Introduction to Endocrinology

• Introduction to endocrinology focuses on the study of hormones and endocrine glands
• The course is taught by Sabha Rabaya at PTUK.

Learning Objectives

By the end of this lecture, students will be able to:

• Define endocrinology and its importance
• Describe major endocrine glands and their functions
• Explain hormone regulation and feedback mechanisms
• Differentiate hormone classes and mechanisms of action
• Discuss clinical applications in laboratory medicine

The Endocrine System

• It comprises a network of cells, tissues, and organs
• These secrete hormones into the surrounding fluid
• Interstitial fluid and blood vessels transport hormones throughout the body
• Endocrinology is the study of hormones, endocrine glands, and their physiological functions

Importance for Medical Laboratory Scientists (MLS)

• MLS diagnose endocrine disorders
• MLS perform hormone assays
• MLS play a key role in monitoring treatment effectiveness

Hormones

• Chemical substances generated in one organ
• Carried by the blood to a target organ where they initiate activity

Endocrine Glands

• Organs that secrete hormones directly into the bloodstream
• Endocrine glands are ductless

Endocrine System Functions

• Acts as a communication network using hormones
• Hormones regulate virtually every physiological process
• It ensures optimal function and adaptation to internal and external changes
• Maintains the body's equilibrium, known as homeostasis

Endocrine Signaling

• A method of communication used by the endocrine system is chemical signaling
• Chemical signals are sent by endocrine organs, which secrete hormones into the extracellular fluid
• Hormones are transported via the bloodstream
• Hormones then bind to receptors on target cells, creating a specific response

Modes of Hormone Action

• Endocrine: Hormone secreted into the bloodstream travels to a distant target tissue, often bound to plasma proteins during transport
• Paracrine: Hormone acts on a neighboring cell
• Autocrine: Hormone acts on the same cell that secreted it
• Intracrine: Hormone acts inside the cell without being released

Hormone Receptors and Target Tissues

• A tissue is a target for a hormone only if it has specific receptors for that hormone
• These receptors are linked to effector mechanisms that trigger physiological effects
• A hormone receptor is a protein or glycoprotein
• Hormone receptors recognize and bind their specific hormone
• Hormone receptors undergo a conformational change upon binding
• Biochemical events are initiated, leading to cellular responses

Relationship to the Nervous System

• Comparison:
  • Nervous system responses are fast and short-lived, using electrical signals through neurons
  • Endocrine system effects are slower and long-lasting, with hormones traveling through the bloodstream
• The endocrine and nervous systems work closely to control the body

Major Endocrine Glands

They include:

• Hypothalamus
• Pituitary
• Pineal
• Thyroid
• Parathyroids
• Adrenals
• Pancreas-Islets of Langerhans
• Thymus
• Ovaries
• Testes

Endocrine Glands and Hormones

• Some glands have both endocrine and nonendocrine functions
• The pancreas has cells for digestion and cells that secrete hormones like insulin and glucagon, which regulate blood glucose
• Organs including the hypothalamus, thymus, heart, kidneys, stomach, small intestine, liver, skin, female ovaries, and male testes contain cells with endocrine function
• Adipose (fat) tissue and even bone tissue has endocrine functions

Hormones

• A hormone only affects the activity of its target cells, which have specific receptors for it
• Once bound, a chain of events leads to the target cell's response
• Hormones regulate physiological processes, contributing to human reproduction, growth, metabolism, fluid and electrolyte balance, sleep, and other functions

Hormone Classification by Chemical Structure:

• Human hormones are divided into two major groups based on chemical structure
  • Hormones derived from amino acids include amines, peptides, and proteins
  • Hormones derived from lipids include steroids

Hormone Classification by Solubility

• Water-soluble hormones bind to membrane receptors
• Lipid-soluble hormones act on intracellular receptors

Amine Hormones

• They derive from modified amino acids, tryptophan or tyrosine
• Melatonin, secreted by the pineal gland, is an example, regulating circadian rhythm

