Endocrinology

Introduction to Endocrinology

  • function and purpose of hormones

  • classification, structure and synthesis of hormones

  • pathways of nervous to endocrine regulation

  • effects of hormone interactions

  • pathologies of the endocrine system 

Anatomy Summary: Hormones

  • Hormone Details:

    • Pineal Gland:

    • Hormone: Melatonin [A]

    • Primary Targets: Brain, other tissues

    • Main Effects: Circadian rhythms; immune function; antioxidant.

    • Hypothalamus (N):

    • Hormone: Trophic hormones [P]

    • Primary Target: Anterior pituitary

    • Main Effects: Release or inhibit pituitary hormones.

    • Posterior Pituitary (N):

    • Hormones: Oxytocin [P], Vasopressin (ADH) [P]

    • Primary Targets: Breast and uterus, Kidney

    • Main Effects: Milk ejection; labor and delivery; behavior, Water reabsorption.

    • Anterior Pituitary (G):

    • Hormones: Prolactin [P], Growth hormone [P], Corticotropin (ACTH) [P], Thyrotropin (TSH) [P], Follicle-stimulating hormone [P], Luteinizing hormone [P]

    • Primary Targets: Breast, Liver, Gonads, many tissues

    • Main Effects: Milk production; growth; cortisol release; thyroid hormone synthesis; egg/sperm sexual hormone production.

    • Thyroid Gland:

    • Hormones: Triiodothyronine (T3) and Thyroxine (T4) [A], Calcitonin [P]

    • Primary Targets: Many tissues, Bone

    • Main Effects: Metabolism, growth, development; regulate plasma Ca2+ levels.

    • Adrenal Cortex:

    • Hormones: Aldosterone [S], Cortisol [S], Androgens [S]

    • Primary Targets: Kidney, many tissues

    • Main Effects: Na+ and K+ homeostasis; glucose homeostasis; sex hormone production.

    • Adrenal Medulla (N):

    • Hormones: Epinephrine, norepinephrine [A]

    • Primary Targets: Many tissues

    • Main Effects: Fight-or-flight response.

    • Pancreas (G):

    • Hormones: Insulin, glucagon, somatostatin, pancreatic polypeptide [P]

    • Primary Targets: Many tissues

    • Main Effects: Metabolism of glucose; assist digestion and nutrient absorption.

    • Others:

    • Thyroid hormones influence basal metabolic rate, enhance catecholamines actions.

    • Thymus gland influences lymphocyte development.

    • Vitamin D regulates calcium absorption.

Chemical Regulating Systems

  • Hormones: Function as cell-to-cell communication molecules.

    • Characteristics:

    • Made in glands or specific cells.

    • Transported via blood to distant target tissues.

    • Activate physiological responses upon binding to receptors.

  • Pheromones: Involved in organism-to-organism communication.

Hormones: Function

  • Hormonal functions include:

    • Rate control of enzymatic reactions.

    • Transport regulation of ions or molecules across membranes.

    • Gene expression and protein synthesis modification.

  • Hormones exert effects at low concentrations (nanomole or picomole range).

  • Hormones circulate everywhere, but they only bind and act on target cells that have the specific receptors for them.

  • Their activity is defined by half-life indicating length of action.

    • short half life = hormone acts quick but effects don’t last long 

    • long half life = hormone stays in bloodstream for longer duration, producing more sustainable effects  

Hormones: Classification

  • Categories:

    • Peptide or Protein Hormones (most hormones)

    • Steroid Hormones

    • Amine Hormones

Hormones: Peptides or Proteins

  • Hormone Types:

    1. Preprohormone: Large, inactive precursor. It more so guides the hormone to the right place inside the cell (usually the ER).

    2. Prohormone: Created by cutting of the signal part and going through post-translational modification

    3. Peptide hormone-receptor complex: When the final, active hormone is released binds to its receptor on a target cell causing signal transduction, conversion of hormone’s signals into physiological responses

Peptide Hormone Synthesis, Packaging, and Release

  1. mRNA binds amino acids into a peptide chain = preprohormone

  2. Enzyme in ER cleave signal sequence = inactive prohormone 

  3. Prohormone passes from ER through the Golgi complex.

  4. Secretory vesicles bud off the Golgi and releases its contents by exocytosis into the extracellular space

  5. The active hormone is released via exocytosis into the circulation for transport to its target

Peptide Hormone-Receptor Complex

  • Mechanism:

