Power Point Week #11

Chapter 18
Mechanisms of
Hormonal Regulation
Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved.
The Endocrine System
 Functions:
 Differentiation of reproductive system and CNS in
fetus
 Stimulation of growth and development
 Coordination of the male and female reproductive
systems
 Maintenance of internal environment
 Adaptation to emergency demands of body
Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. 2
The Endocrine System (Cont.)
From Applegate, E. (2011). The anatomy and physiology learning system (4th ed.). St Louis, MO:
Saunders.
Hormones
 General characteristics:
 Specific rates and rhythms of secretion
• Diurnal, pulsatile, and cyclic and patterns that depend on
circulating substances
 Operate within feedback systems
 Affect only target cells with appropriate receptors
 Excreted by kidneys or deactivated by liver or cellular
mechanisms
Regulation of Hormone Release
 Hormones are released:
 In response to an alteration in the cellular
environment
 To maintain a regulated level of certain substances or
other hormones
 Hormones are regulated by chemical, hormonal,
or neural factors
 Negative feedback
Feedback Loops
Hormone Transport and Action
 Hormones are released into the circulatory
system by endocrine glands
 Target cell
 Upregulation
 Downregulation
 Hormone effects:
• Direct effects
• Permissive effects
Mechanism of Hormone Action
 Water-soluble hormones circulate in free,
unbound forms
 Short-acting response
 Bind to surface receptors
 Lipid-soluble hormones are primarily circulating
bound to a carrier
 Rapid and long-lasting response
 Diffuse freely across the plasma and nuclear
membranes and bind with cytosolic or nuclear
receptors
Mechanism of
Hormone Action (Cont.)
Mechanism of
 Hormone receptors
 Located in the plasma membrane or in the
intracellular compartment of the target cell
Mechanism of
 Water-soluble  Lipid-soluble
hormones hormones
 High molecular weight  Easily diffuse across
 Cannot diffuse across the plasma membrane
the plasma membrane and bind to cytosolic or
nuclear receptors
Mechanism of
 Water-soluble hormones
 First messenger:
• Hormone
• Signal transduction
 Second messenger molecules:
• Calcium
• Cyclic adenosine monophosphate (cAMP)
• Cyclic guanosine monophosphate (cGMP)
• Tyrosine kinase system
• Inositol triphosphate (IP3)
Mechanism of
 Lipid-soluble hormones
 Steroid hormones
Lipid-Soluble Hormones
 Steroid hormone mechanism
From Patton, K.T., & Thibodeau, G.A. (2016). Anatomy & physiology (9th ed.). St Louis, MO:
Mosby.
Structure and Function
of the Endocrine Glands
 Hypothalamic-pituitary axis
 Hypothalamus
Pituitary Gland
Anterior pituitary Posterior pituitary

