The structure of oxytocin or ADH and a co-secreted peptide, either neurophysin I (associated with ADH) or neurophysin II (associated with oxytocin), can be found in each prohormone. These prohormones, known as preprovasophysin and preprooxyphysin, have their N-terminal signal peptide cleaved as they are transported into the endoplasmic reticulum. In the cell bodies of the supraoptic nucleus (SON) and paraventricular nucleus (PVN), the prohormones are packaged in membrane-bound secretory granules in the endoplasmic reticulum and Golgi apparatus. These secretory granules, containing fully processed peptides, are then conveyed through an adenosine triphosphate (ATP)-dependent axonal transport mechanism down the infundibular stalk to axonal termini in the pars nervosa. Light microscopy can reveal expansions of the axonal termini, referred to as Herring bodies, due to the presence of stored secretory granules. When stimulated by neurotransmitters released from hypothalamic interneurons, the neurons depolarize and propagate an action potential down the axon. At the axonal termini, the action potential increases intracellular calcium concentration, leading to exocytosis of ADH or oxytocin along with neurophysins into the extracellular fluid of the pars nervosa. Both hormones and neurophysins enter the peripheral circulation and can be measured in blood.
ADH primarily acts on the kidney to promote water retention (antidiuresis), while oxytocin mainly acts on the pregnant uterus to induce labor and on myoepithelial cells of the breast to facilitate milk letdown during nursing. The regulation and actions of ADH and oxytocin are discussed in detail. The pars distalis of the adenohypophysis consists of five endocrine cell types, producing six hormones. Histologically, the corticotropes, thyrotropes, and gonadotropes are known as pituitary basophils, whereas the somatotropes and lactotropes are referred to as pituitary acidophils.
Fig. 41.4 ). Each prohormone harbors the structure of oxytocin or ADH and a co-secreted peptide, either neurophysin I (associated with ADH) or neurophysin II (associated with oxytocin). These preprohormones are called preprovasophysin and preprooxyphysin. The N-terminal signal peptide is cleaved as the peptide is transported into the endoplasmic reticulum. In cell bodies within the SON and PVN, the prohormones are packaged in the endoplasmic reticulum and Golgi apparatus in membrane-bound secretory granules (
Fig. 41.5 ). The secretory granules are conveyed through a “fast” (i.e., millimeters per hour) adenosine triphosphate (ATP)-dependent axonal transport mechanism down the infundibular stalk to axonal termini in the pars nervosa. During transit of the secretory granule, the prohormones are proteolytically cleaved to produce equimolar amounts of hormone and neurophysin. Secretory granules containing fully processed peptides are stored in the axonal termini. Expansions of the termini due to the presence of stored secretory granules can be observed by light microscopy and are termed Herring bodies.
ADH and oxytocin are released from the pars nervosa in response to stimuli that are primarily detected at the cell body and its dendrites in the SON and PVN. These stimuli are mainly in the form of neurotransmitters released from hypothalamic interneurons. With sufficient stimulus the neurons will depolarize and propagate an action potential down the axon. At the axonal termini the action potential increases intracellular [Ca++] and results in a stimulus-secretion response, with exocytosis of ADH or oxytocin along with neurophysins into the extracellular fluid of the pars nervosa (see
Fig. 41.5). Hormones and neurophysins enter the peripheral circulation, and both can be measured in blood.
Actions and Regulation of ADH and Oxytocin
ADH acts primarily at the kidney to retain water (antidiuresis). The actions of ADH and regulation of ADH secretion were described in . Oxytocin primarily acts on the pregnant uterus to induce labor and on myoepithelial cells of the breast to promote milk letdown during nursing. The actions and regulation of oxytocin are discussed in
The Adenohypophysis
The pars distalis is composed of five endocrine cell types that produce six hormones (
Table 41.1 ). Because of the histological staining properties of the cell types, the corticotropes, thyrotropes, and gonadotropes are referred to as pituitary basophils, whereas the somatotropes and lactotropes are referred to as pituitary acidophils (see
Fig. 41.2B