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CORNELL NS 3410 - Calcium and Vitamin D Synthesis

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NS 3410 1st Edition Lecture 10Outline of Last LectureI. Types of Intracellular CommunicationII. Exocrine GlandsIII. Endocrine GlandsIV. Major Endocrine Organs, Glands, TissuesV. Mechanisms of Hormone ActionOutline of Current LectureI. HormonesII. Endocrine Gland Stimuli: Humoral StimulusIII. Parathyroid GlandIV. Hormonal StimuliV. Vitamin D Synthesis Current LectureI. Hormones- Concentrations of circulating hormone reflect: rate of release, speed of inactivation and removal from the body (half-life; many hormones have short half-lives)- Hormones are removed from the blood by: degrading enzymes, the kidneys, and liver enzyme systems- Target cell activation depends on three factors:-Blood levels of the hormone (free hormone)-Relative number of receptors on the target cell-The affinity of those receptors for the hormoneThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.- Hormones have both stimulatory and inhibitory effects on genomic and non-genomic pathways- Receptor can be down-regulated or up-regulated in response to hormone- Hormone can up-regulate or down-regulate its own productionII. Endocrine Gland Stimuli: Humoral Stimulus- Humoral stimulus is the secretion of hormones in direct response to changing blood levels of ions and nutrients-Example: concentration of calcium ions in the blood; declining blood calcium concentration stimulates the parathyroid glands to secrete parathyroid hormone (PTH), PTH causes calcium concentrations to rise and the stimulus is removed; when serum calcium is elevated, parafollicular cells in the thyroid gland produce calcitonin III. Parathyroid Gland- Contains chief cells that secrete PTH and oxyphil cells whose function is unknown- Parafollicular cells in the thyroid gland produce calcitonin- Chief cells of parathyroid gland are very sensitive to circulating ionized calcium concentrations-They contain calcium sensing receptors, which are G-protein coupled receptors that sense extracellular levels of calcium ions and release parathyroid hormone when calciumlevel is low- Effects of parathyroid hormone:-Drop in ionized calcium leads to stimulation of chief cells in parathyroid gland to releasePTH- humoral effect-PTH has direct effect on kidney to increase calcium reabsorption/ decrease urinary calcium loss and to increase the enzyme that makes active form of vitamin D (1,25-dihydroxyvitamin D)- hormonal effect-PTH has direct effect on bone, stimulating calcium loss from bone-1, 25 dihydroxyvitamin D has direct effects on: intestine to increase calcium absorption from diet-Net result is more calcium in blood from increased absorption from diet, decreased loss from urine and increased release (reabsorption) from boneIV. Hormonal Stimuli- Hormonal stimuli is the release of hormones in response to hormones produced by other endocrine organs- The hypothalamic hormones stimulate the anterior pituatiary and in turn, pituitary hormones stimulate targets to secrete more hormones. Hypothalamic hormones inhibit anterior pituitary with inhibitory hormonesV. Vitamin D Synthesis- UVB from sunlight causes 7-dehydrocholesterol to be converted to previtamin D3 which is then converted to vitamin D3 (all occurs in skin)- In blood, DBP is converted to DBP-D3 (D binding proteins)- Synthesis depends on: season, latitude, age, sunscreen use, skin tone, cultural practices and lifestyle- Excess vitamin D is converted to metabolites instead of forming D3- Reptile lamps can be used for D production: restores vitamin D3 levels in blood like no other lamp- Vitamin D2 is endogenous, in epidermis and vitamin D3 comes from the diet (plant sterols)- Vitamin D Binding Protein (DBP)-Vitamin D is lipophilic- needs carrier protein-DBP-25(OH)D3 is reabsorbed in the proximal tubules of the kidney by the endocytic receptor megalin; preventing the urinary loss of this compound and preserving it for hydroxylation-Ability of tissues to use intracrine pathways of calcitriol synthesis is dependent on uptake of 25(OH)D-Its primary role is to sequester vitamin D sterols in serum: prolong half-life, provide circulating store of 25(OH)D for periods of D insufficiency, minimize urinary losses and slow entry of D into metabolic breakdown pathways- Vitamin D Metabolism-D3 in skin or ingest D2 or D3 in diet-Binds to DBP and travels to liver-Is hydroxylated in liver at 25-position by 25-OHase to form 25(OH)D (calcidiol)-25(OH)D travels bound to DBP to kidney where it is hydroxylated at 1-position by 1-alpha OHase to form the hormone 1,25(OH)2D (calcitriol)-Calcitriol binds DBP, travels to target tissues where it has its effects through genomic and non-genomic


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