Endocrinology and Hormones

Endocrinology and Hormones

• Endocrinology is the study of hormones
• Hormones are responsible for long-term, ongoing bodily functions including:
  • Metabolism and regulation of the internal environment
  • Reproduction, growth, and development
• Hormones are chemical signals secreted into the blood for transport
• Hormones act on a distant target using long distance communication in a slow process
• Many hormones have effects at very low concentrations
• Hormones bind to target cell receptors to initiate responses

Endocrine Glands

• Primary endocrine glands function primarily to secrete hormones
  • Primary endocrine glands in the brain consist of: the hypothalamus, pituitary gland, and pineal gland
  • Primary endocrine glands outside the brain consist of: thyroid gland, parathyroid gland, thymus, adrenal glands, pancreas, and gonads (testes and ovaries)
• Secondary endocrine glands have other functions, with hormone secretion as a secondary activity
  • Examples of secondary endocrine glands consist of: the heart, liver, stomach, small intestine, kidney, and skin

Hypothalamus and Pituitary Gland

• The hypothalamus is a primary endocrine gland
• The hypothalamus secretes hormones that impact numerous body systems
• The pituitary gland is a primary endocrine gland approximately the size of a pea
• The pituitary gland connects to the hypothalamus
• The pituitary gland contains anterior and posterior lobes which are structurally and functionally different

Posterior Pituitary Gland

• Neural tissue composes the posterior pituitary gland's lobe
• A group of neurons regulates the posterior pituitary gland residing in 2 regions of the hypothalamus
  • The supraoptic nucleus' neurons synthesize oxytocin
  • The paraventricular nucleus' neurons synthesize vasopressin, also known as antidiuretic hormone (ADH)
• Vasopressin and oxytocin processing
  • Peptide based chemical messengers
  • Hydrophilic and lipophobic
• Neurons synthesize these hormones in the cell body and package them into secretory vesicles
• Vesicles transport hormones down the axon to its terminal, where they are stored in the posterior pituitary
• The entry of calcium into the cell results in vesicle fusion and hormone release upon signal reception

Posterior Pituitary Hormones

• Oxytocin is released by supraoptic neurons
• Paraventricular neurons release antidiuretic hormone
• The capillary beds in the posterior pituitary receive release of these peptide hormones
• Hormones travel through the bloodstream to target tissues
• Neurohormones refer to hormones secreted by neurons
• Neurosecretory cells are neurons releasing chemical messengers or hormones into the bloodstream
• Smallest blood vessels are capillaries that exchange compounds between surrounding tissues and blood
• Oxytocin activation is induced by pressure on the uterus or infant suckling
  • Oxytocin's target involves cells in the uterus that increase uterine contraction and breast cells for milk letdown
• Antidiuretic hormone (ADH), or vasopressin activation can be induced by an increase in plasma solute concentration
  • ADH target cells increase water reabsorption in the kidney

Anterior Pituitary Gland

• The lobe of the anterior pituitary gland derives from epithelial tissue
• Neurons functioning as neurosecretory cells control it
• It secretes tropic hormones.
• Tropic hormones regulate other hormones, which in turn regulate a third hormone
  • Stimulating tropic hormones stimulate secretion of another hormone
  • Inhibitory tropic hormones decrease secretion of another hormone
• General Pathway
  • Neurosecretory cells release a neurohormone into a capillary bed located in the median eminence of the hypothalamus
  • This hormone travels through the portal vein down the infundibulum into a capillary bed in the anterior pituitary gland
  • The hormone acts on endocrine cells in the anterior pituitary after leaving the capillary bed
• The hypothalamic-pituitary portal system refers to a capillary bed organized in 'series'
• The anterior pituitary lobe contains 5 cell types with 7 different hormones, where 2 hormones are inhibitory and 5 have activating functions
• Various tropic hormones are released and carried to target glands through the bloodstream

Specific Anterior Pituitary Hormones

• Neurons in the hypothalamus release prolactin releasing hormone (PRH) into the median eminence's capillary bed to stimulate prolactin secretion
  • PRH is a 199 amino acid protein
  • Prolactin stimulates endocrine cells in the anterior pituitary, enters systemic circulation and binds to receptors on mammary gland cells to promote development and milk secretion
• Prolactin inhibiting hormone (PIH)/dopamine secreted into the capilary bed to inhibit prolactin
• Cold temperatures stimulate the hypothalamus
• Thyrotropin releasing hormone (TRH), a hydrophilic peptide, is released
  • It travels through the portal vein and triggers the secretion of thyroid stimulating hormone (TSH) in the anterior pituitary
• TSH enters the systemic circulation and binds to cells in the thyroid gland to stimulate the release of thyroid hormone to regulate metabolism
• Corticotropin releasing hormone (CRH) is released to stimulate adrenocorticotropic hormone (ACTH) secretion
• ACTH enters systemic circulation and binds to receptors on adrenal cortex cells which stimulates the release of glucocorticoids such as cortisol
• The secretion of growth hormone (GH) increases when growth hormone releasing hormone (GHRH) is released
  • GH is a 191 AA peptide
  • GH binds to receptors on the liver to stimulate release of insulin-like growth factors (IGF) and increases bone and soft-tissue growth
• Growth hormone inhibiting hormone (GHIH) release decreases GH secretion.
• Gonadotropin releasing hormone (GnRH) stimulates secretion of luteinizing hormone (LH) and follicle stimulating factor (FSH)
• LH and FSH enter systemic circulation
  • LH stimulates estrogen, progesterone, and androgen secretion, and FSH promotes egg and sperm cell development

