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OBJECTIVE The mechanisms mediating hypercortisolemia in depression remain controversial. Adopting the biomarker strategy, we studied adrenocorticotropin (ACTH) and cortisol dynamics in hypercortisolemic and non-hypercortisolemic depressed in-patients, and in normal volunteers. METHOD Deconvolution analysis of 24-h pulsatile secretion, approximate entropy(More)
We have examined the mechanism subserving the in vivo circadian rhythm of cortisol in men. To this end, blood samples were withdrawn at 10-min intervals for 24 h in each of six men to yield well-defined profiles of episodic cortisol release. A novel multiple-parameter deconvolution model was applied to discriminate the number, amplitudes, and durations of(More)
OBJECTIVE To test three theories of hypercortisolemia in depression-hypothalamic overdrive, impaired glucocorticoid feedback, or autonomous cortisol production. METHOD We applied an overnight low-cortisol feedback strategy by administering metyrapone to hypercortisolemic depressed in-patients and control subjects. RESULTS Under metyrapone, the increases(More)
To explore the mechanisms of homeostatic adaptation of the hypothalamo-pituitary-adrenal axis to an experimental low-feedback condition, we quantitated pulsatile (ultradian), entropic (pattern-sensitive), and 24-h rhythmic (circadian) ACTH secretion during high-dose metyrapone blockade (2 g orally every 2 h for 12 h, and then 1 g every 2 h for 12 h). Plasma(More)
The present experiments examine the neuroregulatory hypothesis that the degree of sample-by-sample regularity of hormone output by an interlinked hypothalamopituitary target-organ system monitors the strength of feedback and/or feedforward signaling. To test this postulate and assess its generality, we implemented a total of nine thematically complementary(More)
The ACTH-adrenal axis is a critical stress-responsive system with prominent circadian rhythmicity. To test the basis for the circadian ACTH physiology, we have used 1) a sensitive and specific two-site immunoradiometric assay to estimate plasma ACTH-(1-39) concentrations during intensive (every 10 min) and extended (24-h) blood sampling to capture complete(More)
Short term fasting activates the corticotropic and somatotropic, and suppresses the reproductive, axis in men. Analogous neuroendocrine responses are less well characterized in women. Recently, we identified a negative association between the adipocyte-derived nutritional signaling peptide, leptin, and pulsatile GH secretion in older fed women. In the(More)
A single gene defect of the circadian clock (tau mutation) has recently been described that results in a shortening of the circadian activity cycle of the Syrian hamster. In the homozygous animal, free running activity is shortened by 4 h, resulting in a circadian period of approximately 20 h. Here, we examine the effect of the tau mutation on noncircadian(More)
Testosterone (Te) production declines in the aging male, albeit for unknown reasons. Plausible mechanisms include reduced secretion of GnRH, less feedforward by LH, and/or altered feedback by systemic Te. The present study tests all three postulates in a cohort of 10 young (20-35 yr old) and eight older (50-72 yr old) men. The experimental paradigm(More)