Endocrine

434 Physiology team presents to you:

Mid-Term Revision Done by: Lina AlJurf Omar AlRahbeeni

Transport of Hormones: Endocrine Hormone: Released by Glands

1- Water soluble hormones- hydrophilic or Specialized Cells into circulating Blood and Hormones: Are secretions of ductless glands that (peptides & catecholamine) dissolved in influence the target cells. are directly released into the blood stream. They plasma. can act on cells in the vicinity or on distant target Paracrine: Secreted by cells into extracellular

cells. fluid and affect neighbouring Target cells of 2-Fat soluble hormones – hydrophobic Endocrine glands: pituitary, thyroid, Different Type. Steroids and thyroid hormones transported parathyroid, adrenal, pineal, and thymus. Autocrine: Chemicals that exert their effects bound to plasma proteins (90%). binding to -The pancreas and gonads produce both on same cells that secrete them. proteins helps to: -provide reservoirs -Slow hormones and exocrine products also Liver.

hormones clearance. -The hypothalamus has both neural functions Neurotransmitter: Released by axon and releases hormones. terminals into the synaptic junction and act

locally. Hormone Interactions Examples: -Other tissues and organs that produce hormones: adipose cells, pockets of cells in the Neuroendocrine Hormones: Secreted by 1-Permissiveness: Thyroid hormone has permissive walls of the small intestine, stomach, kidneys, neurons into circulating blood and influence the and heart. effect on growth hormone action target cells.

•Deficiency of thyroid hormone in infants leads to dwarfism. L1-Introduction to Endocrine Cytokines: Peptides released by cells into the

2-Synergism: Blood glucose levels & synergistic extracellular fluid and function as autocrine, effects of glucagon, cortisol and epinephrine Types of Hormones: paracrine or Endocrine Hormones (e.g: Interleukins, Lymphokines). 3-Antagonism: Glucagon antagonizes the action of insulin, Calcitonin and parathyroid hormone have 1-Proteins and Peptides: Including: - anterior antagonistic actions and posterior pituitary - pancreas (insulin and Target cells refer to cells that contain specific glucagon) -parathyroid hormone stored in receptors (binding sites) for a particular hormone. vesicles until needed (Synthesized as

preprohormone > post-translational modification Adenylyl Phospholipid Guanyl Tyrosine Target cell activation depends on: Cyclase Mechanism to prohormone > then hormone). Cyclase Kinase Mechanism 1- Blood levels of the hormone Mechanism 2-Steroids: Secreted by: - Adrenal cortex (cortisol 2- Relative number of receptors on the target cell ACH, LH, FSH GnRH ANP, NO Insulin, and aldosterone) -Ovaries and placenta 3- The affinity of those receptors for the hormone TSH, GHRH TRH IGF-1, (progesterone and estrogen) –Testes Somatostatin Angiotensin II GH, (testosterone). Prolactin ADH (V2), ADH (V1) 3-Derivatives of amino acid tyrosine HCG (Amines): Secreted by: -Thyroid (thyroxin and MSH, CRH Oxytocin triiodothyronine) -Adrenal medulla (epinephrine Calcitonin and norepinephrine) PTH,Glucagon

Anterior pituitary gland is connected to hypothalamus by: Hypothalamic control of posterior pituitary gland:  Hypothalamic-hypophysial portal vessels Hormones are synthesized in the supraoptic ( ADH) Prolactin inhibitory hormone and paraventricular nuclei ( Oxytocin) (PIH) AKA Dopamine: and released in posterior pituitary

Inhibits prolactin secretion

Feedback mechanisms can be: L2-Hypothalamo-pituitary axis Growth hormone hypothalamic regulation: Positive or negative

 Growth hormone releasing hormone (GHRH) o Stimulates release of growth hormone Negative feedback  Growth hormone inhibiting hormone (GHIH) AKA mechanisms can be long or Positive feedback somatostatin short loop reflexes  Release of hormone A stimulates the release o Inhibits release of growth hormone of hormone B

 Hormone B stimulates further release of hormone A Thyroid hormone hpothalamic regulation:  Example: Baby suckles at nipple  oxytocin  Thyrotropin releasing hormone (TRH)  release  milk ejection  baby continues stimulates release of thyroid stimulating suckling  hormone (TSH) from the anterior pituitary stimulates release of thyroid hormones by the thyroid gland  T₃ & T₄ increase  negative feed back Negative feedback

 Release of hormone A stimulates the release of hormone B Gonadotropin releasing hormone  Hormone B inhibits release of hormone A causes release of 2 gonadotropic  Example: rising blood glucose  insulin secretion  glucose Corticotropin-releasing hormone stimulates hormones: uptake by liver and body cells  normal glucose level  insulin release of adrenocorticotropin hormone (ACTH)  Luteinizing & follicle stimulating h.s stimulates release of cortisol by the adrenal cortex secretion stops Factors increasing prolactin: Factors inhibiting  Pregnancy prolactin: Gonadotropins: PIH (dopamine) FSH stimulates gamete (egg or sperm) production  Sleep LH in males: stimulates interstitial cells of the testes (leydig  Surgical & psychological stress cells) to produce testosterone  Exercise

