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      Cortisol, estradiol-17β, and progesterone secretion within the first hour after awakening in women with regular menstrual cycles

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          Abstract

          Cortisol concentration in both serum and saliva sharply increases and reaches a peak within the first hour after waking in the morning. This phenomenon is known as the cortisol awakening response (CAR) and is used as an index of hypothalamus–pituitary–adrenal (HPA) axis function. We examined whether ovarian steroid concentrations increased after awakening as with the CAR in the HPA axis. To do this, cortisol, estradiol-17β (E 2), and progesterone (P 4) concentrations were determined in saliva samples collected immediately upon awakening and 30 and 60 min after awakening in women with regular menstrual cycles and postmenopausal women. We found that both E 2 and P 4 concentrations increased during the post-awakening period in women with regular menstrual cycles, but these phenomena were not seen in any postmenopausal women. The area under the E 2 and P 4 curve from the time interval immediately after awakening to 60 min after awakening (i.e. E 2auc and P 4auc) in women with regular menstrual cycles were greater than those in the postmenopausal women. E 2 and P 4 secretory activity during the post-awakening period was influenced by the phase of the menstrual cycle. E 2auc in the peri-ovulatory phase and P 4auc in the early to mid-luteal phase were greater than in the menstrual phase. Meanwhile, cortisol secretory activity during the post-awakening period was not influenced by menstrual status or the phase of menstrual cycle. These findings indicate that, as with the CAR in the HPA axis function, ovarian steroidogenic activity increased after awakening and is closely associated with menstrual status and phase of menstrual cycle.

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          Most cited references61

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          Light activates the adrenal gland: timing of gene expression and glucocorticoid release.

          Light is a powerful synchronizer of the circadian rhythms, and bright light therapy is known to improve metabolic and hormonal status of circadian rhythm sleep disorders, although its mechanism is poorly understood. In the present study, we revealed that light induces gene expression in the adrenal gland via the suprachiasmatic nucleus (SCN)-sympathetic nervous system. Moreover, this gene expression accompanies the surge of plasma and brain corticosterone levels without accompanying activation of the hypothalamo-adenohypophysial axis. The abolishment after SCN lesioning, and the day-night difference of light-induced adrenal gene expression and corticosterone release, clearly indicate that this phenomenon is closely linked to the circadian clock. The magnitude of corticostereone response is dose dependently correlated with the light intensity. The light-induced clock-dependent secretion of glucocorticoids adjusts cellular metabolisms to the new light-on environment.
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            The cortisol awakening response: more than a measure of HPA axis function.

            In most healthy people morning awakening is associated with a burst of cortisol secretion: the cortisol awakening response (CAR). It is argued that the CAR is subject to a range physiological regulatory influences that facilitate this rapid increase in cortisol secretion. Evidence is presented for reduced adrenal sensitivity to rising levels of ACTH in the pre-awakening period, mediated by an extra-pituitary pathway to the adrenal from the suprachiasmatic nucleus (SCN). A role for the hippocampus in this pre-awakening regulation of cortisol secretion is considered. Attainment of consciousness is associated with 'flip-flop' switching of regional brain activation, which, it is argued, initiates a combination of processes: (1) activation of the hypothalamic pituitary adrenal (HPA) axis; (2) release of pre-awakening reduced adrenal sensitivity to ACTH; (3) increased post-awakening adrenal sensitivity to ACTH in response to light, mediated by a SCN extra-pituitary pathway. An association between the CAR and the ending of sleep inertia is discussed.
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              Free cortisol levels after awakening: a reliable biological marker for the assessment of adrenocortical activity.

              In three independent studies, free cortisol levels after morning awakening were repeatedly measured in children, adults and elderly subjects (total n=152). Cortisol was assessed by sampling saliva at 10 or 15 minute intervals for 30-60 minutes, beginning at the time of awakening for two days (Study 1 and 2) or one (Study 3) day, respectively. In all three studies, free cortisol levels increased by 50-75% within the first 30 minutes after awakening in both sexes on all days. Premenopausal women consistently showed a stronger increase with a delayed peak after awakening compared to men on all days. In Study 2, there was a tendency for lower early morning free cortisol levels for women taking oral contraceptives (p=.10). Stability of the area under the curve (AUC) of the early morning free cortisol levels over the three (Study 1 and 2) or two (Study 3) days ranged between r=.39 and r=.67 (p<.001). Neither age, weight, nor smoking showed an effect on baseline or peak cortisol levels. Sleep duration, time of awakening and alcohol consumption also appeared to be unrelated to early morning free cortisol levels. From these data we conclude that in contrast to single assessments at fixed times, early morning cortisol levels can be a reliable biological marker for the individual's adrenocortical activity when measured repeatedly with strict reference to the time of awakening.
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                Author and article information

                Journal
                J Endocrinol
                JOE
                The Journal of Endocrinology
                BioScientifica (Bristol )
                0022-0795
                1479-6805
                December 2011
                29 September 2011
                : 211
                : 3
                : 285-295
                Affiliations
                [1 ]simpleGraduate School of Integrative Medicine simpleCHA Medical University Yuksam-dong 605, Kangnamgu, Seoul, 135-907Republic of Korea
                [2 ]simpleHormone Research Center simpleChonnam National University Gwangju, 500-757Republic of Korea
                [3 ]simpleDepartment of Obstetrics and Gynecology simpleCL Women's Hospital Gwangju, 502-210Republic of Korea
                [4 ]simpleDepartment of Family Medicine simpleChung-Ang University Medical Center Seoul, 156-755Republic of Korea
                [5 ]simpleDepartment of Life sciences simpleSangmyung University Seoul, 110-743Republic of Korea
                [6 ]simpleResearch Institute of Integrative Medicine simpleHonam Medical Center Gwangju, 506-813Republic of Korea
                Author notes
                (Correspondence should be addressed to R S Ahn; Email: ryunsup@ 123456yahoo.co.kr )
                Article
                JOE110247
                10.1530/JOE-11-0247
                3209794
                21965547
                ed7af128-dc67-43e0-91c0-4f627215af6a
                © 2011 Society for Endocrinology

                This is an Open Access article distributed under the terms of the Society for Endocrinology's Re-use Licence which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 27 September 2011
                : 29 September 2011
                Funding
                Funded by: National Research Foundation of Korea (NRF)
                Award ID: 2010-0013356
                Categories
                Regular Papers

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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