The aim of this review was to examine the evidence for age-related changes of the hypothalamic-pituitary-adrenal (HPA) axis in both physiological and pathological aging, on the basis of the many data in the literature, as well as of our personal findings. A statistically significant circadian rhythmicity of serum cortisol was maintained in elderly subjects, even if with a reduced amplitude of the 24 h fluctuations and a trend to an increase of the serum levels in the evening and at night-time, in comparison with young controls. Furthermore, an age-related impairment of HPA sensitivity to steroid feedback was present in elderly people. The occurrence of senile dementia amplified the changes already present in physiological aging. While the cortisol secretion was generally well maintained in aging, the adrenal production of dehydroepiandrosterone and of its sulfate (DHEAS) exhibited an age-related decline. Therefore, the cortisol/DHEAS molar ratio was significantly higher in elderly subjects and even more in demented ones, than in young controls. Due to the opposite effects of cortisol and DHEAS on the brain and particularly on the hippocampal region, the imbalance between glucocorticoids and androgens occurring in physiological and even more in pathological aging, may have adverse effects on the function of this region, whose key role in learning and memory is well known.

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Age-related changes of the hypothalamic-pituitary-adrenal axis: pathophysiological correlates.

The cholinomimetic agents, physostigmine, neostigmine, and arecoline, and the anticholinergic agents, atropine, scopolamine, and methscopolamine, have been used to explore an acetylcholine hypothesis of affect disorders and stress. Cholinomimetic drugs cause many of the same effects as do naturally occurring stressors. These include increases in negative affect, the induction of affective disorders, increases in stress neuroendocrines including ACThH, cortisol, beta-endorphin, growth hormone, prolactin, epinephrine, and noprepinephrine, increases in blood pressure and pulse rate, and increases in analgesia. These parallel effects, combined with the effect of stress on central acetylcholine activity, suggest a stress-acetylcholine linkage.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/ddr.430040202

Cholinomimetic and anticholinergic drugs used to investigate an acetylcholine hypothesis of affective disorders and stress

The daily rhythm of plasma corticosteroid concentration was studied in nonhypophysectomized rats and in hypophysectomized rats implanted with beeswax pellets containing ACTH and T4. In the first experiment, male hypophysectomized rats were placed on a 12-h light, 12-h dark cycle (onset of light, 0600 h) with food and water available ad libitum. Beeswax pellets containing 1.5 mg ACTH and 150 micrograms T4 were implanted sc in these rats. Beginning 4 days after the implantation of ACTH and T4, daily rhythms of plasma corticosteroid concentration were detected in these rats on 3 successive days. The injection of sodium pentobarbital (40 mg/kg BW) or atropine sulfate (10 mg/kg BW) ip at 1200 h blocked the expected rise in plasma corticosteroid concentration at 1800 h in both these rats and a group of intact rats. In the second experiment, adrenal innervation was disrupted by spinal cord transection at the T-7 level. L-1-transected rats served as operated controls, and a third group was maintained as unoperated controls. One week after surgery, daily rhythms of plasma corticosteroid concentration were present in both unoperated and L-1 controls (P less than 0.01) but not in the T-7-transected rats. Inasmuch as an extrapituitary mechanism was capable of maintaining adrenocortical rhythmicity in hypophysectomized rats and disruption of adrenal innervation suppressed adrenocortical rhythmicity, it was hypothesized that adrenal innervation may be an extrapituitary mechanism which has a role in adrenocortical rhythmicity.

Adrenal Innervation May Be an Extrapituitary Mechanism Able to Regulate Adrenocortical Rhythmicity in Rats

https://www.amjmed.com/article/0002-9343(72)90005-8/pdf

Growth hormone and cortisol responsiveness in Cushing's syndrome. Relation to a possible central nervous system etiology.

A single antibody RIA method for measurement of plasma cortisol concentrations in the bull is described. Antisera were obtained from rabbits immunized against cortisol-3- oxime-bovine serum albumin. By this technique, peripheral cortisol levels were determined in seven adult bulls (one blind) during 24- and 48-h periods, with blood collections every 30 min. Statistical evaluation of the 24-h profiles using time series analysis revealed that cortisol is secreted episodically throughout the day-night cycle (range, 0.4–9.7 ng/ml). Despite individual variability in both frequency and amplitude of secretory episodes, a distinct circadian secretion pattern was recognized. After dividing the 24 h into three 8-h time periods (I, 0900–1700 h; II, 1700– 0100 h; III, 0100–0900 h), a depressed secretory activity with small episodic bursts not exceeding 3.5 ng/ml plasma consistently occurred during time period II. Increased cortisol secretion with high fluctuating levels was evident during time periods I and III. Maxi...

DT Krieger

Papers

Abolition of circadian periodicity of plasma 17-OHCS levels in the cat.