 Pars distalis  Median eminence
 Pars tuberalis  Pituitary stalk
 Pars intermedia  Pars nervosa
 Secretes tropic hormones
Pituitary Gland (Cont.)
From Herlihy, B. (2015). The human body in health and illness (5th ed.). St Louis, MO:
Saunders.
Anterior Pituitary
 Adrenocorticotropic hormone (ACTH)
 Melanocyte-stimulating hormone (MSH)
 Somatotropic hormones
 Growth hormone
 Prolactin
 Glycoprotein hormones
 Follicle-stimulating hormone
 Luteinizing hormone
 Thyroid-stimulating hormone
Anterior Pituitary (Cont.)
 Luteinizing hormone
 β-lipotropin
 β-endorphins
Anterior Pituitary (Cont.)
 Hypophysial portal system
From Hall, J.E. (2016). Guyton and Hall textbook of medical physiology (13th
ed.). Philadelphia, PA: Saunders.
Posterior Pituitary Hormones
 Synthesized with their binding proteins in the
supraoptic and paraventricular nuclei of the
hypothalamus
 Secreted by the posterior pituitary
 Antidiuretic hormone (ADH)
• Controls plasma osmolality
 Oxytocin
• Uterine contractions and milk ejection in lactating women
Pineal Gland
 Located near centre of brain
 Secretes melatonin
 Regulates circadian rhythms and reproductive
systems
 Role in onset of puberty
Thyroid and Parathyroid Glands
 Thyroid gland
 Two lobes lie on either side of the trachea
 Isthmus
 Follicles (follicle cells surrounding colloid)
 Parafollicular cells (C cells)
• Secrete calcitonin
 Regulation of thyroid hormone secretion
• Thyrotropin-releasing hormone and thyroid-stimulating
hormone
Thyroid and Parathyroid
Glands (Cont.)
 Thyroid hormone
 Secreted in response to TSH
 90% T4 and 10% T3
• Most T4 then converted to T3
 Bound to thyroxine-binding globulin, thyroxine-binding
prealbumin, albumin, or lipoproteins
 Affects growth and maturation of tissues, cell
metabolism, heat production, and oxygen
consumption
Glands (Cont.)
 Parathyroid glands
 Small glands located behind the upper and lower
poles of the thyroid gland
 Produce parathyroid hormone (PTH)
• Increases serum calcium and decreases serum phosphate
• Antagonist of calcitonin (thus increases bone resorption and
serum calcium)
• Vitamin D (cofactor) needed for PTH function
Glands (Cont.)
From Fehrenbach MJ, et al. (2012). Illustrated anatomy of the head and neck (4th
ed.), St Louis, MO, Saunders.
Glands (Cont.)
 Thyroid follicle cells
1. Which is TRUE regarding thyroid hormone and
thyroid-stimulating hormone (TSH)?
A. TSH secretion is controlled by positive feedback.

B. TSH is secreted in excess when stimulated by T4.
C. TSH secretion is regulated by thyrotropin-releasing
hormone.
D. Decreased anterior pituitary release of TSH
stimulates thyroid hormone secretion.
Endocrine Pancreas
 Pancreas is both an endocrine and an exocrine
gland
 Houses the islets of Langerhans
 Secretion of glucagon and insulin
 Cells:
• Alpha—glucagon
• Beta—insulin and amylin
• Delta—somatostatin and gastrin
• F cells—pancreatic polypeptide
Endocrine Pancreas (Cont.)
From Patton, K.T., & Thibodeau, G.A. (2016). Structure & function of the body (15th ed.). St Louis, MO: Mosby.
 Insulin
 Synthesized from proinsulin
 Secretion is promoted by increased blood levels of glucose,
amino acids, GI hormones
 Facilitates the rate of glucose uptake into the cells of the body
 Anabolic hormone
• Synthesis of proteins, lipids, and nucleic acids
 Amylin
 Peptide hormone cosecreted with insulin
 Delays nutrient uptake
 Suppresses glucagon secretion
 Insulin action on cells
Redrawn from Levy, M.N., et al. (Eds.). (2006). Berne & Levy principles of physiology (4th ed.). St Louis, MO:
Mosby.
 Glucagon
 Secretion is promoted by decreased blood glucose
levels
 Stimulates glycogenolysis, gluconeogenesis, and
lipolysis
 Pancreatic somatostatin
 Possible involvement in regulating alpha-cell and
beta-cell secretions
 Gastrin, ghrelin, and pancreatic polypeptides
2. Insulin is secreted by the pancreas from which
type of cell?
A. F
B. Beta
C. Delta
D. Alpha
Adrenal Glands
 Located close to upper pole of each kidney
 Adrenal cortex
 80% of an adrenal gland’s total weight
 Zona glomerulosa
 Zona fasciculata
 Zona reticularis
 Adrenal medulla
 Innervated by the sympathetic nervous systems
Adrenal Glands (Cont.)
From Damjanov, I. (2008). Pathophysiology. Philadelphia, PA:

