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      Interrelationships Between Pituitary Hormones as Assessed From 24-hour Serum Concentrations in Healthy Older Subjects

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          Abstract

          Context

          Hormones of the hypothalamic-pituitary-target gland axes are mostly investigated separately, whereas the interplay between hormones might be as important as each separate hormonal axis.

          Objective

          Our aim is to determine the interrelationships between GH, TSH, ACTH, and cortisol in healthy older individuals.

          Design

          We made use of 24-hour hormone serum concentrations assessed with intervals of 10 minutes from 38 healthy older individuals with a mean age (SD) of 65.1 (5.1) years from the Leiden Longevity Study. Cross-correlation analyses were performed to assess the relative strength between 2 24-hour hormone serum concentration series for all possible time shifts. Cross-approximate entropy was used to assess pattern synchronicity between 2 24-hour hormone serum concentration series.

          Results

          Within an interlinked hormonal axis, ACTH and cortisol were positively correlated with a mean (95% confidence interval) correlation coefficient of 0.78 (0.74–0.81) with cortisol following ACTH concentrations with a delay of 10 minutes. Between different hormonal axes, we observed a negative correlation coefficient between cortisol and TSH of -0.30 (-0.36 to -0.25) with TSH following cortisol concentrations with a delay of 170 minutes. Furthermore, a positive mean (95% confidence interval) correlation coefficient of 0.29 (0.22–0.37) was found between TSH and GH concentrations without any delay. Moreover, cross-approximate entropy analyses showed that GH and cortisol exhibit synchronous serum concentration patterns.

          Conclusions

          This study demonstrates that interrelations between hormones from interlinked as well as different hypothalamic-pituitary-target gland axes are observed in healthy older individuals. More research is needed to determine the biological meaning and clinical consequences of these observations.

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          Most cited references49

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          Somatotropic signaling: trade-offs between growth, reproductive development, and longevity.

          Growth hormone (GH) is a key determinant of postnatal growth and plays an important role in the control of metabolism and body composition. Surprisingly, deficiency in GH signaling delays aging and remarkably extends longevity in laboratory mice. In GH-deficient and GH-resistant animals, the "healthspan" is also extended with delays in cognitive decline and in the onset of age-related disease. The role of hormones homologous to insulin-like growth factor (IGF, an important mediator of GH actions) in the control of aging and lifespan is evolutionarily conserved from worms to mammals with some homologies extending to unicellular yeast. The combination of reduced GH, IGF-I, and insulin signaling likely contributes to extended longevity in GH or GH receptor-deficient organisms. Diminutive body size and reduced fecundity of GH-deficient and GH-resistant mice can be viewed as trade-offs for extended longevity. Mechanisms responsible for delayed aging of GH-related mutants include enhanced stress resistance and xenobiotic metabolism, reduced inflammation, improved insulin signaling, and various metabolic adjustments. Pathological excess of GH reduces life expectancy in men as well as in mice, and GH resistance or deficiency provides protection from major age-related diseases, including diabetes and cancer, in both species. However, there is yet no evidence of increased longevity in GH-resistant or GH-deficient humans, possibly due to non-age-related deaths. Results obtained in GH-related mutant mice provide striking examples of mutations of a single gene delaying aging, reducing age-related disease, and extending lifespan in a mammal and providing novel experimental systems for the study of mechanisms of aging.
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            Nonagenarian siblings and their offspring display lower risk of mortality and morbidity than sporadic nonagenarians: The Leiden Longevity Study.

            To compare the risk of mortality of nonagenarian siblings with that of sporadic nonagenarians (not selected on having a nonagenarian sibling) and to compare the prevalence of morbidity in their offspring with that of the offsprings' partners. Longitudinal (mortality risk) and cross-sectional (disease prevalence). Nationwide sample. The Leiden Longevity Study consists of 991 nonagenarian siblings derived from 420 Caucasian families, 1,365 of their offspring, and 621 of the offsprings' partners. In the Leiden 85-plus Study, 599 subjects aged 85 were included, of whom 275 attained the age of 90 (sporadic nonagenarians). All nonagenarian siblings and sporadic nonagenarians were followed for mortality (with a mean+/-standard deviation follow-up time of 2.7+/-1.4 years and 3.0+/-1.5 years, respectively). Information on medical history and medication use was collected for offspring and their partners. Nonagenarian siblings had a 41% lower risk of mortality (P<.001) than sporadic nonagenarians. The offspring of nonagenarian siblings had a lower prevalence of myocardial infarction (2.4% vs 4.1%, P=.03), hypertension (23.0% vs 27.5%, P=.01), diabetes mellitus (4.4% vs 7.6%, P=.004), and use of cardiovascular medication (23.0% vs 28.9%, P=.003) than their partners. The lower mortality rate of nonagenarian siblings and lower prevalence of morbidity in their middle-aged offspring reinforce the notion that resilience against disease and death have similar underlying biology that is determined by genetic or familial factors.
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              Effects of gender and age on the levels and circadian rhythmicity of plasma cortisol.

