Biochemistry

A. Formation and Neurosecretion of Posterior Pituitary Hormones

VP and OT are formed in the cell bodies of neurons located in the hypothalamus. Separate neurons synthesize each type of hormone and its accompanying NP. Neuronal cell bodies synthesizing OT are located primarily, but not exclusively, in the paraventricular nucleus, whereas neuronal cell bodies synthesizing VP are located primarily, but not exclusively, in the supraoptic nucleus. Although there have been claims that the same cell can synthesize both types of hormones, this does not appear to be the case in view of the separate interneuronal stimulation of either secretion product. Figure 4-10A shows a concept of the VP-producing neuron and how the neurosecretion may be signaled and controlled by interneurons, including the osmoreceptor, which represents the primary positive signaling mechanism. Electrical signals from the osmoreceptor will be either on or off, depending on the osmolarity of the extracellular fluids. From this figure, we can see that the hormone is synthesized in the cell body and moves down the long axon extending from the hypothalamus to the nerve ending. The processing of the OT precursor occurs during transport from the cell body to the axonal nerve endings in the posterior pituitary. Curiously, it is reported that mRNA for both OT and VP is transported along the axon; however, the significance of this localization is not clear. It is possible that these axonal messages could be en route to degradation or storage to be used in replenishment at a later time when new synthesis of hormone is required. VP-NP II secretion is stimulated exclusive of OT-NP I release by using the drug nicotine mediated by the stimulation of a cholinergic receptor. OT-NP I can be released specifically through the action of estradiol.

The VP-NP I complex is released by the osmoreceptor, probably via an interneuron that senses the Na+ concentration in surrounding fluids. Its own cellular volume shrinks at elevated salt concentrations, and the ionic changes induce receptor deformation that generates an electrical or chemical signal, which is transmitted to the vasopressinergic neuron. This signal, if electrical, may be transmitted down the axon of the vasopressinergic neuron (possibly along axonal nerve fibers), and in the nerve ending the electrical signal depolarizes the membrane, causing exocytosis of VP-NP II (Figure 4-10B). Other interneurons may convey signals from baroreceptors located in the carotid sinus, aortic arch, and left atrium. The signals impinging on the vasopressinergic neuron may be either electrical or chemical, but in Figure 4-10A, they have been pictured as electrical signals for convenience. The VP-NP II complex permeates local fenestrated capillaries in order to reach general circulation.

Prepro - \fasopressin

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