[ 1hormons 1, april 2015. definitions: hormones are natural secretions of the endocrine system that...

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1 Hormons 1, April 2015

Definitions:

Hormones are natural secretions of the endocrine system thatexert important functional effects upon other tissues inconcentrations.

minute

Exceptions: Epinephrine secreted in large amounts.

Endocrine system: Composed“Endocrine glands”.

of group of glands called

Endocrine glands: Glands that pourthe blood.

their secretion directly to


The endocrine system is an integrated system of small organs(group of glands ) that involve the release of extracellular signaling molecules known as hormones.

The endocrine system carries out a wide variety of physiologicalprocesses through the hormones e.g. regulating metabolism, growth, development and puberty ,and tissue function and also plays a part in determining mood.

The field of medicine that deals with disorders of endocrineglands is endocrinology.


Endocrine system

The Endocrine systemis

1-

2-

3-

consisting of :

Hypothalamus

The pituitary gland

The ThyroidParathyroid

The Thymus

and theGland

Gland4-

5-The Adrenal Glands

6-

7-

8-

The

The

The

Pancreas

Ovaries

Testes


Hormone effects vary widely, but can include:

Stimulation or inhibition of growth.

In puberty hormones can affect mood and mind.

Activation or inhibition of the immune system.

Regulating metabolism.

Preparation for a new phase of life (e.g. puberty, offspring, menopause).

Controlling the reproductive cycle.

caring for

In many cases, one hormone may regulate the production andrelease of other hormones.


Hormone effects

Hormones fall into three chemical classes:

1-•

Amine-derived hormones

are derivatives of single amino acid e.g. tyrosine and tryptophan, e.g. thyroxine.

Peptide hormones (consist of chains of amino acids).

A- Small peptide hormones are TRH and vasopressin.

B- Protein hormones (scores or hundreds of amino acids) e.g. insulin and growth hormone.

C- Glycoprotein hormones (protein hormones bear carbohydrate side chains ) e.g. Anterior Pituitary Hormones LH, FSH and TSH.

2-


Chemical classes of hormones

3- Lipid and phospholipid-derived hormones (Steroidhormones)

derive from lipids e.g. cholesterol and phospholipids.

1- Adrenocorticoids:•

••

Glucocorticoids e.g. Hydrocortisone.

Mineralocorticoids e.g. Aldosterone.2- Sex Hormones:

••

Female sex hormonesMale sex hormones

e.g. Estrogens ande.g. Androgens.

Progestins


Chemical classes of hormones

Cells respond to a hormone when they express a specificreceptor for that hormone.

The hormone binds to the receptor protein, resulting in theactivation of a signal transduction mechanism that ultimately leads to cell type-specific responses.

2 Types of mechanisms of action can be distinguished:1- Hormones with plasma membrane receptors.

e.g. Peptide hormones.

2- Hormones with cytoplasmic or nuclear membrane receptors.e.g. Steroid Hormones.


Mechanisms of Hormonal Actions

These hydrophilic and mostly large hormone molecules bindto receptors on the surface of "target" cells.

These receptors are transmembrane proteins.

Binding of the hormone to its receptor initiates a sequence of intracellular signals that may:

1- alter the behavior of the cell (such as by opening or closing membrane channels) or

2- stimulate (or repress) gene expression in the nucleus by turning on (or off) the promoters and enhancers of the genes.


1- Hormones with plasma membrane receptors e.g. Peptide hormones.

This is the sequence of events:

••

The hormone binds to a site on the extracellular portion of the receptor.Binding of the hormone to the receptor– activates a G protein which initiates the production of a "second

messenger“ e.g. :• cyclic AMP, (cAMP) which is produced by adenylyl cyclase from

ATP

inositol 1,4,5-trisphosphate (IP3)•– The second messenger in turn, initiates a series of intracellular events

such as••

phosphorylation and activation of enzymesrelease of Ca2+ into the cytosol from stores.

– these enzymatic changes activate the transcription factor CREB(cAMP response element binding protein).

Bound to its response element, activated CREB turns on gene transcription.The cell begins to produce the appropriate gene products in response to the hormonal signal it had received at its surface.

