Lecture 17
Principles of
Endocrinology: The Central
Endocrine Glands
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Contents
• General Principles of Endocrinology
• Principles of Hormonal Communication
• The Endocrine Tissues
• Hypothalamus and Pituitary
• Endocrine Control of Growth
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GENERAL PRINCIPLES
OF ENDOCRINOLOGY
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General Principles of Endocrinology
• The endocrine system consists of ductless
endocrine glands scattered throughout body.
• Glands secrete hormones that travel through
blood to target cells.
– Target cells have receptors for binding with a
specific hormone.
– A hormone regulates or directs a particular
function.
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The
Endocrine
System
Figure 6-1, p. 212 Copyright © 2022 by Cengage Canada 5
Hormones
• Nervous system coordinates rapid, precise
responses and is especially important in
mediating body’s interactions with the
external environment
• Endocrine system primarily controls activities
that require duration rather than speed
– Does so with the use of hormones
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Overall Functions of the
Endocrine System
• Regulate organic metabolism and H2O and
electrolyte balance.
• Induce adaptive changes to help body cope
with stressful situations.
• Promote smooth, sequential growth and
development.
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Overall Functions of the
Endocrine System (cont’d)
• Control reproduction.
• Regulate red blood cell production.
• Along with the autonomic nervous system,
control and integrate circulation with the
digestion and absorption of food.
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Tropic Hormones
• Tropic hormones regulate hormone secretion
by other endocrine glands.
• Stimulate and maintain their endocrine target
tissues
– Example: thyroid-stimulating hormone (TSH)
secreted from anterior pituitary stimulates thyroid
hormone secretion by thyroid gland
• Also maintains structural integrity of thyroid gland
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Complexity of Endocrine Function
• A single gland may produce multiple
hormones, and a single hormone may be
secreted by more than one gland.
• A single hormone may have more than one
type of target cell.
• The rate of secretion varies.
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Complexity of Endocrine Function
(cont’d)
• The target cell may be influenced by more
than one hormone.
• A chemical messenger may be either a
hormone or a neurotransmitter.
• Not all endocrine organs are exclusively
endocrine in function.
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Plasma Concentration
• Plasma concentration of each hormone is
normally controlled by regulated changes in
rate of hormone secretion
• Direct regulatory inputs that influence
secretory output of endocrine cells
– Neural input
– Input from another hormone
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Plasma Concentration (cont’d)
• Effective plasma concentration also influenced
by
– rate of removal from blood by metabolic
inactivation and excretion
– rate of activation or its extent of binding to
plasma proteins
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Negative-Feedback Control
• Negative feedback exists when output of a
system counteracts a change in input
• Maintains the plasma concentration of a
hormone at a given level
• Given level is referred to as a set point
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Negative-Feedback Control
Figure 6-2, p. 214 Copyright © 2022 by Cengage Canada 15
Negative-Feedback Control (cont’d)
• The majority of endocrine feedback systems
are negative.
• Some feedback loops are positive-feedback
loops.
– The actions of a hormone cause the further
release of the hormone.
• Role of oxytocin in childbirth (see Fig. 17-30)
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Neuroendocrine Reflexes
• Includes neural as well as hormonal
components
• Purpose of such reflexes is to produce a
sudden increase in hormone secretion in
response to a specific stimulus
• Example is increased secretion of cortisol
during stress response
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Diurnal Rhythm of Cortisol Secretion
Figure 6-3, p. 214 Copyright © 2022 by Cengage Canada 18
Transport, Metabolism, and
Excretion
• Alterations in transport, metabolism and
excretion can be influenced by the hormone’s
plasma concentration.
• Hormones are metabolized by enzyme-
mediated reactions.
• Eliminated from blood by urinary excretion
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Endocrine Disorders
• Can arise from a variety of factors
• Most commonly result from abnormal plasma
concentrations of a hormone caused by
inappropriate rates of secretion
– Hyposecretion
• Too little hormone is secreted
– Hypersecretion
• Too much hormone is secreted
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Table 6-1, p. 215 Copyright © 2022 by Cengage Canada 21
Hyposecretion
• Primary hyposecretion
– Too little hormone is secreted due to abnormality
within gland
– Causes may be genetic, dietary, chemical/toxic,
immunologic, disease processes such as cancer,
iatrogenic, or idiopathic
• Secondary hyposecretion
– Gland is normal but too little hormone is secreted
due to deficiency of its tropic hormone
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Hypersecretion
• Causes: tumours that ignore normal
regulatory input and continuously secrete
excess hormone; immunologic factors
• Primary hypersecretion
– Too much hormone is secreted due to
abnormality within gland
• Secondary hypersecretion
– Excessive stimulation from outside gland causes
oversecretion
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Abnormal Target-Cell
Responsiveness
• Dysfunction can occur because target cells do
not respond adequately to the hormone.
