TheEndocrine System- Introduction · Evening seminar-Physiology-Endocrin. ... blood glucose and...

TheEndocrine System-

IntroductionJudit Rosta

23. 02. 2018

Evening seminar-Physiology-Endocrin.

Basis of multicellular life-

communication:

Cell-cell Neuronal Paracrine Endocrine -widespread

- vs. exocrine (Starling) - hormone-”to set in motion”


Learning Objectives nr.71.,72.

71. Principles of endocrine control systems.

The classification of hormones

Hormone receptors (membrane receptors and intracellular receptors)

Define intracrine effect

The concentration of a hormone in the blood plasma; Plasma hormone binding proteins

Patterns of hormone secretion

Permissive hormonal effect

Hypothalamic factors ( releasing and inhibiting hormones)

Negative feedback control of anterior pituitary hormone secretion at multiple levels

72. Characterization of the hypothalamo-hypophyseal (neuroendocrine) system.


Endocrine System

From: Costanzo, Physiology, 5th Edition Elsevier


The Classification of Hormones

Based on chemical structure

Proteins and polypeptides

3-200 aminoacids

Hypothalamus (releasing and inhibiting hormones)

Pituitary gland (trophic hormones)

Parathyroid gland (PTH)

Pancreas (insulin, glucagon)

Steroid Hormons

Similar to cholesterol

Adrenal Cortex (cortisol,

aldosterone)

Ovaries (estrogen, progesterone)

Testes (testosterone)

Placenta (e.g. hCG)

Amine Hormones

Derivatives of amino acid tyrosine

Thyroid gland (T3,T4)

Adrenal Medullae

(nor/epinephrine)

Somatostatin

Growth Hormone


Hormone Secretion and Transport I.

Proteins and polypeptides

Made in advance and stored in secretory vesicles

Released by exocytosis

Dissolved in plasma

TRH

TRH-receptor

Released TSH

Concentrations in the blood: 1 picogr-1 microgram/ml

Steroid Hormons

synthetized on demands from precursors; parent compound: cholesterol (plasma vs. de

novo)

little hormone storage (but large stores of cholesterol esters)

Release: lipophilic- by diffusion

Transport: lipophilic- carrier proteins


Hormone secretion and transport II.

Amine Hormones

-made in advance and stored in

vesicles (catecholamines)

follicle lumen incorporated to thyroglobulin

-carrier mediated transport or diffusion

-dissolved in plasma in free form/carrier proteins

Thyroglobulin- TG

Concentrations in the blood: 1 picogr-1 microgram/ml

The rates of secretion: micrograms-milligrams/day


Plasma Hormone Binding Proteins

Transport: specific plasma globulins or albumin

Circulating reservoir of hormones: delays metabolism

protect against enzyme-degradation

T3,T4: Thyroxine binding globulin (TBG)

Cortisol: Transcortin

Estrogen, Testosterone: Sex hormone binding proteins

Aldosterone: no transport binding (20min t1/2)

half-life (t½): Catecholamines-sec; Peptide hormones-min; Steroid and thyroid hormones-hours/days

Bound and free hormones are in equilibrium: free hormone that is biologically active

90% circulate in blood as complexes

Solubility: steroid and thyroid hormones are transported by carrier proteins


Hormone Receptors I.

1. Membrane receptors: protein, peptide, and

catecholamine hormones; rapid action

Signal transduction pathway (sec.messengers)

Guyton and Hall Textbook of Medical Physiology 13rd

hormone solubility: lipophylic vs.

hydrophylic

Enzyme-linked Receptors: activated- function

directly as enzymes (intrinsic enzyme

activity)/or rely on enzymes (e.g. JAK) that are

closely associated with the receptor

e.g. receptor for Fibroblast growth factor, Growth

hormone, Insulin, Insulin-like growth factor-1,

Leptin, Prolactin


Hormone Receptors II.

Guyton and Hall Textbook of Medical Physiology 13rd

hormone solubility: lipophylic vs.

hydrophylic

2. In the cell cytoplasm: for different

steroid hormones, hormone-receptor

complex diffuses into nucleus

3. In the cell nucleus: thyroid hormones -

located in direct association with

chromosomes

Costanzo, Physiology, 5th Edition Elsevier


Continous: maintenance of relatively constant concentration of hormone e.g. Thyroid

hormone

Pulsatory secretion: consequences of feedback

controls and limited halflife

hormones are secreted in a burst-like or

episodic manner

„daily rythm” e.g. Testosterone,

„hourly rythm” e.g. Luteinizing Hormone

„cyclic”: e.g. female reproductive hormones frequency

and amplitude of pulses are quite different at different

stages of the reproductive cycle

Gardner DG, Shoback D.: Greenspan Basic & Clinical Endocrinology, 9th Edition

Patterns of Hormone Secretion I.

