Synthesis and Release of Hormones

Hormone synthesis and release can be initiated by both extrinsic and intrinsic factors.2 Extrinsic factors include various environmental stimuli such as pain, temperature, light, and smell. Intrinsic stimuli include various humoral and neural factors. For instance, release of a hormone can be initiated by other hormones. These occurrences are particularly typical of the anterior pituitary hormones, which are controlled by releasing hormones from the hypothalamus. Hormonal release can be influenced by neural input a primary example is the sympathetic neural control of epinephrine and norepinephrine release from the adrenal medulla. Other intrinsic factors that affect hormone release are the levels of ions and metabolites within the body. For instance, parathyroid hormone release is governed directly by the calcium concentration in the bloodstream, and the release of 

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The hypothalamus produces vasopressin (VP), oxytocin, and other hormones (mainly peptides and polypeptides) that regulate the synthesis and release of hormones from the anterior pituitary (Table 8-2). 

Ascorbate and Hormone Balance. The highest concentrations of ascorbate are found in the adrenal and pituitary glands, and the terminal stages of scurvy are just preceded by complete depletion of adrenal ascorbate, leading, it has been frequently stated, to scurvy death from adrenocortical failure. This has caused many to suggest that the ascorbic acid-dehydroascorbic acid system plays an important role in the synthesis and release of hormones of the adrenopituitary axis. The evidence for this is both conflicting and confusing (13, 72, 73,102, 277, 278). 

Iodide and Other Inorganic Anions. When large doses of iodide ion are administered, a transient inhibition of synthesis and release of the thyroid hormones is brought about by the so-called Wolff-Chaikoff effect. 

CRH (Corticotropin releasing hormone) is expressed in the nucleus paraventricularis of the hypothalamus and drives the stress hormone system by activating synthesis and release of corticotropin at the pituitary and in turn corticosteroid from the adrenal cortex. CRH is also expressed at many other brain locations not involved in neuroendocrine regulation, e.g. the prefrontal cortex and the amygdala. Preclinical studies have shown that CRH also coordinates the behavioral adaptation to stress (e.g. anxiety, loss of appetite, decreased sleepiness, autonomic changes, loss of libido). 

Figure 22.1 Pathways projecting to and from the suprachiasmatic nucleus (SCN). Inputs from photoreceptors in the retina help to reset the circadian clock in response to changes in the light cycle. Other inputs derive from the lateral geniculate complex and the serotonergic, Raphe nuclei and help to reset the SCN in response to non-photic stimuli. Neurons in the SCN project to the hypothalamus, which has a key role in the regulation of the reproductive cycle, mood and the sleep-waking cycle. These neurons also project to the pineal gland which shows rhythmic changes in the rate of synthesis and release of the hormone, melatonin...

Large doses of iodide inhibit the synthesis and release of thyroid hormones. Serum T4 levels may be reduced within 24 hours, and the effects may last for 2 to 3 weeks. Iodides are used most commonly in Graves disease patients prior to surgery and to quickly reduce hormone release in patients with thyroid storm. Potassium iodide is administered either as a saturated solution (SSKI) that contains 38 mg iodide per drop or as Lugol s solution, which contains 6.3 mg iodide per drop. The typical starting dose is 120 to 400 mg/day. Iodide therapy should start 7 to 14 days prior to surgery. Iodide should not be... 

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). 

Adipose tissue, fat, is usually thought of as a metabolically sluggish energy reservoir and mechanical and thermal insnlator. It has proved to be much more than that. Adipose tissue influences the body weight, the inunnne response, the control of blood pressure, hemostasis, bone mass, and the fnnctions of thyroid and reproductive glands. It does these things largely on the basis of synthesis and release of a family of adipocyte peptide hormones. 

Many hormones influence the above processes only indirectly by regulating the synthesis and release of other hormones (hormonal hierarchy see p.372). 

Insulin, which is formed in the B cells of the pancreas, has both endocrine and paracrine effects. As a hormone with endocrine effects, it regulates glucose and fat metabolism. Via a paracrine mechanism, it inhibits the synthesis and release of glucagon from the neighboring A cells. 

Many steroid hormones are regulated by this type of axis—e.g., thyroxin, cortisol, estradiol, progesterone, and testosterone. In the case of the glucocorticoids, the hypothalamus releases corticotropin-releasing hormone (CRH or corticoliberin, a peptide consisting of 41 amino acids), which in turn releases corticotropin (ACTFl, 39 AAs) in the pituitary gland. Corticotropin stimulates synthesis and release of the glandular steroid hormone cortisol in the adrenal cortex. 

