Endocrinology Intro: VP 2025

Endocrinology Introduction

• The lecture introduces endocrinology for VP 2025, taught by Clara Camargo, DVM, CertAqV

Learning Objectives

• Understand how hormones regulate homeostasis
• Define classical vs non-classical endocrine glands
• Differentiate chemical messengers
• Differentiate hormone chemical structures and their characteristics
• Understand hormone-receptor interactions

The Endocrine System

• Definition: integrated network of multiple hormone-releasing glands and organs with different embryologic origins
• Hormones signal neighboring or distant target cells
• Coordinates and integrates cellular activity within the whole body
• These cellular activities include digestion, reproduction, electrolyte balance, energy balance, fuel mobilization, growth, response to injury, mood, and stress

Endocrine System Concepts

• The endocrine system allows physiological processes to be coordinated and regulated
• Uses chemical messengers called hormones
• Amplification of signals is an important characteristic
• Small amounts of hormone can activate the formation of many messenger molecules

Synthesis and Secretion of Hormones

• Synthesized by a gland and secreted into the circulatory system
• Transports to distant target organs/cells
  • Long distance effect, for example, pancreatic and thyroid hormones
• Hormones produced, secreted and acting locally
• For example, immune cells triggering local/regional response
• Synthesized and secreted via direct neuroendocrine stimulation
  • For example, the hypothalamus

Endocrine System Components

• Works with the CNS/PNS and immune system
• Neuroendocrine is the integrated nervous and endocrine systems
• The three core components are endocrine glands, hormones, and target cells/organs

Classical Endocrine Glands

• Classical endocrine glands include the hypothalamus, pineal, parathyroid, pituitary, thyroid, adrenal glands, ovaries, testes, and pancreas
• The hypothalamus releases GHRH, CRH, TRH, GnRH, somatostatin, and PIH/Dopamine
• The pineal gland releases melatonin
• The parathyroid releases PTH
• The adenohypophysis releases GH, ACTH, MSH, TSH, FSH, LH, and prolactin
• The neurohypophysis releases vasopressin/ADH and oxytocin
• The thyroid releases T3, T4, and calcitonin
• The adrenal glands release aldosterone, cortisol, androgens, and catecholamines
• The ovaries release estrogens and progesterone
• The testes release testosterone
• The pancreas releases insulin, glucagon, and somatostatin

Non-Classical Endocrine Glands

• Non-classical endocrine glands include the heart, intestines, kidney, placenta, and adipose tissue
• The heart releases atrial natriuretic peptide (ANP)
• The intestines release cholecystokinin, gastrin, secretin, somatostatin, motilin, neurotensin, gastric inhibitor peptide, and vasoactive intestinal peptide
• The kidney releases calcitriol and erythropoietin
• The placenta releases gonadotropin, estrogen, progesterone, inhibin, and relaxin
• Adipose tissue releases leptin, adiponectin, and resistin

Hormone Definition

• Hormones are chemical substances produced and secreted by specialized endocrine glands/cells in minute (very low) concentrations
• They are transported by the vascular system or interstitial fluid, affecting target cells/tissues
• Synthesized and released from classical endocrine tissue/gland
• Synthesized and released from non-classical endocrine tissue/glands and other organs
• Some signaling molecules can also act as hormones
  • For example, neurotransmitters such as dopamine can be considered hormones when secreted by the hypothalamus
• Can act locally or on a distant target cell

General Properties of Hormones

• Bind to specific receptors
• Slow onset of action if acting on the genetic machinery to initiate/inhibit transcription of genes, taking a few hours to days
• Absence of enzymatic activity, unable to catalyze any intracellular enzymatic reaction directly
• Signal transduction: activation (first messenger) of a cascade of intracellular signaling (second messenger system)
• Feedback mechanism regulation, either negative or positive
• Metabolic clearance rate: after eliciting desired biological effects, they are rendered inactive and/or eliminated from the circulation by the liver and kidneys

Chemical Messenger Classifications

• Chemical messengers are released from various cells, aiding in communication and coordination between different tissues
• Neurotransmitters are released by axon terminals and act on nearby nerve cells
  • Affect nerve cell functions
• Endocrine hormones are released by specialized glands into the blood, acting on target cells
• Neuroendocrine hormones are released by neurons into the blood, acting on target cells
• Paracrines are released by cells into the ECF, acting on nearby cells
• Autocrines are released by cells into the ECF, acting on the same cell
• Cytokines are released by immune cells, acting as immunomodulators

Neuroendocrine Hormones

• Are secreted by neuroendocrine tissue into the bloodstream due to neuronal stimulation
• Target cells in different organs or tissues at another location in the body
• ADH (vasopressin) and oxytocin are produced by the hypothalamus and secreted by the posterior pituitary into the blood plasma

Endocrine Hormones

• Synthesized and released by glands or specialized cells into the bloodstream
• Target cells are at another location in the body
  • Insulin from Beta cells of the pancreas is an example
  • Cortisol from the adrenal cortex of the adrenal gland is another example

