Neurovascular hypothesis

1
Neurovascular hypothesis

• Harris hypophysectomy experiments
• CNS provides drive for pituitary
• Hypothalamic lesion experiments
• Electrical stimulation experiments
• Crude hypothalamic extract experiments

2
Endocrine Hypothalamus

• Below thalamus
• Forms walls, floor of 3rd ventricle
• Median eminence lower portion of tuber cinereum
• ME made of nerve endings is vascularized
• Hypothalamus made of nuclei
• Examples PVN, SON
• Parvocellular neurons regulate anterior pituitary
• Magnocellular neurons synthesize oxytocin,
  vasopression

3
Hypophysiotropic hormones Thyrotropin-releasing
hormone

• TRH 1st identified by Guillemin and Schally
• Cell bodies of TRH neurons present in DM, SCN,
  VMN
• 3 amino acids in length
• Cleavage of proTRH yields TRH
• Stimulates TSH, prolactin, growth hormone
• Subject to negative feedback

4
Hypophysiotropic hormonesSomatostatin

• Along with GHRH, regulates release of GH
• Pulses every 3-4 hours
• Surge during first few hours of sleep
• 14 aa in length
• synthesized from 28 aa prohormone
• inhibits GH secretion
• Present in POA, periventricular nucleus of
  hypothalamus

5
Somatostatin, contd.

• Also present in pancreas, gut
• Inhibits TRH-stimulated TSH secretion
• Accounts for stress-induced decrease in GH

6
Growth Hormone Releasing Hormone (GHRH)

• 44 aa in length
• 1st isolated from pancreatic tumor
• Generates pulsatile GH secretion
• Immunoneutralize GHRH gt no pulses
• Immunoneutralize somatostatin gt elevate baseline
• Present in VMN
• Stimulate VMN gt GH levels increase

7
Gonadotropin-releasing hormone (GnRH)

• Decapeptide
• Produced by neurons of POA, arcuate nucleus
• Immunoneutralize GnRH
• Testicular atrophy
• Block preovulatory LH surge
• Secreted in pulses
• Subject to negative, positive feedback

8
GnRH, contd.

• Pulse frequency differentially regulates LH, FSH
  secretion
• Birds and fish have gt1 form of GnRH

9
Corticotropin-Releasing Hormone (CRH)

• 41 aa
• CRH neurons present in PVN
• Immunoneutralize gt ACTH levels decline
• Highly conserved
• Pulsatile (every 1-3h)
• Peaks before waking
• Subject to negative feedback

10
Prolactin Inhibiting Factor (PIF)

• PIF dopamine
• Primary neural mechanism regulating prolactin
  secretion
• Pituitary transplant studies
• In vitro experiments

11
Prolactin Releasing Factor (PRF)

• Component of hypothalamic extracts can stimulate
  prolactin secretion
• TRH?

12
MSH Release Inhibiting Factor (MIF)

• Hypothalamic lesions gt MSH levels rise
• Transplant intermediate lobe to extracranial site
  gt MSH levels rise
• Dopamine
• Direct innervation from PVN?