Basics of Endocrinology

Hasan AYDIN, MD

Yeditepe University Medical Faculty

Endocrinology and Metabolism

Definitions

• Endocrinology- the study of hormone and glandular

abnormalities

• Hormones- biologically active substances secreted by glands

– Endocrine- hormones that have a biological effect far away

– Paracrine- hormones that have a biological effect nearby

– Autocrine- hormones that have a local effect

H

H

Endocrine System

Secretory cell

Neuron

Target

Neuroendocrine System Nervous System

H

Paracrine Actions

• Paracrine-actions – sex steroids in the ovary – angiotensin II in the kidney– platelet-derived growth factor released by platelets.

• Juxtacrine actions – some hematopoietic growth factors

Autocrine Action

• Insulin released by the pancreatic islet B cells

• Somatostatin can inhibit its own release from pancreatic D cells

Hormones

• Substances released by endocrine glands and

transported through the bloodstream to tissues where

they act to regulate specific functions.

• These actions are mediated by binding of the hormone to

receptor molecules.

• Allosteric effectors that alter conformation of the

receptors to which they bind.

Functions of Hormones

• Growth and development: Thyroid, GH, Sex Steroids, Cortisol

• Reproduction: Estrogen, Testosterone, FSH, LH, Thyroid

• Homeostasis: Thyroid, Cortisol

• Changes in environment: Cortisol, Thyroid Aldosterone

Hormones can interact with each other

GHT-4

Proteinsynthesis

Gluconeo

genesisHRMetabTemp

Skeletal

growth

Organ growth

Sex steroids

Hormone Classification

• Proteins- TSH, insulin, PTH

• Amino acids- thyroid hormones (T3 and T4), epinephrine

• Steroids- cortisol, aldosterone, testosterone

Mechanism of Action of Hormones

• Circulate in blood stream bound to transporter proteins or free

• Free hormone is the active hormone

• Enter cells to alter biological activity

Hormone Action: peptide and cathecolamines

TSHR

effect

2ndmessenger

T-4I

I I

I

TSH

TSH R

protein

Hormone Action: Steroid, Thyroid

T-3

TBG

β-receptorsIncreased HR

T-3T-3 R T-3

T-3

R

R

Hormone Regulation

• Feedback loops

• Circadian rhythms

• Receptor specificity

• Receptor concentration

Phenomenon of Negative Feedback

Phenomenon of Positive Feedback

Target Organ

Hypothalamus

+ -

+

-

-

-

?

Short LoopFeedback

Pituitary

Long LoopFeedback

Feedback Regulation of the Anterior Pituitary:

Feedback Mechanisms: Rhythms

Circhoral rhythms are ''about an hour,''

Circadian rhythms are ''about a day''

Circatrigantan rhythms are ''about a month,''

Circannual rhythms are ''about a year.'‘

Endocrine Rhythms

0800 2000 0800

ACTH

0800 2000 0800

Cortisol

0800 2000 0800

TSH

0800 2000 0800

GH

0800 2000 0800

Testosterone

0800 2000 0800

LH

The Subunit Confers Specificity

β - Subunits

α- Subunit

TSH

LH hCG

FSH

Precursor Type of compound Example of hormone

Protein

Protein Growth hormone

ACTHPeptide

ThyroxineAmino acid

CholesterolSteroid

Cortisol

1,25 OHD3

Amino acidTripeptide

Modified amino acid Epinephrine

TRH

Fatty acid

Retinoid

Eicosanoid

Retinoic acid

Prostoglandin E1

Precursors of Hormones

Receptors

Receptors

• Cellular proteins that have bifunctional properties of both

• Recognition

• Signal activation

Receptors

• Catecholamines

• Prostoglandins

• ACTH

• Glukagon

• PTH

• TSH

• LH

• Somatostatin

• Insulin

• GH

• TGF-b

Cell surface receptors:

Receptors

Nuclear receptors:

– Steroid hormones

– Vitamin D

– Thyroid hormones

– Retinoids

Effector 1 ResponseEffector 2Hormone

Receptor

± ±±

Regulation of Responsiveness to Hormones

H1

H2

R1 G1 E1

R2 G2 E1

Range

of Possible

Pathways

Interaction Between Hormone Response System

Classification of Hormones: Types of Ligands:

