Cortisol levels after cold exposure are independent of adrenocorticotropic hormone stimulation

Abstract

We previously showed that postmortem serum levels of adrenocorticotropic hormone (ACTH) were significantly higher in cases of hypothermia (cold exposure) than other causes of death. This study examined how the human hypothalamic-pituitary-adrenal axis, and specifically cortisol, responds to hypothermia. Human samples: Autopsies on 205 subjects (147 men and 58 women; age 15-98 years, median 60 years) were performed within 3 days of death. Cause of death was classified as either hypothermia (cold exposure, n = 14) or noncold exposure (controls; n = 191). Cortisol levels were determined in blood samples obtained from the left and right cardiac chambers and common iliac veins using a chemiluminescent enzyme immunoassay. Adrenal gland tissues samples were stained for cortisol using a rabbit anti-human polyclonal antibody. Cell culture: AtT20, a mouse ACTH secretory cell line, and Y-1, a corticosterone secretory cell line derived from a mouse adrenal tumor, were analyzed in mono-and co-culture, and times courses of ACTH (in AtT20) and corticosterone (in Y-1) secretion were assessed after low temperature exposure mimicking hypothermia and compared with data for samples collected postmortem for other cases of death. However, no correlation between ACTH concentration and cortisol levels was observed in hypothermia cases. Immunohistologic analyses of samples from hypothermia cases showed that cortisol staining was localized primarily to the nucleus rather than the cytoplasm of cells in the zona fasciculata of the adrenal gland. During both mono-culture and coculture, AtT20 cells secreted high levels of ACTH after 10-15 minutes of cold exposure, whereas corticosterone secretion by Y-1 cells increased slowly during the first 15-20 minutes of cold exposure. Similar to autopsy results, no correlation was detected between ACTH levels and corticosterone secretion, either in mono-culture or co-culture experiments. These results suggested that ACTH-independent cortisol secretion may function as a stress response during cold exposure.

Morphological and biochemical changes in the pancreas associated with acute systemic hypoxia

“…Our previous studies have shown that asphyxia, a hypoxic condition does not induce any noticeable response in the blood cortisol level. We did find that exposure to cold induces a response in blood cortisol levels [50]. In this study blood cortisol levels did not differ markedly between the different causes of death.…”

Anterior pituitary gland synthesises dopamine from l‐3,4‐dihydroxyphenylalanine (l‐dopa)

“…Cell lines culture AtT20: This mouse ACTH-secreting pituitary adenoma cell line was chosen to carry out our research because they are of pituitary origin and can modulate the release of ACTH upon stimulation with CRH. AtT20 cells are widely used for assessing the effects of different stimulus on cell renewal, viability and ACTH secretion (22)(23)(24)(25)(26)(27)(28). These cells lack functional D2 receptors (29,30).…”

Prolonged Extreme Cold Water Diving and the Acute Stress Response During Military Dive Training

“…The disparity between the current findings and those previously reported is likely due to the exposure duration. The acute rise of cortisol immediately following submersion that has been previously reported may have occurred in the current effort; however, as duration of submersion and cold exposure persisted, negative feedback inhibition of continued cortisol secretion likely attenuated the response (De Kloet et al, 1998;Shida et al, 2020)-except in individuals under perceived physiological stress. The inverse relationship between CORT and foot temperature indicated a heightened stress response in individuals nearing dive termination criteria of skin temperatures of 10 °C.…”