Lecture 7: Feedback loops and Hypothalamic-Pituitary-Adrenal Axis

Negative feedback loop

Can have more than 2 steps

Output (hormone) decreases its own output

Endocrine systems regulated at hypothalamus

Most things that alter negative feedback affect the hypothalamus

Sensitivity of negative feedback can be altered

Stress, sleep,age

Positive feedback loop

Signals increases its own output

Less common in physiology

Cannot continue forever

Adrenal cortex

3 layers that produces specific class of hormones

• Zona glomerulosa: Mineralocorticoids

• Zona fasiculata: Glucocorticoids

• Zona reticularis: Sex steroids (secretes weak androgens)

Zona glomerulosa

Secretes aldosterone which regulates K+ and water

Mineralcorticoids

K+ and water regulations necessary for life

Most important hormone produced by adrenal gland

Aldosterone secretions

High K+ and angiotensin 2 increase aldosterone

Doesn’t involve hypothalamus

Aldosterone

Increase activity of principle cells in distal tubule and collecting ducts

Increase Na/K pumps activities to reabsorb more water

3 main actions

• Sodium reabsorbtion

• Potassium excretion

• Water conservation

Controlled by 2 negative feedback loops

Zona fasciculata

Secretes glucocorticoids

• Cortisol and corticosterone

Hypothalamic pituitary adrenal (HPA) Axis

Regulates glucocorticoid production

The pituitary

Synthesizes POMC in response to CRH

1. CRH reaching posterior pituitary via portal system

2. CRH binds to receptor

3. Anterior pituitary produces more POMC

ACTH

Stimulates production of cortisol and corticosterone

Cortisol and corticosterone are made from cholesterol

Diffuses out of cell after produced

Stimulates transcription of mRNA in target cells

Effects of cortisol

Increase serum glucose concentration, decrease inflammation by supporting immune system

Shift most tissues toward lipids and proteins for energy

Muscle decreases protein content (increase AA in blood)

Adipocytes releases lipids into circulation

Liver produces glucose

Increase Plasma glucose

Decrease release of pro inflammatory signals, decrease capillary permeability, decrease fever, decrease inflammation

Stress major regulators of HPA Axis

Short term (Good) and long term (bad)

Short term effects

• Increase glucose for brain and muscle

• Ignore injury

Long term effects

• Increased infections

• Loss of muscle mass

• Weakening of skin

Addisons’s Disease

Adrenal insufficiency

Lack of cortisol

• Lack of gluconeogenesis

• Cannot maintain glucose concentrations between meals

Lack of aldosterone

• Lack of Na+ and water reabsorption

• Gradual decrease in blood pressure

• Darkening of skin: No cortisol leads to loss of negative feedback. Major increase of POMC production

Cushing Syndrome

Hyperadrenalism

Too much cortison

• Adrenal tumor- secreted cortisol

• Pituitary tumor- secreting ACTH

Increased plasma glucose

loss of muscle

Weakening of Skin

Weakened immune system

Role of adrenal dehydroepiandrosterone (DHEA)

Humans, DHEA peaks in early 20’s and declines with age

Humans, higher concentrations than any other steroid

Other mammals have much lower concentrations

Effects of DHEA

DHEA unlikely to be biologically important most of the time

DHEA is commercially available

Sold as dietary supplement (not regulated)

Purity not validated

Effects unknown (not existent)

DHEA

Produced in brain

May affect brain function

Effect are mixed of cognition