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maintain homeostasis
Closeness Receptor Specificity
extensive use of negative
feedback
Rapid Onset Delayed Onset
high-level integration in brain
ability to influence processes in
Short Duration Prolonged Duration
distant regions of body
both systems use chemicals for
Rapid Response Regulation
transmission of information
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NS vs ES in homeostasis: Differences
Nervous system is hard-wired with signalling molecule delivered precisely to
point where it is needed
This means that only a few different signalling molecules are required as they do not
affect any cells except at their site of delivery
In nervous system specificity is conferred by hard-wiring: neurotransmitter
is delivered directly and specifically to cell which has receptor and responds
to transmitter
In endocrine system, where hormones are delivered to all cells, specificity
comes only from expression of the receptor for hormone.
Only cells with receptors for a hormone can respond to that particular hormonal signal
Marc Imhotep Cray, MD
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Overview of Endocrine System
Classes of Hormones
Hormones can be divided into five major classes:
1. amino acid derivatives such as dopamine, catecholamine, and thyroid hormone
2. small neuropeptides such as gonadotropin-releasing hormone (GnRH), thyrotropin-
releasing hormone (TRH), somatostatin, and vasopressin
3. large proteins such as insulin, luteinizing hormone (LH), and PTH produced by classic
endocrine glands
4. steroid hormones such as cortisol, estrogen, progesterone and testosterone that are
synthesized from cholesterol-based precursors and
5. vitamin derivatives such as retinoids (vitamin A) and vitamin D
As a rule
amino acid derivatives and peptide hormones are water-soluble and
interact with cell-surface membrane receptors
Steroids, thyroid hormones, vitamin D, and retinoids are lipid-soluble and
interact with intracellular--cytoplasmic & nuclear--receptors
Marc Imhotep Cray, MD
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Chemical Classes and Hormones
Amino acid derivative Proteins
Epinephrine (adrenaline) Insulin
Thyroid hormones (T3, T4) Insulin-like growth actors (IGFs )
Peptides Growth hormone (GH)
Thyrotropin-releasing hormone (TRH) Prolactin (PRL)
Gonadotropin-releasing hormone (GnRH) Placental lactogen (PL)
Vasopressin Parathyroid hormone (PTH)
Oxytocin (OT) Steroid
Vasoactive intes tinal peptide (VIP) Estrogens (e.g. estradiol)
Glucagon Androgens (e.g.
Adrenocorticotropic hormone (ACTH) testosterone)
Somatostatin Progesterone
Glycoproteins Cortisol
Thyroid-stimulating hormone (TSH) Aldosterone
Follicle-stimulating hormone (FSH) Vitamin derivatives
Luteinizing hormone (LH) vitamin A
Chorionic gonadotropin (CG) vitamin D
Marc Imhotep Cray, MD
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Overview of Endocrine System cont.
Hypothalamus
One of most important function of hypothalamus is to link the
nervous system to the endocrine system via pituitary gland
(hypophysis)
Marc Imhotep Cray, MD Costanzo LS. BRS Physiology. 5th ed. (Board review series). New York: Elsevier; 2009.
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Overview of Endocrine System cont.
Overall Function
A hormone is a substance secreted into bloodstream by one
tissue but has actions at remote tissues
Marc Imhotep Cray, MD Mulroney SE & Myers AK. Netter's Essential Physiology 2nd Ed. Philadelphia: Elsevier, 2016.
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Overview of Endocrine System cont.
Sites and mechanisms of hormone action
Body releases a wide range of endogenous substances,
including: neurotransmitters from neuronal cells (e.g.
acetylcholine), hormones (e.g. insulin) or cytokines (e.g.
interferon), that alter function of target cells
Hormones act on their specific receptors located on or within
their target cells
Receptor activation by hormones is translated into response
in a variety of ways
1. At cell membrane receptors
2. At cytoplasmic receptors
3. At nuclear receptor
Marc Imhotep Cray, MD
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Overview of Endocrine System cont.
