Spring 2023 Dentistry Lec 2 Endocrine PDF

Physiology for Dentistry Students Endocrine 2 Fatima Daoud. MD. PhD. Pituitary Hormones and Their Control by the Hypothalamus Chapter 75 Biological Actions of Growth Hormone HGH Liver Adipose tissue ↓ Glucose uptake ↑ Lipolysis ↓ Adiposity ↑ RNA synthesis ↑ Protein synthesis ↑ Gluconeogenesis ↑ Soma...

Physiology for Dentistry Students Endocrine 2 Fatima Daoud. MD. PhD. Pituitary Hormones and Their Control by the Hypothalamus Chapter 75 Biological Actions of Growth Hormone HGH Liver Adipose tissue ↓ Glucose uptake ↑ Lipolysis ↓ Adiposity ↑ RNA synthesis ↑ Protein synthesis ↑ Gluconeogenesis ↑ Somatomedin Bone, heart, lung ↑ Protein synthesis ↑ RNA synthesis ↑ DNA synthesis ↑ Cell size and number ↑ Organ size ↑ Organ function IGFs Muscle ↓ Glucose uptake ↑ Amino acid uptake ↑ Protein synthesis ↑ Lean body mass Chondrocytes ↑ Amino acid uptake ↑ Protein synthesis ↑ RNA synthesis ↑ DNA synthesis ↑ Collagen ↑ Chondroitin sulfate ↑ Cell size and number  Linear growth Regulation of Growth Hormone Secretion Growth hormone is secreted in a pulsatile pattern. ** Hypersecretion (measure IGF-1) Hypothalamohypophyseal-GH Axis _ Hypothalamus + GHRH Somatostatin _ + _ Somatotrope Growth hormone + Liver IGF-I Regulation of Growth Hormone Secretion Stimulation Glucose decrease Free fatty acid decrease Amino acid increase (arginine) Fasting Prolonged caloric deprivation Stress Exercise Puberty Androgens and estrogens Sleep Inhibition Somatostatin Glucose increase Free fatty acid increase Somatomedins Growth hormone (exogenous) Senescence **Provocative tests that stimulate the somatotroph are necessary to assess GH deficiency (GHD) because basal GH levels are frequently very low even in normal individuals. Insulin-induced hypoglycemia (insulin tolerance test [ITT]) is the gold standard test for assessing GH reserve. ****When growth hormone is administered directly into the blood of an animal over a period of hours, the rate of endogenous growth hormone secretion decreases. This demonstrates that growth hormone secretion is subject to typical negative feedback control, as is true for essentially all hormones. The nature of this feedback mechanism and whether it is mediated mainly through inhibition of GHRH or enhancement of somatostatin, which inhibits growth hormone secretion, are uncertain. Regulation of Growth Hormone Secretion Physiological Functions of Growth Hormone **Effect of extreme protein deficiency on the plasma concentration of growth hormone in the disease kwashiorkor. Also shown is the failure of carbohydrate treatment but the effectiveness of protein treatment in lowering growth hormone concentration. **Under acute conditions, hypoglycemia is a far more potent stimulator of growth hormone secretion than is an acute decrease in protein intake. Conversely, in chronic conditions, growth hormone secretion seems to correlate more with the degree of cellular protein depletion than with the degree of glucose insufficiency. Abnormalities of Growth Hormone Secretion Gigantism and Acromegaly @theconversation.com @Macleod’s clinical examination **Gigantism → large quantities of growth hormone are produced. All body tissues grow rapidly, including the bones (before adolescence). → hyperglycemia, degeneration of B cells, 10 percent will develop full-blown diabetes mellitus. →panhypopituitarism → general deficiency of pituitary hormones usually causes death in early adulthood →microsurgical removal of the tumor or by irradiation of the pituitary gland. **Acromegaly → If an acidophilic tumor occurs after adolescence—that is, after the epiphyses of the long bones have fused with the shafts—the person cannot grow taller, but the bones can become thicker and the soft tissues can continue to grow → Enlargement in the bones of the hands and feet and in the membranous bones, including the cranium, nose, bosses on the forehead, supraorbital ridges, lower jawbone, and portions of the vertebrae, because their growth does not cease at adolescence. Consequently, the lower jaw protrudes forward (Prognathism), sometimes as much as half an inch, the forehead slants forward because of excess development of