hypothalamic pituitary thyroid calcium 1-13

8/14/2019 Hypothalamic Pituitary Thyroid Calcium 1-13

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HYPOTHALAMIC

AND PITUITARYHORMONES


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Functional Anatomy of the

Hypothalamus and Pituitary Gland

The hypothalamus is a region of the brain

that controls an immense number of bodily

functions It is located in the middle of the base of

the brain, and encapsulates the ventral

portion of the third ventricle.


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Optic chiasm

Hypthalamus

Pituitary Gland


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HYPOTHALAMIC

HORMONES


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HYPOTHALAMIC HORMONES

Controls the release of pituitary hormones

Hypothalamic hormones are released from

the hypothalamic nerve fiber endingsaround the capillaries of the hypothalamic-

hypophysial system in the pituitary stalk

Released in a pulsatile manner


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Growth-hormone-releasing

hormone (GHRH) Also known as growth-hormone-releasing

factor (GRF or GHRF) orsomatocrinin

a 44-amino acid peptide hormoneproduced in the arcuate nucleus of the

hypothalamus


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GHRH is released from neurosecretory

nerve terminals of these arcuate neurons,

and is carried by the hypothalamo-hypophysial portal circulation to the

anterior pituitary gland where it stimulates

growth hormone secretion


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The actions of GHRH are opposed by anotherhypothalamic hormone, somatostatin, alsoknown as "growth-hormone-inhibiting hormone"

(GHIH). Somatostatin is released from neurosecretory

nerve terminals of periventricular somatostatinneurons, and is carried by the hypothalamo-

hypophysial portal circulation to the anteriorpituitary where it inhibits GH secretion byhyperpolarising the somatotropes.


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Somatostatin and GHRH are secreted in

alternation, giving rise to the markedly

pulsatile secretion of GH. Howeverrecently it had been discovered that

somatostatin does not affect the secretion

of GH


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The amino acid sequence of GHRH is:

Tyr - Ala - Asp - Ala - Ile - Phe - Thr - Asn - Ser -Tyr - Arg - Lys - Val - Leu - Gly - Glu - Leu - Ser -

Ala - Arg - Lys - Leu - Leu - Gln - Asp - Ile - Met -Ser - Arg - Glu - Gln - Gly - Glu - Ser - Asn - Gln -Glu - Arg - Gly - Ala - Arg - Ala - Arg - LeuNH2


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Somatostatin

a peptide hormone that regulates the

endocrine system and affects

neurotransmission and cell proliferation viainteraction with G-protein-coupled

somatostatin receptors and inhibition of the

release of numerous secondary hormones


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Somatostatin has two active forms produced

by alternative cleavage of asingle preproprotein: one of 14amino acids, the other of 28amino acids.

Somatostatin is secreted not onlyby cells of the hypothalamus butalso by delta cells of stomach,intestine, and pancreas. It bindsto somatostatin receptors.

Somatostatin

Octreotide


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Octreotide

is an octopeptide that mimics natural

somatostatin pharmacologically, though is

a more potent inhibitor of growth hormone,glucagon, and insulin than the natural

hormone

S t t ti i l ifi d i hibit h h i ti


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Somatostatin is classified as an inhibitory hormone, whose main actions

are to:Inhibit the release of growth hormone (GH)Inhibit the release of thyroid-stimulating hormone (TSH)

Suppress the release of gastrointestinal hormonesGastrinCholecystokinin (CCK)SecretinMotilin

Vasoactive intestinal peptid (VIP)Gastric inhibitory polypeptide (GIP)Enteroglucagon (GIP)

Lowers the rate of gastric emptying, and reduces smooth muscle

contractions and blood flow within the intestine.

Suppress the release of pancreatic hormonesInhibit the release of insulinInhibit the release of glucagon

Suppress the exocrine secretory action of pancreas

Somatostatin opposes the effects of Growth Hormone-Releasing

Hormone (GHRH)


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Corticotropin-releasing hormone

(CRH) originally named corticotropin-releasing

factor(CRF), and also called

corticoliberin, is a polypeptide hormoneand neurotransmitter involved in the stress

response


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(CRH) produced by neuroendocrine cells in the

paraventricular nucleus of the hypothalamus

The portal system carries the CRH to theanterior lobe of the pituitary, where it stimulates

corticotropes to secrete corticotropin (ACTH)

and other biologically active substances (for

example -endorphin).