Autocrine Hormones

• Secreted by cells into the ECF and affect the cell itself
  • IL-6 in cancer cells and IL-1 in monocytes are examples

Paracrine Hormones

• Secreted by cells into the ECF and affect neighboring target cells
• Fibroblast growth factor can improve wound healing by triggering cell proliferation

Neurotransmitters

• Released by axon terminals, acting on nearby cells
• Facilitate communication between neurons, or between neurons and target cells
• Skeletal muscle fiber and glands are examples of target cells
• Signals are limited in the distance traveled and the area of the cell influenced
  • Synaptic cleft and neuromuscular junction are examples
• Acetylcholine, norepinephrine, and GABA are examples

Cytokines

• Secreted by immune cells into the extracellular fluid or blood
• Function as autocrine, paracrine, or endocrine signal molecules
• Act as immunomodulators
  • Interleukins are released from T helper cells to act on other immune cells
  • Leptin is a cytokine produced by adipocytes, participating in inflammatory responses
    • It can also act as an endocrine hormone, suppressing hunger

Protein and Peptide Hormones

• These hormones comprise the majority of hormones
• Insulin, ACTH, PTH, and CCK are examples
• LH, FSH, and TSH (glycoproteins) are also included
• Usually synthesized as inactive molecules in the ER (pre-prohormone)
• Cleaved in the Golgi apparatus (prohormone → hormone)
• Packaged into secretory granules awaiting secretion
• Hydrophilic, and circulate unbound in the blood
• Have a short half-life of at most 30 minutes
• Binds to cell surface receptors (plasma membrane)
• Hormone-receptor complex activates signal transduction

Amine Hormones

• Derived from the modification of amino acids
• Hydrophilic (except thyroid hormones, which are hydrophobic)
• Derived from the amino acid tyrosine
• T3, T4 (thyroid hormones) and catecholamines (dopamine, NE, Epinephrine) are examples
• Half-life depends on the hormone
  • Epinephrine = 1 minute, Thyroxine = 7-10 days
• Circulate unbound in the blood
  • Except T3 and T4, which require carrier proteins
  • Thyroxine-binding globulin (TBG) and Albumin both carrier proteins produced by the liver
• Can bind to cell membrane receptors and nuclear receptors (thyroid hormones)

Steroid Hormones

• Hormones derived from cholesterol
• Adrenocortical hormones (glucocorticoids, mineralocorticoids) and sex hormones (estrogens, progesterone, androgens) are examples
• Cells producing steroid hormones have an abundance of lipid droplets containing cholesterol esters and mitochondria & smooth endoplasmic reticulum (SER)
• There is no storage of steroid hormones within the cell
• Cells which synthesize these hormones can store cholesterol (precursor molecule)
• Secreted immediately after synthesis by simple diffusion across the cell membrane because of their lipophilic nature
• Synthesis and secretion of steroid hormones occur in a tightly coupled manner
• The rate of hormone secretion is controlled by the rate of synthesis
• Steroid metabolic clearance rates are usually constant
• The concentration of steroids in plasma is usually a good reflection of the synthesis and secretion rate

Hormone - Receptor Interaction

• Protein hormones have specific receptors on target tissue plasma membranes
  • Cell surface receptors, like GPCRs and RTK
• Steroid hormones have specific intracellular receptors in the cytoplasm or nucleus
• Specificity and affinity of receptor and hormone allow hormones to be in low concentration in the blood and still produce significant tissue response
• Termination of the action of a hormone includes:
  • Dissociation of the hormone from the receptor, decreasing plasma concentrations of the hormone
  • Metabolization through tissue-specific degradation and liver-kidney excretion
  • Internalization of the receptor-hormone complex through endocytosis (desensitization)

Hormone - Receptor Interaction Cont.

• Down-regulation is a mechanism in which a hormone decreases the number or affinity of its receptors in a target tissue
  • May occur by decreasing the synthesis of new receptors, increasing the degradation of existing receptors, or inactivating receptors
  • Reduces the sensitivity of the target tissue when hormone levels are high for an extended period
• Up-regulation is a mechanism in which a hormone increases the number or affinity of its receptors in a target tissue
• May occur by increasing the synthesis of new receptors, decreasing the degradation of existing receptors, or activating receptors
• A hormone can also up-regulate the receptors for other hormones
  • Estrogen, for example, can up-regulate its receptors in the uterus and up-regulate the receptors for LH in the ovaries

Hormone Clearance

• Hormone clearance is the process in which hormones are removed from the bloodstream
• Involves hormone metabolic breakdown and excretion by the liver and/or kidneys
• Peptide hormones are degraded via proteolysis, primarily in the liver and kidneys
• Steroid and thyroid hormones undergo biotransformation in the liver and other peripheral tissues
• Metabolic clearance rate is the rate at which hormones are cleared from the body and varies between different hormones
• MCR = Rate of the disappearance of hormone from plasma/Concentration of hormone