    1. Hormone binds to surface receptor. This causes a chain of events in the cell without the hormone ever entering it. 

    2. Enzyme activation - activated receptor triggers enzymes inside the cell membrane or cytoplasm

    3. Open channels - Some receptors directly or indirectly open ion channels (can change electrical/chemical environment)

    4. Second messengers are small molecules produced inside the cell in response to the first messenger (the hormone).

    5. Cellular response - the signal leads to a specific physiological change in the target cell

Steroid Hormones: Features and Action

  • Characteristics:

    • Cholesterol-derived, lipophilic, can enter target cell

    • Activation of DNA in cytoplasm or nucleus for protein synthesis.

    • Slow-acting with longer half-lives.

  • Examples: Cortisol, estrogen, testosterone.

  • Action: 

  1. steroid hormones travel via plasma protein carriers (because they are hydrophobic)

  2. bind to receptor in cytoplasm or nucleus OR bind to membrane receptors that use second messenger systems to create rapid cellular responses

  3. receptor-hormone complex binds to DNA and turn genes on (activate) or off (repress) depending on the signal

  4. Activated genes make mRNA (messenger RNA), which carries the genetic instructions out of the nucleus to the cytoplasm.

  5. Translation produces new proteins for cell processes

Amine Hormones: Features

  • Derived from one of two amino acids 

    • tyrosine 

    • tryptophan 

  • examples:

    • thyroid hormones

    • catecholamines

      • epinephrine

      • norepinephrine

      • dopamine

Comparison of Hormones

  • Peptide Hormones:

    • Synthesis and Storage: Made in advance; stored in secretory vesicles.

    • Release from Parent Cell: Via exocytosis.

    • Transport in Blood: Dissolved in plasma.

    • Half-life: Short.

    • Location of Receptor: Cell membrane; activates second messenger systems.

    • Examples: Insulin, parathyroid hormone.

  • Steroid Hormones:

    • Synthesis: On-demand from precursors.

    • Release from Parent Cell: Simple diffusion.

    • Transport in Blood: Bound to carrier proteins.

    • Half-life: Long.

    • Location of Receptor: Cytoplasm or nucleus.

    • Examples: Estrogen, cortisol.

  • Amine Hormones:

    • Derived from: Tyrosine and tryptophan.

    • Examples: Catecholamines (epinephrine, norepinephrine).

Endocrine Reflex Pathways

  • endocrine reflex pathway- feedback loop your body uses to detect changes and correct them using hormones

  • Steps of endocrine reflex:

    1. Stimulus - a change in the body that needs correction (ex: low blood sugar)

    2. Afferent signal - tells the body what changed 

    3. Integration - decision making step, control center processes the information and decides how to respond (ex: integrating center could be an endocrine gland itself like the pancreas releasing glucagon to raise blood sugar) 

    4. Efferent signal (the hormone) - hormone travels through the bloodstream to target cells 

    5. Physiological action - the effect of the hormone causes on target cells or tissues (ex: glucagon tells the liver to release stored glucose → blood sugar rises back to normal)

    6. Negative feedback - once the body returns to normal levels, the system shuts off the response to the original stimulus to prevent overcorrection/hormone overproduction 

Control of Hormone Secretion

  • Control by various stimuli:

    • Nervous System: Direct regulation.

    • Chemical Changes: In blood composition.

    • Hormonal: Distension/stretch or other hormones influence secretion patterns.

Pituitary Gland Anatomy

  • Anterior Pituitary: True endocrine gland of epithelial origin (secretes GH, TSH, ACTH, PRL, FSH, LH).

  • Posterior Pituitary: Extension of neural tissue; stores hormones like oxytocin and vasopressin. This back part does not actually make hormones, only stores and releases hormones back by the hypothalamus

  • Infundibulum connects pituitary to the brain.

Anterior Pituitary Hormones

  • Cell Types:

    • Somatotrophs: secrete growth hormone (GH).

    • Thyrotrophs: secrete thyroid stimulating hormone TSH.

    • Corticotrophs: secrete adrenocorticotropic hormone ACTH.

    • Lactotrophs: secrete prolactin (PRL).

