Stress Hormones, the Brain and Behavior

What is stress?

I t is “a real or interpreted threat to the physiological or psychological integrity of an individual that results in physiological and/or behavioral responses. In biomedicine, stress often refers to situations in which adrenal glucocorticoids and catecholamines are elevated because of an experience.” McEwen, B. (2000) In G. Fink (Ed.) Encyclopedia of Stress, Vol. 3. San Diego: Academic Press.

What is stress? stress stimulus? “I’m under a lot of stress.” subjective experience? “I’m feeling stressed out.” depression deviation from homeostasis? hunger, thirst, fatigue endocrine response? circulating stress hormones

Two types of stress 1. Systemic stress physiological threat 2. Processive stress potential or eventual threat In adults, responses to processive, but not systemic, stress is blocked by lesions of the hippocampus Systemic stress is also referred to as physiological stress, and processive stress is oten referred to as psychological stress

Hypothalamus Adenohypophysis Adrenal Cortex Target tissues Control of Stress Hormones Indirect Loop Short Loop Direct Loop CRF (aka CRH) Corticotrophin (aka ACTH) Cortisol or Corticosterone neural inputs (limbic system) This is usually referred to as the “HPA axis,” but is now often called the “LHPA axis.”

Paraventricular Nucleus

(CRF)

As with thyroid hormones and sex hormones One can ask, are there “organizational effects” and “activational effects”?

Stress hyporesponsive period Meany, M.J., Sapolsky R.M. * McEwen, B.S. (1985) The development of the glucocorticoid receptor system in the rat limbic brain: I. Ontogeny and autoregulation. Developmental Brain Research, 18,

Avishai-Eliner, S., Brunson, K.L., Sandman, C.A. & Baram, T.Z. (2002) Stressed-out, or in (utero)? Trends Neurosci., 25, CRH mRNA CRH mRNA

Hippocampus Low concentration of bioactive receptors Hypothalamus Diminished CRF content: potentially reduced CRF during stress Pituitary Diminished ACTH content Adult concentrations of bioactive receptors Paucity of AUX receptors (CBG) Adrenal Cortex Involution of the fetal zone Neonatal SHRP Little impact of CORT on hippocampal function, thus diminution of inhibitory feedback signal to hypothalamic CRF system. Basal adrenocortical activity is unsuppressible. Attenuated CRF signal to the pituitary during stress Exaggerated impact of CORT on pituitary function due to heavy nuclear uptake of CORT. The pituitary, already limited in its function, is desensitized to the limited CRF signal. Limited secretory capacity

Stress hyporesponsive period Meany, M.J., Sapolsky R.M. * McEwen, B.S. (1985) The development of the glucocorticoid receptor system in the rat limbic brain: I. Ontogeny and autoregulation. Developmental Brain Research, 18,

Levine, S. (2005) Developmental determinants of sensitivity and resistance to stress. Psychoneuroendocrinology, 30,

Knackstedt, M.K., Hamelmann, E. & Arck, P.C. (2005) Mothers in stress: Consequences for the offspring. Am. J. Reprod. Immunol., 54,

Knackstedt, M.K., Hamelmann, E. & Arck, P.C.(2005) Mothers in stress: Consequences for the offspring. Am. J. Reprod. Immunol., 54, Maternal stress perception leads to prolonged activation of the HPA axis within the maternal organism. This induces increased levels of CRH. CRH suppress es progesterone secretion and therefore diminishes the levels of progesterone induced blocking factor (PIBF), an important immune modulator during pregnancy. CRH also leads to an augmentation of circulation glucocorticoids. This leads to a shift from Th2 to a Th1 immunity resulting in increased expression of TNF-a at the feto–maternal interface. Elevated expression of TNF-α is associated with increased apoptosis in the placenta as well as priming the fetal immune system. Most likely, high levels of Th1 cytokines at the feto–maternal interface evoke counteracting mechanism leading to immunosuppression and a predisposition of the immune system towards atopic disease. Augmented levels of glucocorticoids have a negative feedback on growth hormone release leading to fetal growth restriction. Low birth weight in turn predisposes to type II diabetes, (Tumor Necrosis Factor)

Stress increases placental CRH to fetus; CRH excitatory inputs to hippocampal neurons facilitates synaptic development in low levels but is excitotoxic at high levels Avishai-Eliner, S., Brunson, K.L., Sandman, C.A. & Baram, T.Z. (2002) Stressed-out, or in (utero)? Trends Neurosci., 25,

activity-dependent modulation of neuronal growth and differentiation by glucocorticoids (membrane effects)

Avishai-Eliner, S., Brunson, K.L., Sandman, C.A. & Baram, T.Z. (2002) Stressed-out, or in (utero)? Trends Neurosci., 25,

Also, maternal stress can cause feedback inhibition of testosterone secretion from fetal testes; less masculinized and less defeminized males Altered development of the hippocampus results in altered responses to stressful stimuli, especially processive (psychological) stressors

cholesterol