Principles

Of Endocrinology
 Motto

You are your hormones

HORMONE: Gr. Hormao = Excite
Hormone: chemical substance secreted from
specialized cells/ tissue / gland into the blood
stream that act on distant tissues, usually in a
regulatory fashion.

Endocrinology: the science that studies hormones

secretion and signaling which coordinate and
control the function of multiple organs and
processes
 Hormones function
 Growth and development: direct effect or mediated by second

messengers (IGF1).

 Homeostasis maintenance: e.g. hydro-electrolitic and acid-basic

equilibrium, blood pressure (BP), cardiac frequency, bone mass,

lean and adipose.

 Energy production and expenditure: transforming of food into

energy and fuel storage

 Behaviour: stress response, food and water intake, sexual

behavior, etc.

 Reproduction: gametogenesis, sexual dimorphism (anatomic and

behavioral).
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 Hormones Effects
 One hormone- multiple actions: e.g. Testosterone
induces male sexual differentiation of the embryo,
development of the male urogenital tract,
gametogenesis, body hair areal, sebaceous glands
secretion, muscle anabolism, behavior
 One function can be regulated by multiple
hormones: e.g. blood glucose – insulin lowers
postprandial glycaemia; glucagon, adrenalin and
noradrenalin, cortisol and GH increase glucose
output from storage during fasting, in order to
maintain normal blood glucose level .
The Major Systems of Intercellular
Regulation and Communication
The Nervous System:
Signals by neurotransmiters from the brain through the
nervous fibers to the peripheral organs with reflex arc.
Responds quickly with short acting effect
The Endocrine system
Signals by secreting hormones into the blood stream that bind
to receptors in various organs. Responds slowly with long
acting effect
The Immune system
Signals by secreting antibodies or cytokines from immune
cells in order to protect the body from external aggression
(bacteria, viruses) or internal abberant malignant cells
Intercellular Communication
Endocrine regulation: inter-organ
communication through hormones
released in the blood stream
Paracrine regulation: paracrine
factors ensure adjacent cell
communication
Autocrine/Intracrine:
signaling within the same cell
Neuroendocrine signaling :
hormones from brain to organs
Neurotransmitters regulation :
neuronal network
 Particularities Of Endocrine
Tissues/Glands

 Highly specialized structures for processing

pre/prohormone substances to hormones
 High synthesis rate of hormones and storage

 Responds to specific regulators which ensure

proper control of hormone release in the blood
stream, usually fom storage vesicles
ENDOCRINE GLANDS
 ENDOCRINE TISSUES
Brain (Hypothalamus) neurohormones, neurotransmitters
Adipose tissue: leptin, adiponectin, resistin, estrogenes
Heart: Atrial natriuretic peptide (ANP), Brain natriuretic
peptide (BNP)
Liver: IGF1, 25(OH)Vit D
Kidney: 1,25(OH)Vit D, renin, erythropoietin
Gastrointestinal tract: Ghrelin, GLP1,GLP2, glicentin, secretin,
CCK, PYY
Immune cells: Antibodies, cytokines
Bone Marrow: trompopoetin
Muscle : Irisin
Bone: Osteocalcin, FGF23
Placenta: hCG, hPL, estrogens, progesterone,etc.
Endocrine Glands

Endocrine tissues
 Chemical Structure Of Hormones
Hydrophylic Hormones
1. Peptides
- Polypeptides HGH (191aa), PRL (198aa)
- Glycopeptides: LH, FSH, TSH
- Medium peptides: insulin, glucagon
- Small peptides: TRH (3aa)
2.Amines:derived of a single aa (TYR) Adrenalin, NA,
Lypophylic Hormones
1. Steroids derived from cholesterol
- Cortisol, aldosterone, DHEA, testosterone, Estrogenes,
Progesterone
- vitamin D , 25 (OH) vit D, 1,25 (OH)2vit.D.
2. Amines: Thyroid hormones – T3, T4
 Main Human Hormones
Site of Peptides Sterolic Deriv. AAC
secretion hormones
Hypotalamus TRH
CRH
GnRH
GHRH
Ghrelin
SMS
AVP /ADH
Oxitocin
 Main Human Hormones
Site of Peptides Sterolic Deriv. AAC
secretion hormones
Pituitary GH
PRL
POMC: ACTH, MSH
TSH
LH
FSH

Pineal Melatonin
Gland Serotonin
 Main Human Hormones

Site of Peptides Sterolic Deriv. AAC

secretion hormones
Thyroid Calcitonin Thyroxin (T4)
Triiodothyronin
(T3)
Parathyroid PTH

Kidney Renin 1,25(OH) vit D

Erythropoietin
 Main Human Hormones

Site of Peptides Sterolic Deriv. AAC

secretion hormones
Pancreas Insulin
Glucagon
Somatostatin
Amylin
Pancreatic
polypeptide
 Main Human Hormones

