Next, the posterior pituitary

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. Prepro-oxytocin -lys-arg- -lys-arg- H2N- -COOH H2N- Signal peptide Processing in rough ER (loss of signal peptide) H2N- H2N- Pro-oxytocin H2N- -lys-arg- -lys-arg- -COOH Processing in Golgi – hydrolysis of lys-arg bonds Oxytocin Neurophysin I Oxytosin carrier protein in axon Figure 2. Prepro-oxytocin. Proteolytic maturation proceeds from top to bottom

5. Prepro-vasopressin -lys-arg- -lys-arg- H2N- -COOH Signal peptide Processing in rough ER (loss of signal peptide) Pro-vasopressin H2N- -lys-arg- -lys-arg- -COOH Processing in Golgi – hydrolysis of lys-arg bonds Vasopressin Neurophysin II ADH carrier protein in axon Glycoprotein 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 neuronsprerequisite:antidromic identification to verify axon target

15. Rat hypothalamus exposed for in-vivo electrophysiologyUnder 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.