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(CRH) Role in parturition

CRH is also synthesized by the placenta

and seems to determine the duration ofpregnancy


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Thyrotropin-releasing hormone

(TRH) also called thyrotropin-releasing factor

(TRF), thyroliberin orprotirelin, is a

tripeptide hormone that stimulates the releaseof thyroid-stimulating hormone and prolactinby the anterior pituitary

TRH is produced by the hypothalamus and

travels across the median eminence to thepituitary via the hypophyseal portal system


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(TRH) In addition to the brain, TRH can also be

detected in other areas of the body includingthe gastrointestinal system and pancreaticislets

Medical preparations of TRH are used indiagnostic tests of thyroid disorders

It is used in pharmacology to test theresponse of the anterior pituitary gland and inacromegaly


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(TRH) The sequence of TRH was first determined and

the hormone synthesized by Roger Guillemin

and Andrew V. Schally in 1969. Its molecularweight is 359.5 Da and its structure is:

(pyro)Glu-His-Pro-NH2


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Gonadotropin-releasing

hormone 1 (GNRH1) is a peptide hormone responsible for the release of

FSH and LH from the anterior pituitary

GNRH1 is synthesized and released by the

hypothalamus

GnRH was previously called LHRH (luteinizing

hormone-releasing hormone)


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hormone 1 (GNRH1) The gene, GNRH1, for the

GNRH1 precursor islocated on chromosome 8.

This precursor contains 92amino acids and isprocessed to GNRH1, adecapeptide (10 aminoacids) in mammals.

pyroGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-GlyCONH2.
http://en.wikipedia.org/wiki/Image:GNRH1_structure.png


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hormone 1 (GNRH1) GNRH1 is considered a neurohormone, a

hormone produced in a specific neural cell and

released at its neural terminal A key area for production of GNRH1 is the

preoptic area of the hypothalamus, that

contains most of the GNRH1-secreting

neurons. GNRH1 is secreted in the

hypophysial portal bloodstream at the median

eminence


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hormone 1 (GNRH1) The portal blood carries the GNRH1 to the

pituitary gland, which contains the gonadotropecells, where GNRH1 activates its own receptor,gonadotropin-releasing hormone receptor(GNRHR), located in the cell membrane

GNRH1 is degraded by proteolysis within a fewminutes.


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hormone 1 (GNRH1) In males, GNRH1 is secreted in pulses at

a constant frequency, but in females the

frequency of the pulses varies during themenstrual cycle and there is a large surge

of GNRH1 just before ovulation.


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hormone 1 (GNRH1) GNRH1 activity is very low during

childhood, and is activated at puberty

During the reproductive years, pulseactivity is critical for successfulreproductive function as controlled byfeedback loops

However, once a pregnancy isestablished, GNRH1 activity is notrequired
http://images.google.com/imgres?imgurl=http://www.biopsychiatry.com/dopamine/dopamine.jpg&imgrefurl=http://www.biopsychiatry.com/dopamine/&h=267&w=152&sz=8&hl=en&start=1&tbnid=w4i-VW5Tm8SLSM:&tbnh=113&tbnw=64&prev=/images%3Fq%3DDopamine%26svnum%3D10%26hl%3Den%25


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Dopamine

In the brain, dopamine functions as aneurotransmitter, activating dopamine receptors

Dopamine is also a neurohormone released by the

hypothalamus Its main function as a hormone is to inhibit the

release of prolactin from the anterior lobe of thepituitary

Dopamine has the chemical formula (C6H3(OH)2-CH2-CH2-NH2)

Its chemical name is 4-(2-aminoethyl)benzene-1,2-dioland it is abbreviated "DA."
http://images.google.com/imgres?imgurl=http://www.biopsychiatry.com/dopamine/dopamine.jpg&imgrefurl=http://www.biopsychiatry.com/dopamine/&h=267&w=152&sz=8&hl=en&start=1&tbnid=w4i-VW5Tm8SLSM:&tbnh=113&tbnw=64&prev=/images%3Fq%3DDopamine%26svnum%3D10%26hl%3Den%25