Peptide and Protein Hormones

• Made from Multiple amino acids that link
• Examples include antidiuretic hormone (ADH), a pituitary hormone for fluid balance and growth hormone, produced by the pituitary gland

Steroid Hormones

• They derive from lipid cholesterol
• Reproductive hormones like testosterone and estrogens are steroid hormones
• Steroid hormones are hydrophobic
• Lipid-derived hormones must travel in blood bound to a transport protein due to blood being water-based

Hormone Action and Feedback

• Hormones bind to trigger biological responses
• Hormone receptors are either inside the cell or within the cell membrane
• The receptor initiates signaling events that result in the target cell's response
• Receptors recognize molecules with specific shapes and side groups and respond only to those hormones being recognized
• The same receptor type may be on cells in different body tissues, triggering different responses
• Response triggered by a hormone depends, not only on the hormone, but also on target cell

Hormone Action: Target Cell Response

Cells respond to hormone signal include:

• Stimulation of protein synthesis
• Activation or deactivation of enzymes
• Alteration in cell membrane permeability
• Altered mitosis and cell growth
• Stimulation of secretion of products
• A hormone can induce different responses in a given cell

Hormone Regulation and Feedback

• Negative Feedback: further hormone secretion is inhibited when adequate hormone levels are reached, examples include thyroid hormone regulation
• Positive Feedback: additional hormones are released in response to an original hormone release, an example is oxytocin in childbirth

Summary

• Endocrinology studies hormones and endocrine glands
• The endocrine system regulates body functions
• Major endocrine glands include hypothalamus, pituitary, thyroid etc
• Hormone lab tests are essential for diagnosis

Introduction to the Hypothalamic-Pituitary Axis

• The hypothalamus and pituitary gland work together to regulate many bodily functions
• The hypothalamus is located in the brain controls the pituitary gland
• The hypothalamus and the pituitary gland communicate either hormonally or via nervous signals regulating homeostasis
• The hypothalamic-pituitary axis (HPA) is a critical link between the nervous and endocrine systems

Hypothalamus

• Located at the base of the brain, above the pituitary gland
• Contains neurons, glial cells, and specialized secretory cells
• The hypothalamus produces hormones that regulate pituitary glands activity
• The hypothalamus regulates a range of physiological activities
  • Regulating Fluid balance
  • Hunger
  • Thirst
  • Body temperature
  • Sexual activity
• Integrates brain info and responds to variety of stimuli including light, odors, and stress
• Regulates emotions, blood pressure, and heart rate.

Hypothalamic Hormones and Functions

• Growth hormone-releasing hormone (GHRH): Regulates growth by stimulating GH release
• Somatostatin (growth hormone-inhibiting hormone) (GHIH): Inhibits growth hormone release and TSH secretion
• Dopamine (Prolactin-inhibiting hormone, PIH): Regulates lactation by inhibiting prolactin secretion
• Thyrotropin-releasing hormone (TRH): Controls metabolism by stimulating TSH & prolactin release
• Gonadotropin-releasing hormone (GnRH): Controls reproductive function by stimulating FSH & LH secretion
• Corticotropin-releasing hormone (CRH): Manages stress response by stimulating ACTH release
• Hypothalamic hormones act as on/off switches for the pituitary

Pituitary Gland

• Description: small, pea-shaped gland found at the base of the skull within a bony structure beneath the hypothalamus
• Also called the "master gland" because controls so many other glands
• Structure: two parts:
  • Anterior Pituitary (Adenohypophysis): produces its own hormones
  • Posterior Pituitary (Neurohypophysis): stores and releases hormones made by the hypothalamus

Posterior Pituitary

• Controlled by nerve signals in hypothalamus
• composed of neurons
• It does not secrete its own hormones
• region of hormone storage.

