Molecular–cellular mechanisms of adrenal and sex glands hormones action. Eucosanoids: prostoglandins,

tromboxans, leucotriens.

EPINEPHRINE GLANDS Two parts:

-cortex-medulla

Hormones of medulla - catecholamines

Epinephrine, norepinephrine and DOPA Nature – derivatives of tyrosine Excretion is regulated by sympathetic

nervous system and brain cortex

Norepinephrine Epinephrine

Stress and The Adrenal Glands

Functions:Stress hormones. Contraction of vessels,

increase the blood pressure, accelerate pulse. Contraction of uterus muscles. Epinephrine relaxes the muscles of bronchi and intestine.

On carbohydrate metabolism:-activates the decomposition of glycogen in liver

and muscles-activates glycolysis, PPC, TAC and tissue

respirationOn protein metabolism-accelerate the decomposition of proteinsOn lipid metabolism-activates lipase, mobilization of lipids and their

oxidation

Hormones of cortex - corticosteroids

There are more than 50 corticosteroids Nature – steroids Are synthesized from cholesterol

Two groups-glucocorticoids (protein, carbohydrate

and lipid metabolism)-mineralocorticoids (mineral metabolism)

Glucocorticoids

Most important: corticosteron, cortison, hydrocortison

Synthesis is regulated by ACTHAre transported combined with proteinsHalf-life time – till 1 hourIn the decomposition17-ketosteroids

are formed (excretion with urine). Diagnostic significance – index of the function of cortex of epinephrine glands and testis

Adrenals

Kidney

Posterior Pituitary Gland

Hypothalamus

AnteriorPituitary Gland

ACTH

Stress Circadian

rhythm

CRH

(-)

Glucocorticoids, Catecholamines, etc..

Glucocorticoids, Catecholamines, etc..

Muscle: Net loss of aminoAcids (glucose)

Liver: Deamination of

proteins into amino acids,

gluconeogenesis (glucose)

Fat Cells: Free fatty

acid mobilization

Heart rate: Increased

Immune system: altered

Hypothalamopituitary adrenal (HPA) axis: Negative Feedback

Glucocorticoid Analogues

Functions

• Antiinflammatory, antiallergic, antiimmune

• Adaptive effect• Maintain the blood pressure• Maintain the volume of extracellular

liquid

Effect on protein metabolism

• Stimulate catabolic processes in connective, lymphoid and muscle tissues

• Activate protein synthesis in liver• Stimulate amino transferases• Stimulate the urine biosynthesis

Effect on the carbohydrate metabolism

Increase the glucose level• Activate gluconeogenesis• Inhibit hexokinase (glycolisis)

Effect on the lipid metabolism

• Activate lipolysis• Activate the conversion of FA

into carbs

MineralocorticoidsThe most important hormone:

aldosteronExcretion is controlled by rhenin-

angiothensin systemFunctions:-activate the

reabsorption of Na, water and Cl in kidney canaliculi

- Promotes the excretion of К ions via the kidneys, skin and saliva

Aldosteron

Disorders of the function of epinephrine gland

cortexInsufficiency: Addison disease

(bronze disease)Causes: -injury of epinephrine gland cortex-insufficient production of ACTHBlood pressure

decrease, loss of weight, weakness, anorexia.Hyperpigmentation - bronze skin

Hyperproduction: Kushing syndromCauses: hypeplasia or tumor of

epinephrine gland cortexObesity, particularly of the trunk and face (“moon face“) with sparing of the limbs; striae (stretches of the skin)Proximal muscle weaknessHirsutism (facial male-pattern hair growth)Insomnia, impotence, amenorrhoea, infertilityHeart diseases, hypertensionPolyuria, hypokalemia hyperglycemia, glucosuria (steroid diabetes) Kidney bonesDepression, anxietyHyperpigmentation

Aldosterone hyperproductionCauses: -aldosteroma

Symptoms:-hypokaliemia-hypernatriemia-hyperchloremia-hypervolemia-edema,

hypertension

A little amount of female sex hormones is formed in male organism and vice versa.

Female – estrogens, progesteron.

Male – androgens.

Sex hormones

Are synthesized in:-sex glands-placenta-cortex of epinephrine

glands

• Androgens – testosterone – dehydroepiandrosterone (DHEA) – dehydroepiandrosterone sulfate (DHEAS) – androstenedione – dihydrotestosterone (DHT)

• Estrogens – estradiol – estrone – estriol

• Progestagens – progesterone

Estradiol

Cholesterol

Pregnenolone

Progesterone

Corticosterone

11-Desoxy-corticosterone

18-Hydroxy- corticosterone

ALDOSTERONE

17-α- Hydroxy pregnenolone

11- Desoxy- cortisol

17- Hydroxy progesterone

21,β hydroxylase

CORTISOL

11,β hydroxylase

Dehydro-epi androsterone

Andro-stenedione

Oestrone

Oestriol

TESTOSTERONE OESTRADIOL

ACTH

EstrogensNature: steroidsEstradiol – is formed in follicles of

ovariumEstron and estriol – are formed in liver

and placenta in the metabolism of estradiol

Estradiol estriol

Functions of estrogensDevelopment of the female reproductive

system organs Ability to fertility in reproductive period

Biochemical functions of estrogens

Anabolic action on the tissues of reproductive organs

Inhibit the exit of Ca from bones (osteoporosis in menopause)

ProgesteronNature: steroidIs formed in corpus luteum, placenta

and epinephrine glands

Functions of progesteronPrepares the endometrium of uterus to

implantation of ovumInhibits the uterus contraction during

pregnancyStimulates the growth of mammary

glands

AndrogensTestosteron

Nature: steroidIs formed in the interstitial cells of

testisIs excreted as 17-кetosteroids

Functions of testosteroneDevelopment of the primary sex

featuresDevelopment of the secondary sex

featuresStimulates spermatogenesis

Biochemical functions of testosterone

Strong anabolic action (stimulates the synthesis of NA, proteins, phospholipids) – increases the mass of muscles

Keeps the Ca and P in organism

Derivatives of androgens – active anabolics

Major Classes of EicosanoidsMajor Classes of Eicosanoids

• Prostaglandins

• Thromboxanes

• Prostacyclins

• Leukotrienes

Precursors of EicosanoidsPrecursors of Eicosanoids

• Arachidonic acid (ω6)• Eicosatrienoic acid (-linolenic acid, ω6)

• Eicosapentaenoic Acid (ω3)

Prostaglandins – Structural FeaturesProstaglandins – Structural Features

CYCLO-OXYGENASE CYCLO-OXYGENASE PATHWAY PATHWAY

PG and TX synthesisPG and TX synthesis

2GSH

2GSSG

PGF2a

PGE 9-keto reductase

PGI2PGI synthase

TXA2TXA synthase

LipoxygenaseLipoxygenase pathway pathway

Mechanism of Aspirin ActionMechanism of Aspirin Action