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PITUITARY

HORMONES


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GROWTH HORMONE (GH)

Also called somatropin or somatotropin

Synthesized in somatotropes, a subclass of the

pituitary acidophilic cells The genes for human growth hormone are

localized in the q22-24 region of chromosome 17


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Disulfide bonds


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GROWTH HORMONE (GH)

Peptides released by neurosecretory

nuclei of the hypothalamus into the portal

venous blood surrounding the pituitary arethe major controllers of GH secretion by

the somatotropes.


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GROWTH HORMONE (GH)

Growth hormone releasing hormone

(GHRH) from the arcuate nucleus of the

hypothalamus and ghrelin* promote GHsecretion, and somatostatin from the

periventricular nucleus inhibits it.


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Secretes GHRH


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Ghrelin is a hormone produced by P/D1 cells

lining the fundus of the human stomach that

stimulate appetite Ghrelin levels increase before meals and

decrease after meals

It is considered the counterpart of the hormone

leptin, produced by adipose tissue, whichinduces satiation when present at higher levels.


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Much of the growth hormone in the

circulation is bound to a protein (growth

hormone binding protein, GHBP) which isderived from the growth hormone receptor


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Growth hormone receptor is a member of

the cytokine receptor superfamily.

One growth hormone molecule binds toone receptor and then recruits a second

receptor to form a dimer through which

signalling occurs.


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The effects of growth hormone on the

tissues of the body can generally be

described as anabolic


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Height growth in childhood is the best knowneffect of GH action, and appears to bestimulated by at least two mechanisms:

1. GH directly stimulates division andmultiplication of chondrocytes of cartilage.

These are the primary cells in the growing ends(epiphyses) of children's long bones


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2. GH also stimulates production of insulin-like growth factor 1 (IGF1, formerly known

as somatomedin C), a hormone

homologous to proinsulin

The liver is a major target organ of GH for

this process, and is the principal site ofIGF-1 production


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GROWTH HORMONE (GH)

GH secretion is also affected by negative

feedback from circulating concentrations

of GH and IGF-1


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EFFECTS OF GROWTH

HORMONE Stimulators of GH secretion include exercise,

hypoglycemia, dietary protein, and estradiol. Inhibitorsof GH secretion include dietary carbohydrate andglucocorticoids.

Increases the transport of amino acids into muscle cellsand also increases protein synthesis

Antagonizes the effects of insulin

Decreases the peripheral utilization of glucose

Increases hepatic glucose glucose production viagluconeogenesis


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EFFECTS OF GROWTH

HORMONE In liver, GH increases liver glycogen

Promotes the release of free fatty acids and glycerol fromadipose tissue

Increases oxidation of free fatty acids in the liver Promotes a positive calcium, magnesium, and phosphate

balance

Causes retention of sodium, potassium and chloride ions

Promotes the growth of long bones

Stimulates lactogenesis

G ti d fi i i i t d


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Genetic deficiencies associated

with GH

GH-deficient dwarfs lack the ability tosynthesize or secrete GH, and these short-statured individuals respond well to GHtherapy

Pygmies lack the IGF-1 response to GH butnot its metabolic effects; thus in pygmies thedeficiency is post-receptor in nature

Laron dwarfs have normal or excess plasmaGH, but lack liver GH receptors and have low

levels of circulating IGF-1. The defect inthese individuals is clearly related to aninability to respond to GH by the productionof IGF-1


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The production of excessive amounts of

GH before epiphyseal closure of the long

bones leads to gigantism When GH becomes excessive after

epiphyseal closure, acral bone growth

leads to the characteristic features of

acromegaly


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PROLACTIN Peptide hormone

synthesized and secretedby lactotrope cells in theanterior pituitary gland

Prolactin is a single chainpolypeptide of 199 aminoacids with a molecularweight of about 24,000

daltons The molecule is folded due

to the activity of threedisulfide bonds


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Pituitary prolactinsecretion is regulated byneuroendocrineneurons in thehypothalamus, mostimportantly byneurosecretorydopamine neurons ofthe arcuate nucleus,

which inhibit prolactinsecretion.


