BIOS5130 –

HUMAN
PHYSIOLOGY AND
DISEASE 2
Week 9 Lecture Part 1 –
welcome and endocrine
system introduction.
Dr Emma Hargreaves

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 SUBJECT SPECIFIC LEARNING
OUTCOMES
• Describe the structural organization and function of specific physiological systems of
the body
• Understand how the body systems act in an integrated manner to maintain
homeostasis.
• Describe how malfunction of physiological systems gives rise to disease, using specific
examples.
• Appreciate the relationship between physiology, anatomy and medicine

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 MODULE CONVENOR
Module Convenor : Dr Emma Hargreaves ([email protected])

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 MODULE TEACHERS

Prof John Dickenson ([email protected])

Prof Darren Griffin ([email protected])

Dr Peter Ellis ([email protected])

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 WEEKLY STRUCTURE
Lecture learning topics
• Week 9 - Endocrinology, Dr Emma Hargreaves
• Week 10-14 Nervous System, Dr Emma Hargreaves
• Week 16-17 Muscles, Prof John Dickinson
• Week 18-19 Reproduction, Prof Darren Griffin
• Week 20 Reproduction, Dr Peter Ellis
Workshops
• Week 12 OR 13, problem solving practice, Dr Emma Hargreaves. Split into groups as per your
timetable – check your group now and plan for it – it is compulsory and you CANNOT change
groups
Assessments
• Problem solving test. To be provided in the timetabled slot Week 16 and submitted via Moodle
• Exam (2 hour)
Feedback
• Week 18, feedback on problem solving assessment, Dr Emma Hargreaves
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 TEXTBOOK

Human physiology : an integrated

approach
ISBN: 
9781292259628
Personal Author: 
Silverthorn, Dee Unglaub, 1948- author.
Edition: 
Eighth, global edition.

Strongly advise you to buy a copy if you can

and you don’t have it already from BIOS3070
Physical copies in the library
15 e-copies available via the library through
this link

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 ENDOCRINOLOGY

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 ENDOCRINOLOGY - summary

Chapter 7 Silverthorn

• Hormones and their classification

• Endocrine Organs
• Hormone release: Simple and complex endocrine
reflex pathways
• Endocrine Disorders

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 WHAT IS A HORMONE?
• A chemical secreted into the bloodstream for transport to a distant
tissue
• All hormones bind to target cell receptors which may be:
Membrane bound; cytosol; nucleus
• Initiates a response in the target cell type. Some examples how
hormones can alter target activity are:
 altering rate of enzyme reactions
 regulating transport across the cell membrane
 regulating gene expression
• Alters cell activity at very low concentrations (nanomolar 10-9 or
picomolar 10-12)

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 HORMONES PART 1
Source Hormone Chemical Target/Effect
Class
Pineal gland Melatonin Amine Circadian rhythm
Hypothalamus Various releasing and inhibiting Peptide Regulate hormone release from
hormones: PRH and PIH; TRH; CRH; anterior pituitary
GHRH and GHIH; GnRH
Posterior pituitary Oxytocin Peptide Breast milk ejection, uterine
contractions
Vasopressin Kidney- water balance
(Antidiuretic hormone)
Anterior pituitary Prolactin Peptide Milk production
Growth hormone (GH) Growth/metabolism
Corticotropin (ACTH) Cortisol release
Thyrotropin (TSH) Thyroid hormone release
Follicle stimulating hormone (FSH) Egg/sperm production; sex
Luteinizing hormone (LH) hormone production
Thyroid Triiodothyronine, thyroxine Amine Metabolism, growth,
development
Calcitonin Peptide Plasma calcium levels

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 HORMONES PART 2
Source Hormone Chemical Class Target/Effect

Parathyroid Parathyroid hormone Peptide Plasma calcium levels

Thymus Thymosin, thymopoietin Peptide Lymphocyte development
Heart Atrial natriuretic peptide Peptide Kidney- increases sodium
excretion
Liver Angiotensinogen Peptide Regulates aldosterone secretion,
blood pressure
Insulin-like growth factors Growth
Stomach/Small Intestine Gastrin, cholecystokinin, secretin Peptide Digestion and absorption

Pancreas Insulin, glucagon, somatostatin, Peptide Metabolism of glucose and other

pancreatic polypeptide nutrients
Adrenal cortex Cortisol Steroid Stress response
Aldosterone Electrolyte balance
Androgens Sex hormones
Adrenal medulla Adrenaline Amine Fight-or-flight responses
Kidney Erythropoietin Peptide Red blood cell production
1,25 dihydroxy-vitamin D3 (Calcitriol) Steroid Increases calcium absorption by
intestine
Skin Vitamin D3 Steroid Precursor of calcitriol
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 HORMONES PART 3
Source Hormone Chemic Target/Effect
al Class
Testes Androgen Steroid Sperm production,
secondary sex
characteristics
Inhibin Peptide FSH secretion
Ovaries Estrogens and Steroid Egg production,
progesterone secondary sex
characteristics
Peptide FSH secretion
Inhibin Uterine muscle
Relaxin (pregnancy) relaxation
Adipose tissue Leptin Peptide Food intake,
metabolism

(There is a similar table in Silverthorn Ch 7.)

