Endocrine Control of Growth and Metabolism PDF

Endocrine control of growth and metabolism CHAPTER 23 1 Endocrine overview 23.1 Endocrine review 23.5 Tissue and bone growth 23.2 Adrenal gland ◦ Bone anatomy ◦ Glucocorticoids ◦ Bone growth...

Endocrine control of growth and metabolism CHAPTER 23 1 Endocrine overview 23.1 Endocrine review 23.5 Tissue and bone growth 23.2 Adrenal gland ◦ Bone anatomy ◦ Glucocorticoids ◦ Bone growth ◦ Cortisol ◦ Length ◦ Mineralocorticoids ◦ Width ◦ Sex steroids 23.6 Calcium balance 23.3 Thyroid ◦ Parathyroid ◦ Thyroid hormone ◦ Bone remodeling 23.4 Growth hormone ◦ Insulin-like growth factor 2  Hypothalamic-pituitary axis Hypothalamus RH Releasing TRH CRH hormone (RH) Pituitary gland Anterior lobe Negative feedback Hormone 1 Hormone 1 (from pituitary) TSH ACTH Endocrine Endocrine Thyroid Adrenal organ target organ gland cortex Hormone 2 Hormone 2 Thyroid (from endocrine hormones Glucocorticoids target organ) Target cells Note that the systemic response can also provide negative feedback Endocrine review 3  Endocrine responses Hormone receptors can be in The target response can be the altered by ◦ Plasma membrane ◦ Amount of hormone ◦ Cytosol ◦ Number of receptors ◦ Nucleus Pathologies are typically Hormone binding can cause due to ◦ Increased cell signaling ◦ Hypersecretion ◦ Increased gene expression ◦ Hyposecretion ◦ Abnormal target cell responses Endocrine review 4  Adrenal gland anatomy Adrenal medulla is part of the sympathetic branch ◦ Predominantly secretes epinephrine ◦ Helps mobilize fuel sources Adrenal gland 5  Adrenal cortex Zona glomerulosa Produces ~2 dozen steroids ◦ Each zone produces different enzymes, leading to different hormones Zona fasciculata ◦ Steroids are cholesterol derivatives Similar steroids may bind to the same receptor ◦ Intracellular enzymes typically inhibit the wrong steroid Zona reticularis Adrenal gland 6  Adrenal cortex Zona glomerulosa Zona glomerulosa ◦ Produces mineralocorticoids ◦ Aldosterone ◦ Regulates electrolytes Zona fasciculata Zona fasciculata ◦ Produces glucocorticoids ◦ Cortisol ◦ Regulates glucose levels Zona reticularis Zona reticularis ◦ Produces sex steroids ◦ Androgens ◦ Estrogens Adrenal gland 7  ACTH controls cortisol secretion How did CRH reach the anterior Circadian rhythm Stress pituitary? Hypothalamus – CRH Cortisol secretion varies long-loop negative feedback ◦ Highest in the morning All nucleated cells are targets Anterior precursor ACTH – pituitary ◦ Induces gene expression Adrenal cortex Cortisol Immune Liver Muscle Adipose system tissue Adrenal gland 8  Cortisol elevates blood glucose Permissive effect on Circadian rhythm Stress ◦ Catecholamines Hypothalamus – ◦ Blood vessels are more sensitive to CRH vasoconstriction long-loop negative feedback ◦ Glucagon ◦ Accelerates gluconeogenesis – Anterior precursor ACTH pituitary Liver generates glucose using ◦ Released fatty acids Adrenal ◦ Released amino acids cortex Cortisol Immune Liver Muscle Adipose Cortisol is essential for system tissue life, protects against Function Gluco- Protein hypoglycemia (low blood suppressed neogenesis catabolism Lipolysis glucose) Adrenal gland 9  Cortisol depresses the immune response Anti-inflammatory effects Circadian rhythm Stress ◦ Inhibits white blood cell migration Hypothalamus ◦ Reduced cytokine synthesis CRH – long-loop negative feedback Depresses antibody formation ◦ Reduced protein synthesis Anterior precursor ACTH – pituitary High levels used to treat ◦ Allergic reactions Adrenal ◦ Arthritis cortex Cortisol ◦ Organ transplantation ◦ Effects of high doses on CRH and ACTH? Adrenal gland 10  Adrenal Gland Disorders Hypercortisolism What effects do you expect on ◦ Blood glucose levels ◦ Skeletal muscle ◦ Adipose tissues ◦ Appetite Most commonly seen in Cushing’s syndrome ◦ Abnormal fat deposits Caused by: Adrenal tumors Pituitary tumors Adrenogenital syndrome (AGS)- hypersecretion of androgens Cortisol therapy Enlarged sex organs, premature onset of puberty Prenatal AGS results in female newborns with masculinized genitalia Adrenal gland 11  Thyroid anatomy Larynx Thyroid follicle Capillary Thyroid gland C cells Follicular cells Trachea Colloid Capsule of connective tissue C cells secrete calcitonin Follicular cells secrete ◦ Limited secretion in non- thyroid hormone pregnant, non-lactating ◦ Stored within the colloid adults Thyroid 12  Thyroid hormone Consists of two forms ◦ T3 (most active) ◦ T4 (most abundant) ◦ # = # of iodine atoms ◦ Iodine deficiency leads to goiter Stored in the colloid Has long-lasting metabolic effects Thyroid 13  TSH controls thyroid hormone secretion Most cells have TH receptors Tonic release Effects include Hypothalamus TRH – ◦ Increased O2 consumption ◦ Heat production ◦ Increased metabolism of all Anterior Negative feedback pituitary macronutrients – ◦ Promoting growth hormone TSH expression during childhood ◦ Promoting neural development Thyroid gland T 4 , T3 T4 T3 Systemic metabolic effects Thyroid 14 Control of T3 & T4 Secretion  Negative feedback  Low blood levels stimulate hypothalamus to release TRH  stimulates pituitary to release TSH  TSH stimulates thyroid gland to raise blood levels 15 Thyroid Gland Disorders Hypothyroidism ◦ Low metabolic rate, sluggishness, sleepiness, weight gain, constipation, dry skin and hair, cold sensitivity ◦ Endemic goiter (goiter = enlarged thyroid gland) ◦ dietary iodine deficiency, no TH, no - feedback, increased TSH Hyperthyroidism ◦ Weight loss, tremors, nervousness ◦ Toxic goiter (Graves disease) ◦ antibodies mimic TSH, increased TH, exophthalmos 16  Growth is shaped by Hormones ◦ Growth hormone ◦ TH ◦ Insulin ◦ Sex steroids Nutrients ◦ Protein ◦ Calories ◦ Vitamins & minerals Absence of chronic stress Genetics 80% of variation in height is determined by DNA Growth hormone 17  GHRH and GHIH regulate GH secretion Circadian rhythm Anabolic peptide hormone Stress and cortisol ◦ Uses a transport protein Fasting Ghrelin = Ghrelin hunger ◦ Acts as a trophic hormone and as hormone a non-trophic hormone Hypothalamus Somatostatin – GHRH + from Note the feedback loops stomach + – – + Anterior pituitary GH What is the – integrator? Liver and other tissues Insulin-like growth factors Growth hormone 18  GH and IGF promote growth Circadian rhythm Stress-- GH increases blood glucose via Stress and cortisol Fasting Excess ◦ Lipolysis cortisol Ghrelin inhibits ◦ Gluconeogenesis growth Hypothalamus Normal ◦ Reduced glucose uptake by cortisol is Somatostatin – skeletal muscle GHRH + needed for growth + – GH + IGF stimulate – + ◦ Protein synthesis Anterior pituitary ◦ Bone growth GH – IGF stimulates ◦ Cartilage growth Liver and other tissues Insulin-like growth factors Cartilage Blood Bone and growth glucose tissue growth Growth hormone 19  GH pathologies Excess GH leads to André René Roussimoff Insufficient GH leads to dwarfism Andre the Giant ◦ Gigantism ◦ Acromegaly Robert Wadlow: tallest person in recorded history for whom there is irrefutable evidence Actress Lavinia Warren Growth hormone 20  Bone structure All bones contain ◦ Compact bone ◦ Spongy bone Bone tissue consists of ◦ Specialized cells ◦ Specialized matrix Compact bone Trabeculae of spongy bone issue and bone growth 21  Bone tissue: Matrix Hydroxyapatite crystals Collagen fibers allow provide strength flexibility ◦ Made of numerous calcium ◦ One-third of bone mass salts ◦ Tolerate