–

–


Hormones with plasma membrane receptors


Steroid hormones, being hydrophobic molecules, diffuse freelyinto all cells.

However, their "target" cells contain cytoplasmic and/or nuclear proteins that serve as receptors of the hormone.

The hormone binds to the receptor and the complex binds to hormone response elements - stretches of DNA within the promoters of genes responsive to the hormone.

The hormone/receptor complex acts as a transcription factorturning target genes "on" (or "off").


2- Hormones with cytoplasmic or nuclear membrane receptors.

Hormones with cytoplasmic or intercellular membrane receptors


• The levels of hormones circulating in blood are tightly controlled bythree homeostatic mechanisms:

1- When one hormone stimulates the productionsecond suppresses the production of the first.

Example: FSH and estrogens

of a second, the

•

2- Antagonistic pairs of hormones.Example: Insulin and Glucagon•

3- Hormone secretion is increased (or decreased)substance whose level is decreased (or increased)

Example: level of Ca2+ and parathyroid hormone

by the sameby the hormone.

•


Hormone Regulation

Synthetic or Semisynthetic compounds that fits same hormonalreceptors to give similar action.

However they differ from natural hormones in being orallyactive, prolonged action and or more specific in their effectse.g. Diethylsttilbestrol.

Uses:

Hormones and their analogs case of deficiency

are used as replacement therapy in


Hormonal analogs

They are of two types due to their mechanism of inhibition:Inhibition of Hormone synthesis:

They inhibit the final step or intermediate steps in the biosynthetic pathway of the hormone e.g. Antithyroid drugs.

Receptor Antagonists

They block the receptor sites e.g. Clomiphene that block the estrogenic receptors.

1-

2-

UsesThey are used in case of excessive secretions of hormones.


Hormonal Antagonists


Hypothalamus

The hypothalamus is a portion of the brain that contains anumber of small nuclei with a variety of functions.

One of the most importantlink the nervous system to pituitary gland.

functions of the hypothalamusthe endocrine system via the

is to

It synthesizes and secreteshypothalamic-releasing or

neurohormones, often–inhibiting hormones,

calledand these in hormones.turn stimulate or inhibit the secretion of pituitary

The hypothalamusfatigue, anger, and

controls body temperature, hunger, thirst,circadian cycles.


Anatomy

The hypothalamus is an integral part of the substance of the brain.

A small cone-shaped structure,

it projects downward, ending in

the pituitary stalk, a tubular

connection to the pituitary gland.Tumors or inflammations in the

hypothalamus or pituitary gland

may result in severe visual

defects or total blindness.


1-2-

3-

4-

5-

Corticotropin-releasing hormone (CRH)

Gonadotropin-releasing hormone (GNRH)

Growth-hormone-releasing hormone (GHRH),

Thyrotropin-releasing hormone (TRH),

Somatostatin (also known as growth hormoneinhibiting hormone (GHIH)

6- Dopamine (prolactin-inhibiting hormone) (PIH)


The hypothalamic hormones


The pituitary gland

The pituitary gland is a small oval endocrine gland that liesat the base of the brain, nestled in a bony structure.

It is sometimes called the master gland of the body becauseall the other endocrine glands depend on its secretions for stimulation.

It secretes many important hormones that have differenteffect on other glands in the body.

Whenthings

The pituitary gland is not workingcan go wrong in the body.

correctly , many


Anatomy

The pituitary is divided into two distinct lobes that arise from different embryological sources:

•

1- The anterior (front) lobe, oradenohypophysis.

2- The posterior (back) lobe, orneurohypophysis.

• The two sections of the pituitarygland produce a number ofdifferentdifferent

44

hormones which act ontarget glands or cells .

Hormons 1, April 2015

The pituitary gland hormones are Classified into:

• Somatotropic Hormones:1-2-3-

Growth Hormone (GH).Prolactin (Prl).Placental Lactogen (PL).

• Glycoprotein Hormones:1-2-3-4-

Luteinizing Hormone (LH).Follicle-Stimulating HormoneChrionic Gonadotropin (CG).

(FSH).

