Feedback loops, Processing hormones from precursors, equine PPID

Question 1

Feedback mechanisms

Answer 1

Help to maintain physiological homeostasis by maintaining the levels of hormones
- Too much or too little result in adverse effects

Question 2

Basic feedback mechanism steps

Answer 2

1. Physiological imbalance away from set point
2. Tells an endocrine gland to release hormone
3. Hormone acts on target organ
4. Organ responds to hormone
5. Response tells the endocrine to stop producing the hormone

Question 3

Feedback loop of Growth Hormone Secretion (anterior pituitary example)

Answer 3

1. Inhibitors or stimulators act on median eminence (telling it to produce or inhibit production of growth hormone)
   - Stimulator: Growth hormone releasing hormone
   - Inhibitor: Somatostatin
2. Growth hormone acts on liver to produce IGF-1
3. Increase in IGF (results in long-loop feedback)
   - Stimulates somatostatin production
   - Inhibits growth hormone releasing hormone
   - Inhibits growth hormone

NOTE: all components have ultrashort-loop feedback which can inhibit their own production

Question 4

Long-loop feedback

Answer 4

Feedback from target tissue feeding back to the brain or pituitary

Question 5

Short-loop feedback

Answer 5

Feedback from pituitary to the brain

Question 6

Ultra-short loop feedback

Answer 6

Feedback occurring in the same location that the hormone was produced

Question 7

Feedback loop of oxytocin secretion (posterior pituitary example)

Answer 7

1. Suckling triggers sensory nerve impulses that are sent to the brain
2. Triggers oxytocin from the hypothalamus and posterior pituitary AND lactocytes in the mammary alveoli to produce milk in response to nerve impulses
3. Oxytocin triggers myoepithelial cells to squeeze milk from alveoli so it drains into lactiferous ducts and pools in the lactiferous sinus before being discharged through nipple
4. Results in an increased milk production
5. When suckling stops, sensory trigger stops and milk production will stop

Question 8

Proopiomelanocortin (POMC)

Answer 8

• Precursor to ACTH and other hormones
• Produced at anterior pituitary pars intermedia (anterior lobe)

Question 9

Normal processing of POMC to ACTH and other hormones

Answer 9

In pars distalis:
1. ACTH component of POMC is cleaved from it using prohormone convertase 1

• Stimulated by corticotropin-releasing hormone (CRH) from brain

In pars intermedia:
1. ACTH component of POMC is cleaved from it using prohormone convertase 1
2. ACTH is immediately converted to alpha-melanocyte-stimulating hormone (MSH) and corticotropin-like intermediate lobe peptide (CLIP) by prohormone convertase 2

• All Inhibited by dopamine from brain

Question 10

Pituitary pars intermedia disease (PPID)

Answer 10

Equine cushings disease

Reduced dopamine release from hypothalamus results in more POMC and excess ACTH production from pars intermedia
- Conversion of ACTH to alpha-MSH and CLIP is not able to keep up
- ACTH goes and stimulates cortisol stimulation from the adrenal gland

Question 11

Pergolide

Answer 11

• A dopamine agonist
• Used to treat PPID in horses