Hormone synthesis and release

Some neonates born to mothers with Graves disease will be hyperthyroid at delivery. Antithyroid drug therapy (propylthiouracil 5-10 mg/kg per day or methimazole 0.5-1 mg/kg per day) may be required for up to 12 weeks. One drop per day of SSKI may be used in the first few days to rapidly reduce thyroid hormone synthesis and release. 

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... 

Animals employ several mechanisms to prevent excessive hormone synthesis and release. The most prominent of these is feedback inhibition. The hypothalamus and anterior pituitary are controlled by the target cells they regulate. For example, TSH release by the anterior pituitary is inhibited when blood levels of T3 and T4 rise (Figure 16.10). The thyroid hormones inhibit the responsiveness of TSH-synthesizing cells to TRH. In addition, several tropic hormones inhibit the synthesis of their releasing factors. 

Sketch the biochemical pathway for thyroid hormone synthesis and release and indicate the sites of action of antithyroid drugs. 

Ageing is accompanied by a decrease in iodine uptake by the thyroid gland, and a reduction in thyroid hormone synthesis and release. There is a decrease in the rate of production of thyroxine (T4) in the thyroid gland, and a decrease in triiodothyronine (T3) production, due to a decreased conversion rate of T4 to T3 by 5 -monodeiodi-nase in the peripheral tissues (Mariotti et ai, 1995). 

In a recent review, Thompson and Bannigan [373] noted that Cd accumulates in the ovary with age and is associated with decrements in oocyte development. Whereas several animal studies noticed decreased ovarial steroid hormone synthesis and release in rats following CLCE [374,375], in vitro studies have demonstrated increased progesterone production (reviewed in [376]). The reasons for these differences are unclear. 

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. 

While these steroids directly regulate sexual function, their synthesis and release are, in turn, controlled by gonadotropins — polypeptide hormones produced by the pituitary gland. The biology and medical applications of the gonadotropins are outlined in Chapter 8. Sex hormones produced naturally may be classified into one of three groups ... 

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. 

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. 

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