• This can be caused by a lack of receptors for
the hormone or the lack of an enzyme
essential for carrying out the response.
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Target Cells
• The target-cell receptors for a particular
hormone can be deliberately altered as a
result of physiological control mechanisms.
• The response to a given plasma concentration
of hormone can be fine-tuned by varying the
number of receptors available for hormone
binding.
• The number of receptors in a target cell does
not remain constant.
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Down Regulation
• When the plasma concentration of insulin is
chronically elevated, the total number of
target-cell receptors for insulin is reduced as a
direct result of the effect an elevated level of
insulin has on the insulin receptors.
– Known as down regulation
– Locally acting negative-feedback mechanism that
prevents target cells from overreacting to high
concentration of insulin
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PRINCIPLES OF
HORMONAL
COMMUNICATION
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Hydrophilic and Lipophilic
• Hydrophilic hormones are highly water
soluble and have low lipid solubility.
– Insulin
• Lipophilic hormones have high lipid solubility
and are poorly soluble in water.
– Thyroid hormone
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Table 6-2, p. 217 Copyright © 2022 by Cengage Canada 29
Comparison of Two Steroid Hormones,
Testosterone and Estradiol
Figure 6-4, p. 217 Copyright © 2022 by Cengage Canada 30
The Mechanisms of Synthesis,
Storage, and Secretion
• Hydrophilic peptide hormones are synthesized
and secreted by the same steps used for other
proteins.
• Lipophilic steroid hormones are formed from
the precursor cholesterol.
• All are carried by the blood, but not all are
transported in the same manner.
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The Mechanisms of Synthesis,
Storage, and Secretion (cont’d)
• The hydrophilic peptide hormones are
transported simply dissolved in the plasma.
• Lipophilic steroids and thyroid hormones
mostly circulate in the blood, bound to plasma
proteins.
• Only the small, unbound, freely dissolved
fraction of a lipophilic hormone is biologically
active.
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The Mechanisms of Synthesis,
Storage, and Secretion (cont’d)
• Catecholamines are unusual in that only about
50 percent of these hydrophilic hormones
circulate as free hormone.
– The other 50 percent are loosely bound to the
plasma protein albumin.
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Hormones and Intracellular
Proteins
• Hormones must bind with target-cell
receptors specific to them.
• Each interaction produces a highly
characteristic response.
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Location of Receptors for Hydrophilic
and Lipophilic Hormones
• Hormones can be grouped into two
categories:
– Hydrophilic peptides and catecholamines bind
with specific receptors located on the outer
plasma membrane surface of the target cells
(poorly soluble in lipid).
– Lipophilic steroids and thyroid hormones bind
with receptors inside of the target cells (easily
pass through lipids).
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General Means of Hydrophilic and
Lipophilic Hormone Action
• A few hydrophilic hormones, upon binding
with a target cell’s surface receptors, change
the cell’s permeability.
• Most surface-binding hydrophilic hormones
function by activating second-messenger
systems.
• All lipophilic hormones function mainly by
activating specific genes in a target cell.
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Hydrophilic Hormones Target
Proteins
• Bind to surface membrane receptors, produce
effects through a second-messenger system
• Two major second-messenger pathways
– cAMP (cyclic adenosine monophosphate)
– Calcium
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Mechanism of
Action of
Hydrophilic
Hormones via
Activation of the
Cyclic AMP
Second-Messenger
System
Figure 6-5, p. 220 Copyright © 2022 by Cengage Canada 38
Mechanism of
Action of
Hydrophilic
Hormones via
Concurrent
Activation of the
Ca2+ Second-
Messenger
Pathway and the
DAG Pathway
Figure 6-6, p. 221
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39
Amplification of the Initial Signal by a
Second-Messenger Pathway
Figure 6-7, p. 222 Copyright © 2022 by Cengage Canada 40
Activation of Genes by Lipophilic
Hormones
Figure 6-8, p. 223 Copyright © 2022 by Cengage Canada 41
Hormonal Responses versus Neural
Responses
• Compared with neural responses, which are
brought about within milliseconds, hormone
action is relatively slow and prolonged.
