Adrenal Cortex Hormones

Corticosteroids Immunity & Inflammation

reduced

Tissue Phosphorylase

Glycogen Glucose

Mineralocorticoids

Kidneys Retain Na+ Retain H2O Retain pressure

‘Health risk?”

1. Steroid passively diffuses across cell membrane.

2. The steroid is bound by receptor in cytoplasm.

3. There is a change in the conformation of the steroid receptor.

4. The steroid-receptor complex moves into the cell nucleus.

5. The steroid-receptor complex associates with the chromatin (DNA) and initiates genetic transcription. (The receptor is a transcription factor.)

6. Synthesis of messenger RNA (mRNA) changes.

7. The mRNA moves into the cytoplasm where it is translated into protein.

8. The protein(s) are processed into their final form.

Mechanism of steroid and thyroid hormone action

Steroids: schema to depict diversity of mechanisms for

their immediate, intermediate and long-term actions in

neurons

a: Levels of regulationb: Effects on membrane

properties

Negative Feedback

• Most biological systems operate with negative feedback

• protects against overstimulation

• In the HPA axis, negative feedback via ACTH and cortisol serves to limit excitability of CRF neurons and reduce the impact of their stimulation by a stressor

Negative feedback: an important mechanism to regulate release and maintain homeostasis in the HPA axis

• As levels of both ACTH and cortisol increase, they feed back negatively via receptors on anterior pituitary corticotrophs and hypothalamic CRF secreting neurons, respectively.

Figure 18.5

Hypothalamic Control over the Endocrine System: the rapid “neural” pathway from PVN parvocellular neurons that project to spinal sympathetic

preganglionic neurons whose axons directly innervate adrenal medulla

What is special about adrenomedullary sympathetic preganglionic neurons?

• Most preganglionic neurons that form the spinal outflow for the peripheral sympathetic nervous system send their axons to a ganglia where they synapse with the postganglionic neurons

• EXCEPT the preganglionic neurons that innervate the adrenal medulla where the pathway is direct to the chromaffin cells, which serve as analogues of the postganglionic neurons

• This cholinergic innervation is via the splanchnic nerve, and triggers the chromaffin cells to release adrenaline and noradrenaline in proportion to the firing frequency of adrenomedullary preganglionic neurons

450ms

450ms

40mV

10mV

Cell 1

Cell 1Cell 2

Cell 2

Cell 1 Cell 2

Adrenal Medulla: histology

Noradrenaline and adrenaline synthesis

Adrenal Medulla Hormones

Adrenaline& Noradrenaline

Speed heart beat

Constrict vessels Increase breathing

Dilate airways

Perspire

Tissue Phosphorylase Lipase

Glycogen Fat

Glucose Fatty Acids(Also ‘targets’ of Sympathetic nerves)

Summary:HPA axis and hypothalamic-spinal-adrenal axis

HYPO

“Stressors” (from PNS or Cortex)

PIT

KidneyADRENAL GLAND

ACTH

Sympathetic

Cortex Medulla

MineralocorticoidsCorticosteroids

AdrenalineNoradrenaline

Features of the mammalian adrenal gland

• Encased in a connective tissue capsule attached to the upper edge of the kidneys

• Gland is partitioned into cortex and medulla

• Organ is richly vascularized, distinct capillary beds supply medulla and cortex

• Medulla: – arteries penetrate the cortex without branching

– fairly homogeneous, composed of chromaffin cells

– unique directly innervation by sympathetic preganglioninc neurons

– chromaffin cells are analogous to sympathetic postganglion neurons

– produce adrenaline (75-80%) and noradrenaline (25-30%)

• Cortex: – its own blood supply, three distinct functional zones

– Zona glomerulosa, outermost, thin, produces mineralocorticoids (aldosterone)

– Zona fasiculatat, middle, thickest, produces glucocorticoids (cortisol)– Zona reticulosa, innermost, thin, produces sex steroid (androgens)

What the heck is “Stress”?

“Stressed – Who Me?”

Human Bio

Ways toHave fun

GolfCooking

SleepingFishingMadeSimple

Types of stress

Stressors in Your Life?

Some definitions of stress

Triad of systems mediate response to stress

• Stress = any condition that threatens homeostasis

• GAS (General Adaptation Syndrome) is our bodies response to stress-causing factors

• Three phases to GAS– Alarm phase (immediate, fight or flight, directed by

the sympathetic nervous system)– Resistance phase (dominated by glucocorticoids)– Exhaustion phase (breakdown of homeostatic

regulation and failure of one or more organ systems)

Hormones and stress

GAS: immediate response

Schematic “overview” of the neural components of a stress “response”

Alarm → Resistance phase: bringing the HPA axis and glucocorticoids into play