Site of Peptides Sterolic Deriv. AAC

secretion hormones
Adrenals
• Cortex Cortisol
Aldosterone
DHEA
• Medulla Adrenalin
Noradrenalin
 Main Human Hormones

Site of Peptides Sterolic hormones Deriv.

secretion AAC

Testes Inhibines Testosterone

Activines Dihidrotestosterone
Follistatin
AMH
Ovaries Inhibines Estradiol
Activines Estrone
Follistatin Estriol
AMH Progesterone
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Transport
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Adapted from
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Steroid Hormone
Synthesis
Hormonal Secretion Control

Main regulatory
mechanism for endocrine
secretion is the feed-back
loop that it is closed by

- target gland hormones

- ions: Ca, Na
- metabolites: glucose
- other hormones: SMS,
IGF1
- osmolality / extracellular
volume (AVP, renin,
aldosterone)
 Mechanism of Hormone Action

Receptors: specialized structures on the

target organs that have hormone-binding
loci and work by

o Recognizing and binding a certain

hormone
o Conveying information for hormone action
in the target organ
 Types Of Hormonal Receptors

Membrane Receptors (peptide hormones)

• prot. G coupled receptors (Adr, GnRH, PTH, TSH)

• protein-kinase coupled receptors (insulina)
• cytokine receptors (GH, PRL, ANP. IL)

Intracellular Receptors (steroid or thyroid hormones)

• Type 1 Cytoplasmatic R: GCR, MCR, ER ,AR

• Type 2: Nuclear R : TR, retinoic X
 Prot. G Coupled Receptor activate Ser/Treonin
kinases via second messengers e.g. Adenylate
Cyclase - cAMP, Guanylate Cyclase, diacylglycerol,
calmodulin

EFFECTS :
o Changes in cytosolic enzymes activity (e.g. PKA)
o Activate signal transducers and transcription factors
Tyr Kinase Receptors
Hormone binds the receptor and induces dimerization of R that
activates TyrK function inducing a cascade of phosphorylation that
ultimately activates gene transcription of proteins that will produce
the hormone specific effect
 Steroid Hormone Receptors

DBD
Steroid Hormone Receptors
Mechanism that ensures specificity of MR in
human

F = cortisol
E = cortisone
11β- HSD2 =
11β-hydroxisteroid
dehydrogenase II
MR =
mineralocorticoid
receptor
Selective ER Modulation
 Endocrine Disorders

 Syndromes of hormonal deficit

 Syndromes of hormonal excess
 Neoplastic gland disorders
 Dysregulation of hormonal clock
 Ectopic hormonal secretion
 Disorders of the hormonal receptor signaling
 Disorders of hormone synthesis/ transport/
inactivation
 Polyglandular autoimmune syndromes: PAS
 Multiple Endocrine Neoplasia MEN
 Endocrine Disorders

 Syndromes of hormonal deficit

 Syndromes of hormonal excess
 Neoplastic gland disorders
 Dysregulation of hormonal clock
 Ectopic hormonal secretion
 Disorders of the hormonal receptor signaling
 Disorders of hormone synthesis/ transport/
inactivation
 Polyglandular autoimmune syndromes: PAS
 Multiple Endocrine Neoplasia MEN
 Endocrine Disorders

 Syndromes of hormonal deficit

 Syndromes of hormonal excess
 Neoplastic gland disorders
 Dysregulation of hormonal clock
 Ectopic hormonal secretion
 Disorders of the hormonal receptor signaling
 Disorders of hormone synthesis/ transport/
inactivation
 Polyglandular autoimmune syndromes: PAS
 Multiple Endocrine Neoplasia MEN
 Diagnosis of Endocrine
Disorders
Clinical signs and symptoms
Measuring hormones in the blood stream
– Basal test
– Dynamic tests: stimulation or inhibition
Imagistic Diagnosis
Immunohistochemical diagnosis
Genetic Testing
 Hormonal Therapies
Hormonal substitution:
GH in pituitary dwarfism
Insulin in diabetes mellitus
Cortisone in Addison’s disease
Hormonal suppressive Therapies
 Long acting GnRH agonists in breast/prostate cancer
 Immunosuppressive Corticotherapy
Assisted Reproduction Therapies: GnRH pump,
FSH, LH
Osteoporosis treatment : PTH, bisphosphonates
 What we don’t know
Many hormones that bind “orphan” receptors, yet
to be discovered
Many diagnostic tests are severely limited as they
only look at hormones in the blood stream, not in
the target organs
No satisfactory tools for assessing receptor
function
Not yet possible to prevent endocrine tumors or
autoimmune diseases
Not always the best treatment for a satisfactory
QoL of patients with endocrine disorders
Endocrine disurptors
 Take Home Message

Endocrinology is the most creative branch of

medicine, fascinating for some, occult for
others, it reveals the versatile
transformative possibilities of the body.
 https://www.britannica.com/science/human
-endocrine-system

TEDxSF - Dr. John Gray - 4/27/10 –

YouTube
https://www.youtube.com/watch?v=FXmgsm
u3V4U