• Hormonal responses persist for a period of
time after the hormone is no longer bound to
its receptor.
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THE ENDOCRINE
TISSUES
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Table 6-3, p. 225 Copyright © 2022 by Cengage Canada 44
Table 6-3 (cont’d), p. 225 Copyright © 2022 by Cengage Canada 45
Table 6-3 (cont’d), p. 225 Copyright © 2022 by Cengage Canada 46
Table 6-3 (cont’d), p. 225 Copyright © 2022 by Cengage Canada 47
HYPOTHALAMAUS
AND PITUITARY
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The Anterior and Posterior Glands
• Pituitary has two anatomically and
functionally distinct lobes
– Posterior pituitary gland
• Nervous tissue (neurohypothysis)
– Anterior pituitary gland
• Glandular epithelial tissue (adenohypophysis)
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Hypothalamus and Pituitary
• The pituitary is a small gland located at the
base of the brain.
• Connected to hypothalamus by a thin
connecting stalk
• Pituitary gland consists of two anatomical and
functionally distinct lobes
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Anatomy of the Pituitary Gland
Figure 6-9, p. 227 Copyright © 2022 by Cengage Canada 51
Hypothalamus and Pituitary
(cont’d)
• Anterior pituitary is composed of glandular
epithelial tissue and is called adenohypophysis
• Posterior pituitary is composed of nervous
tissue and is called neurohypophysis
• Anterior and posterior glands’ release of
hormones from both anterior and posterior
pituitary is controlled by hypothalamus
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The Hypothalamus and Posterior
Pituitary
• Along with hypothalamus, forms
neuroendocrine system
– Does not actually produce any hormones
• Stores and releases two small peptide
hormones
– Vasopressin
• Conserves water during urine formation
– Oxytocin
• Stimulates uterine contraction during childbirth and
milk ejection during breastfeeding
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Relationship of
the Hypothalamus
and Posterior
Pituitary
Figure 6-10, p. 228 Copyright © 2022 by Cengage Canada 54
Anterior Pituitary Hormones:
Mostly Tropic
• Anterior pituitary hormones are mostly tropic.
• Secretes six different peptide hormones that it
produces itself
– Tropic hormones
• Thyroid-stimulating hormone (TSH)
– Stimulates secretion of thyroid hormone
• Adrenocorticotropic hormone (ACTH)
– Stimulates secretion of cortisol by adrenal cortex
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Anterior Pituitary Hormones:
Mostly Tropic (cont’d)
– Tropic hormones (cont’d)
• Follicle-stimulating hormone (FSH)
– In females, stimulates growth and development of ovarian
follicles; promotes secretion of estrogen by ovaries
– In males, required for sperm production
• Luteinizing hormone (LH)
– In females, responsible for ovulation and luteinization;
regulates ovarian secretion of female sex hormones
– In males, stimulates testosterone secretion
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Anterior Pituitary Hormones:
Mostly Tropic (cont’d)
– Growth hormone (GH)
– Primary hormone responsible for regulating overall body
growth; important in intermediary metabolism
– Not a tropic hormone
• Prolactin (PRL)
– Enhances breast development and milk production in females
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Functions of
the Anterior
Pituitary
Hormones
Figure 6-11, p. 230 58
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Hypothalamic Releasing and
Inhibiting Hormones
• Hypothalamic releasing and inhibiting
hormones help regulate anterior pituitary
hormone secretion.
• Two most important factors that regulate
anterior pituitary hormone secretion
– Hypothalamic hormones
– Feedback by target-gland hormones
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Role of the Hypothalamic
Releasing and Inhibiting Hormones
• Secretion of each anterior pituitary hormone
is stimulated or inhibited by one or more
hypothalamic hypophysiotropic hormones.
– Releasing hormones
– Inhibiting hormones
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Table 6-4, p. 231 Copyright © 2022 by Cengage Canada 61
Role of the Hypothalamic-
Hypophyseal Portal System
• A portal system is a vascular arrangement in
which blood flows from one capillary bed
through a connecting vessel to another
capillary bed.