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Prolactin has many effects, the most important

of which is to stimulate the mammary glands to

produce milk (lactation).

Increased serum concentrations of prolactin

during pregnancy cause enlargement of the

mammary glands of the breasts and increasesthe production of milk.

However, the high levels of progesterone during

pregnancy act directly on the breasts to stop

ejection of milk. It is only when the levels of thishormone fall after childbirth that milk ejection is

possible.


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Another effect, recently discovered by theUniversity of Paisley and the Technische

Hochschule Zrich, is to provide the bodywith sexual gratification after sexual acts

The hormone represses the effect ofdopamine, which is responsible for sexualarousal, thus causing the male's refractoryperiod. The amount of prolactin can be anindicator for the amount of sexual

satisfaction and relaxation. Unusual highamounts are suspected to be responsiblefor impotence and loss of libido


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The prolactin receptor, a member of the

hematopoietin/cytokine receptor

superfamily, is ubiquitously expressed by

cells in the immune system

Certain subpopulations of lymphocytes

synthesize and secrete biologically active

prolactin, which suggests that prolactin

can act as an autocrine and/or paracrine

factor to modulate the activities of cells ofthe immune system.


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Tumors of prolactin-secreting cells

cause amenorrhea and galactorrhea in

women Excess PRL is associated with

gynecomastia and impotence in men


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CHORIONIC

SOMATOMAMMOTROPIN (CS) OR

HUMAN PLACENTAL LACTOGEN

(HPL)

a polypeptide placental hormone structure and function is similar to that of human

growth hormone

modifies the metabolic state of the mother during

pregnancy to facilitate the energy supply of the

fetus

HPL is an anti-insulin.

No definite funcion in humans


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GLYCOPROTEIN

HORMONES


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GLYCOPROTEIN HORMONES

Each of the glycoprotein hormones isan ( : ) heterodimer, with the asubunit being identical in all membersof the family

The biological activity of the hormoneis determined by the b-subunit, which

is not active in the absence of the asubunit


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GLYCOPROTEIN HORMONES

The molecular weight of the gonadotropins FSH,

LH, and CG is about 25,000, whereas that of the

thyroid tropic hormone TSH is about 30,000

All members of the glycoprotein family

transduce their intracellular effects via the

receptor, G-protein, adenylate cyclase, second-

messenger system


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GONADOTROPINS

Responsible for gametogenesis and

steroidogenesis in the gonads


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FSH (Follicle-stimulating

hormone) a hormone synthesised and secreted by

gonadotropes in the anterior pituitary

gland


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hormone) In the ovary FSH stimulates the growth of immature

Graafian follicles to maturation

As the follicle grows it releases inhibin, which shuts off

the FSH production

In men, FSH enhances the production of androgen-

binding protein by the Sertoli cells of the testes and is

critical for spermatogenesis

FSH and LH act synergistically in reproduction


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FSH is a glycoprotein Protein dimer contains 2

polypeptide units, labelledalpha and beta subunits.

The alpha subunits of LH,FSH, TSH, and hCG areidentical, and contain 92 aminoacids

FSH has a beta subunit of 118amino acids (FSHB) that

confers its specific biologicaction and is responsible forinteraction with the FSH-receptor

The sugar part of the hormoneis composed of fructose,

galactose, mannose ,galactosamine, glucosamine,and sialic acid, the latter beingcritical for its biologic half-life

The half-life of FSH is 3-4hours.


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hormone) The gene for the alpha subunit is located

on chromosome 6

The gene for the FSH beta subunit islocated on chromosome 11 and is

expressed in gonadotropes of the pituitary

cells, controlled by GnRH, inhibited byinhibin, and enhanced by activin


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FSH

High FSH levels are typical in menopause

Diminished secretion of FSH can result in

failure of gonadal function(hypogonadism).


