Hypothalamic hormones actions

For their work on hypothalamic hormones, Schally and Guillemin shared the Nobel Prize in Physiology or Medicine in 1977, along with Rosalyn Yalow, who (with Solomon A. Berson) developed the extraordinarily sensitive radioimmunoassay (RIA) for peptide hormones and used it to study hormone action. RIA revolutionized hormone research by making possible the rapid, quantitative, and specific measurement of hormones in minute amounts. 

Hypothalamic hormones (Figure 7.9) can modulate a wide variety of actions throughout the... 

Many tests substances change the secretion of hypothalamic hormones, either by direct action or more generally by a feedback effects at the hypothalamic level. Under these conditions, the tissue concentration in hypothalamic specimens of treated rats is of interest, especially because several hypothalamic peptide assays are available and can be measured in the same specimen. In contrast to the tissue concentration, for many hypothalamic hormones it is difficult to measure the circulating concentrations, due to analytical problems of low concentration and rapid inactivation by enzymes. Circulating concentrations would also change immediately due to the interference of anesthesia and of the autopsy procedure. It is therefore recommended to take samples of hypothalamic tissue, and control samples of cerebral cortical tissue. 

However, it is now known to exist in various nerve tracts and neuroendocrine tissues and it has general inhibitor actions. It can also inhibit release of other pituitary hormones (including thyroid-stimulating hormone (TSH) and prolactin). other endocrine hormones including pancreatic hormones (insulin and glucagon), peptide hormones from a variety of neuroendocrine tumours (e.g. VIPomas and glucagonomas) and also the release of most intestinal hormones. It is produced in the gut, the pancreas and in some peripheral nerves (see hypothalamic hormones PITUITARY hormones). Somatostatin is a cyclic peptide of 14 residues (SRIF-14) but is formed from a precursor of 28 residues (SRIF-28). 

As its name implies, the neurohypophysis is derived embryonically from nervous tissue. It is essentially an outgrowth of the hypothalamus and is composed of bundles of axons, or neural tracts, of neurosecretory cells originating in two hypothalamic nuclei. These neurons are referred to as neurosecretory cells because they generate action potentials as well as synthesize hormones. The cell bodies of the neurosecretory cells in the supraoptic nuclei produce primarily antidiuretic hormone (ADH) and the cell bodies of the paraventricular nuclei produce primarily oxytocin. These hormones are then transported down the axons to the neurohypophysis and stored in membrane-bound vesicles in the neuron terminals. Much like neurotransmitters, the hormones are released in response to the arrival of action potentials at the neuron terminal. 

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. 

As to the primary developmental actions of testosterone, growth and differentiation appear to be involved. Testosterone or estradiol stimulates outgrowth of neurites from developing hypothalamic neurons that contain estrogen receptors [14, 15]. This is believed to be one of the principal aspects of testosterone action that increases the number and the size of neurons within specific hypothalamic nuclei in males, compared to females [1, 14, 15]. 5a-DHT may have a similar effect on androgen-sensitive neurons. Differentiation of target neurons also occurs in adult brain tissue, hormones like estradiol can evoke responses that differ between adult male and female rats [1,14,15],... 

Pinilla L, Gonzalez LC, Tena-Sempere M, Aguilar E (2001) Evidence for an estrogenlike action of raloxifene upon the hypothalamic-pituitary unit raloxifene inhibits luteinizing hormone secretion and stimulates prolactin secretion in ovariectomized female rats. Neurosci Lett 311 149-152... 

Rettori V, Wenger T, Snyder G, Dalterio S, McCann SM. (1988). Hypothalamic action ofdelta-9-tetrahydrocannabinol to inhibit the release of prolactin and growth hormone in the rat. Neuroendocrinology. 47(6) 498-503. 

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. 

Control of thyroid function via thyroid-pituitary feedback is also discussed in Chapter 37. Briefly, hypothalamic cells secrete thyrotropin-releasing hormone (TRH) (Figure 38-3). TRH is secreted into capillaries of the pituitary portal venous system, and in the pituitary gland, TRH stimulates the synthesis and release of thyrotropin (thyroid-stimulating hormoneTSH). TSH in turn stimulates an adenylyl cyclase-mediated mechanism in the thyroid cell to increase the synthesis and release of T4 and T3. These thyroid hormones act in a negative feedback fashion in the pituitary to block the action of TRH and in the hypothalamus to inhibit the synthesis and secretion of TRH. Other hormones or drugs may also affect the release of TRH or TSH. 

The many effects of lithium on thyroid physiology and on the hypothalamic-pituitary axis and their clinical impact (goiter, hypothyroidism, and hyperthyroidism) have been reviewed (620). Lithium has a variety of effects on the hypothalamic-pituitary-thyroid axis, but it predominantly inhibits the release of thyroid hormone. It can also block the action of thyroid stimulating hormone (TSH) and enhance the peripheral degradation of thyroxine (620). Most patients have enough thyroid reserve to remain euthyroid during treatment, although some initially have modest rises in serum TSH that normalize over time. 

The hypothalamic control of the posterior pituitary is quite different than that of the anterior and intermediate lobes. Specific neurons have their cell bodies in certain hypothalamic nuclei. Cell bodies in the paraventricular nuclei manufacture oxytocin, whereas the supraoptic nuclei contain cell bodies that synthesize ADH. The axons from these cells extend downward through the infundibulum to terminate in the posterior pituitary. Hormones synthesized in the hypothalamic cell bodies are transported down the axon to be stored in neurosecretory granules in their respective nerve terminals (located in the posterior pituitary). When an appropriate stimulus is present, these neurons fire an action potential, which causes the hormones to release from their pituitary nerve terminals. The hormones are ultimately picked up by the systemic circulation and transported to their target tissues. 

Dopamine agonists with central actions are of considerable value for the treatment of Parkinson s disease and prolactinemia. These agents are discussed in Chapter 28 Pharmacologic Management of Parkinsonism Other Movement Disorders and Chapter 37 Hypothalamic Pituitary Hormones. 

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