• Critical link between brain and much of
endocrine system
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Control of Hypothalamic Releasing
and Inhibiting Hormones
• Receive abundant input of information from
brain
• Hypophysiotropic neurons controlled by
various chemical inputs that reach
hypothalamus
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Vascular Link between the Hypothalamus
and Anterior Pituitary
Figure 6-13, p. 233 Copyright © 2022 by Cengage Canada 64
ENDOCRINE
CONTROL OF
GROWTH
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Growth Hormone
• Growth depends on growth hormone but is
influenced by other factors
– Genetic determination of an individual’s
maximum growth capacity
– An adequate diet
– Freedom from chronic disease and stressful
environmental conditions
– Normal levels of growth-influencing hormones
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Growth Hormone (cont’d)
• Not continuous
• Factors responsible for promoting growth are
not the same throughout growth period
• Fetal growth
– Promoted largely by hormones from placenta
– GH plays no role in fetal development
– Postnatal growth spurt
• Displayed during first two years of life
– Pubertal growth spurt
• Occurs during adolescence
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Normal Growth Curve
Figure 6-14, p. 234 Copyright © 2022 by Cengage Canada 68
Metabolic Actions of GH Unrelated
to Growth
• Specific metabolic effects of growth hormone
are
– increased rate of protein synthesis
– increased fatty acid mobilization
– decreased rate of glucose/glycogen use
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Growth-Promoting Actions of GH
on Soft Tissues
• Increasing the number of cells (hyperplasia)
• Increasing the size of cells (hypertrophy)
• Also increases the number of cells by
stimulating cell division and preventing
apoptosis
– Programmed cell death
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Somatomedins
• Exerts metabolic effects not related to growth
– Referred to as insulin-like growth factors (IGF)
– Increase fatty acid levels in blood by enhancing
breakdown of triglyceride fat stored in adipose
tissue
– Increase blood glucose levels by decreasing
glucose uptake by muscles
– Two somatomedins—IGF-I (IGF-1) and IGF-II (IGF-
2)—have been identified.
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IGF-I
• IGF-I synthesis is stimulated by GH and
mediates much of this hormone’s growth-
promoting actions.
• The concentration of IGF-I in the blood
plasma normally mimics the rate of secretion
of GH.
• The association with IGF-I allows the effects of
GH to be more prolonged.
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IGF-II
• Production of IGF-II is not influenced by GH.
• IGF-II is primarily important during fetal
development.
• Although IGF-II continues to be produced
during adulthood, its role in adults remains
unclear.
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Basic Physiological Actions of GH
The following are the basic physiological actions of
GH—accomplished either directly or through
somatomedins (IGFs):
•Decreased glycogen synthesis
•Reduced glucose use
•Increased lipolysis (breakdown of stored fat)
•Increased use of fatty acids
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Basic Physiological Actions of GH
(cont’d)
• Metabolic sparing of glucose and amino acids
• Increased amino acid transport across cell
membrane
• Increased protein synthesis
• Increased collagen synthesis
• Increased cartilage growth
• Promotion of hypertrophy and hyperplasia of
tissues
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Secretion: Growth Hormone-
Releasing Hormone and Growth
Hormone-Inhibiting Hormone
• Two antagonistic regulatory hormones
involved in controlling growth hormone
secretion
– Stimulatory (GHRH)
– Inhibiting (GHIH)
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Factors That Influence GH
Secretion
• Diurnal rhythm
• Response to exercise
• Stress
• Low blood glucose
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Control of
Growth
Hormone
Secretion
Figure 6-16, p. 240 78
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Growth Hormone Deficiency
• Due to pituitary defect or hypothalamic
dysfunction
• Hyposecretion of GH in child is one cause of
dwarfism
• Deficiency in adults produces relatively few
symptoms
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Growth Hormone Excess
• Most often caused by tumor of GH-producing
cells of anterior pituitary
• Symptoms depend on age of individual when
abnormal secretion begins
– Gigantism is caused by overproduction of GH in
childhood before the epiphyseal plates close.
– Acromegaly occurs when GH hypersecretion
occurs after adolescence.
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Examples of the Effect of Abnormalities in
Growth Hormone Secretion on Growth
Figure 6-17, p. 241 Copyright © 2022 by Cengage Canada 81
Progressive Development of Acromegaly
Figure 6-18, p. 241 Copyright © 2022 by Cengage Canada 82
Other Hormones
• Other hormones besides growth hormone are
essential for normal growth:
– Thyroid hormone
• Growth severely stunted in hypothyroid children
• Hypersecretion does not cause excessive growth.
– Insulin
• Deficiency often blocks growth
• Hyperinsulinism often spurs excessive growth.
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Other Hormones (cont’d)
– Androgens
• Play role in pubertal growth spurt, stimulate protein
synthesis in many organs
• Effects depend on presence of GH
– Estrogens
• Effects on growth prior to bone maturation not well
understood
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