ANP 1105A - Anatomy & Physiology I
•
Basic Cellular Physiology & the Anatomy and Physiology of the
Cardiovascular, Lymphatic & Respiratory Systems
Lecture 10 - Introduction to the Endocrine System
Presented by: Dr. Stephen Gee
Faculté de médecine | Faculty of Medicine
uOttawa.ca
Marieb and Hoehn 11th Ed. – Chapter 16
(pp. 601-611)
16.1 The endocrine system is one of the body’s two major
control systems
16.2 The chemical structure of a hormone determines how it
acts
16.3 Hormones act through second messengers or by
activating specific genes
16.4 Three types of stimuli cause hormone release
16.5 Cells respond to a hormone if they have a receptor for
that hormone
16.6 The hypothalamus controls release of hormones from
the pituitary gland in two different ways
** Includes Focus Figure 16.1
Lecture Outline
The Endocrine System - Overview
• Acts with NS to coordinate, integrate activity of
virtually all cells
• Hormones  blood
• Responses slower, longer
lasting
• Controls and integrates
– Reproduction, growth, development
– Blood electrolyte, water, nutrient balance
– Regulation of cellular metabolism, energy balance
• Mobilizes body defenses
• Endocrinology: study of hormones, endocrine organs
Endocrine Glands
• Pituitary, thyroid, parathyroid,
adrenal, and pineal glands
• Hypothalamus: neuroendocrine
• Exocrine + endocrine: Pancreas,
gonads, placenta
• Others: adipose cells, thymus, cells
in walls of small intestine,
stomach, kidneys, heart
Ducts
Hormones
• Long-distance chemical signals
• Travel in blood or lymph
Hormones – Two Main Classes
• Amino acid derivatives, peptides, and proteins
• Steroids - Synthesized from cholesterol
TH
DBH
Tyr  L-Dopa  NE
Hormone Targets
Only target cell activity is affected.
• Alter plasma membrane permeability and/or
membrane potential
• Stimulate gene transcription and/or protein
translation
• Activate or deactivate enzymes (via phosphorylation)
• Induce secretory activity
• Stimulate mitosis (cell division)
Hormone Signal Transduction
Water-soluble: (aa–based except thyroid hormone)
• Cannot enter cell
• Act on PM receptors  2nd messengers
• e.g. cAMP; PIP(4,5)2- Ca2+; cGMP; etc.
Lipid-soluble: (steroid and thyroid hormones)
• Can enter cell
• Act on intracellular receptors  directly activate
genes
Mechanism of Hormone Action: cAMP
Cyclic AMP
• Cyclic AMP (cAMP) is produced
from ATP through the action of
Adenylate Cyclase enzyme
(ON)
• cAMP is rapidly degraded by
the enzyme
phosphodiesterase (OFF)
Cyclic AMP Signaling Mechanism
• Enzyme cascades amplify signals
Cyclic AMP Activation of Transcription
• Stimulates gene
transcription via the
cAMP response element
binding protein (CREB)
Cytoplasm
P
Nucleus
PKC Activation by DAG and Ca2+
PI(4,5)P2
DAG
DAG
P
P
C1A
C1B
C2
PLC-b
PKCa
Cytoplasm
P
IP3
P P
PKC
activation
P
P P
IP3R
Endoplasmic
reticulum
Ca2+
release
Ca2+
Ca2+
Mechanism of Lipid-soluble Hormones
1.Steroid hormone diffuses through PM,
binds intracellular receptor
2.Receptor-hormone complex enters
nucleus.
1
3.Receptor-hormone complex binds
specific DNA region.
2
3
4.Binding initiates transcription to
mRNA.