Regulation of Anterior Pituitary Hormones

• Hypothalamic tropic hormones that stimulate the anterior pituitary include: PRH, TRH, CRH, GHRH, and GnRH
• Hypothalamic tropic hormones that inhibit the anterior pituitary include: PIH (dopamine) and GHIH (somatostatin)
• Breasts, thyroid glands, adrenal cortices, livers, and gonads respond to pituitary tropic hormones

Thyroid Gland

• Two thyroid hormones are synthesized, T4 (tetraiodothyronine) and T3 (triiodothyronine)
• Formed from thyroglobulin and iodide, lipophilic hormones are created via enzymatic activity
• A butterfly-shaped gland located on the ventral side of the trachea
• It's a primary endocrine gland

Thyroid Hormone Synthesis

• TSH binds stimulate the receptors on thyroid follicular cells
• T3 and T4 are processed and removed from the thyroglobin protein
• The lipophilic hormones enter the bloodstream
• T3 and T4 receptors are located in the cell's cytosol and nucleus

Adrenal Gland

• A primary gland located above the kidney, referred to as the suprarenal gland
• Possesses 2 defined regions, the outer adrenal cortex (80%) and the inner adrenal medulla

Adrenal Cortex

• Secretion of adrenocorticoids (cholesterol) is stimulated by adrencorticotropic hormone (ACTH)
  • Includes adreno (adrenal gland), corti (cortex), and oids (steroids)
• Aldosterone regulates sodium and potassium secretion by the kidney
• Androgens facilitate reproductive and minor physiological functions
• Cortisol, regulates metabolism, blood glucose, and stress responses. The cortisol hormone can be responded to in all nucleated cells.

Adrenal Medulla

• Chromaffin cells in the adrenal medulla secrete catecholamines into the bloodstream
• 80% epinephrine/adrenaline is released during stress or excitation, increasing heart rate
• 20% norepinephrine
• 1% dopamine

Sympathetic Innervation of Adrenal Medulla

• The adrenal medulla releases epinephrine using a direct sympathetic preganglionic neuron
• Postganglionic or efferent neurons do not form typical neuron terminals
• Neuroeffector junctions are formed from association with chromaffin cells
• Varicosities are bulges in the axon where neurotransmitter storage and release occurs
• Action potentials open voltage gated calcium channels, causing calcium entry and subsequent synaptic vesicle fusion.
• The neurotransmitter acetylcholine (ACh) is then released into the neuroeffector junction.
• When acetylcholine binds to receptors, flow to: skeletal muscle, heart, and liver increases

Pancreas

• Primary endocrine gland located behind and below the stomach
• Exocrine and endocrine gland
• Exocrine function is performed by acinar cells, and secrete digestive enzymes into the duodenum
• Endocrine function performed by alpha and beta cells
• Beta cells secrete glucagon, while alpha cells secrete insulin

Pancreas: Insulin/Glucagon

• Absorption of nutrients is no longer occurring after several hours of eating
• For plasma level maintenance, the body starts to break down proteins, fats, and glycogen for energy
• The change requires changes in metabolic activities controlled by insulin and glucagon
• Following a meal, beta cells in the pancreas will increase glucose uptake in response to movement of glucose into the bloodstream to signal insulin release
• Glucose converts to ATP with high cellular ATP levels, which triggers the release of insulin in Beta cells.

Insulin: Effects on other cells

• Circulating insulin binds to receptors present on the surface of many different cell types (excluding liver and CNS cells)
• This results the delivery of transporters and reduces the glucose concentration in the plasma.

Glucagon

• A decrease in blood glucose will stimulates the release by alpha cells into the blood stream.
• Glucagon encourages the liver
• The released glycerol then converts into fatty acids and leads to catabolism

Fast and Slow-Twitch Muscle Fibers

• Individual muscles typically consist of all 3 types of fibers in different proportions using different mechanisms that are not mixed in a motor unit

Fast-Twitch Glycolytic Fibers

• Rapid ATP production resulting in fewer ATP fuel units
• Lower oxidative phosphorylation, but possess high concentration of glycolytic enzymes that are known to generate lactate acid which contribute to fatigue
• White muscle fibers with larger cross sectional diameters

Slow-Twitch Oxidative Fibers

• Smaller diameters with high quantities of mitochondrial, oxygen-binding myoglobin proteins and capillaries
• Low lactate accumulation, primarily use oxidative phophorylation, enriched with mitochondria, slow ATP generation and more resistant to fatigue