the supraorbital ridges, the nose increases to as much as twice normal size, the feet require size 14 or larger shoes, and the fingers become extremely thickened so that the hands are almost twice normal size. In addition to these effects, changes in the vertebrae ordinarily cause a hunched back, which is known clinically as kyphosis. Finally, many soft tissue organs, such as the tongue, the liver, and especially the kidneys, become greatly enlarged. **If an acidophilic tumor occurs after adolescence—that is, after the epiphyses of the long bones have fused with the shafts—the person cannot grow taller, but the bones can become thicker and the soft tissues can continue to grow Posterior Pituitary Gland and Its Relation to the Hypothalamus Posterior pituitary hormones Antidiuretic hormone (ADH) (vasopressin). Oxytocin **If the pituitary stalk is cut above the pituitary gland but the entire hypothalamus is left intact, the posterior pituitary hormones continue to be secreted normally, after a transient decrease for a few days; they are then secreted by the cut ends of the fibers within the hypothalamus and not by the nerve endings in the posterior pituitary. The reason for this is that the hormones are initially synthesized in the cell bodies of the supraoptic and paraventricular nuclei and are then transported in combination with “carrier” proteins called neurophysins down to the nerve endings in the posterior pituitary gland, requiring several days to reach the gland. **ADH is formed primarily in the supraoptic nuclei, whereas oxytocin is formed primarily in the paraventricular nuclei. Chemical Structures of ADH and Oxytocin ❖Both oxytocin and ADH (vasopressin) are polypeptides, each containing nine amino acids. Their amino acid sequences are the following: ❖Vasopressin: Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-GlyNH2 ❖Oxytocin: Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-GlyNH2 ❖Note that these two hormones are almost identical except that in vasopressin, phenylalanine and arginine replace isoleucine and leucine of the oxytocin molecule. The similarity of the molecules explains their partial functional similarities. Physiological Functions of Antidiuretic Hormone ❖ In the presence of ADH, the permeability of the collecting ducts and tubules to water increases greatly and allows most of the water to be reabsorbed as the tubular fluid passes through these ducts, thereby conserving water in the body and producing very concentrated urine. 1 High blood osmotic ADH production ❖ Increased extracellular fluid osmolarity stimulates antidiuretic hormone secretion → the osmoreceptor ❖Low blood volume and low blood pressure stimulate ADH secretion 5 Low blood osmotic pressure stimulates hypothalamic osmoreceptors pressure inhibits hypothalamic osmoreceptors Osmoreceptors Osmoreceptors 2 activate the 6 Inhibition of osmoneurosecretory cells receptors reduces or that synthesize and stops ADH secretion release ADH Hypothalamus 3 Nerve impulses liberate ADH from axon terminals in the posterior pituitary into the bloodstream ADH → Atrial stretch receptors , the baroreceptors Target tissues 4 Kidneys retain more water, which decreases urine output Sudoriferous Arterioles constrict, (sweat) glands which increases decrease water blood pressure loss by perspiration from the skin **Somewhere in or near the hypothalamus are modified neuron receptors called osmoreceptors. When the extracellular fluid becomes too concentrated, fluid is pulled by osmosis out of the osmoreceptor cell, decreasing its size and initiating appropriate nerve signals in the hypothalamus to cause additional ADH secretion. **The atria have stretch receptors that are excited by overfilling. When excited, they send signals to the brain to inhibit ADH secretion. Conversely, when the receptors are unexcited as a result of underfilling, the opposite occurs, with greatly increased ADH secretion. Decreased stretch of the baroreceptors of the carotid, aortic, and pulmonary regions also stimulates ADH secretion.. Oxytocin ❖ Oxytocin causes contraction of the pregnant uterus. ❖ Oxytocin aids in milk ejection by the breasts. Oxytocin causes milk to be