Endocrine

• Endocrinology


  The study of hormones and their effects on the body
• Hormones


  Chemical messengers in the body that spur on activity
• Feedback mechanism


  To maintain the constancy of chemical composition of extracellular and intracellular fluid
• Regulation: Hypothalamic-Pituitary-Target Organ Axis (HPT axis)

  1. Positive feedback mechanism (increase production)

  2. Negative feedback mechanism (decrease production)

  
• Positive feedback: Increased in the product also increases the activity of the system and the production rate
• Negative feedback: Increased in the product decreases the activity of the system and the production rate
• HPT axis and specific hormones

  • Hypothalamus hormone - CRH
  • Pituitary hormones - ACTH
  • Target glands - Adrenal gland
  • Effector hormones - Glucocorticoid, Mineralocorticoid, Catecholamine
  • Hypothalamus hormone - TRH
  • Pituitary hormone - TSH
  • Target gland - Thyroid gland
  • Effector hormones - T3 & T4
  • Hypothalamus hormone - GnRH
  • Pituitary hormones - LH/FSH
  • Target glands - Ovaries/Testes
  • Effector hormones - Sex Steroid
  • Hypothalamus hormone - GHRH
  • Pituitary hormone - GH
  • Target - Bone
  • Effector hormone - Insulin-like Growth Factor

  
• Mechanism of hormone action

  Binding of hormone to a specific receptor molecule on the cell surface or cell interior
• Types of hormone action

  • Autocrine - Acts directly upon themselves
  • Paracrine - Acts adjacent to the cells of origin
  • Intracrine - Acts within the cells of origin without ever exiting the cells
  • Endocrine - Secreted in one location and release into blood circulation, bind to specific receptor to elicit physiologic response
  • Juxtacrine - Secreted in endocrine cells and remains in relation to plasma membrane acts on immediately adjacent cell by direct cell to cell contact
  • Exocrine - Secreted in endocrine cells and interacts with receptors of cells at distant site

  
• Prohormone


  Biochemically inactive hormone
• Hormone classification by structure

  • Protein or peptides
  • Steroid
  • Amines
  • Fatty acids
• Hormone transport proteins


  • Only free (unbound) fraction exhibits hormone activity
  • Changes in transport protein concentration affects the hormone activity
• Transport proteins and associated hormones

  • Cortisol Binding Protein (CBG) - Cortisol
  • Sex Hormone Binding Protein (SHBG) - Estradiol, Testosterone
  • Thyroid-Binding globulin (TBG) - T3, T4
  • Thyroxine-Binding Prealbumin - T4
  • Albumin - All hormones

  
• Hypothalamus


  The "Master Switchboard" portion of the brain that produces hormones secreted by the posterior pituitary gland

  
• Hypothalamic products and target effects

  • GnRH - Stimulates release of FSH & LH
  • TRH - Stimulates release of TSH & Prolactin
  • CRH - Stimulates release of ACTH
  • GH-RH - Stimulates release of GH
  • Somatostatin - Inhibits release of GH

  
• Pituitary gland


  The "Master Gland" that secretes hormones with circadian rhythm

  
• Anterior pituitary gland cell types and hormones

  • Somatotrophs - Growth hormone
  • Lactotrophs/Mammotrophs - Prolactin
  • Thyrotrophs - TSH
  • Gonadotrophs - LH & FSH
  • Corticotrophs - ACTH

  
• Anterior pituitary hormones, target glands, and feedback hormones

  • Luteinizing Hormone (LH) - Gonad (tropic) - Progesterone
  • Follicle Stimulating Hormone (FSH) - Gonad (tropic) - Inhibin
  • Thyroid Stimulating Hormone (TSH) - Thyroid (tropic) - T3 & T4
  • Adrenocorticotropic Hormone (ACTH) - Adrenal (tropic) - Cortisol
  • Growth Hormone - Multiple (direct effector) - IGF-1
  • Prolactin - Breast (direct effector) - Unknown

  
• Growth hormone/Somatotropin


  Most abundant of all pituitary hormones, structurally similar to prolactin and human placental lactogen, antagonizes insulin action, stimulates protein synthesis and anabolic metabolism, stimulates the liver to produce insulin-like growth factors (IGFs)
• Causes of growth hormone deficiency

  • In adults - Pituitary adenoma, complete/partial failure of adenohypophysis, GH insensitivity
  • In children - Pituitary dwarfism, Laron's dwarfism
• Acromegaly


  Pathologic or autonomous GH excess, usually due to a pituitary tumor, results in diffused skeletal growth when occurred after puberty
• Gigantism


  Impressive height before epiphyseal closure, from GH excess (longitudinal)
• Signs and symptoms of acromegaly

  • Bony soft tissue growth, progressive enlargement of the hands and feet as well as growth of facial bones, arthritis, organomegaly, hypermetabolic condition, diabetes, hypertension, gaps between teeth
• Growth hormone deficiency diagnostic test

  1. Screening - Physical activity (exercise test)

  2. Confirmatory - Insulin tolerance test/Insulin-induced hypoglycemia stimulation test (gold standard), Arginine stimulation test
• Growth hormone excess diagnostic test

  1. Screening - Somatomedin C or Insulin-like Growth Factor 1 (IGF-1)

  2. Confirmatory - Glucose suppression test (OGTT)

  
• Prolactin


  Functions in the initiation and maintenance of lactation; also acts as a stress hormone
• Stimuli for prolactin


  • Physiologic - Nursing or nipple stimulation, stress, exercise, pregnancy

  
• Hyperprolactinemia


  The most common hypothalamic pituitary disorder, may result in anovulation/hypogonadism: amenorrhea and galactorrhea
• Oxytocin


  Nanopeptide that stimulates contraction of the gravid uterus and lactation
• Anti-diuretic hormone/Arginine vasopressin


  Sensitive to changes in serum osmolality and blood volume, examples of major stimuli are dehydration, emetic stimulus, physical and emotional stress

  
• Types of diabetes insipidus

  • True/Hypothalamic/Neurogenic/Cranial/Central DI - Deficiency of ADH with normal ADH receptor
  • Nephrogenic DI - Normal ADH but abnormal ADH receptor (renal resistance to ADH)
• Diabetes insipidus diagnostic test


  No details provided

  
• Gonadotropins


  Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) aid in spermatogenesis and ovulation

  
• Hormonal cascade for reproduction

  1. Hypothalamus - GnRH

  2. Anterior Pituitary (gonadotroph) - FSH & LH

  3. Testis - Testosterone

  4. Ovary - Estradiol & Progesterone

  5. Placenta - hCG, Estrogen & Progesterone

  
• Regulation of male reproduction

  • Testes have two functions: exocrine (sperm secretion) and endocrine (testosterone production)
  • Sertoli cells are the "nurse cells" that are targets of FSH and produce inhibin
  • Leydig cells produce testosterone for anabolic effects
• Regulation of female reproduction - Menstrual cycle

  1. Ovarian cycle - Follicular phase, Luteal phase

  2. Uterine endometrial cycle - Proliferative phase, Secretory phase

  
• The menstrual cycle begins with uterine endometrium shedding (Day 1)
• Leydig cells


  Interstitial cells that produce testosterone for anabolic effect in male anatomy
• Leydig cells


  • Produce inhibin which has negative feedback on gonadotrophs, decreasing FSH but not LH
  • Produce testosterone

  
• Regulation of female reproduction

  1. Menstrual cycle

  2. Ovarian cycle

  3. Uterine endometrial cycle