Intro to Endocrine Physiology; Hypothalamus-Pituitary

• Hormones


  Chemical signals (ligands) used for cell-to-cell communication, secretion is regulated, bind to receptors on/in target cells
• Classic Endocrine glands

  • Pituitary
  • Thyroid
  • Parathyroid
  • Adrenal
  • Pancreas
  • Ovary
  • Testis

  
• Dysregulation of endocrine glands leads to disease
• Disease can arise from hyposecretion, hypersecretion, and/or non functional receptors
• Cell to cell communication


  Minimally need Signal —> Receptor —> Response

  
• Types of cell communication

  • Neural
  • Autocrine/Paracrine
  • Endocrine/Hormonal

  
• Endocrine communication can be complex, involving multiple endocrine glands
• Thyroid hormone example

  Hypothalamus secretes TRH, TRH stimulates Anterior Pituitary to release TSH, TSH stimulates Thyroid gland to release T3 and T4

  
• Form fits function

  Hormones have different forms (structures) which leads to different characteristics and functions
• Major hormone classes

  • Peptide/protein
  • Catecholamines
  • Steroid
  • Iodothyronines or thyroid hormones
• Hydrophilic vs. Hydrophobic


  Water loving vs. water hating, Hydrophilic = Polar, Hydrophobic = Non-Polar, Lipophilic is to Hydrophobic as lipophobic is to Hydrophilic
• Blood is an aqueous solution. How can hydrophobic (non-polar) steroid hormones travel through the blood?
• Binding proteins


  Sex-hormone binding globulin (SHBG), thyroid binding globulin (TBG), cortisol binding globulin (CBG) bind the cognate steroids with high specificity, Albumin binds non-specifically to all steroids, but with low affinity, Binding proteins increase the half-life of hormones, Free hormone = active, bound hormone = inactive
• Circulating hormone concentrations depend on binding proteins
• If binding protein concentration in the blood increases, total hormone concentration increases
• Peptide/protein hormones are stored in granules/vesicles until they are signaled to be released
• Polar hormone signaling

  Polar molecules can't pass through the hydrophobic cell membrane, Need to bind to a receptor embedded in the cell membrane, Hormone binding directly opens ion channels (ionotropic) or stimulates secondary messenger cascades (metabotropic), Cellular responses occur FAST (milliseconds - minutes)
• Steroid producing cells do NOT have all enzymes = limits hormone produced
• Thyroid hormones behave like polar and non-polar hormones

  T3 and T4 are stored in cytoplasmic vesicles until stimulated by TSH (polar-like), T3 and T4 travel through the circulation bound to albumin and TBG (non-polar-like)

  
• Norepinephrine causes vasoconstriction of vascular smooth muscle in skin, but vasodilation of vascular smooth muscle that perfuses skeletal muscle
• Hormone "behavior" summary

  Polar hormones are stored in vesicles, bind to membrane receptors, responses are fast, Non-polar hormones can pass through cell membrane, bind to intracellular receptors, responses are slow

  
• Endocrine glands and their hormonal secretions

  • Hypothalamus - TRH, CRH, GnRH, GHRH, SRIF
  • Anterior Pituitary - TSH, ACTH, FSH, LH, GH, Prolactin
  • Posterior Pituitary - ADH, Oxytocin
  • Thyroid Gland - T3, T4
  • Parathyroid Gland - PTH
  • Adrenal glands - Epinephrine, Norepinephrine, Cortisol, Aldosterone
  • Pancreas - Insulin, Glucagon
  • Ovaries - Estrogen, Progesterone
  • Testes - Testosterone
  • Liver - Angiotensinogen

  
• Homeostasis is regulated through negative feedback
• Negative feedback = the end response counteracts the initial stimulus
• If TRH release stopped, TSH would decrease, If too much TSH was released, T3 and T4 would increase, If too much T3 or T4 was released, TRH and TSH would decrease
• Peripheral Hormonal Conversions


  Less active hormone is secreted, then converted by enzymes to a more active form in tissues, e.g. T4 to T3, Vitamin D3 to 1,25 (OH)2D3, Angiotensinogen to Angiotensin II
• Hypothalamus


  Neural tissue in the brain, superior to the pituitary gland, integrates sensory stimuli and communicates with the pituitary gland

  
• Pituitary gland

  Has 2 distinct lobes - anterior and posterior pituitary, the posterior pituitary is derived from nervous tissue, the anterior pituitary is derived from oral ectoderm, they both release hormones into the circulation in response to stimulation from the hypothalamus

  
• Hypothalamic connection to the posterior pituitary gland

  Neurons in the Supraoptic nuclei (SON) and Paraventricular nuclei (PVN) project to the posterior pituitary gland, Axons travel through the median eminence and pituitary stalk, where nerves terminate in the posterior pituitary

  
• Posterior Pituitary Gland


  Magnocellular cell bodies found in the hypothalamus synthesize hormones, Action potentials stimulate the release of hormones from the posterior pituitary gland into the vascular capillary bed, Hormones travel through the bloodstream to target organs

  
• Anterior Pituitary Gland


  Parvocellular neurons in the hypothalamus secrete releasing hormones into portal vessels, These hormones stimulate the anterior pituitary cells to release different tropic hormones into the bloodstream, Those hormones travel to distant target tissues to stimulate secretion of other hormones

  
• The pituitary gland is encased by the sphenoid bone, thus, Anterior Pituitary tumors can compress the optic chiasm leading to vision loss
• Anterior Pituitary Gland Secretes


  • FLAT PiG

  
• Relationship between hormones in the hypothalamus, anterior pituitary, and target glands

  Hypothalamus releases releasing hormones, which stimulate the anterior pituitary to release tropic hormones, which then stimulate target glands to release their hormones

  
• Tropic cells in the anterior pituitary


  Stimulate other cells, the cell name tells you what's being stimulated

  
• Anterior Pituitary Cell Types and Hormones

  • Gonadotrope - FSH/LH, Thyrotrope - TSH, Corticotrope - ACTH, Lactotrope - Prolactin, Somatotrope - Growth Hormone

  
• Growth Hormone Axis


  Hypothalamus releases GHRH, which stimulates the anterior pituitary to release GH, GH then acts on the liver and bone to release IGF-1

  
• Somatostatin


  Inhibits GH release from the anterior pituitary

  
• Growth Hormone


  Has both anabolic and catabolic effects, anabolic in the fed state, catabolic in the fasted state

  
• GH secretion changes throughout life, with high levels during childhood and adolescence, and declining levels in adulthood