HPA-axis

HPA-axis stands for

Hypothalamic-Pituitary-Adrenal axis

  • Hypothalamus: stress accumilator

  • Pituitary gland: secretes stuff

  • Adrenal glands (cortex): on top of the kidneys, like little hats

    • Adrenal glands consist of a cortex and a medulla


Glucocorticoids

  • CORTS

    • Cortisol

    • Corticosterone

  • Glucose (metabolism) + adrenal cortex (synthesis) + steroid (structure)


CORT effects

Behavioural effects

  • “Fight-or-flight” response

  • Self preservation

  • Abandonment of offspring

Physiological effects

  • Fat metabolism

  • Digestion

  • Circulation


Explain the HPA-axis

The hypothalamus detects some stress and releases a hormone to the pituitary gland, which then excretes a hormone to the adrenal cortex, which releases CORT into the blood. (allostatic process)

  • The blood eventually reaches back to the hypothalamus and pituitary gland, which triggers them to turn off their excretion (negative feedback), back to homeostasis.

    • The procedure is not meant to be chronic, just enough to get the animal out of a potentially dangerous situation


Glucocorticoid receptors

  • Glucocorticoid receptor (GR)

  • Mineralocorticoid receptor (MR)

MR easily binds to CORT, and animals always have some level of CORT in their bodies. MR is then “occupied” by the CORT as a baseline. When CORT is in abundance (such as during the HPA-axis), the GR also bind to CORT, which is what triggers this whole thing.

  • When the intracellular receptors bind to CORT, GR and MR migrate to the nucleus for gene expression

  • (young animals more sensitive due to this)


Stressors can be

  • Physical

    • e.g. capture, handling

  • Chemical

    • e.g. pollution, low oxygen

  • Perceived

    • e.g. sound/presence of a predator


Stress responses can be divided into

  • Primary response

    • e.g. increase in hormone levels

  • Secondary response

    • e.g. metabolic changes, changes in immune function

  • Tertiary response

    • e.g. changes in whole animal health (growth, reproduction, disease resistance), behavioural changes (feeding, aggression)



CORT effects on the immune system

  • Suppresses the immune response directly and indirectly

    • affects the cells participating in immune- and inflammatory reactions

Short-term:

  • for self-preservation, e.g. suppressing the immune system so you don’t get sick during fight/flight

Long-term

  • Body more susceptible to disease due to suppressed immune system


Treatment with CORT

  • One of the most prescribed drugs

  • Used with all diseases involving inflammatory processes

  • Severe side effects if used chronically (they are steroids after all…)


How does CORT suppress the reproductive system?

  • (You don’t have time for offspring during stressful times!)

  • Influence the synthesis of gonadal steroids (testosterone, oestrogen…) by downregulation of gonadotrophins + direct effects on the ovaries/testis

“ Stress impacts on the reproductive axis at the hypothalamus (to affect GnRH secretion) and the pituitary gland (to affect gonadotrophin secretion). Different stressors have different effects and there are differences in response to short- and long-term stress. Many short-term stresses don’t affect reproduction. “


HPA-axis and circadian rhythm?

Circadian rhythm is driven by the pineal gland

  • CORT production is peaking in early morning and declines throughout the day, only rising after midnight


HPA-axis and sex

  • Females are often shown to have higher responses to cortisol than males

Non-lactating more prone to stress than lactating ewes



CORT-levels can be affected by

  • Time of day

  • Sex

  • X-gene environment

  • Genetics

  • Lactation

  • Age (lower with age)

  • Environment

Corticosteroid binding globulins (CBGs)

  • Main protein carrying CORT in blood

    • 80-90% of CORTs in the bloodstream bind to CBGs


How can CBGs affect CORT levels?

  • Even if CORT levels changes, CBG levels can change proportionally so the free CORT concentrations remain static

    • found in house sparrows

  • CBG concentrations can change while CORT levels don’t, which changes the concentrations of free CORT

    • happens in tree lizards


How to measure CORT

  • Blood

  • Urine

  • Hair/Feathers

  • Saliva

  • Feces


How to analyse CORT

  • Radioimmunoassay — RIA

    • radioactivity to trace hormone

      • more sensitive, but need isotopic labs (can use small concentrations)

    • antibodies bind to specific antigens

      • Your sample with unknown concentration of CORT mixed with a sample with known concentration of CORT

        • Put a drop of each sample into (something), radioactively labelled antigen

          • they compete for the antibodies

            • rinse

            • we use this sample for how many % they had (e.g. 100% —> no CORT in your sample as the known sample bound all antibodies)

  • Enzymeimmunoassay — ELISA

    • via enzymes

    • anti-body + antigen that binds, no competition

    • The more CORT, the more antibody-antigen bonds.

      • anti-human IgG enzyme can bind to the bond, adding a substrate and changes colour due to all of the above.

      • big colour change= a lot of bonds