Saunders. From Kierszenbaum, A. (2002). Histology and cell biology. St Louis,
MO: Mosby.
 Adrenal cortex
 Stimulated by adrenocorticotropic hormone (ACTH)
 Glucocorticoid hormones
• Direct effects on carbohydrate metabolism
• Anti-inflammatory and growth-suppressing effects
• Most potent naturally occurring glucocorticoid is cortisol
 Mineralocorticoid hormones
• Affect ion transport by epithelial cells
 Increase the activity of the sodium pump of the epithelial cells
 Cause sodium retention and potassium and hydrogen loss
• Most potent naturally occurring mineralocorticoid is
aldosterone
 Regulated by the renin-angiotensin system
 Adrenal estrogens and androgens
• Estrogen secretion by the adrenal cortex is minimal
• Adrenal cortex secretes weak androgens
 Androgens are converted by peripheral tissues to stronger
androgens such as testosterone
 Adrenal medulla
 Chromaffin cells (pheochromocytes)
• Secrete the catecholamines epinephrine (majority) and
norepinephrine
 Release of catecholamines has been characterized
as a “fight or flight” response
 Catecholamines promote hyperglycemia
Aldosterone
Aging and the Endocrine System
 Organ atrophy and weight loss with vascular
changes
 Decreased secretion and clearance of hormones
 Variable change in receptor binding and
intracellular responses
Case Study:
Discussion Questions
A 24-year-old mother visits her obstetrician’s office 1 week
after delivering her baby. She is having trouble with
breastfeeding and milk expression. The obstetrician
prescribes a nasal spray that will stimulate the posterior
pituitary to release which hormone?
A. Oxytocin
B. Prolactin
C. Calcitonin
D. Incretin
Case Study:
Discussion Questions (Cont.)
As the young mother is walking to her car, she
becomes aware that someone is following her. Her
body responds with a “fight or flight” response,
which is regulated by the adrenal medulla’s
secretion of which hormone?
A. Cortisol
B. Catecholamines
C. Glucocorticoids
D. Androgens
Chapter 19
Alterations of Hormonal Regulation
Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved.
Mechanisms of
Hormonal Alterations
 Failure of feedback systems
 Dysfunction of an endocrine gland
 Secretory cells are unable to produce, obtain, or
convert hormone precursors
 Endocrine gland synthesizes or releases
excessive amounts of hormone
Mechanisms of
Hormonal Alterations (Cont.)
 Endocrine gland fails to produce adequate
amounts of hormone
 Increased hormone degradation or inactivation
 Ectopic hormone release
Target Cell Failure
 Cell surface receptor–associated disorders:
 Decrease in number of receptors
 Impaired receptor function
 Presence of antibodies against specific receptors
 Antibodies that mimic hormone action
 Unusual expression of receptor function
 Intracellular disorders:
 Defects in postreceptor signaling cascades
 Inadequate synthesis of second messenger
Alterations of the
Hypothalamic-Pituitary System
Diseases of the
Posterior Pituitary
 Syndrome of inappropriate antidiuretic hormone
secretion (SIADH)
 Hypersecretion of ADH
 For diagnosis, normal adrenal and thyroid function
must exist
 Clinical manifestations are related to enhanced renal
water retention, hyponatremia, and serum hypo-
osmolality
Diseases of the
Posterior Pituitary (Cont.)
 Diabetes insipidus
 Insufficiency of ADH
 Polyuria and polydipsia
 Partial or total inability to concentrate the urine
 Neurogenic
• Insufficient amounts of ADH
 Nephrogenic
• Inadequate response to ADH
 Psychogenic
 Manifestations are related to enhanced water excretion,
hypernatremia, and serum hyperosmolality
Diseases of the Anterior Pituitary
 Hypopituitarism
 Pituitary infarction
• Sheehan’s syndrome
• Hemorrhage
• Shock