LH in females: maturation of ovarian follicle  Stimulation of the nipple Synthesis & release of estrogens & progesterone  TRH

Pituitary gland hormones mnemonic: ADH Receptors

“GOAT FLAP” V₁ a  vasoconstri. Prolactin Anterior pituitary: Growth hormone, Thyroid V₁ b  ↑ ACTH Stimulates milk production by the breasts stimulating hormone, Follicle stimulating hormone, V₂  located in Luteinizing hormone, ACTH, Prolactin principle cells  Posterior pituitary: Oxytocin, ADH increases water

reabsorption in Growth hormone: L3,4-Pituitary kidneys  Produced by: somatotropic cells  Stimulates most cells, mainly bone and skeletal muscles gland  Promotes protein synthesis (anabolic effect) ADH disorders  Encourages the use of fats for fuel SIADH  hyponatremia and hypo-osmolality due to continued  Decreases glucose uptake in tissues, increases its production secretion of ADH by liver Neurogenic Diabetes Insipidus  failure of hypophysis to

 Metabolic actions are direct synthesize or secrete ADH  Most effects are mediated indirectly by somatomedins Nephrogenic diabetes insipidus  failure of kidney to respond to (IGF1) ADH

Factors stimulating GH: Factors inhibiting GH: ↑GH leads to: Oxytocin stimuli: ↓Glucose ↑Glucose Acromegaly in adults Hugging, touching, orgasm Oxytocin ↓FFA ↑FFA Gigantism in childhood In both sexes  Stimulates uterine ↑aminoacid (arginine) Somatostatin ↓ GH leads to: Stress contraction Fasting, prolonged caloric deprivation Somatomedins Dwarfism in childhood Ejaculation  Triggers milk ejection stress, exercise, puberty, androgens, sleep GH senscence Inhibited by: alcohol

Remember! Oxytocin and autism GH counteracts in general the effects of insulin on glucose and lipid metabolism, but shares Autistic group have significantly lower plasma oxytocin levels than in the non-autistic. protein anabolic properties with insulin.

Metabolism Effects of Thyroid Hormone : Steps of Synthesis: 1-Carbohydrates: TH stimulates all aspects of carbohydrate 1. Iodide pump. metabolism: 9 2. Thyroglobulin Increase glucose uptake by the cells. synthesis. 9 Increase glycogenolysis. 9 Increase gluconeogenesis. 3. Oxidation of iodide to 9 Increase rate of absorption from the GIT. iodine. 2-Fats: Essentially all aspects of fat metabolism are also 4. Iodination of enhanced under the TH: tyrosine. 9 Increase lipolysis. 9 Decrease of Cholesterol in the blood (Hypocholesteremia). 5. Coupling. 3-Proteins: Overall effect is catabolic leading to decrease in 6. Endocytosis of muscle mass. In contrast to GH which thyroglobulin. has anabolic effect.

7. Fusion of lysosomes. - Thyroid Hormones Release to Tissues: 1. T4 & T3 readily diffuse through the cell membrane. 8. Hydrolysis of peptide 2. Stored in the targeted tissues (days to weeks). -not shown in image- bonds. 3. 90% of T4 is deionized to T3 by idoinase enzyme. 9. Release of T3 and T4 L5,6- Thyroid Gland and thyroid Disorders 4. In the nucleus, T3 mainly binds to thyroid hormone receptor and influence transcription of genes. 10. Deiodination of DIT and MIT by Thyroid deiodinase

(Recycling). Cretinism: A condition of severely stunted physical and mental growth due to Effects of Thyroid Hormone: untreated 1-CVS: increase pump. congenital deficiency of thyroid hormones (congenital 2-CNS: In Peri-natal Period >Maturation hypothyroidism). of CNS Causes: In Adult > Hyperexcitability 1-Congenital lack of thyroid gland (congenital cretinism). 3-Bones: bone formation, ossification, and bone 2-Genetic deficiency leading to failure to produce hormone. maturation. 3-Iodine lack in the diet (endemic cretinism). 4-GIT: Increase in Appetite, Symptoms: increase motility > Diarrhea. 5-Respiratory: Increase o Infant is normal at birth but abnormality appears within ventilation rate - Increase weeks - Protruding tongue - Dwarf with short limbs. dissociation of oxygen from Mental retardation. Hb by increasing RBC 2,3- o Often umbilical hernia. DPG (2,3 diphosphoglycerate). o Delayed appearance of teeth. 6-Increase in BMR. Treatment: Changes are irreversible unless treatment is given early.