expressed from the alveoli into the ducts of the breast so that the baby can obtain it by suckling **The suckling stimulus on the nipple of the breast causes signals to be transmitted through sensory nerves to the oxytocin neurons in the paraventricular and supraoptic nuclei in the hypothalamus, which causes release of oxytocin by the posterior pituitary gland. The oxytocin is then carried by the blood to the breasts, where it causes contraction of myoepithelial cells that lie outside of and form a latticework surrounding the alveoli of the mammary glands. In less than a minute after the beginning of suckling, milk begins to flow. This mechanism is called milk letdown or milk ejection. Thyroid Metabolic Hormones CHAPTER 76 Thyroid gland **Located inferior to larynx and anterior to the trachea. Thyroid gland ❖ Thyroid follicles produce thyroid hormones Thyroxine or tetraiodothyronine (T4) Triiodothyronine (T3) Both increase BMR, stimulate protein synthesis, increase use of glucose and fatty acids for ATP production Thyroid gland ❖ Parafollicular cells or C cells produce calcitonin Lowers blood Ca2+ by inhibiting bone resorption. Synthesis and Secretion of the Thyroid Metabolic Hormones ❖93% thyroxine, and 7% triiodothyronine. ❖All the thyroxine is eventually converted to triiodothyronine in the tissues. ❖Triiodothyronine is about four times as potent as thyroxine, but it is present in the blood in much smaller quantities and persists for a much shorter time than does thyroxine. ❖Iodine is required for formation of thyroxine **To prevent iodine deficiency, common table salt is iodized with about 1 part sodium iodide to every 100,000 parts sodium chloride. Synthesis and Secretion of the Thyroid Metabolic Hormones apical membrane basal membrane ❖Formation and secretion of thyroglobulin. (Influenced by TSH). Follicle ❖Iodide trapping (influenced by tsh). ❖Oxidation of the iodide ion (peroxidase) ❖Iodination of tyrosine and formation of the thyroid hormones—“organification” of thyroglobulin Blood **The first stage in the formation of thyroid hormones is transport of iodides from the blood into the thyroid glandular cells and follicles. The basal membrane of the thyroid cell has the specific ability to pump the iodide actively to the interior of the cell. This is achieved by the action of a sodium-iodide symporter (NIS), which co-transports one iodide ion along with two sodium ions across the basolateral (plasma) membrane into the cell. The energy for transporting iodide against a concentration gradient comes from the sodium-potassium ATPase pump, which pumps sodium out of the cell, thereby establishing a low intracellular sodium concentration and a gradient for facilitated diffusion of sodium into the cell. This process of concentrating the iodide in the cell is called iodide trapping. **Iodide is transported out of the thyroid cells across the apical membrane into the follicle by a chloride-iodide ion counter-transporter molecule called pendrin. The thyroid epithelial cells also secrete into the follicle thyroglobulin that contains tyrosine amino acids to which the iodide ions will bind. **Each molecule of thyroglobulin contains about 70 tyrosine amino acids. *’ The first essential step in the formation of the thyroid hormones is conversion of the iodide ions to an oxidized form of iodine that is then capable of combining directly with the amino acid tyrosine. This oxidation of iodine is promoted by the enzyme peroxidase. Synthesis and Secretion of the Thyroid Metabolic Hormones apical membrane basal membrane ❖Coupling DIT, MIT Follicle ❖Pinocytosis of thyroglobulin ❖Proteases cleavage ❖Recycling of MIT, DIT (Deiodinase) ❖Secretion of T3, T4 bound to thyroxine-binding globulin Blood Storage of Thyroglobulin. The thyroid gland is unusual among the endocrine glands in its ability to store large amounts of hormone. Each thyroglobulin molecule contains up to 30 thyroxine molecules and a few triiodothyronine molecules. This supply the body with its normal requirements of thyroid hormones for 2 to 3 months. Therefore, when synthesis of thyroid hormone ceases, the physiologic effects of deficiency are not observed for several months.