 Others:
• Head trauma
• Infections
• Tumours
Diseases of the Anterior
Pituitary (Cont.)
 Panhypopituitarism
• ACTH deficiency
• TSH deficiency
• FSH and LH deficiency
• GH deficiency
Pituitary (Cont.)
 Hyperpituitarism
 Commonly caused by a benign, slow-growing pituitary
adenoma
 Manifestations:
• Headache and fatigue
• Visual changes
• Hyposecretion of neighbouring anterior pituitary hormones
Pituitary (Cont.)
 Hypersecretion of growth hormone (GH)
 Acromegaly
• Hypersecretion of GH during adulthood
 Giantism
• Hypersecretion of GH in children and adolescents
Pituitary (Cont.)
 Hypopituitary dwarfism and pituitary giantism
From Patton, K.T., & Thibodeau, G.A. (2013). Anatomy & physiology (8th ed.). St Louis, MO:
Mosby.
Pituitary (Cont.)
 Hypersecretion of prolactin
 Caused by prolactinomas
• In females, increased levels of prolactin cause amenorrhea,
galactorrhea, hirsutism, and osteopenia
• In males, increased levels of prolactin cause hypogonadism,
erectile dysfunction
Alterations of Thyroid Function
 Hyperthyroidism
 Thyrotoxicosis
 Graves’ disease
• Pretibial myxedema
 Hyperthyroidism resulting from nodular thyroid
disease
• Goitre
 Thyrotoxic crisis (thyroid storm)
Alterations of Thyroid
Function (Cont.)
Thyrotoxicosis (Graves’ Disease)
From Belchetz, P., & Hammond, P. (2003). Mosby’s color atlas and text of
diabetes and endocrinology. Edinburgh: Mosby.
Alterations of Thyroid Function
 Hypothyroidism
 Primary hypothyroidism
• Autoimmune thyroiditis (Hashimoto’s disease)
• Subacute thyroiditis
• Painless thyroiditis
• Postpartum thyroiditis
• Myxedema coma
 Congenital hypothyroidism
Manifestations of
Thyroid Alterations
From Damjanov, I. (2012). Pathology for the health professions (4th ed.). St Louis, MO:
Saunders.
Thyroid Carcinoma
 Most common endocrine malignancy
 Ionizing radiation most common cause
 Treated with thyroidectomy, suppression
therapy, radiation, and chemotherapy
Alterations of
Parathyroid Function
 Hyperparathyroidism
 Primary hyperparathyroidism
• Excess secretion of PTH from one or more parathyroid
glands
 Secondary hyperparathyroidism
• Increase in PTH secondary to chronic hypocalcemia
 Manifestations:
• Hypercalcemia
• Hypophosphatemia
• Hypercalciuria: kidney stones
• Pathological fractures
Alterations of
Parathyroid Function (Cont.)
 Hypoparathyroidism
 Abnormally low PTH levels
 Usually caused by parathyroid damage in thyroid
surgery
 Manifestations:
• Hypocalcemia
 Chvostek’s and Trousseau’s signs
• Hyperphosphatemia
1. Which condition is associated with polyuria and
polydipsia?
A. Diabetes insipidus
B. Hypoparathyroidism
C. Hyperthyroidism
D. Graves’ disease
Type 1 Diabetes Mellitus
 Types:
 Idiopathic type 1
 Autoimmune type 1
 Pancreatic atrophy and specific loss of beta
cells; hyperglycemia when 80 to 90% cells lost
 Macrophages, T-cytotoxic cells, antibodies
 Alterations in insulin, amylin, glucagon
Type 1 Diabetes Mellitus (Cont.)
 Genetic susceptibility
 Environmental factors
 Immunologically mediated destruction of beta cells
 Manifestations:
 Hyperglycemia
 Polydipsia
 Polyuria
 Polyphagia
 Weight loss
 Fatigue
Type 2 Diabetes Mellitus
 Ranges from insulin resistance with relative
insulin deficiency to insulin secretory defect with
insulin resistance
 Caused by genetic-environmental interaction
 Risk factors are age, obesity, hypertension,
physical activity, and family history
 Metabolic syndrome
Type 2 Diabetes Mellitus (Cont.)
 Initial insulin resistance
 Later loss of beta cells
 Manifestations (nonspecific): fatigue, pruritus,
recurrent infections, visual changes, or symptoms of
neuropathy; often overweight, dyslipidemic,
hyperinsulinemic, and hypertensive
Other Types of Diabetes Mellitus