    • Gonadotrophs: secrete two gonadotropins:

      • Follicle-stimulating-hormone (FSH)

      • Luteinizing hormone (LH)

Hypothalamic Control

  • Release of hormones by the anterior pituitary is regulated by the hypothalamus

  • Ex: Growth hormone–releasing hormone (GHRH), Thyrotropin-releasing hormone (TRH).

Hypothalamic-Hypophyseal Portal System 

  • a special network of blood vessels that directly connects the hypothalamus to the anterior pituitary gland 

  • This system allows the hypothalamus to send hormones quickly and efficiently to the anterior pituitary without those hormones getting diluted in the general bloodstream

    1. neurons synthesizing trophic hormones release them into capillaries of the portal system 

    2. portal vessels carry the trophic hormones directly to the anterior pituitary 

    3. endocrine cells release their hormones into the second set of capillaries for distribution to the rest of the body

Thyroid gland

  • butterfly shaped 

  • 2 cells types

    • follicular cells produce: T3 and T4

    • parafollicular cells produce: calcitonin

  • most cells of the body have receptors for T3 and T4

    • typically initiate gene transcription and protein synthesis 

  • functions include: 

    • increased basal metabolic rate 

    • enhance actions of catecholamines

    • regulate development and growth of nervous tissue and bones

  • hyperthyroidism

    • increases oxygen consumption and metabolic heat production 

    • increase protein catabolism and may cause muscle weakness

    • Hyperexcitable reflexes and psychological disturbances

    • Influence B-adrenergic receptors in the heart (high heart rate and force of contraction

  • hypothyroidism 

    • slow metabolic rate and oxygen consumption 

    • decreased protien synthesis 

    • negative effects on the nervous system 

    • slow heart rate

Parathyroid gland

  • small round masses of glandular tissue partially embedded in the thyroid gland 

  • contains secretory “chief” cells

    • release parathyroid hormone (PTH) 

    PTH is a major regulator in extracellular Ca+2, Mg+2and HPO4-2 concentrations

Role of calcium in the body

  • important intracellular signal

  • structural functions- physical strength of bone matrix and help hold cells together at tight junctions

  • cofactors in blood coagulation 

  • required for the normal excitability of neurons and all types of muscle

  • bone is a depot for stored Ca+2 

    • osteoblasts deposit calcium as they create new bone matrix

    • osteoclasts break down bone matrix during bone resorption

Hormonal Control of Calcium Balance

parathyroid hormone (released when plasma Ca+2 is low)

  • mobilizes calcium from bone

  • enhances renal reabsorption of calcium

  • stimulates release of calcitriol (increases intestinal calcium absorption)

calcitonin (released when plasma Ca+2 is high)

  • decreases bone resorption

  • increases renal calcium excretion 

Adrenal Glands

  • 2 in the body (top of the kidney)

  • two different tissue types and layers 

    • inner medulla- produces catecholamine hormones

    • outer medulla- produces a variety of steroid hormones 

  • consists of three layers/zones

    • zona glomerulosa - secrete mineralcorticoids (maintain mineral levels of the blood)

    • zona fasciculata - secrete glucocorticoids (affect glucose homeostasis)

    • zona reticularis - secrete androgens (steroid hormones that have masculinizing effects)

  • adrenal medulla- extension of sympathetic nervous system

    • norepinephrine

    • epinephrine 

  • cortisol of adrenal cortex

    • helps the body cope with long-term stress. It protects against hypoglycemia by stimulating catabolism of energy stores.

Pineal gland

  • found in the brain

  • secretes melatonin

    • amine hormone derived from serotonin 

pancreatic hormones

  • alpha cells- secrete glucagon

  • beta cells- secrete insulin

  • delta cells- secrete somatostatin 

  • F cells- secrete pancreatic polypeptide

Pathologies of Endocrine System

  • Hypersecretion: Excess hormone due to tumors or conditions such as Graves’ disease.

  • Hyposecretion: Deficient hormones like thyroid hormone (goiter) and insulin (diabetes).

  • Abnormal receptor activity (downregulation) or transduction anomalies can also lead to disorders.

Cushing's Syndrome

  • Condition: Hypercortisolism with specific symptoms including central adiposity and osteoporosis.

  • Diagnostic Tests: Dexamethasone suppression test, urine cortisol levels, imaging studies.

  • causes of hypercortisolism

    • adrenal tumor that autonomously secretes cortisol (primary) 

    • pituitary tumor that autonomously secretes ACTH (secondar)