The impact of the HPA axis on human health

Since it is almost impossible to separate the effects of ageing and cumulative stress on the regulation of the HPA axis, it might be of interest to examine how the HPA axis activity is associated with diseases that are characteristic of ageing. This assumes that the insults on the HPA axis of wear and tear are an unavoidable consequence of ageing. Longevity runs in families and 'successful' ageing is likely to have genetic components. Perturbations of the regulation of the HPA axis and associated neuroendocrine reactions and disease risk factors are linked to molecular genetic characteristics. Although this molecular genetic information is so far preliminary and superficial, it might serve to generate ideas of new approaches to the problem of neurendocrine—endocrine and autonomic ageing.

This information has largely been obtained from two population studies, one in men and one in women. Since the primary aim of these studies was not to study the effects of ageing, they included subjects born in the same year, the men born in 1944

and the women in 1956. This approach was chosen to avoid the confounding influence of age. Nevertheless, the information obtained might be useful for the interpretation of the influence of daily life stressors on neuroendocrine health, or abnormalities and their associations to disease or disease precursors, characteristic of older subjects.

In these studies it was thought to be important to examine the status of the HPA axis during ordinary daily life. Measuring the easily disturbed HPA axis during abnormal, potentially stressful conditions, such as in a laboratory or hospital, does not provide the information needed in an attempt to examine the impact of daily life on, for example, cortisol secretion. If, in addition, venipuncture is involved, then the risk for disruption of a steady state increases due to the exquisite sensitivity of the systems being examined. For these reasons saliva cortisol was measured. The advantages of this procedure are that saliva can easily be collected under any conditions (except sleep) and saliva cortisol contains the free active fraction of circulating cortisol. Saliva was collected during several predetermined time points including morning, afternoon and evening, and perceived stress was registered by the proband. The reaction to a standardized lunch was determined. A dexamethasone suppression test was performed, also under 'free-living' conditions, with a lower (0.5 mg) than conventional (1.0 mg) dose in order to improve sensitivity. In this way, an impression of the basal and stimulated (food intake and reported perceived stress) activity of the HPA axis was obtained as well as the function of the feedback inhibitory loop. These measurements were then set in relation to a number of psychological, socioeconomic and lifestyle factors, other hormones, as well as conventional metabolic and haemodynamic risk factors for disease (Rosmond et al 1998, Baghaei et al 2001).

The sensitivity of the HPA axis as mirrored by saliva cortisol measurements is clearly demonstrated by another recent study where saliva cortisol was measured at random times during a working day, with perceived stress and mood being reported before each sampling. The results showed that the measurements were influenced not only by the stress perceived immediately before sampling, but also by the memory of previously experienced stress, anticipated stress and mood. Cortisol levels varied 20-fold over the day and were proportional to the reported perceived psychological impacts (Smyth et al 1998). This study demonstrates the necessity of measuring the activity of the HPA axis under ordinary, daily conditions, which are those presumably affecting disease-generating mechanisms over a prolonged period of time.

0 0

Post a comment