Thyroid-Stimulating Hormone (TSH).• Pro-Opiomelanocortin (POMC) derived Hormones:

1-2-3-

Corticotropin (ACTH).Melanocyte-Stimulating Hormones: Lipotropins: β-LPH, -LPH

α-MSH, β-MSH.


Thyroid-Stimulating Hormone (TSH) or thyrotropin.

Adrenocorticotrophic Hormone (ACTH).

Luteinising Hormone (LH).

Follicle-Stimulating Hormone (FSH).

Prolactin (PRL).

Growth Hormone (GH).

Melanocyte-Stimulating Hormone (MSH).


Anterior Pituitary Hormones

TSH is a peptide hormone synthesized and secreted bythyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid gland.

of two subunits, the α andTSH is a glycoprotein and consiststhe β subunit.

The β subunit (TSHB) is unique todetermines its function.

TSH, and therefore

It stimulates the growth of thyroid cells and leads to increasedblood flow through the gland.


Thyroid-stimulating hormone (TSH), Thyrotropine.

Controlling thyroid hormone levels

TSH stimulates the thyroid gland tosecrete the hormones thyroxine (T4)and triiodothyronine (T3).

Somatostatin has an opposite effect onthe pituitary production of TSH, decreasing or inhibiting its release.

The level of T3 and T4 in the blood hasan effect on the pituitary release of TSH; when the levels of T3 and T4 are low, the production of TSH is increased, and, on the converse, when levels of T3 and T4 are high, TSH production is decreased.


Diagnostic use

TSH levels are tested in the blood of patients suspected of suffering from excess (hyperthyroidism), or deficiency (hypothyroidism) of thyroid hormone.

In general, a standard reference range for TSH for adultsbetween 0.4 and 5.0 mIU/L.

The therapeutic target range TSH level for patients on treatment ranges between 0.3 to 3.0 mIU/L.

is

Both TSH and T3 and T4 should be measured to ascertainwhere a specific thyroid dysfunction is caused by primary pituitary or by a primary thyroid disease.


Therapeutic use

A drug, recombinant human(rhTSH), called Thyrogen.

TSH

The rhTSH is used inwith thyroid cancer.

patients


Gonadotropins are protein hormones secretedcells (7% of the pituitary gland).

by gonadotrope

They includes:

1-2-

3-

Luteinizing Hormone (LH).Follicle-Stimulating Hormone

Chrionic Gonadotropin (CG).(FSH).

They were given this name due to their effect on Gonads.


Gonadotropins

Structures:They are glycoproteins, which composed of two subunits α andβ.

The α-subunit is similar in all hormones and contains two N- linked oligosaccharide chains.

The β-subunit is specific for each hormone.

In LH, TSH it contains one N-linked oligosaccharide chain, while in CG and FSH it contain two N-linked oligosaccharide chains.

Secretion:LH and FSH are secreted from the Gonadotropes (7%) of theAnterior Pituitary.

CG secreted by the placenta.


Regulation:– Stimulation: Gonadotropin-Releasing Hormone from

hypothalamus (Gn RH).

Inhibition: Feed back mechanism by sex hormones. CG produced by placenta after fertilization.

the

––

Physiological effects:In Males:

••

LH: Stimulate production of androgens by Leydig cells.FSH: Enhance normal sperm production by Sertoli cells.

In Females:••

LH: Induce Ovulation and stimulate Progesterone production.FSH: Enhance production of Estrogen and development of follicles.


StructureLH is a heterodimeric glycoprotein.

its structure is similar to the other glycoprotein hormones, (FSH), (TSH), and human (hCG).The protein contains 2 glycopeptidic subunits, α and the β subunit, that are non-covalently associated (i.e. without any disulfide bridge linking them).The α subunits of LH, FSH, TSH, and hCG are identical, and contain 92 amino acids.The β subunits vary (121 amino acids) (LHB) that confers its specific biologic action and is responsible for the specificity of the interaction with the LH receptor.


Luteinizing hormone (LH)

ActivityIn both males and females, LH is essential for reproduction.

In the maleLH acts upon the Leydig cells of the testis and is responsible for the production of testosterone, that exerts both endocrine activity and intratesticular activity on spermatogenesis.females

LH triggers ovulation thereby not only releasing the egg, but also initiating the conversion of the residual follicle into a corpus luteum that, in turn, produces progesterone to prepare the endometrium for a possible implantation.LH is necessary to maintain luteal function for the first two weeks.