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LH (Luteinizing hormone)

a hormone synthesized and secreted

by gonadotropes in the anterior lobe

of the pituitary gland It is necessary for proper

reproductive function


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In the female, an acute rise of LH the

LH surge triggers ovulation

In the male, where LH had also beencalled Interstitial Cell Stimulating

Hormone (ICSH), it stimulates Leydig

cell production of testosterone


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Alpha subunit same as FSH

LH has a beta subunit of 121 amino acids (LHB)

that confers its specific biologic action and isresponsible for interaction with the LH receptor

This beta subunit contains the same amino acids

in sequence as the beta sub unit of hCG and

both stimulate the same receptor


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LH

However, the hCG beta subunit contains an

additional 24 amino acids, and both hormones differ

in the composition of their sugar moieties

The different composition of these oligosaccharides

affects bioactivity and speed of degradation

The biologic half-life of LH is 20 minutes, shorter than

that of FSH (3-4 hours) or hCG (24 hours).


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LH

The gene for the alpha subunit is located onchromosome 6

The luteinizing hormone beta-subunit gene is localized in

the LHB/CGB gene cluster on chromosome 19 In contrast to the alpha gene activity, beta LH subunit

gene activity is restricted to the pituitary gonadotropiccells

It is regulated by the gonadotropin releasing hormonefrom the hypothalamus

Inhibin, activin, and sex hormones do not affect geneticactivity for the beta subunit production of LH.


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LH

LH levels are normally low during

childhood and high after menopause in

women The detection of the LH surge has

become useful for people who want to

know when ovulation occurs


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Diminished secretion of LH can result in

failure of gonadal function (hypogonadism)

This condition is typically manifest inmales as failure in production of normal

numbers of sperm

In females, amenorrhea is commonlyobserved.


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Human Chorionic Gonadotropin

(hCG) a peptide hormone produced in

pregnancy, that is made by the embryo

soon after conception and later by thesyncytiotrophoblast


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hCG

Its role is to prevent the disintegration of thecorpus luteum of the ovary and thereby maintainprogesterone production that is critical for a

pregnancy in humans hCG may have additional functions, for instance

it is thought that it affects the immune toleranceof the pregnancy

Early pregnancy testing generally is based onthe detection or measurement of hCG.
http://en.wikipedia.org/wiki/Image:HCG_structure.png


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hCG

hCG is an oligosaccharide glycoprotein composed of 244amin acids with a molecular mass of 36.7 kDa

It is heterodimeric, with an (alpha) subunit identical tothat of luteinizing hormone (LH), follicle-stimulating

hormone (FSH), and thyroid-stimulating hormone (TSH)and (beta) subunit that is unique to hCG

hCG is encoded by six highly homologous genes whichare arranged in tandem and inverted pairs onchromosome 19

The two subunits create a small hydrophobic coresurrounded by a high surface area to volume ratio 2.8times that of a sphere. The vast majority of the outeramino acids are hydrophilic
http://en.wikipedia.org/wiki/Image:HCG_structure.png


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hCG is also secreted by some cancers

including teratomas, choriocarcinomas

and islet cell tumors hCG is extensively used as a parenteral

medication in fertility therapy in lieu of

luteinizing hormo


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As hCG supports the corpus luteum,

administration of hCG is used in certain

circumstances to enhance the productionof progesterone

In the male, hCG injections are used to

stimulate the leydig cells to synthesizetestosterone


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In the world of performance enhancing

drugs, hCG is increasingly used in

combination with various AnabolicAndrogenic Steroid (AAS) cycles.

hCG mimics LH and helps restore /

maintain testosterone production in thetestes


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Thyroid-stimulating hormone (also

known as TSH orthyrotropin)

is a hormone synthesized and secreted by

thyrotrope cells in the anterior pituitary

gland which regulates the endocrinefunction of the thyroid gland


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TSH

TSH stimulates the thyroid gland to secrete thehormones thyroxine (T4) and triiodothyronine(T3)

TSH production is controlled by a ThyrotropinReleasing Hormone, (TRH), which ismanufactured in the hypothalamus andtransported to the pituitary gland, where itincreases TSH production and release

Somatostatin is also produced by thehypothalamus, and has an opposite effect on thepituitary production of TSH, decreasing orinhibiting its release.


