1. Next, the posterior pituitary Different anatomical structure Different hormones (VP, Oxy) Different functions Distinct pathophysiology

2. Hypothalamic Control of Posterior Pituitary Secretion (a summary) Magnocellular neurons in SON and PVN synthesize precursor peptides for vasopressin (antidiuretic hormone) or oxytocin) Products are packaged into neurosecretory vesicles and transported in axons forming the hypothalamo- hypophyseal tract Vesicles are stored in posterior pituitary. Release by exocytosis is controlled by neuroendocrine reflexes.

3. Neurohypophysial hormones: similar nonapeptides, derived from different precursors

4. Figure 2. Prepro-oxytocin. Proteolytic maturation proceeds from top to bottom Processing in rough ER (loss of signal peptide) Pro-oxytocin -lys-arg- -COOH H 2 N- Signal peptide Prepro-oxytocin -lys-arg- -COOHH 2 N- Oxytocin Neurophysin I Oxytosin carrier protein in axon Processing in Golgi – hydrolysis of lys-arg bonds H 2 N-

5. Processing in rough ER (loss of signal peptide) Pro-vasopressin -lys-arg- -COOH H 2 N- Signal peptide Prepro-vasopressin -lys-arg- -COOHH 2 N- Vasopressin Neurophysin II ADH carrier protein in axon Glycoprotein Processing in Golgi – hydrolysis of lys-arg bonds Figure 2. Processing of prepro-vasopressin.

6. Schema to represent steps in neuropeptide synthesis, transport and release

7. Neurohypophysis: histology

8. EM image of neurosecretory granules packed into Herring bodies in neurohypophysial axon terminals

9. Hormone storage and release from neurohypophysial axon terminals

10. Immunocytochemical visualization of vasopressin- and oxytocin-synthesizing neurons Upper box, coronal section through the hypothalamic paraventricular nucleus (PVN) Lower box, section through the hypothalamic supraoptic nucleus (SON) VP, dark, Oxy light brown NB: VP, Oxy in separate cells, applies to both male and female brain

11. Physiology of Oxytocin Secretion In females, 2 unique roles: Milk ejection: sensory stimulation of the nipple induces firing of oxytocin cells, release of oxytocin into the blood, activation of oxytocin receptors in breast myoepithelial cells and milk expulsion Delivery of the fetus: distention of the uterus at term triggers firing of oxytocin neurons, releasing oxytocin as a hormone into the blood; occupany of oxytocin receptors in uterine smooth muscle induces contractions that assist in expulsion of the fetus.

12. Lactation is a cooperation between anterior and posterior pituitary hormones. Prolactin released from the anterior pituitary lactotrophs promotes milk production; oxytocin released from posterior pituitary storage sites promotes contraction of myoepithelial cells and milk expulsion

13. Structure of the oxytocin receptor

14. In-vivo electrophysiology of oxytocin-secreting neurosecretory neurons prerequisite:antidromic identification to verify axon target

15. Rat hypothalamus exposed for in-vivo electrophysiology Under anesthesia, removal of the sphenoid bone and dura mater exposes the ventral surface of the hypothalamus from the optic chiasm to the posterior pituitary. A stimulating electrode positioned in the posterior pituitary allows activation of axon terminals of neurosecretory neurons. A recording micropipette positioned near the junction of the middle and anterior cerebral arteries serves to record extracellular activity from antidromically-identified supraoptic nucleus neurons.