The regulation of calcitonin synthesis and release from the parafollicular C cells of the thyroid gland is calcium dependent. Rising serum calcium is the principal stimulus responsible for calcitonin synthesis and release. Other hormones, such as glucagon, gastrin, and serotonin, also stimulate calcitonin release. Calcitonin has been isolated in tissues other than the parafollicular C cells (parathyroid, pancreas, thymus, adrenal), but it is not known whether this material is biologically active. 

These are used to inhibit the functional activity of hypersecretive thyroid gland. The hypersecretion leads to the development of thyrotoxicosis. The antithyroid agents acts by interfering with the synthesis and release of thyroid hormones. They are classified as in table 8.4.1. 

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. 

Figure 11-9 Scheme showing synthesis and release of diacylglycerol and inositol phosphates and their regulation of calcium concentration in response to hormonal stimulation. 

Angiotensin II has a variety of effects. By constricting blood vessels it raises blood pressure, and by stimulating thirst centers in the brain it increases blood volume. Both angiotensins II and III also act on the adrenal gland to promote the synthesis and release of aldosterone. Most of the effects of angiotension II are mediated by 359-residue seven-helix G-protein linked receptors which activate phospholipase C.p q qr Like other steroid hormones aldosterone acts,via mineralocorticoid receptors, to control transcription of a certain set of proteins. The end effect is to increase the transport of Na+ across the renal tubules and back into the blood. Thus, aldosterone acts to decrease the loss of Na+ from the body. It promotes retention of water and raises... 

Adrenocorticotropin is a peptide hormone produced in the anterior pituitary. Its primary endocrine function is to stimulate synthesis and release of cortisol by the adrenal cortex. Corticotropin can be used therapeutically, but a synthetic derivative is more commonly—and almost exclusively—used to assess adrenocortical responsiveness. A substandard adrenocortical response to exogenous corticotropin administration indicates adrenocortical insufficiency. 

For a hormone to have a specific effect on gene activity, any increase in enzyme activity must result from de novo synthesis by newly formed mRNA. This increase in enzyme activity may or may not precede any general increase in metabolic activity. From the foregoing discussion on chromatin activity, it is clear that plant hormones largely either increase the activity of polymerase I or increase the synthesis of total RNA s. Claims that the hormones "activate" chromatin-bound polymerases and "modulate" the number of active sites on the chromatin (21) have not been substantiated. There are only two known examples of hormone-induced synthesis of specific mRNA s. The classic example is the barley aleurone cells, in which GA treatment induces de novo synthesis and release of K-amylase (58, 59, 60), protease (61), and possibly as many as ten proteins (62). 

The adrenal glands are located anatomically above the kidneys. They comprise a three-layer cortex and a medulla. The medulla is the source of catecholamines such as epinephrine, the fight-or-flight hormone. The cortex is the source of aldosterone, the primary mineralocorticoid that is involved in the regulation of sodium reabsorption in the kidneys. In addition, the cortex is also the source of steroids known as glucocorticoids, of which cortisol is the principal endogenous representative. Synthesis and release of cortisol is under the control of adrenocorticotropic hormone (ACTH). 

The thyroid-pituitary-hypothalamus axis controls thyroid hormone homeostasis. Thyrotropin-releasing hormone (TRH), released from the hypothalamus, stimulates the synthesis and release of thyroid-stimulating hormone (thyrotropin, TSH) from the anterior pituitary. TSH increases the release of thyroid hormones by several mechanisms, including stimulation of the I pump. While lower than normal levels of T3 and T4 cause an exaggerated response of the pituitary to TRH, released thyroid hormones, in feedback control, blunt the stimulating action of TRH on the pituitary. For further discussion of TSH and TRH biochemistry, see, for example, the review by Kannan48. 

Induction of de novo synthesis of a-amylase by GA in isolated aleurone layers is evident after a lag period of approximately 8 hr following administration of the hormone. In keeping with hormone responses generally, GA must be present continuously if the de novo synthesis of hydrolases is to be sustained. Synthesis of new RNA is essential to the GA-induction of de novo synthesis of hydrolases. Actinomycin D, an inhibitor of RNA synthesis, inhibits the synthesis and release of a-amylase if the inhibitor is presented during the first 7 to 8 hr after treatment. Inhibitors of protein synthesis, such as cycloheximide, also inhibit GA-induction of hydrolases. And, interestingly, abscisic acid, a growth-inhibiting hormone, inhibits GA-induced a-amylase synthesis as well. 

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