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 HORMONE INTERACTIONS

• Synergistic: the combined effect of two or more hormones is greater than the sum of their
individual effects e.g. glucagon, cortisol and adrenaline in blood glucose regulation

• Permissive: one hormone requires another in order fully to exert its effect. e.g. thyroid hormone
required for maturation of the reproductive system in presence of gonadotropins/sex hormones,
even though thyroid hormone cannot stimulate maturation of the reproductive system itself.

• Antagonistic: two or more hormones have opposing effects on a physiological response e.g.
glucagon and insulin in blood glucose regulation

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 CLASSIFICATION OF HORMONES

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 PEPTIDE HORMONE PRODUCTION

from Human Physiology, Silverthorn

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 PEPTIDE HORMONE PRODUCTION –
POST-TRANSLATIONAL PROCESSING

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 PEPTIDE HORMONE ACTION VIA RECEPTORS
Receptor enzymes G-protein coupled receptors
GPCR
Receptor
Effector
Tyrosine
G-protein
kinase domain

• Receptor tyrosine kinases

Second
have intrinsic kinase activity messenger

• Tyrosine kinase linked (Phosphorylation)

receptors lack intrinsic kinase Changes to open-close state of ion channels; modification
to existing proteins, synthesis of new proteins
activity and activate cytosolic
kinases Cellular response
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 STEROID HORMONE STRUCTURE
Aldosterone
Testosterone
Cortisol Estradiol

Cholesterol:
the parent compound for
from Human Physiology, Widmaier, Raff, Strang all steroid hormones
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 STEROID HORMONE ACTION VIA RECEPTORS

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from Human Physiology, Silverthorn
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 AMINE HORMONE STRUCTURE

G-protein coupled Nuclear

receptors receptors

from Human Physiology, Silverthorn

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from Human Physiology, Silverthorn
 HORMONES MEDIATE LONG-DISTANCE
COMMUNICATION
(Example shown is a peptide hormone)

Hormones: secreted by
endocrine glands or cells into
the blood

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from Human Physiology, Silverthorn
 REGULATION OF HORMONE RELEASE
•Reflex control pathways with feedback loops

• Many, but not all, involve the nervous system

1.Simple reflexes:

- one cell senses the stimulus and secretes hormone e.g. parathyroid hormone

- multiple stimuli regulate secretion of one hormone e.g. insulin

2.Complex reflexes: multiple hormones acting in a hierarchy / multiple integrating

centres e.g. hypothalamic-pituitary hormones

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 SIMPLE ENDOCRINE REFLEX – PARATHYROID
HORMONE

• One cell
• One stimulus
• Response provides
negative feedback

23 www.kent.ac.uk from Human Physiology, Silverthorn

 ANOTHER (SLIGHTLY LESS) SIMPLE ENDOCRINE REFLEX:
MULTIPLE STIMULI FOR RELEASE OF A SINGLE HORMONE

Insulin release controlled by:

• Blood glucose
• Food intake/neural control
• Intestinal peptides
•Response provides negative feedback

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from Human Physiology, Silverthorn
 COMPLEX ENDOCRINE REFLEXES:
HYPOTHALAMIC-PITUITARY PATHWAY

diagram from Human Physiology, Silverthorn

• Anterior pituitary (adenohypophysis): true endocrine gland of epithelial origin

• Posterior pituitary (neurohypophysis): extension of neural tissue connected to
the hypothalamus by the infundibulum
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 POSTERIOR PITUITARY

Secretes two hormones:

1. Oxytocin

2. Vasopressin
(Antidiuretic hormone)

These are synthesized in

the hypothalamus and
transported to the posterior
pituitary for storage and
release

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from Human Physiology, Silverthorn
 HYPOTHALAMIC NEUROHORMONES CONTROL
HORMONE RELEASE FROM ANTERIOR PITUITARY
TRH: thyrotropin-releasing hormone

CRH: corticotropin-releasing hormone

GHRH: growth hormone-releasing hormone

GHIH: growth hormone-inhibiting hormone

GnRH: gonadotropin-releasing hormone

PRH: prolactin-releasing hormone

PIH: prolactin-inhibiting hormone

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from Human Physiology, Silverthorn
 HYPOTHALAMIC – ANTERIOR PITUITARY PATHWAY

• Many control the secretions of another endocrine gland and hence are referred
to as trophic hormones
• Roger Guillemin, Andrew Schally, Rosalyn Yalow - Nobel prize in Physiology or
Medicine 1977 for isolation and analysis of peptide neurohormones.
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diagram from Human Physiology, Silverthorn
 HYPOTHALAMIC-ANTERIOR PITUITARY
PATHWAY: NEGATIVE FEEDBACK LOOPS