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TSH

TSH consists of two subunits, the alpha

and the beta subunit. The subunit is

identical to that of hCG, LH, and FSH The (beta) subunit is unique to TSH, and

therefore determines its function


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TSH

The TSH receptor is found mainly on

thyroid follicular cells

Stimulation of the receptor increases T3and T4 production and secretion

Stimulating antibodies to this receptor

mimic TSH action and are found inGraves' disease


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TSH

The alpha chain is located on chromosome 6

The beta chain is located on chromosome 1


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TSH

TSH levels are tested in the blood of

patients suspected of suffering from

excess (hyperthyroidism), or deficiency(hypothyroidism) of thyroid homone

P i il Ab l Pit it


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Primarily Abnormal Pituitary

Function

Higher than normal levels of TSH combined with highlevels of thyroid hormone (T3 and T4) may indicate

dysfunction of the hypothalamus and pituitary gland In this case, a high TSH is often produced by a benign

tumor of the pituitary (adenoma) Conversely, low levels of TSH, while blood levels of T3

and T4 are also low, indicates abnormally low function of

the pituitary, known as hypopituitarism

P i il Ab l Th id f ti


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Primarily Abnormal Thyroid function

On the other hand, abnormally high levels ofThyroid hormone, due to overproduction in thethyroid, results in low TSH levels

This occurs in diseases such as hyperthyroidismor Grave's disease Conversely, an underproduction of T3 and T4

caused by diseases such as congenitalhypothyroidism (cretinism), hypothyroidism orthyroid hormone resistance, gives rise to anincrease in the measured TSH.

PROOPIOMELANOCORTIN


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PROOPIOMELANOCORTIN

(POMC)

The POMC gene is expressed in both theanterior and intermediate lobes of thepituitary gland

The primary protein product of the POMCgene is a 285 amino acid precursor that canundergo differential processing to yield atleast 8 peptides, dependent upon the

location of synthesis and the stimulusleading to their production.


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ACTH

secreted from corticotropes in the anterior

lobe of the pituitary gland in response to

the hormone corticotropin-releasinghormone (CRH) released by the

hypothalamus.


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ACTH

ACTH acts through the stimulation of cellsurface ACTH receptors, which areprimarily located on the adrenocorticalcells

ACTH stimulates the cortex of the adrenalgland and boosts the synthesis of

corticosteroids, mainly glucocorticoids butalso mineralcorticoids and sex steroids(androgens).


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ACTH

Together with ACTH the hormones

lipotropin, melanocyte-stimulating

hormone (MSH), -endorphin and met-enkephalin are also released

ACTH is also related to the circadian

rhythm in many organisms.


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Cleavage sites are indicated by the numbers 1 to 7

and consist of the sequences, Arg-Lys, Lys-Arg or

Lys-Lys

ACTH- adrenocorticotropic hormone

CLIP- corticotropin-like intermediate lobe

peptide

MSH-melanocyte-stimulating hormone


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ACTH

Excessive production results in Cushingssyndrome causing:

1. Negative N, K, and P balance

2. Na retention

3. Glucose intolerance

4. Increased plasma fatty acids

5. Decreased circulating eosinophils andlymphocytes


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ENDORPHINS


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ENDORPHINS

Bind to CNS receptors like opiates and

may play a role in pain perception

MELANOCYTE-STIMULATING


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MELANOCYTE STIMULATING

HORMONE (MSH)

Stimulates darkening of the skin

POSTERIOR PITUITARY


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POSTERIOR PITUITARY

HORMONES

Nonapeptides oxytocin and vasopressin These substances are synthesized as

prohormones in neural cell bodies of the

hypothalamus and mature as they pass downaxons in association with carrier proteinstermed neurophysins

The axons terminate in the posterior

pituitary, and the hormones are secreteddirectly into the systemic circulation


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Neurophysin is a carrier protein with a size of10 KDa and containing 90 to 97 aminoacids thattransports neurohypophysial hormones alongaxons, from the hypothalamus to the posteriorlobe of the pituitary.