In


FSH regulates the development, growth, pubertal maturation,and reproductive processes of the body.

FSH and (LH) act synergistically in reproduction.

StructureFSH is a glycoprotein. Each monomeric unit is a protein molecule with a sugar attached to it

The α subunits is identical with LH, FSH, TSH, and hCG.identical and contain 92 amino acids.

The β subunits consists of 118 amino acids.

are


Follicle-stimulating hormone (FSH)

Activity

FSH regulates the development, growth, pubertal maturation, and reproductive processes of the human body.

In both males and females, FSH stimulates the maturation of germ cells.In males, FSH stimulates maturation of seminiferous tubulesand spermatogenesis.

FSH enhances the production of androgen-binding protein by the Sertoli cells of the testes.

In females, FSH initiates follicular growth, specifically affecting granulosa cells. With the concomitant rise in inhibin B, FSH levels then decline in the late follicular phase.

•

•


High LH and FSH levelsIt may be a sign of:Premature menopause also known as Premature Ovarian Failure.

Poor ovarian reserve also known as Premature OvarianGonadal dysgenesis, Castration and Testicular failure.

Aging.

Low LH and FSH levelsConditions with very low FSH secretions are:

Polycystic Ovarian Syndrome,

Polycystic Ovarian Syndrome + Obesity + Hirsutism

Kallmann syndrome, Hypothalamic suppression,

Hypopituitarism, Hyperprolactinemia,Gonadotropin deficiency.

+ Infertility


Its principal effects are increased production and release ofcorticosteroids, as cortisol from the adrenal cortex.It is a segment of a much larger prohormone glycoprotein molecule called pro-opiomelanocortin (POMC).

StructureACTH consists of 39 amino acids, the first 13 of which may be cleaved to form α-melanocyte-stimulating hormone (α- MSH).After a short period of time, ACTH is cleaved into α- melanocyte-stimulating hormone (α-MSH) and CLIP, a peptide with unknown activity in humans.


Adrenocorticotropic hormoneCorticotropin or ACTH

Function

ACTH acts through the stimulation of cell surface ACTH receptors, (located on adrenocortical cells of the adrenal cortex).

This results in the following:

stimulate growth of the cells adrenal cortex and secretion of the gluco- and mineral-corticosteroids.

α- and β-melanotropin (melanocyte-stimulating hormone, MSH), which increases pigmentation of the skin.

β-lipotropin (LPH), which stimulates the release of fatty acidsadipose tissue.

from

small fragmentendorphin.

of ACTH thought to improve memory; and β-


Control

• Feed-back inhibition by corticosteroids.

Uses

• Diagnoses of adrenal insufficiency.


The melanocyte-stimulating hormones (collectively referredto as MSH or intermedins) are a class of peptide hormones that in nature are produced by cells in the intermediate lobe of the pituitary gland.

Melanocyte-stimulating hormone gets its name because of itscontain the blackeffect on

pigment,melanocytes (skin cells) thatmelanin.


Melanocyte-Stimulating Hormone (MSH)

Structure of MSH• Melanocyte-stimulating hormone belongs to a group called the

melanocortins.

This group includes ACTH, α-MSH, β -MSH and γ-MSH;

these peptides are all cleavage products of pro-opiomelanocortin(POMC).

α-MSH is the most important melanocortin for pigmentation.

••

•

Function• They stimulate the production and release of melanin

(melanogenesis) by melanocytes in skin and hair.

MSH signals to the brain have effects on appetite andarousal.

• sexual


StructureProlactin is a single-chain polypeptide of 199 amino acids.Its structure is similar to that of growth hormone and placental lactogen.

EffectsIt stimulates the mammary glands to produce milk (lactation). Increased serum concentrations of prolactin during pregnancy causeenlargement of the mammary glands of the breasts and increases theproduction of milk.

The amount of prolactin can be an indicator for the amount of sexual satisfaction and relaxation. Unusually high amounts are suspected to be responsible for impotence and loss of libido.It also decreases normal levels of sex hormones e.g. estrogen in women and testosterone in men.


