Lecture 17

Lecture 17
Principles of
Endocrinology: The Central
Endocrine Glands
Copyright © 2022 by Cengage Canada 1

Contents
• General Principles of Endocrinology
• Principles of Hormonal Communication
• The Endocrine Tissues
• Hypothalamus and Pituitary
• Endocrine Control of Growth

GENERAL PRINCIPLES
OF ENDOCRINOLOGY

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.

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

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.

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.

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

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.

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.

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

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

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

Negative-Feedback Control

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)

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

Diurnal Rhythm of Cortisol Secretion

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

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

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

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

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.

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.
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

PRINCIPLES OF
HORMONAL
COMMUNICATION

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

Comparison of Two Steroid Hormones,
Testosterone and Estradiol

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.

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.
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.

Hormones and Intracellular
Proteins
• Hormones must bind with target-cell
receptors specific to them.
• Each interaction produces a highly
characteristic response.

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).
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.

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

Mechanism of
Action of
Hydrophilic
Hormones via
Activation of the
Cyclic AMP
Second-Messenger
System

Mechanism of
Action of
Hydrophilic
Hormones via
Concurrent
Activation of the
Ca2+ Second-
Messenger
Pathway and the
DAG Pathway
Figure 6-6, p. 221

Copyright © 2022 by Cengage Canada
39
Amplification of the Initial Signal by a
Second-Messenger Pathway

Activation of Genes by Lipophilic
Hormones

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.

THE ENDOCRINE
TISSUES

Table 6-3 (cont’d), p. 225 Copyright © 2022 by Cengage Canada 45
HYPOTHALAMAUS
AND PITUITARY

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)

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

Anatomy of the Pituitary Gland

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

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
Relationship of
the Hypothalamus
and Posterior
Pituitary

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

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

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

Functions of
the Anterior
Pituitary
Hormones
Figure 6-11, p. 230 58

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

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

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

Control of Hypothalamic Releasing
and Inhibiting Hormones
• Receive abundant input of information from
brain
• Hypophysiotropic neurons controlled by
various chemical inputs that reach
hypothalamus

Vascular Link between the Hypothalamus
and Anterior Pituitary

ENDOCRINE
CONTROL OF
GROWTH

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

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
Normal Growth Curve

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

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

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.

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.

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.

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

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
Secretion: Growth Hormone-
Releasing Hormone and Growth
Hormone-Inhibiting Hormone
• Two antagonistic regulatory hormones
involved in controlling growth hormone
secretion
– Stimulatory (GHRH)
– Inhibiting (GHIH)

Factors That Influence GH
Secretion
• Diurnal rhythm
• Response to exercise
• Stress
• Low blood glucose

Control of
Growth
Hormone
Secretion
Figure 6-16, p. 240 78

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

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.

Examples of the Effect of Abnormalities in
Growth Hormone Secretion on Growth

Progressive Development of Acromegaly

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.

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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