This protein is necessary to prevent diffusion ofpeptide hormones out of the axons

Hormones of the posterior lobe of the pituitaryare synthesized in hypothalamic nuclei and are

packaged in secretory granules with theirrespective neurophysins.

Vasopressin or antidiuretic


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Vasopressin or antidiuretic

hormone (ADH)

Arginine vasopressin (AVP), also known

as argipressin orantidiuretic hormone

(ADH), is a human hormone that is mainlyreleased when the body is low on water

It causes the kidneys to conserve water by

concentrating the urine and reducing urinevolume.


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ADH

A very similar substance, lysine

vasopressin (LVP) orlypressin, has the

same function in pigs and is often used inhuman therapy.


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Vasopressin is a peptide hormoneliberated from a preprohormone precursorthat is synthesized in the hypothalamus asit is transported to the posterior pituitary

Most of it is stored in the posterior part ofthe pituitary gland to be released into the

blood stream; some of it is also releaseddirectly into the brain.


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Vasopressin is secreted from the posteriorpituitary gland in response to reductions inplasma volume and in response to increases in

the plasma osmolality Secretion in response to reduced plasma

volume is activated by pressure receptors in theveins, atria, and carotids

Secretion in response to increases in plasmaosmotic pressure is mediated by osmoreceptorsin the hypothalamus


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ADH

Many factors influence the secretion ofvasopressin; for instance, ethanol andcaffeine reduce vasopressin secretion

The resulting decrease in waterreabsorption by the kidneys leads to ahigher urine output

Angiotensin II stimulates the secretion ofvasopressin

ADH


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Vasopressin acts on three different receptors,

termed V1a, V1 and V2. The receptors aredifferently expressed in different tissues, and exert

different actions:

1. V1a - vasoconstriction, gluconeogenesis in the liver,

platelet aggregation and release of factor VIII andvon Willebrand factor.

2. V1b - corticotropin secretion from the pituitary gland

3. V2 - control of free water reabsorption in the

collecting ducts of the kidneys (especially the

cortical and outer medullary collecting ducts)


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ADH

Activation of adenylate cyclase causesincrease in cAMP which leads to the insertionof aquaporin-2 (AQP2) channels (water

channels) into the apical membrane of thecells lining the collecting duct

This allows water to be reabsorbed down anosmotic gradient, and so the urine is more

concentrated.


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ADH

The vasopressins are peptides consistingof nine amino acids (nonapeptides)

The amino acid sequence of argininevasopressin is Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly, with the cysteine residuesform a sulfur bridge

Lysine vasopressin has a lysine in place ofthe arginine.


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ADH

Decreased vasopressin release or

decreased renal sensitivity to vasopressin

leads to diabetes insipidus, a conditionfeaturing hypernatremia (increased blood

sodium content), polyuria (excess urine

production), and polydipsia (thirst).


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ADH

High levels of vasopressin secretion

(syndrome of inappropriate antidiuretic

hormone, SIADH) and resultanthyponatremia (low blood sodium levels)

occurs in brain diseases and conditions of

the lungs


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Oxytocin

(Greek: "quick birth") is a mammalian

hormone that also acts as a

neurotransmitter in the brain In women, it is released mainly after

distension of the cervix and vagina during

labor, and after stimulation of the nipples,facilitating birth and breastfeeding


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Oxytocin is released during orgasm in

both sexes

In the brain, oxytocin is involved in socialrecognition and bonding, and might be

involved in the formation of trust between

people.


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Oxytocin is made in magnocellularneurosecretory cells in the supraopticnucleus and paraventricular nucleus of the

hypothalamus and is released into theblood from the posterior lobe of thepituitary gland

Oxytocin is also made by some neurons inthe paraventricular nucleus that project toother parts of the brain and to the spinalcord.


