Neurobiochemistry I: Pituitary / Hypothalamus

Objectives

Neurobiochemistry I: Pituitary / Hypothalamus 1. Identify the molecular etiologies of diabetes insipidus. 2. Define the chemistry of ADH/vasopressin and oxytocin, and develop that they are coded for by related genes which also code for their respective neurophysin carriers. 3. Describe how the secretion of ADH/vasopressin and oxytocin is controlled at the physiological and biochemical levels. 4. Discuss the mechanism whereby ADH/vasopressin controls water channels in the cells of the distal convoluted tubules of the kidney. 5. List the actions of oxytocin, including CNS effects, and differentiate how a number of neuromodulator peptides induce a desired behavior which coordinates with their systemic functions. 6. List the hypothalmic releasing and inhibiting factors and explain the biochemical mechanism, including second messengers, in general terms. 7. Diagram the proposed model for the effects of GHRH and somatostatin on adenylate cyclase.

Neurobiochemistry II: Growth Hormone / Prolactin 1 Discuss the close chemical relationship between growth hormone (GH) and prolactin (PRL), as well as between their receptors. 2. List the actions of GH and define which ones are mediated by IGF-I. 3. Compare and contrast IGF-I and insulin, especially with respect to their receptors and how tissues differentially respond to these two similar peptides. 4. Distinguish that the IGF-I receptor is a tyrosine kinase in the insulin receptor family, while the PRL and GH receptors do not posses this activity and must recruit cytoplasmic tyrosine kinases called JAKÕs. 5. Discuss the tissue specific distribution of GH receptor. 6. Identify the biochemical actions of PRL and its interrelationship to estrogen function.

Thyroid Hormone System / Iodine 1. Compare and contrast the biochemistry and symptoms of clinical hypothyroidism and hyperthyroidism (Graves Disease). 2. Explain the chemistry and significance of T4 and T3, and how a nutritionally required element, iodine, is incorporated into these molecules. 3. Delineate the biochemical steps in the biosynthesis of T4 and T3. 4. Identify the nutritional deficiency, specific enzyme defects and the immune causes of goiter. 5. Describe the biochemistry of the TRH-TSH-T4 axis, with special reference to second messengers in target cells and general structures of hormones. 6. Draw the mechanism whereby T4 is activated to T3 in peripheral target cells and via a nuclear receptor, T3 induces transcription of genes coding for oxidative enzymes, Na-K-ATPase, GH, -adrenergic receptors etc.

Calcium Homeostasis / PTH / Vitamin D 1. Describe the physiology of calcium homeostasis in terms of the feedback controls of PTH, CT and 1,25(OH)2D3 synthesis and release. 2. Explain how bone mineral (Ca2+) is both laid down to provide the strength of the endoskeleton and mobilized to maintain serum calcium levels. 3. List the pathophysiology of hyperparathyroidism, hypoparathyroidism, pseudohypoparathyroidism, rickets and osteoporosis. 4. Discuss the actions of calciotropic hormones at bone (osteoblasts and osteoclasts), kidney and intestine; develop the biochemical mechanisms in outline form. 5. List the general chemical compositions of PTH, CT and 1,25(OH)2D3 and differentiate how they arise biochemically from their respective precursors. 6. Discuss the 1,25(OH)2D3 receptor as a member of the superfamily of steroid/thyroid hormone receptors that bind to DNA.

Adrenal Steroid Hormone Biosynthesis 1. Define the function, regulation and significance of the P-450scc / 20,22 lyase enzyme in converting cholesterol to pregnenolone. 2. Delineate the biosynthesis of aldosterone in the zona glomerulosa, noting the unique presence of 18-OHase and lack of 17-OHase in these cells. 3. Describe the metabolic formation of cortisol in the zona fasciculata/reticularis, especially the key role of the 17-OHase and the shuttling of steroids in and out of the mitochondria. 4. Delineate biochemically the bodyÕs reaction to emotional and physical stress, noting particularly the acute effects of epinephrine (glycogenolysis) and the chronic action of glucocorticoids (gluconeogenesis) and -endorphins (analgesic). 5. Explain the biochemical action of ACTH on the zona fasciculata/reticularis cells, which 2+ mediated primarily by cAMP and secondarily by IP3/Ca and DAG.