24-hours Profile of Testosterone and LH Secretion

The rates of secretion: micrograms-milligrams/day


Patterns of Hormone Secretion II.

daily rythm (highest at night)

gender

age

Increased by

stress, exercise, ghrelin…

Growth Hormone (GH): pulsatile pattern with bursts of secretion occuring every 2 hours

Plasma GH:

adult 1.6-3 ng/ml

child 6 ng/ml

starvation 50 ng/ml

Growth Hormone in Aging Lila S Chertman, MD, George R Merriam, M.D., and Atil Y Kargi, M.D. Endotext 2015

sleep sleep

24-hours Profile of GH Secretion

Clinically: GnRH pulsatility is critical in fertility (inhibition with e.g. prolonged administration of GnRH agonist)- gonadal steroidogenezis is suppressed (endometriosis)


Measurement of Hormone

Concentrations in the Blood

Radioimmunoassay (RIA)

ELISA

Berson and Yellow 1960, Nobel Prize in 1977

Sensitivity: 0.001 ug/ml

Competition for the antigen binding sites

1 picogr-1 microgram

per ml

Assays: total hormone concentrations vs. free

hormone concentrations


Define intracrine effect

“intracrine” effect: the actions of a peptide hormone within that synthesizes it by

binding to intracellular receptors/ or intracellular action of internalized peptide

hormones

Intracrines: steroids, peptide hormones (Angiotensin II, prolactin, GH) and factors

(growth factors-EDF,PDGF,NGF-; interferon-γ; endogenous opiates)

Intracrine action can modulate cellular function over time and thereby play a role in

the maintenance of hormonal responsiveness and in cellular differentiation.

The term „intracrine” comes from: Re RN, Bryan SE. Functional intracellular renin-angiotensin systems may exist in multiple tissues. Hypertens Clin Exp Theory Pract. 1984;A6(suppl 10 & 11):1739–1742.

a regulatory factor acts within

the cell


Permissive Hormonal Effect

„Permissive”: the presence of one hormone, at a certain concentration, is

required in order to allow a second hormone to fully affect the target cell

Permissive hormons e.g. thyroid hormones, cortisol

A specific hormone is needed for the function of another

hormone

epinephrine+norepinephrine on cardiac rate- together even greater increase

than the sum of their individual effects (additive)

testosterone+FSH-each stimulates different stages of spermatogenezis,

both needed to complete sperm development (complementary)

Synergistic effect: hormones work together to produce a particular result


Permissive Hormonal Effect II.

Thyroxin is needed for the function of Epinephrine in fatty acid release (induces synthesis

of epinephrine receptor)

Estrogen- responsiveness of the uterus to Progesterone (induces the formation of receptor

proteins for progesterone)

Thyroid hormones exert permissive effect upon the anabolic and metabolic effects of

Growth Hormone

Cortisol plays role in potentiating vasoactive responses to catecholamines

Vitamin-D has a permissive role in the phosphaturic effect of Parathyroid hormone


hormone

...does not initiate the changes but even at small amounts permits certain

processes:


Permissive Hormonal Effect III.


hormone

Permissive effects of Glucocorticoids:

CORTISOL does not initiate the changes but even at small amounts permits certain processes;

in the absence of glucocorticoids many normal functions become deficient

-interacts in a permissive fashion with glucagon (gluconeogenezis) and

catecholamines (vasoconstriction, bronchodilation, lipolysis)

glucocorticoids are essential for survival when stress is severe


Identify Hypothalamic Factors

HYPOTHALAMUS:

Growth hormone–releasing hormone (GHRH),

Growth hormone inhibitory hormone (Somatostatin)

Thyrotropin-releasing hormone (TRH)

Corticotropin-releasing hormone (CRH)

Dopamine or prolactin-inhibiting factor (PIH)

Gonadotropin-releasing hormone (GnRH)

Thyroid-stimulating hormone (TSH)

Adrenocorticotropic hormone (ACTH)

Prolactin (PRL)

Follicle-stimulating hormone (FSH)

Luteinizing hormone (LH)

ANTERIOR PITUITARY:

Growth hormone (GH)

Identify appropriate hypothalamic factors control the

secretion of each of the anterior pituitary hormones

HYPOTHALAMUS

ANTERIOR PITUITARY


Hypothalamic Factors – Route of

TransportHYPOTHALAMO-HYPOPHYSEAL PORTAL SYSTEM

median eminence

nutrients

olfactory stimuli

water

hormonespain

sinuses

sup.hypophys.artery

Method: hypothalamic neurons secrete

hormones into the tissue fluids, immediately

be absorbed into portal vessels

and carried directly to the sinuses of the

anterior pituitary gland

Structure: fenestrated capillaries (enter via-

exit through)

Function: fast communication (rapid

exchange), small amount of hormone needs

hypothalamic-hypophyseal portal vessels

glandular cells

IIIrd ventricle

vein


Hypothalamus Controls Pituitary

Secretion

GnRH

FSH,LH

SomatostatinGHRH

GH

TRH

TSH

T3, T

4

CRH

ACTH

Cortisol, Aldosterone, DHEA

Estrogen

Estrogen, Progesterone, TestosteroneGuyton and Hall Textbook of Medicine

PIH

PRL

PITUITARY GLAND

HYPOTHALAMUS


Endocrine Feedback Loop

Endocrine Organ:

Regulated Variable

Secreted HormoneNegative

Feedback

Blood calcium

Endocrine glands e.g. pancreas

and parathyroid gland- controlled

by the regulated variable e.g.

blood glucose and calcium

Gardner DG, Shoback D.: Greenspan Basic & Clinical Endocrinology, 9th Edition

Parathyroid Hormone

(PTH)

Decreased calcium level

Calcium Feedback to Regulate PTH Secretion


Feedback Control of Pituitary Hormone

Secretion

Short-loop, Long-loop feedback signals

controlled variable: synthesis of hormones, secretory rate of the hormone, degree of

activity of the target tissue

Hypothalamus (releasing and inhibiting hormones)

Adenohypophysis (trophic hormones)

Target Tissue (peripheral hormones)

+

+

Positive

feedback

causes additional

secretion of the

hormone-until an

appropriate

concentration

Negative

feedback

prevent

oversecretion


+Feedback Control of Anterior Pituitary

Hormone Secretion

Hormonal Profile of

estradiol LH and FSH

Sustained increase in estradiol in the late follicular phase triggers the massive burst of LH secretion that just precedes ovulation

Positive

feedback

Regulation of Prolactin

Secretion

Prolactin inhibits its ownsecretion by increasingthe secretion of dopamine


-

GHRHSomatostatin

Stimulates protein synthesis and overall growth of most cells and tissues

Somatomedins (IGF)

GH

Metabolic effects

HYPOTHALAMUS

Increased metabolism, growth and development

TSH

TRH

Stimulates synthesis and secretion of thyroid hormones

T3, T4

TBP

PITUITARY GLAND

Feedback Control of Anterior Pituitary

Hormone Secretion

Negative

Feedback


ACTH

CRH

Na+-retentio

Stimulates synthesis and secretion of adreno-cortical hormones

Cortisol

Helps elevate glucose level, supports growth,

restrains immune responses

HYPOTHALAMUS

Aldosterone

-Feedback Control of Anterior Pituitary

Hormone Secretion

Negative

Feedback


1.embryology.med.unsw.edu.au; 2.2013 Enc Britannica, Inc.; 3.,4.Mouse models of male infertility-Cooke and Saunders Nature Reviews Genetics 3(10):790-801 November 2002/; 5.radiologykey.com

GnRH

FSH

Estrogen

2.

4.

HYPOTHALAMUS

LHinhibin

-Feedback Control of Anterior Pituitary

Hormone Secretion

Negative

Feedback

The Endocrine System-Organs

SMALL INTESTINE

Secretin Stimulates pancreatic acinar cells to release bicarbonate

and water, Peptide

Cholecystokinin Stimulates gallbladder contraction and release

of pancreatic enzymes, Peptide

ADIPOCYTES

Leptin Inhibits appetite, stimulates thermogenesis, Peptide

KIDNEY

Renin Catalyzes conversion of angiotensinogen to angiotensin I

(acts as an enzyme), Peptide

1,25-Dihydroxycholecalciferol Increases intestinal absorption of

calcium and bone mineralization, Steroid

Erythropoietin Increases erythrocyte production, Peptide

The HUMAN SKIN: CRH/propiomelanocortin axis, steroidogenesis, vitamin D.Sex steroids


Excessive amounts of a hormone

may be secreted by tumors e.g. „Phaeochromocytoma”-adrenal medulla-

catecholamines overproduction

non-physiological stimulator of the receptor such as an antibody e.g. „Graves diseae”-

hyperthyroidism

increased prolactin secretion-e.g. interruption of the hypothalamic-hypophysial tract-

loss of tonic inhibition by dopamine, cons.: infertility (GnRH inhibition)

A lack of hormone effect

autoimmune destruction of beta-cells „Diabetes TI”

No production/ production of a biologically inactive hormone (e.g. thyroid hormones-

idodide deficiency) „cretenism”, myxoedema

hormone receptor structural abnormality (hormone resistance)

Endocrine Disorders

Összevont szeminárium-Élettan-

Endokrin.

Adrenocortical hormones:

Cushing’s Syndrome: hypersecretion of AC hormones due to pituitary tumor or steroid

administration; redistribution of fat (cause: administration of steroids (i.e. prednisone) for

transplant patients, asthma, and chronic inflammatory disorders)

Addison’s Disease: hyposecretion of AC hormones due to autoimmunity or disease

(mental lethargy, anorexia, nausea, vomiting, weight loss, hypoglycemia, muscle weakness, ↑K+,

↓Na+, ↓bp, dehydration, arrhythmias, cardiac arrest, ↑skin pigmentation)

Growth Hormone:

Dwarfism: hyposecretion of GH during growth years (treatment = oral GH therapy)

Gigantism: hypersecretion of GH during growth years

Acromegaly: hypersecretion of GH during adulthood (Bones of hands, feet, cheeks, and jaw

thicken; soft tissues also grow)

Endocrine Disorders

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