Sites and mechanisms of hormone action (2)
Binding of a hormone to its receptor initiates intracellular events
that direct hormone’s action
Raff RB, Rawls SM, Beyzarov EP. Netter's Illustrated Pharmacology, Updated
Edition. Philadelphia: Sanders, 2014
Marc Imhotep Cray, MD
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Functional anatomy of endocrine and
metabolic systems
Endocrine and metabolic systems regulate seven major bodily
functions (detail slides follow)
Brown TA, Brown D. USMLE Step 1 Secrets, 3rd Ed. Saunders, 2013
Marc Imhotep Cray, MD
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Hormone 2nd -messenger systems (signal transduction)
McInnis M., Mehta S. Step-up to USMLE Step 1 2015 Edition. Wolters Kluwer, 2015
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*Mechanism using a G protein, as shown in D (Next slide)
Hormone 2nd messenger systems, GPCRs
G-protein mechanism
1. Messenger system before
hormone binding
ATP, adenosine triphosphate; cAMP, cyclic adenosine monophosphate; DAG, diacylglycerol; IP3, inositol triphosphate; PIP2,
phosphatidylinositol 4,5-bisphosphate.
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Basic Concepts (4) Hormone Receptors cont.
2. Intracellular receptors: (steroid hormones, TH, retinol & vitamin D)
Intracellular receptors bind hydrophobic (lipophilic) hormones
(which penetrate plasma membrane easily) such as
Cortisol
Aldosterone
Estrogen Note:
Progesterone Nuclear Receptors T3, T4, Estrogen, Progesterone,
Testosterone
Testosterone Cytoplasmic Receptors Glucocorticoids &
T3/T4 Mineralocorticoids
Retinol
vitamin D
inside cell-either in cytoplasm or nucleus
Intracellular receptors modulate transcription rate of specific
Marc Imhoteptarget
Cray, MD genes to change levels of cellular proteins
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Summary: molecular-cellular mechanisms of
hormone action (illustrations next 6 slides)
Hormones act on their specific receptors located on or within
their target cells
Ledger:
ACTH, adrenocorticotropic hormone; ANP, atrial natriuretic peptide; cAMP, cyclic adenosine
monophosphate; cGMP, cyclic guanosine monophosphate; CRH, corticotropin-releasing hormone; FSH,
follicle-stimulating hormone; GH, growth hormone; GHRH, growth hormone–releasing hormone; GnRH,
gonadotropin-releasing hormone; hCG, human chorionic gonadotropin; IGF, insulin-like growth factor;
IP3, inositol triphosphate; NO, nitric oxide; PDGF, platelet-derived growth factor; PTH, parathyroid
hormone; T3, triiodothyronine; T4, thyroxine; TRH, thyrotropin-releasing hormone; TSH, thyroid stimulating hormone.
Marc Imhotep Cray, MD
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Hypothalamic-pituitary signaling pathways
Response of an anterior pituitary gland cell to a hypothalamic
factor (neurohormone) is initiated when hypothalamic factor
(a peptide) binds to specific G protein-coupled receptors
located on plasma membrane of appropriate anterior pituitary
cell type
Kelly LJ. Essentials of Human Physiology for Pharmacy. Boca Raton: CRC Press, 2004.
56
Pathophysiologic & Pharmacologic Concepts
Hypopituitarism may be partial or complete and may result
from hypothalamic disease (leading to deficiency of
hypothalamic-releasing hormones) or intrinsic pituitary
disease(causing pituitary hormone deficiency)
McInnis M., Mehta S. Step-up to USMLE Step 1 2015 Edition. Wolters Kluwer, 2015.
Marc Imhotep Cray, MD
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Hypothalamus
Hypothalamus, which is a part of CNS and not a gland,
produces many releasing and inhibitory hormones which control
secretion of anterior pituitary hormones
Hypothalamic hormone/factor Chemical nature
1. Thyrotropin releasing hormone (TRH) Tripeptide
2. Corticotropin releasing hormone (CRH) Peptide (41 AAs)
3. Gonadotropin releasing hormone (GnRH), Decapeptide
(LH-RH/FSH-RH)
4. Prolactin release inhibitory hormone (PRIH) Dopamine
5. Growth hormone releasing hormone (GHRH) Peptide (40, 44 AAs)
6. Somatostatin (Growth hormone release Peptide (14 AA)
inhibitory hormone)
Kumar V, Abbas AK. Robbins and Cotran Pathologic Basis of Disease 9th Ed. Philadelphia: Saunders, 2015.