 Maturity onset diabetes of youth (MODY)
 Beta-cell function or insulin action affected by
autosomal dominant mutations
 Gestational diabetes mellitus (GDM)
 Any degree of glucose intolerance with onset or first
recognition during pregnancy
Acute Complications
of Diabetes Mellitus
 Hypoglycemia
 Diabetic ketoacidosis (DKA)
 Hyperosmolar hyperglycemic syndrome (HHS)
Diabetic Ketoacidosis
Chronic Complications
of Diabetes Mellitus
 Microvascular disease
 Diabetic retinopathy
 Diabetic nephropathy
 Diabetic neuropathies
 Macrovascular disease
 Cardiovascular disease
 Stroke
 Peripheral vascular disease
 Infection
2. A 12-year-old patient develops pancreatic
atrophy with loss of beta cells. Which condition
does this patient most likely have?
A. Diabetes type 1
B. Diabetes type 2
C. Hypothyroidism
D. Diabetes insipidus
Alterations of Adrenal Function
 Disorders of the adrenal cortex:
 Cushing’s disease
• Excessive anterior pituitary secretion of ACTH
 Cushing’s syndrome
• Manifestations resulting from chronic excess cortisol
Cushing’s Disease
From Zitelli, B.J., et al. (2012). Zitelli and Davis’ atlas of pediatric physical diagnosis (6th ed.). London: Saunders.
Alterations of Adrenal Function
 Disorders of the adrenal cortex
 Congenital adrenal hyperplasia
 Hyperaldosteronism
• Primary hyperaldosteronism (Conn’s syndrome)
• Secondary hyperaldosteronism
Alterations of Adrenal
Function (Cont.)
 Hypersecretion of adrenal androgens and estrogens
• Feminization
• Virilization
Virilization
From Thibodeau, G.A., & Patton, K.T. (2010). The human body in health &
disease (4th ed.). St Louis, MO: Mosby.
Function (Cont.)
 Disorders of the adrenal cortex
 Adrenocortical hypofunction
• Addison’s disease (primary adrenal insufficiency)
 Addisonian crisis
• Secondary hypocortisolism
Function (Cont.)
 Disorders of the adrenal medulla
 Adrenal medulla hyperfunction
• Caused by tumours derived from the chromaffin cells of the
adrenal medulla
 Pheochromocytomas
• Secrete catecholamines on a continuous or episodic basis
Case Study
A 12-year-old boy is brought to the emergency
department by his mother. She informs the staff
that he is breathing heavily and smells funny.
Laboratory tests confirm that the child is in DKA.
During DKA, insulin counter-regulatory hormones,
such as catecholamines and cortisol, increase.
Case Study: Discussion Question
What is the result of profound insulin deficiency?
A. Decreased fat mobilization

B. Activation of glucose-forming pathways in
the liver
C. Increased glucose uptake
D. Activation of bicarbonate buffering
Case Study
While her son is in the hospital, the mother has been
drinking coffee in an attempt to stay awake at the bedside.
She begins to complain of a severe headache. She informs
the staff that the headache is usually related to an increase
in her blood pressure. Although she has been prescribed a
medication and has been taking it regularly, she continues
to have issues. She is sweating and feels her heart racing.
She is transported to the emergency department. She
undergoes a barrage of tests and, 2 days later, her
physician is ready to discuss her diagnosis of
pheochromocytoma.
Case Study: Discussion Question
Her symptoms are caused by an excessive
production of what substance?
A. Norepinephrine
B. Cortisol
C. Thyroid-stimulating immunoglobulins (TSIs)
D. Growth hormone

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Chapter 18

Anterior pituitary Posterior pituitary

A. TSH secretion is controlled by positive feedback.

From Damjanov, I. (2008). Pathophysiology. Philadelphia, PA:

Alterations of Hormonal Regulation

A. Decreased fat mobilization

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