Hypothalamic and Hypophyseal Hormones

Mechanism of Action An antipsychotic that blocks postsynaptic dopamine receptor sites in brain. Has alpha-adrenergic blocking effects, and depresses the release of hypothalamic and hypophyseal hormones. Therapeutic Effect Suppresses psychotic behavior. 

Thioxanthenes, such as flupenthixol and clopenthixol, are similar in structure to the phenothiazines. The therapeutic effects are similar to those of the piperazine group. Antipsychotic thioxanthenes are thought to benefit psychotic conditions by blocking postsynaptic dopamine receptors in the brain. They also produce an alpha-adrenergic blocking effect and depress the release of most hypothalamic and hypophyseal hormones. However, the concentration of prolactin is increased due to blockade of prolactin inhibitory factor (PIF), which inhibits the release of prolactin from the pituitary gland. 

Thioxanthenes work primarily by blocking post-synaptic dopamine-mediated neurotransmission by binding to dopamine (DA-1 and DA-2) receptors. In addition to significant antidopaminergic action, the thioxanthenes also possess weak anticholinergic and serotonergic blockade, moderate a-adrenergic blockade, quinidine-like effects, and depress the release of most hypothalamic and hypophyseal hormones. Thioxanthenes may also inhibit presynaptic dopamine auto receptors. 

Located in close proximity to the primary capillary plexus in the hypothalamus are specialized neurosecretory cells. In fact, the axons of these cells terminate on the capillaries. The neurosecretory cells synthesize two types of hormones releasing hormones and inhibiting hormones (see Table 10.2). Each of these hormones helps to regulate the release of a particular hormone from the adenohypophysis. For example, thyrotropin-releasing hormone produced by the neurosecretory cells of the hypothalamus stimulates secretion of thyrotropin from the thyrotrope cells of the adenohypophysis. The hypo-thalamic-releasing hormone is picked up by the primary capillary plexus travels through the hypothalamic-hypophyseal portal veins to the anterior pituitary leaves the blood by way of the secondary capillary plexus and exerts its effect on the appropriate cells of the adenohypophysis. The hypophyseal hormone, in this case, thyrotropin, is then picked up by the secondary capillary plexus, removed from the pituitary by the venous blood, and delivered to its target tissue. 

Effect of glucocorticoid administration on adrenocortical cortisol production (A). Release of cortisol depends on stimulation by hypophyseal ACTH, which in turn is controlled by hypothalamic corticotropin-releasing hormone (CRH). In both the hypophysis and hypothalamus there are cortisol receptors through which cortisol can exert a feedback inhibition of ACTH or CRH release. 

As discussed previously, the neurohypophysis has a direct anatomical connection to the hypothalamus. Therefore, the hypothalamus regulates the release of hormones from the neurohypophysis by way of neuronal signals. Action potentials generated by the neurosecretory cells originating in the hypothalamus are transmitted down the neuronal axons to the nerve terminals in the neurohypophysis and stimulate the release of the hormones into the blood. The tracts formed by these axons are referred to as hypothalamic-hypophyseal tracts (see Figure 10.2). The action potentials are initiated by various forms of sensory input to the hypothalamus. Specific forms of sensory input that regulate the release of ADH and oxytocin are described in subsequent sections in this chapter. 

The adenohypophysis does not have a direct anatomical connection with the hypothalamus therefore, regulation of hormone secretion by way of neuronal signals is not possible. Instead, these two structures are associated by a specialized circulatory system and the secretion of hormones from the adenohypophysis is regulated by hormonal signals from the hypothalamus (see Figure 10.2). Systemic arterial blood is directed first to the hypothalamus. The exchange of materials between the blood and the interstitial fluid of the hypothalamus takes place at the primary capillary plexus. The blood then flows to the adenohypophysis through the hypothalamic-hypophyseal portal veins. Portal veins are blood vessels that connect two capillary beds. The second capillary bed in this system is the secondary capillary plexus located in the adenohypophysis. 

For complete functional evaluation of the hypothalamic-hypophyseal-adrenal axis one can use synthetic corticorelin (corticotropin-releasing hormone), which is available in both human (hCRH) and ovine (oCRH) forms (1). 

Protirelin is a synthetic tripeptide that stimulates the hypophyseal secretion of thyrotrophin (thyroid-stimulating hormone, TSH). It is used mainly for diagnostic purposes in dynamic tests of pituitary and hypothalamic... 

Figure 16.1 Hypothalamic-pituitary system. The hypothalamus receives various types of impulses and responds by secreting appropriate release and release-inhibiting factors. These migrate to the anterior or intermediate pituitary via the hypophyseal portal vein system and elicit the secretion of various tropic or non tropic hormones. For instance, when the organism is exposed to cold, blood TSH levels increase when under stress, blood ACTH levels rise. In some animals, the absence of light causes the release of a-MSH.

Arterial blood reaches the pituitary gland via the superior hypophyseal artery, a branch of the internal carotid artery. Venous blood is supplied through a venous portal system that originates in the median eminence of the hypothalamus and ends in sinusoidal capillaries of the pituitary gland. This venous system is known as the hypothalamic-hypophyseal portal system. This system carries neurosecretory hormones from the hypothalamus to the adenohypophysis. These hypothalamic factors stimulate or inhibit the release of hormones from the adenohypophysis. Retrograde flow from the adenohypophysis to the median eminence of the hypothalamus is also believed to occur. With upstream flow, pituitary hormones can reach the hypothalamus and influence hypothalamic function through a short feedback loop. 

Many studies reveal that there appears to be a functional relationship between L-tryptophan and a number of hormones. Data from several studies suggest the L-tryptophan may act on receptors of some hormones and vice versa. Also, the absence or excess of dietary tryptophan appears to affect hormone levels in blood. Speculation as to how this comes about is that the close relationship of levels of L-tryptophan and especially of serotonin is involved. Thus, serotonin probably acts to influence the secretion of anterior pituitary hormones via effects on hypothalamic hypophyseal releasing and release-inhibitory factors. 

Peptide-secreting cells of the hypothalamic-hypophyseal circuits originally were described as neurosecretory cells, receiving synaptic information from other central neurons, yet secreting transmitters in a hormone-like fashion into the circulation. The transmitter released from such neurons was termed a neurohormone, i.e., a substance secreted into the blood by a neuron. These hypothalamic neurons also may form traditional synapses with central neurons, and cytochemi-cal evidence indicates that the same substances that are secreted as hormones from the posterior pituitary (oxytocin, arginine-vasopressin see Chapters 29 and 55) mediate transmission at these sites. Thus, the designation hormone relates to the release at the posterior pituitary and does not necessarily describe all actions of the peptide. 

The neurohumoral control of hypophyseal activity is at present perfectly established Several mediators reaching the anterior lobe through the portal vessels have been extracted from hypothalamic tissue acting selectively on the elaboration and liberation of the various pituitary hormones. 

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