Anterior Pituitary

• Controlled via hormones from hypothalamus
• Hormones are hypothalamic releasing and inhibitory
• Composed of glandular epithelium

Anterior Pituitary Hormones

Hormones secreted from anterior pituitary and their function include:

• Growth Hormone (GH): targets liver, bones, muscles, and stimulates growth, metabolism, protein synthesis
• Thyroid-Stimulating Hormone (TSH): targets Thyroid to stimulates thyroid hormone (T3 & T4) production
• Adrenocorticotropic Hormone (ACTH): targets Adrenal cortex to Stimulate cortisol production in order to assist in management of stress
• Follicle-Stimulating Hormone (FSH): targets Ovaries/testes and to stimulate the production of an egg and sperm
• Luteinizing Hormone (LH): targets Ovaries/testes in order to Stimulate ovulation & testosterone production
• Prolactin (PRL): targets Mammary glands to Stimulate milk production during lactation

Posterior Pituitary

Hormones secreted from anterior pituitary include:

• Antidiuretic Hormone (ADH): targets Kidneys to Promote water retention, regulate blood pressure
• Oxytocin: targets Uterus & mammary glands to Stimulate labor contractions & milk ejection

Anterior Pituitary Gland Cell Types

This consists of:

• Somatotrophs: GH-secreting cells
• Lactotrophs: PRL-secreting cell
• Thyrotrophs: TSH-secreting cells
• Corticotrophs: produce ACTH
• Gonadotrophs: produce LH and FSH

Pituitary Hormones

• Commonly target other endocrine glands
• Control metabolism, adult development, reproduction, growth and equilibrium/Homeostasis

Hypothalamus Hormones and Pituitary Control

• Growth hormone–releasing hormone (GHRH) stimulates GH secretion (half-life 3-7 min)
• Somatostatin (growth hormone–inhibiting [GHIH]) inhibits GH and TSH secretion (half-life 2-3 minutes)
• Dopamine inhibits PRL secretion (short half-life)
• Thyrotropin-releasing hormone (TRH) regulates TSH (half-life 6 minutes)
• Gonadotropin-releasing hormone (GnRH) stimulates LH and FSH secretion (half-life 2-4 minutes)
• Corticotropin-releasing hormone (CRH) stimulates ACTH secretion, with a biphasic half-life from human placenta and levels increase during late pregnancy and delivery

The Hypothalamus, GH, and Pituitary Interplay

• Corticotrophin Releasing Hormone (CRH) is controlled through a negative feedback which signals pituitary to make adrenocorticotrophic hormone (ACTH)
• ACTH then signals the adrenal glands to make glucocorticoid hormones such as cortisol
• System involves Hypothalamic pituitary adrenal axis (or HPA axis)
• Cortisol then travels back to the hypothalamus and pituitary gland - lowering CRH and ACTH production

Growth Hormone

• GH releasing hormone and Somatostatin work together for GH - nerve cells regulate levels
• After high levels are reached - somatostatin is released

Common Hypothalamus Problems

• Tumors: alter hormone production leading to other conditions

Case Study

• Patient with unexplained weight gain, fatigue, ultimately diagnosed with hypothalamic dysfunction
  • A 34-year-old male
  • Also reporting polyuria and sleep issues
• Problems and Issues
  • Age/Sex: 34-year-old male
  • Rapid weight gain (12 kg in 6 months).
  • Excessive thirst
  • Frequent urination
  • No known history of metabolic disorders, diabetes, or psychiatric illness
  • Sedentary lifestyle
• Findings
  • BMI: 32.1 kg/m²
  • Blood Pressure: 125/80 mmHg
  • Mild daytime sleepiness
• Endocrine Signs: Truncal obesity Slightly puffy face Fatigue Decreased libido

Laboratory Results

• Testing involved includes:
• Brain MRI (Pituitary-Hypothalamic Axis): 4mm hypothalamic lesion
  • Hypothalamic-Pituitary Stimulation Testing
  • Blunted response in growth hormone-releasing hormone (GHRH) stimulation test
  • Abnormal suppression of ACTH in dexamethasone suppression test

Diagnosis

• Hypothalamic dysfunction
  • Secondary to hypothalamic lesion
• Leading to:
  • Hypothalamic obesity
  • Hypogonadotropic hypogonadism.
  • Mild hyperprolactinemia
  • Secondary adrenal insufficiency