distortion ◦ Two-thirds of bone mass is calcium phosphate Collagen fibers, atomic force Scanning electron microscopy microscopy; arrows = protein (Lee lab at Berkeley) bridges (Fantner et al., 2005) issue and bone growth 22  Bone tissue: Cells Endosteum Osteoblast Osteogenic Osteoid cell Medullary cavity Matrix Stem cell that produces Immature bone cell that osteoblasts; also in secretes organic components periosteum of matrix Medullary Ruffled Matrix cavity border Osteocyte Osteoclast Canaliculi Matrix Mature bone cell that maintains the bone matrix; Multinucleate cell that trapped osteoblasts secretes acids and enzymes to dissolve bone matrix Bone remodeling: Balance between deposition and resorption issue and bone growth 23  Compact versus spongy bone issue and bone growth 24  Bone growth: Length Amount of bone growth Compact bone Dividing chondrocytes add length to bone Chondrocyte Chondrocytes Cartilage produce cartilage Direction of Disintegrating growth Epiphyseal plate Old chondrocytes chondrocyte disintegrate Osteoblast Diaphysis Osteoblasts lay Newly down bone on calcified top of cartilage bone Estrogen is needed for closure of plates in both males and females issue and bone growth 25  Bone growth: Width issue and bone growth 26  Bone growth requirements Hormones ◦ GH ◦ IGF ◦ Androgens High impact ◦ Stimulate longitudinal bone growth exercise helps build ◦ Estrogen– both sexes! bone ◦ Closure of plates ◦ Mineral density Mechanical stress These determine an individual’s height issue and bone growth 27  Calcium is an essential mineral Required for ◦ Exocytosis ◦ Muscle contractions ◦ Activity of many enzymes ? Contributes to tight junctions Aids in clotting Vegetables, Alters neuronal excitability figs, nuts/seeds ◦ Decreases Na+ permeability also have calcium without hormones Calcium homeostasis 28  Calcium balance in the body Calcium intake occurs via ◦ Paracellular route Small intestine Dietary Ca2+ Calcium ◦ Hormone-induced transcellular calcium in feces route * Some calcium is secreted ◦ Note: binding proteins keep into the small intestine. intracellular [Ca2+] low Bone (99%) ECF (0.1%) Passive Kidney Calcium output occurs via Ca2+ filtration Ca2+ in kidney Ca 2+ ◦ Kidneys tubules ◦ Hormones can alter reabsorption Electrochemical Active Plasma calcium regulated by gradient transport three hormones free Ca2+ Ca2+ in urine Cells 0.9% Calcium homeostasis 29  Hormones regulate calcium homeostasis Hormon Small Bone Kidneys e intestine PTH Increased via Increased Increased effect on bone reabsorption vitamin D3 resorption Calcitriol Increases Promotes Promotes absorption bone reabsorption resorption Calcitoni Decreases Increases n bone secretion resorption Calcium homeostasis 30 31  The parathyroid glands Two major cell types ◦ Parathyroid (principal) cells secrete parathyroid hormone (PTH) ◦ Oxyphil cells have an unknown role! What effect did PTH have on blood calcium levels? Calcium homeostasis 32  PTH helps generate calcitriol Also stimulated by prolactinEndogenous precursors Diet Sunlight on skin Vitamin D Liver Intermediate + Plasma Kidney PTH Ca2+ – Calcitriol Bone, kidney, + and intestine Plasma Ca2+ Calcium homeostasis 33  Parathyroid disorders Hypoparathyroidism Hyperparathyroidism ◦ Leads to a rapid decline in blood ◦ Leads to calcium ◦ Soft bones ◦ Effect on neurons? ◦ Increased calcium and ◦ Can be fatal within 2-3 days potassium blood levels ◦ Typically caused by accidental ◦ Kidney stones removal of parathyroids or ◦ Usually caused by tumors damage to blood supply Calcium homeostasis 34  Osteoporosis Resorption outpaces deposition Particularly prevalent in spongy bone Exacerbated by low estrogen Calcium homeostasis 35