4
5.mRNA directs protein synthesis
(translation)
– Proteins have various functions
(e.g. metabolic, structural, or
secreted)
5
Endocrine Gland Stimuli and Regulation
Three types:
NS can modify
stimulation or
inhibition of
endocrine glands to
override normal
endocrine controls
• e.g. under severe
stress,
hypothalamus
and SNS override
insulin to allow
blood glucose
levels to increase
(-)
• Insulin
• Aldosterone
Blood hormone levels controlled by negative feedback systems
• Hormone effects on target organs can inhibit further release
• Levels vary within narrow, desirable range
Target Cell Specificity
• Target cells must have specific receptors for hormone
– e.g. ACTH receptors found only on certain cells of adrenal
cortex, thyroxin receptors found on nearly all cells
• Activation depends on 3 factors:
1. Blood hormone levels
2. Relative number of receptors on/in target cell
3. Affinity (strength) of receptor for hormone
• Hormone levels influence receptor number on target cells
– Up-regulation: more receptors in response to low levels
– Down-regulation: less receptors; desensitizes target cells
to prevent overreacting to persistently high levels
Half-Life, Onset, Duration of Activity
• Hormones circulate in blood free or bound
– Steroids and thyroid hormone attached to plasma proteins
– All others circulate without carriers
• Concentration of circulating hormone reflects:
1. Rate of release
2. Speed at which it is inactivated and removed from body
• Removed from blood by degrading enzymes, kidneys or liver
– Half-life: time required for level of hormone in blood level to
decrease by half (< 1 min to a week)
• Response Time: Immediate or hours to days (steroids)
– Some inactive until they enter target cells
• Response Duration: secs to hrs
– Effects may disappear rapidly as blood levels drop, but some may
persist for hours at low blood levels
– Half-life, onset, and duration of hormone activity - dependent on
water or lipid soluble
Lipid- versus Water-Soluble Hormones
Hypothalamus – Pituitary Gland
Neuro-secretory organ connected to
pituitary gland (hypophysis) via
infundibulum
• Secretes 8 hormones, has 2 lobes:
Posterior pituitary: neural tissue
derived from down-growth of brain
- secretes neurohormones
• Posterior lobe + infundibulum =
neurohypophysis
Anterior pituitary (adenohypophysis):
glandular tissue derived from oral
mucosa
Infundibulum
Anterior Pituitary (adenohypophysis)
• True hormone-producing gland made of glandular epithelium
1. Parvocellular
neurosecretory cells: small
neurons within PVN - axons
project to median
eminence, terminals
secrete releasing or
inhibiting hormones into
primary capillary plexus.
2. Hypophyseal portal veins
lead to anterior pituitary
PVN
1
2
3
3. Secondary capillary plexus
empties into general
circulation
Median Eminence
The Hypophyseal Portal System
Hypothalamic neurons synthesize
releasing and inhibiting hormones 1
•
•
•
•
•
•
Growth hormone-releasing hormone (GHRH)
Somatostatin (SS)(GHIH)
Thyrotropin-releasing hormone (TRH)
Corticotropin-releasing hormone (CRH)
Gonadotropin-releasing hormone (GnRH)
Prolactin-inhibiting hormone (PIH)
(dopamine)
• Hypothalamic hormones released into
special blood vessels control release of
anterior pituitary hormones 2
• Blood vessels carry peptide hormones
to anterior pituitary – regulate hormone
secretion into systemic circulation 3
Anterior Pituitary Hormones
3
cAMP
Secretes 6 different peptide hormones
o Growth hormone (GH)
o Prolactin (PRL)
o Thyroid-stimulating hormone (TSH)
o Adrenocorticotropic hormone (ACTH)
o Follicle-stimulating hormone (FSH)
o Luteinizing hormone (LH)
Tropins (tropic hormones)
regulate secretion of other
hormones
Hypothalamic – Pituitary - Target Organ System
Posterior Pituitary
• Axon terminals of hypothalamic neurons and
associated blood vessels (neurohypophysis)
1. PVN neurons synthesize
oxytocin; SON neurons
synthesize antidiuretic
hormone (ADH)
1
2. Transported down axons of
hypothalamic-hypophyseal
tract to posterior pituitary
3. Stored in axons terminals
4. Arriving APs cause release
into blood
2
Neurohypophysis
3
4
Summary of Homeostatic Mechanisms
Two key homeostatic regulatory systems:
Autonomic nervous system
• sympathetic versus parasympathetic
• (sensory and) motor neural pathways
• fast response
Endocrine system
• hormones released into extracellular fluid and often
travel to target organs via bloodstream
• slower response time but response can be long-lived
• different chemical classes of hormones with
associated mechanisms of action