Hypothalamic-releasing hormones, synthesis

The role of hypothalamic releasing hormones on synthesis of pituitary hormones cannot be fully described at present and it is possible that if it is established that release is secondary to synthesis, some modification of this nomenclature may be desirable. The term "factor" should be retained only for those principles the specificity of action of idiich is in doubt or not established (MRF, MSH-releasing factor Growth hormone-inhibiting factor, GIF), but not for those that are obviously artifacts. 

The synthesis and release of both FSH and LH from the pituitary is stimulated by a hypothalamic peptide, gonadotrophin-releasing hormone (also known as gonadorelin, LH-releasing hormone, or LH/FSH-releasing factor). 

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 hypothalamic-pituitary-thyroid axis. Acute psychosis or prolonged exposure to cold may activate the axis. Hypothalamic thyroidreleasing hormone (TRH) stimulates pituitary thyroid-stimulating hormone (TSH) release, while somatostatin and dopamine inhibit it. TSH stimulates T4 and T3 synthesis and release from the thyroid, and they in turn inhibit both TRH and TSH synthesis and release. 

Figure 33-2. Hypothalamic-pituitary-adrenal axis. Corticotropin-releasing hormone (CRH) acts to increase pituitary ACTH secretion, which enhances steroid hormone synthesis by the adrenal, including production of cortisol (hydrocortisone), which controls CRH/ACTH secretion via negative feedback.

The anterior pituitary releases GH in 6 to 8 pulsatile bursts over a 24 h period the major portion is released just prior to deep sleep. Its secretion is controlled by hypothalamic peptides GH-releasing hormone stimulates GH secretion, while somatostatin inhibits it. GH stimulates the synthesis of insulin-like growth factor-1 (IGF-1 somatomedin C) mainly, but not solely, in the liver. GH and IGF-1 receptors are widely scattered throughout the body, and both hormones exert important metabolic actions in various tissues, especially muscle and bone. 

ACTH adrenocorticoh ophic hormone is a peptide hormone released by anterior pituitary cells in response to shessful stimuli that causes the synthesis and release of cortisol (corticosteroid) from the adrenal cortex. It is an important component of the hypothalamic-pituitary-adrenal (HPA) axis. ACTH is released from pro-opiomelanocortin and secreted from corticotropes in response to corticotropin-releasing hormone (CRH) released by the hypothalamus. 

Two neuropeptides, corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) are released from parvoceUular neurons in the hypothalamic PVN to initiate a stress response. The terminal endings of these neurons, located in the median eminence of the hypothalamus, release CRH and AVP into the hypothalamic-hypophysial portal vessel system, where they travel to the anterior pituitary. The two neuropeptides act syn-ergistically on pituitary corticotrophs to activate the synthesis of pro-opiomelanocortin (POMC). This peptide, discussed in detail below, is processed to produce several peptides including adrenocorticotrophic hormone (ACTH), or corticotropin. ACTH released from corticotrophs travels via the bloodstream to act on cells in the zona fasciculata layer of the adrenal cortex, stimulating the synthesis and release of the glucocorticoids, cortisol (in humans) or corticosterone (in rodents). 

The episodic secretion of the hypothalamic hormone, gonadotrophin-releasing hormone (GnRH), stimulates synthesis and release of the gonadotrophins. LH (luteinizing hormone) and FSH (follicle-stimulating hormone), from the anterior pituitary. Despite the names, both gontidotrophins act cooperatively on the ovaries in the woman and the testes in the man to stimulate sex hormone secretion and reproductive processes. 

FIGURE 56-5 Regulation of thyroid hormone secretion. Myriad neural inputs influence hypothalamic secretion of thyrotropin-releasing hormone (TRH). TRH stimulates release of thyrotropin (TSH, thyroid-stimulating hormone) from the anterior pituitary TSH stimulates the synthesis and release of the thyroid hormones and T,. and T, feed back to inhibit the synthesis and release of TRH and TSH. Somatostatin (SST) can inhibit TRH action, as can dopamine and high concentrations of glucocorticoids. Low levels of L are required for thyroxine synthesis, but high levels inhibit thyroxine synthesis and release. 

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