Persistent Neuroendocrine Changes in Multiple Hormonal Axes after a Single or Repeated Stressor Exposures

Abstract

Many researchers have studied acute responses to stress in animals and how they are modified by prior stressor exposure, but relatively few have examined whether responses to stressors might last for prolonged periods of time. We have previously demonstrated that trough plasma corticosterone levels in rats are elevated for three to five days after single or repeated exposures to mild restraint and inescapable tailshock. The current study measured other aspects of the adrenal axis, and activity in other neuroendocrine systems, 24 hours after one or three consecutive exposures to the same stress paradigm. The data indicated persistent activation of the adrenal axis and prolactin levels, whereas the thyroid and reproductive hormone axes were inhibited after either one or three stress sessions. These changes are remarkable in that one would have expected acute responses to even intense stressors to have ended within hours after the end of the stressor. It will be important to understand the interactions among these responding neuroendocrine systems and to know how long such persistent changes last. Finally, it will be critical to understand the relative contributions of neuroendocrine and psychological factors in maintaining these persistent neuroendocrine changes after exposure to intense stressors.

Relation between the Hypothalamic-Pituitary-Thyroid (HPT) Axis and the Hypothalamic-Pituitary-Adrenal (HPA) Axis during Repeated Stress

“…These results support previous studies indicating that acute foot-shock [33], tail-shock [15], LPS [14], immobilization [12], and restraint [20] can cause a decrease in peripheral thyroid hormone levels. And, more pertinent to the current experimental design, the current results parallel previous studies demonstrating that repeated exposure to tail-shock [15] or a non-habituating stress paradigm [34] can cause a significant decrease in peripheral thyroid hormone measurements.…”

“…For example, immobilization has been shown to both increase and decrease thyroid hormone levels [9,10,11,12]. Noise stress has been shown to increase TSH levels [13], and other stressors, such as lipopolysaccharide (LPS) injection [14] and inescapable tail-shock [15] have been shown to reduce levels of thyroid hormones. The stress-induced decrease in thyroid hormones appears to be mediated, in part, by changes in hypothalamic drive to the axis.…”

Regulation of TRH neurons and energy homeostasis-related signals under stress

“…Various forms of long-term psychogenic stress decrease TSH and TH serum levels in rats (Armario & Castellanos 1984, Servatius et al 2000, but reports on Trh expression are scarce. Constriction injury of sciatic nerve decreases Trh mRNA levels in the whole hypothalamus as well as serum TH levels (Kilburn-Watt et al 2010).…”

Opiate Masking of Stress-Induced Hypervigilance: The Cause of Delayed Symptom Presentation in PTSD

“…In contrast, startle response magnitude can be elicited within several minutes pharmacologically using several compounds, most notably corticotrophin-releasing hormone (CRH) (Swerdlow et al 1989;Lee et al 1994;Risbrough et al 2003;Servatius et al 2005). CRH is a key element for the stress response as it is involved in communicating between centers of the brain that organize the autonomic and endocrine responses (Takahashi 2001;Rivier et al 2003), and it is elevated in rats in the for several hours following shock exposure (Servatius et al 2000). Given the discrepancy in the timing of stress-enhanced startle reactivity and CRH-enhanced startle reactivity, we hypothesized that there may be an additional physiological response to the stressor that overrides and masks the exaggerated startle that should be evident shortly after CRH is elevated.…”