Age-Related Changes in Hypothalamic-Pituitary-Adrenal Axis Activity of Male C57BL/6J Mice

Dalm, Sergiu; Enthoven, Leo; Meijer, Onno C.; Mark, Maaike H. van der; Karssen, Adriaan M.; Kloet, E. Ronald de; Oitzl, Melly S.

doi:10.1159/000089555

Cited by 68 publications

(51 citation statements)

References 80 publications

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“…These results are consistent with previous experiments examining age-related changes in HPA activity of male C57BL/6 mice and have been explained as a consequence of a relative hyposensitivity of the adrenal with aging in mice (Dalm et al 2005). By contrast, the L-PGDS KO mice did not experience age-associated changes in basal HPA axis hormones; ACTH did not increase with age under either diet.…”

Section: Discussionsupporting

confidence: 92%

The lipocalin-type prostaglandin D2 synthase knockout mouse model of insulin resistance and obesity demonstrates early hypothalamic–pituitary–adrenal axis hyperactivity

Evans

Islam²,

Urade³

et al. 2012

Journal of Endocrinology

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Obesity and diabetes are closely associated with hyperactivation of the hypothalamicpituitary-adrenal (HPA) axis. In this study, the diet-induced obese C57BL/6 mouse was used to test the hypothesis that chronically elevated metabolic parameters associated with the development of obesity such as cholesterol and glucose can aggravate basal HPA axis activity. Because the lipocalin-type prostaglandin D 2 synthase (L-PGDS) knockout (KO) mouse is a model of accelerated insulin resistance, glucose intolerance, and obesity, it was further hypothesized that HPA activity would be greater in this model. Starting at 8 weeks of age, the L-PGDS KO and C57BL/6 mice were maintained on a low-fat or high-fat diet. After 20 or 37 weeks, fasting metabolic parameters and basal HPA axis hormones were measured and compared between genotypes. Correlation analyses were performed to identify associations between obesity-related chronic metabolic changes and changes in the basal activity of the HPA axis. Our results have identified strong positive correlations between total cholesterol, LDL-cholesterol, glucose, and HPA axis hormones that increase with age in the C57BL/6 mice. These data confirm that obesity-related elevations in cholesterol and glucose can heighten basal HPA activity. Additionally, the L-PGDS KO mice show early elevations in HPA activity with no age-related changes relative to the C57BL/6 mice.

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Section: Discussionsupporting

confidence: 92%

The lipocalin-type prostaglandin D2 synthase knockout mouse model of insulin resistance and obesity demonstrates early hypothalamic–pituitary–adrenal axis hyperactivity

Evans

Islam²,

Urade³

et al. 2012

Journal of Endocrinology

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show abstract

“…Interestingly, the zenith of plasma CORT in our mice on an FVB/NJ background relative to the onset of the dark phase of the light:dark cycle was earlier than reported in other strains of mice. In C57BL/6J and Swiss mice the peak plasma CORT concentration occurred at the beginning of the dark phase (Dalm et al, 2005;Lechner et al, 2000). For the purposes of our study the important finding was that the circadian pattern of CORT secretion was similar in both genotypes (WT and KO).…”

Section: Measurementsmentioning

confidence: 71%

Unaltered hormonal response to stress in a mouse model of fragile X syndrome

Qin

Smith

2008

Psychoneuroendocrinology

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SummaryReports in the clinical literature and studies of fmr-1 knockout mice have led to the hypothesis that, in addition to mental retardation, fragile X syndrome is characterized by a dysregulation of hypothalamic-pituitary-adrenal axis function. We have systematically examined this hypothesis by studying the effects of stress on adrenocorticotrophic hormone and corticosterone levels in adult, male fmr1 knockout mice. Initially we determined the circadian rhythms of the plasma hormone levels in both wild type and fmr1 knockout mice and established the optimal time to impose the stress. We found no genotypic differences in the circadian rhythms of either hormone. We studied two types of stressors, immobilization and spatial novelty; spatial novelty was 5 min in an elevated plus-maze. We varied the duration of immobilization and followed the time course of recovery of hormones to their pre-stress levels. Despite the lower anxiety exhibited by fmr-1 knockout mice in the elevated plus maze, hormonal responses to and recovery from this spatial novelty were similar in both genotypes. Further, we found no genotypic differences in hormonal responses to immobilization stress. The results of our study indicate that, in FVB/NJ mice, the hormonal response to and recovery from acute stress is unaltered by the lack of fragile X mental retardation protein.

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“…For these studies mature adult control (7.5-mo) and aged (22-mo) C57BL/6J female mice were employed.  Dalm et al, [486] employed 3-, 9-, and 16-month old C57BL/6J mice to examine the age-related changes in hypothalamic-pituitary-adrenal (HPA) activity. The highest AUC values over 24h periods were shown by 9-months old mice as compared to 3-months and 16-months old mice.…”

Section: Wistar Ratsmentioning

confidence: 99%

Impact of Aging on Steroid Hormone Biosynthesis and Secretion

Zaidi¹

2013

TOLSJ

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Steroid hormones are lipophilic, low-molecular weight organic compounds all of which are derived from cholesterol. They are primarily synthesized by steroidogenic glands such as gonads (ovary and testis), the adrenal gland and, during pregnancy, by the placental trophoblasts. Limited steroid synthesis also takes place in the brain. Steroid hormones are crucial for the proper functioning of the body. They mediate a wide variety of vital physiological functions, ranging from maintaining normal reproductive function and secondary sexual characteristics, to regulating virtually every metabolic process in the body. Like many age-related endocrine disorders, aging also progressively impacts the tissue-specific synthesis and secretion of steroid hormones. The goal of this review is to summarize the effects of aging on steroid hormone synthesis and secretion by the adrenal gland and gonads of both human and experimental animal models, to describe the potential involvement of excessive oxidative stress in mediating age-related alterations in steroidogenesis, and to discuss the possible underlying mechanisms involved.

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Age-Related Changes in Hypothalamic-Pituitary-Adrenal Axis Activity of Male C57BL/6J Mice

Cited by 68 publications

References 80 publications

The lipocalin-type prostaglandin D2 synthase knockout mouse model of insulin resistance and obesity demonstrates early hypothalamic–pituitary–adrenal axis hyperactivity

The lipocalin-type prostaglandin D2 synthase knockout mouse model of insulin resistance and obesity demonstrates early hypothalamic–pituitary–adrenal axis hyperactivity

Unaltered hormonal response to stress in a mouse model of fragile X syndrome

Impact of Aging on Steroid Hormone Biosynthesis and Secretion

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