              Data from rodent studies indicate that cumulative stress exposure may accelerate senescence and offer a theory to explain differences in the rate of aging. Cumulative exposure to glucocorticoids causes hippocampal defects, resulting in an impairment of the ability to terminate glucocorticoid secretion at the end of stress and, therefore, in increased exposure to glucocorticoids which, in turn, further decreases the ability of the hypothalamo-pituitary-adrenal axis to recover from a challenge. However, the consensus emerging from reviews of human studies is that basal corticotropic function is unaffected by aging, suggesting that the negative interaction of stress and aging does not occur in man. In the present study, a total of 177 temporal profiles of plasma cortisol from 90 normal men and 87 women, aged 18-83 yr, were collected from 7 laboratories and reanalyzed. Twelve parameters quantifying mean levels, value and timing of morning maximum and nocturnal nadir, circadian rhythm amplitude, and start and end of quiescent period were calculated for each individual profile. In both men and women, mean cortisol levels increased by 20-50% between 20-80 yr of age. Premenopausal women had slightly lower mean levels than men in the same age range, primarily because of lower morning maxima. The level of the nocturnal nadir increased progressively with aging in both sexes. An age-related elevation in the morning acrophase occurred in women, but not in men. The diurnal rhythmicity of cortisol secretion was preserved in old age, but the relative amplitude was dampened, and the timing of the circadian elevation was advanced. We conclude that there are marked gender-specific effects of aging on the levels and diurnal variation of human adrenocorticotropic activity, consistent with the hypothesis of the "wear and tear" of lifelong exposure to stress. The alterations in circadian amplitude and phase could be involved in the etiology of sleep disorders in the elderly.
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                Author and article information

                Journal
                J Clin Endocrinol Metab
                J. Clin. Endocrinol. Metab
                jcem
                The Journal of Clinical Endocrinology and Metabolism
                Oxford University Press (US )
                0021-972X
                1945-7197
                April 2020
                19 December 2019
                19 December 2019
                : 105
                : 4
                : dgz253
                Affiliations
                [1 ] Section Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center , RC Leiden, The Netherlands
                [2 ] Section Endocrinology, Department of Internal Medicine, Leiden University Medical Center , RC Leiden, The Netherlands
                [3 ] Section Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center , RC Leiden The Netherlands
                [4 ] Department of Public Health, Center of Healthy Aging, University of Copenhagen , Copenhagen, Denmark
                Author notes
                Correspondence and Reprint Requests: Evie van der Spoel, Section Gerontology and Geriatrics, Department of Internal, Medicine, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands. E-mail: e.van_der_spoel@ 123456lumc.nl .
                Author information
                http://orcid.org/0000-0002-7112-4145
                http://orcid.org/0000-0001-6276-2834
                http://orcid.org/0000-0002-3076-1551
                Article
                dgz253
                10.1210/clinem/dgz253
                7065845
                31853555
                29fc7fbb-bda7-439a-9b59-0116a8715744
                © Endocrine Society 2019.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 13 July 2019
                : 17 December 2019
                : 11 March 2020
                Page count
                Pages: 14
                Funding
                Funded by: European Commission, DOI 10.13039/501100000780;
                Award ID: Health-F2-2010–259772
                Award ID: 666869
                Funded by: Leiden University Medical Center, DOI 10.13039/501100005039;
                Funded by: Novo Nordisk Fonden, DOI 10.13039/501100009708;
                Award ID: 17OC0027812
                Categories
                Clinical Research Article
                AcademicSubjects/MED00250

                Endocrinology & Diabetes
                human,pituitary hormones,time series data,cross-correlation,cross-approximate entropy,familial longevity

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