Prolactin

It stimulates growth and cell reproduction andregeneration in humans and other animals.

It is a 191-amino acid, single-chain polypeptide hormonewith two disulfide bonds that is synthesized, stored, andsecreted by the somatotroph cells (40% of the gland).

It is stimulated by growth hormone-releasing hormone(GHRH; also knownsomatostatin.

as somatocrinin) and is inhibited by


Growth Hormone (GH, somatotropin)

Functions of GH

Main pathways in endocrine regulation of growth.

Effects of growth hormone on the tissues of the body can generally be described as anabolic (building up).Increased height during childhood.

It stimulates production of insulin-like growth factor 1 (IGF-1), a hormone homologous to proinsulin which has growth-stimulating effects on a wide variety of tissues.Growth hormone has many other effects on the body e.g.: Increases calcium retention, and strengthens and increases themineralization of bone.

Increases muscle mass. Promotes lipolysisIncreases protein synthesis.Stimulates the growth of all internal organs excluding the brain.


Excesses• The most common disease of GH excess is a pituitary tumor

composed of somatotroph cells of the anterior pituitary.

• Prolonged GH excess thickens the bones ofand toes (acromegaly).

the jaw, fingers

Deficiencies• In children, growth failure and short stature

major manifestations of GH deficiency.

Adults with GHD present with non-specific

(Dwarfism) are the

• problemsincluding truncal obesity with a relative decrease in musclemass and, decreased energy and quality of life.


Dwarfism


Uses of Growth Hormone:

Replacement therapy for children with GH deficiency. Administered intramuscular or subcutaneous.

Controversial treatment:

GH treatment to reverse effects of aging in older adults.GH treatment to enhance weightAthletic enhancement

loss in obesity.

Sources:Recombinant DNA technology.


it is largely a collection of axonal projections from thehypothalamus that terminate behind the anterior pituitary gland.

Two major neurohypophyseal hormones are synthesized:

1- vasopressin (antidiuretic hormone2- oxytocin

[ADH])

Functionally,secretion site

therefore, the posterior lobe isonly.

a storage and


The Posterior Pituitary (Neurohypophysis)

Oxytocin is a peptide of nine amino acids (a nonapeptide).The sequence is cys – tyr – ile – gln – asn – cys – pro – leu – gly(CYIQNCPLG).The cysteine residues form a sulfur bridge.

Oxytocin is responsible for uterine contractions, both before and delivery.

It is also important after delivery, as it continues to cause the myometrium to contract.

after

These contractions help constrict the blood vessels and bring about adecrease in the amount of vaginal bleeding after delivery.

Oxytocin is also responsible for milk ejection duringcontraction of the myoepithelial cells in the lactating

breastfeeding, bymammary gland.


Oxytocin

Arginine vasopressin (AVP), also known as vasopressin, orantidiuretic hormone (ADH), is a hormone found in most mammals, including humans.Vasopressin is a peptide hormone that inhibits or preventsformation of urine.

the

StructureThe vasopressins are peptides consisting of nine amino acids(nonapeptides).The amino acid sequence of arginine vasopressin is Cys-Tyr-Phe- Gln-Asn-Cys-Pro-Arg-Gly, with the cysteine residues forming a sulfur bridge.Lysine vasopressin has a lysine in place of the arginine.


Antidiuretic Hormone (ADH)

Function

It plays a key role in homeostasis, and the regulation of water, glucose, and salts in the blood.

AVP regulates the body's retention of water; it is released when the body is dehydrated and causes the kidneys to conserve water, thus concentrating the urine, and reducing urine volume.

In high concentrations, it also raises blood pressureinducing moderate vasoconstriction.

It has a variety of neurological effects on the brain, been found, for example, to influence pair-bonding

by

havingin voles.


Role in disease

Decreased vasopressin release leads to diabetes insipidus, acondition featuring hypernatremia (increased blood sodium concentration), polyuria (excess urine production), and polydipsia (thirst).

High levels of AVP secretion (syndrome of inappropriateantidiuretic hormone, SIADH) and resultant hyponatremia (low blood sodium levels) occurs in brain diseases and conditions of the lungs (Small cell lung carcinoma).


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