Next, the posterior pituitary

• Different anatomical structure

• Different hormones (VP, Oxy)

• Different functions

• Distinct pathophysiology

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.

Neurohypophysial hormones:similar nonapeptides,

derived from different precursors

Figure 2. Prepro-oxytocin. Proteolytic maturation proceeds from top to bottom

Processing in rough ER (loss of signal peptide)

Pro-oxytocin

-lys-arg- -lys-arg- -COOHH2N-

Signal peptide

Prepro-oxytocin

-lys-arg- -lys-arg- -COOHH2N-

Oxytocin Neurophysin IOxytosin carrier protein

in axon

Processing in Golgi – hydrolysis of lys-arg bonds

H2N-

H2N-

H2N-

Processing in rough ER (loss of signal peptide)

Pro-vasopressin

-lys-arg- -lys-arg- -COOHH2N-

Signal peptide

Prepro-vasopressin

-lys-arg- -lys-arg- -COOHH2N-

Vasopressin Neurophysin IIADH carrier protein in

axon

Glycoprotein

Processing in Golgi – hydrolysis of lys-arg bonds

Figure 2. Processing of prepro-vasopressin.

Schema to represent steps in neuropeptide synthesis, transport and release

Neurohypophysis: histology

EM image of neurosecretory granules packed into

Herring bodies in neurohypophysial axon terminals

Hormone storage and release from neurohypophysial axon terminals

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

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.

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

Structure of the oxytocin receptor

In-vivo electrophysiology of oxytocin-secreting neurosecretory neurons

prerequisite:antidromic identification to verify axon target

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.