Transcript Stress Hormones - University of Florida

Stress Hormones,
the Brain
and
Behavior
What is stress?
What is stress?
It 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
Control of
Stress Hormones
neural inputs
(limbic system)
Hypothalamus
Indirect
Loop
Short
Loop
CRF
(aka CRH)
Adenohypophysis
Direct
Loop
Corticotrophin
(aka ACTH)
Adrenal Cortex
Cortisol or
Corticosterone
Target tissues
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, 159-164.
CRH
mRNA
CRH
mRNA
Avishai-Eliner, S., Brunson, K.L., Sandman, C.A.
& Baram, T.Z. (2002) Stressed-out, or in (utero)?
Trends Neurosci., 25, 518-524.
Neonatal SHRP
Hippocampus
Low concentration of bioactive receptors
Little impact of CORT on hippocampal
function, thus diminution of inhibitory
feedback signal to hypothalamic CRF
system. Basal adrenocortical activity
is unsuppressible.
Hypothalamus
Diminished CRF content:
potentially reduced CRF during stress
Attenuated CRF signal to the pituitary
during stress
Pituitary
Diminished ACTH content
Adult concentrations of bioactive receptors
Paucity of AUX receptors (CBG)
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.
Adrenal Cortex
Involution of the fetal zone
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, 159-164.
Levine, S. (2005) Developmental determinants
of sensitivity and resistance to stress.
Psychoneuroendocrinology, 30, 939-946.
Knackstedt, M.K., Hamelmann, E. & Arck, P.C.
(2005) Mothers in stress: Consequences for the
offspring. Am. J. Reprod. Immunol., 54, 63-69.
(Tumor Necrosis
Factor)
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,
Knackstedt, M.K., Hamelmann, E. & Arck, P.C.(2005) Mothers in stress:
Consequences for the offspring. Am. J. Reprod. Immunol., 54, 63-69.
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, 518-524.
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, 518-524.
Altered development of the
hippocampus results in
altered responses to stressful
stimuli, especially processive
(psychological) stressors
Also, maternal stress can
cause feedback inhibition of
testosterone secretion from
fetal testes;
less masculinized and
less defeminized males
cholesterol