• Agonist

• Antagonist

• Partial agonist-partial antagonist

• Mixed or Heterologous Agonists-Antagonists

Classes of Hormone Action

Progesterone

Cortisol

Tamoxifen

Spironolactone

Glucocorticoid

Mineralocorticoid

Progestin

Glucocorticoid

Estrogen

Estrogen

Mineralocorticoid

Androgen

Agonist

Partial agonist-antagonist

Mixed agonist-antagonist

Antagonist

Neuroendocrinology

• Neurotransmitter

– Synthesized in the cell body of the neuron

– Travels down the axon

– Stored in synaptic vesicles

– Released upon depolarization

– Mediates synaptic transsmission between two

neurons

– Paracrine action

Neurotransmitter Receptors

Nicotinic cholinergic

Serotonergic

Dopaminergic

GABA

Muscarinic

• Alfa 1 adrenergic

• Alfa 2 adrenergic

• Beta 1 adrenergic

• Beta 2 adrenergic

Neurotransmitter and Hormones

• Catecholamines

• TRH

• Dopamine

• CRH

• CGRH

• Somatostatin

• GnRH

• VIP

• Gastrin

• Secretin

• Cholecystokinin

Hypothalamic-Pituitary Relations• The hypothalamus regulates

– temperature, – appetite, – thirst, – sexual behavior, – defensive reactions such as rage and fear, – body rhythms

• The hypothalamus contains two types of neurosecretory cells– Neurohypophysial neurons traverse the hypothalamic-pituitary

stalk and release vasopressin (ADH) and oxytocin from nerve endings in the posterior pituitary

– Hypophysiotropic neurons release hormones into the median eminence and thence into the hypothalamic-pituitary vessels.

Hypothalamic - Anterior Pituitary Relations

• Stimulating hormones (releasing hormones) – TRH, – GnRH, – CRH, – GHRH, – Prolactin-releasing factor and – ADH

• Inhibitory hormones – Somatostatin and – Dopamine.

Precursor Phenomenon

(Prehormones)

Biosynthesis of Hormones: Precursors

Pro-Opiomelanocortin (POMC)

β-LPH

LPH β-EndorphinACTHN-Terminal Peptide

α-MSH

Hormone Transport

• Bind to plasma protein

– Steroid

– Thyroid hormones

– Vitamin D

– GH

– Vasopressin

– Oxytocin

• Free

– Peptid hormones

(ACTH, insulin,

glucagon, PTH etc)

Regulation of the Endocrine System

• Hormone concentration

– Production rates

– Delivery to the target tissue

– Degradation

– Freestanding

Actions of Hormones

• Developmental effects• Cell growth & cancer• Central nervous system effects• Effects on metabolism• Effects on cardiovascular & renal function• Effects on mineral & water metabolism• Effects on skeletal functions• Effects on reproductive function• Release of other hormones• Effects on immunologic functions

Clinical Endocrinology

• Hypofunction of a gland

• Hyperfunction of a gland

• Receptor defect

• Second messenger defect

Endocrine Hypofunction

• Congenital defects in hormone biosynthesis

• Autoimmune destruction of glands

• Surgery or trauma to glands

• Infiltration by tumors, infection

Endocrine Hyperfunction

• Hormone secreting pituitary tumor

• End organ secreting tumor

• Autoimmune disease

• Inflammation/Infection

• Iatrogenic/Facticious

• Ectopic hormone secreting tumor

Causes of Hypo or Hyperfunction

Defects in Sensitivity to Hormones

• Partial or complete resistance to the hormone

• Secondary hormone hypersecretion

Down-regulation

Assessment of Glandular Activity

• Measure the end organ hormone

• Measure the pituitary regulating hormone

• Suppression tests-to evaluate for hormone overactivity

• Stimulation tests-to evaluate for underactivity

• Imaging studies

The Players

Other endocrine organs

•endothelial vascular cells

•adipocytes

•heart

•bone

•liver

•kidney

•????

Conclusions

• Hormones are essential for normal growth, development, metabolism, energy, reproduction etc.

• Hormones are tightly regulated by multiple systems

• Both over and underproduction of hormones leads to clinical disease