The adenohypophysis releases five hormones that are in turn under the control of various stimulatory and inhibitory
hypothalamic releasing factors. TSH, Thyroid-stimulating hormone (thyrotropin); PRL, prolactin; ACTH, adrenocorticotropic
hormone (corticotropin); GH, growth hormone (somatotropin); FSH, follicle-stimulating hormone; LH, luteinizing hormone.
The stimulatory releasing factors are TRH (thyrotropin-releasing hormone), CRH (corticotropin-releasing hormone), GHRH
(growth hormone-releasing hormone), GnRH (gonadotropin-releasing hormone). The inhibitory hypothalamic influences
comprise PIF (prolactin inhibitory factor or dopamine) and growth hormone inhibitory factor (GIH or somatostatin). 66
Hormonal Feedback Regulatory Systems
Feedback control , both negative and positive, is a fundamental feature of
endocrine systems
Each of major hypothalamic-pituitary- hormone axes is governed by negative
feedback, a process that maintains hormone levels within a relatively narrow
range
These regulatory loops include both positive (e.g., TRH, TSH) and negative
(e.g., T 4 , T 3 ) components, allowing for precise control of hormone levels
Marc Imhotep Cray, MD
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Feed-forward and Feed-back Mechanisms
Hypothalamic Releasing Hormone
Key to understanding endocrine
pharmacology are feed-forward
and feed-back mechanisms that Pituitary Tropic (Signal) Hormone
govern how “releasing” factors
in hypothalamus control release
of hormones in pituitary Target Glands
(regulatory/tropic hormones)
that in turn cause release of Second-tier Hormone
second-tier hormones that Negative
target multiple organs within Feedback
body Organ-System Effect
Marc Imhotep Cray, MD
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Negative and Positive Feedback Regulation
In most cases, a hypothalamic– pituitary–target gland axis is
regulated by negative feedback, whereby tropic hormone of
anterior pituitary gland has negative feedback effects on
hypothalamus and target gland hormone has negative
feedback effects on both hypothalamus and anterior pituitary
By way of these mechanisms levels of target gland hormone
are maintained within normal physiological range
N.B. Positive Feedback
Although negative feedback is primary homeostatic mechanism in endocrine system,
rare examples of positive feedback exist (e.g., menstrual cycle ). These positive
feedback mechanisms are, by nature, self-limited, as dictated by need for homeostasis in
physiological systems.
Golan DE et.al. Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy 3rd Ed. Lippincott Williams & Wilkins, 2012
+, stimulant; –, inhibitor; ACTH, adrenocorticotropic hormone; CRH, corticotropin-releasing hormone; FSH, follicle-
stimulating hormone; GH, growth hormone; GHRH, growth hormone–releasing hormone; GnRH, gonadotropin-
releasing hormone; LHRH, luteinizing hormone-releasing hormone; LH, luteinizing hormone; PRH, prolactin-releasing
hormone; SRIH, somatotropin-releasing inhibiting hormone; TRH, thyrotropin releasing hormone; TSH, thyroid-
stimulating
Marc Imhotephormone.
Cray, MD
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Some disorders often requiring applications
of endocrine and metabolic medications:
Kibble J , Cannarozzi ML. Pathophysiology Flash Cards. New York: McGraw-Hill, 2013
See next slide for hypermedia to further study tools and resources.
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Further study tools and resources:
Inside the Endocrine System BMS Cloud Folder:
Endocrine System Pathology Outline
Endocrine System Pathology Ppt.
Endocrine Pathology Case 1 SDL Tutorial
Endocrine Pathology Case 2 SDL Tutorial
Endocrinology Tutorial 1 Postpartum Necrosis
Endocrinology Tutorial 2 MEN Syndromes
Endocrinology Tutorial 3 Anterior Pituitary
Diabetes mellitus Type 1 SDL Tutorial
Diabetes mellitus Type 2 SDL Tutorial
Endocrine Pathology Clinical Vignettes
Endocrine Pathology Rapid Review Notes
Also see Medical Pathology Cloud Folder
Marc Imhotep Cray, MD
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