• Hormones act as negative feedback signals

from Human Physiology, Silverthorn

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 COMPARING SIMPLE AND COMPLEX ENDOCRINE
PATHWAYS

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from Human Physiology, Silverthorn
 ENDOCRINE DISORDERS
Three basic causes:
• Hormone excess leading to exaggerated response. Due to hypersecretion e.g. as a consequence of
endocrine gland tumours or other causes
 Gigantism, acromegaly: pituitary adenoma
 Grave’s disease: enlarged thyroid (goiter) due to production of thyroid- stimulating
immunoglobulins
• Hormone deficiency leading to reduced response
 Due to hyposecretion e.g. as a consequence of atrophy of glands, genetic defects
 Pituitary dwarfism: loss of growth hormone
 Addison’s disease: tuberculosis or autoimmune atrophy of adrenal cortex
 Hashimoto’s disease: autoimmune destruction of thyroid gland tissue
• Defects in hormone receptors or associated intracellular signalling pathways leading to altered
responsiveness to hormone.
 Pseudohypoparathyroidism: mutations in G-protein coupled receptor
 Hyperinsulinemia: downregulation of receptors due to sustained high insulin levels

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 GROWTH HORMONE DISORDERS

GH excess: acromegaly & pituitary gigantism

Medicine 20: 133-141 (1956)
GH deficiency: pituitary dwarfism (not shown)
from American Journal of

from New England Journal of Medicine 340: 524 (1999)

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 DIAGNOSIS OF ENDOCRINE DISORDERS

• Generally straightforward in simple endocrine reflexes involving only one gland,

e.g. parathyroid

• More difficult in complex endocrine reflexes, e.g. hypothalamic-pituitary system

• Requires knowledge of feedback loops

• Primary disorders: problem in last endocrine tissue in a reflex pathway

• Secondary disorders: problem in endocrine tissues producing trophic hormones
i.e. pituitary, hypothalamus

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 CUSHING’S SYNDROME POTENTIAL PATHOLOGIES

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 LEARNING OUTCOMES
Hormones and their classification
• Define a hormone and outline the source and functions of the major hormones of the body
• Describe, with specific examples, and in a comparative manner, the three major classes of hormone
(peptide, steroid, amine) including their synthesis, release and mechanisms of action.

Control of hormone release

• Discuss, using examples, how hormone release is regulated, considering simple and complex endocrine
reflexes and their feedback loops
• Describe the role of the hypothalamus and pituitary gland in endocrine control
– Hormones secreted by hypothalamus and pituitary
– Distinction between posterior and anterior pituitary
– Hypothalamic-anterior pituitary pathway

Endocrine Disorders
• Overview the primary causes of endocrine disorders using specific examples. Consider extra reading on
details of a few specific disorders (Moodle Book)
• Understand how knowledge of negative feedback loops in endocrine pathways aids diagnosis of complex
endocrine disorders Reading: Chapter 7 Human Physiology, Silverthorn
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 HAVE A 10 MINUTE COMFORT BREAK

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WHERE IS YOUR THYROID?

www.kent.ac.uk Slide 37
 THYROID HORMONES
• Thyroid gland makes thyroid hormone
• Thyroid hormone helps to control metabolism
• Hypothalamus - thyrotropin-releasing hormone (TRH)
• Anterior pituitary gland stimulated by TRH release
thyroid-stimulating hormone (TSH).
• TSH is released into the blood and binds to the
thyroid-releasing hormone receptor (TSH-R) in
thyroid
• Stimulates synthesis of thyroid hormones T3 and T4

www.kent.ac.uk Slide 38
 GRAVES DISEASE

• Over activity of the thyroid gland – Named after Dr

Graves
• Autoimmune antibodies stimulate over production of
thyroid hormone
• Can also be termed thyrotoxicosis or
hyperthyroidism
• Thyroid gland may become large and swollen (‘a
goitre’).
• Most common in young women Girgis, Christian & Champion, Bernard & Wall, Jack.
(2011). Current Concepts in Graves' Disease. Therapeutic
advances in endocrinology and metabolism. 2. 135-44.
10.1177/2042018811408488.

www.kent.ac.uk Slide 39
SYMPTOMS OF GRAVES DISEASE

• Irritability and ‘swings’ in emotion; nervousness or anxiety

• Weight loss in spite of a good appetite
• Palpitations (fast or irregular heart beat)
• Sweating and feeling hot
• Shaking or tremor
• Poor sleep
• Muscle weakness, with difficulty getting out of a chair or climbing stairs
• Frequent bowel movements
• In women who are having periods, these may become light and scanty or stop altogether.

Graves disease - Brighton and Sussex University Hospitals NHS Trust (bsuh.n
hs.uk)
www.kent.ac.uk Slide 40
RUNNING PROBLEM – GRAVES DISEASE

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Q1 AND Q2 RUNNING PROBLEM

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 Q3 AND Q4 RUNNING PROBLEM

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 Q5 RUNNING PROBLEM

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 Q6 RUNNING PROBLEM

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 RUNNING PROBLEM Q7 AND Q8

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