated with ophthalmologic outcomes such as intraocular pressure, preoperative and postoperative visual acuity, and the visual improvement after surgery. Results: Follicle-stimulating Hormone showed a positive correlation with the logarithm of the minimal angle of resolution value of postoperative visual acuity (Pearson's correlation, 0.583; P = 0.009). This significance was maintained after age or preoperative visual acuity was adjusted (P = 0.006 and P = 0.013, respectively). Testosterone also showed a positive correlation with intraocular pressure before and after adjustment for age (P = 0.027 and P = 0.033, respectively). Conclusions: Sex steroid and Tropic Hormones may be associated with postoperative ophthalmologic outcomes in the postmenopausal women undergoing vitrectomy. Further larger scale studies will be necessary to confirm these preliminary results.