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In the pituitary gland, oxytocin is packaged

in large, dense-core vesicles, where it is

bound to neurophysin


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Oxytocin is a peptide of nine amino acids (a

nonapeptide)

The sequence is cysteine - tyrosine - isoleucine -

glutamine - asparagine - cysteine - proline -

leucine - glycine (CYIQNCPLG)

The cysteine residues form a sulfur bridge

Oxytocin has a molecular mass of 1007 daltons


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Oxytocin receptors are expressed by the

myoepithelial cells of the mammary gland,

and in both the myometrium andendometrium of the uterus at the end of

pregnancy

Due to its similarity to vasopressin, it canreduce the excretion of urine slightly

THYROID HORMONES


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THYROID HORMONES

Require the trace element iodine for

biologic activity

Thyroglobulin is the precursor of T4

(Tetraiodothyronine or thyroxine) and

T3 (Triiodothyronine)


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Thyroglobulin is produced on rough

endoplasmic reticulum has a molecular

weight of 660,000

It is glycosylated and contains more

than 100 tyrosine residues, which

become iodinated and are used to

synthesize T3 and T4

STEPS IN THYROID


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HORMONE SYNTHESIS

A Na+/K+-ATPase-driven pump

concentrates iodide (I-

) in thyroidcells, and the iodide is transported

to the follicle lumen


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In the follicle lumen, it is oxidizedby a

thyroperoxidase found only in thyroid

tissue.Thiourea drugs, which are antithyroid

drugs, act on this step


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The addition of oxidized iodide to tyrosine

residues of thyroglobulin is catalyzed by

the same thyroperoxidase enzyme,

leading to the production of thyroglobulincontaining monoiodotyrosyl (MIT) and

diiodotyrosyl (DIT) residues. This

reaction is called organification.


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The thyronines, T3 and T4, are formed bycombining MIT and DIT residues on thyroglobulinin a process called coupling

The thyroid is the only tissue that can oxidize I

toa higher valence state, an obligatory step in I

organification and thyroid hormone biosynthesis


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Lysosomal proteases degrade

thyroglobulin releasing amino acids

and T3 and T4, which are secreted intothe circulation

(Organification)

Thiourea

drugs


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*inherited enzyme defects occur, causing goiter

activity is primarily controlled by TSH


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T3 and T4 are very hydrophobic and require a

carrier protein for delivery to target tissues.

In the plasma, T3 and T4 are bound to a

carrier glycoprotein known as thyroxin-binding globulin (TBG) and are

disseminated throughout the body in this

form


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Drugs such as phenytoin and

salicylates compete with T3 and T4

for binding to TBG


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A peripheral deiodinase in target tissues

such as pituitary, kidney, and liver

selectively removes Iodide from the 5'

position of T4 to make T3 80% of circulating T4 is converted to T3.

This conversion is inhibited by

propylthiouracil (PTU) and Propranolol


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Thyroid hormones act by binding to

cytosolic receptors very similar to

steroid hormone receptors


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The thyronines act on the body to increasethe basal metabolic rate, affect proteinsynthesis and increase the body's

sensitivity to catecholamines These hormones also regulate protein, fat,

and carbohydrate metabolism, affecting

how human cells use energeticcompounds.


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In the embryo, thyroid hormone is

necessary for normal development.

Hypothyroidism in the embryo isresponsible for cretinism, which is

characterized by multiple congenital

defects and mental retardation

Effects of thyroxine


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Increased cardiac output

Increased heart rate

Increased ventilation rate Increased basal metabolic rate

Development of brain

Thickens endometrium


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Thyroid stimulating autoantibodies

(TSAb) also activate the human thyroid

TSH receptor, leading to thehyperthyroidism of Graves' disease.

TSAbs bind to the TSH receptor and

mimic the TSH stimulation of the gland

by increasing intracellular cAMP


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Any enlargement of the thyroid is called a goiter

Insufficient Free T3 or T4 results in hypothyroidism

causing slow heart rate, diastolic HPN, Sluggishness,

constipation, cold intolerance, and dry skin

Excess thyroid hormone results in thyrotoxicosis. Its

symptoms are the opposite of hypothyroidism


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HORMONES THAT

REGULATE CALCIUM

METABOLISM


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There is approx. 1 kg of Ca in the body,99% of which is in bone where it formshydroxyapatite crystals with

phosphates Ionized calcium, which is not

complexed with organic acids or bound

to proteins, is the biologically activefraction of calcium


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Low ionized calcium levels causes

tetanic convulsions, while elevated

calcium causes muscle paralysis and

coma

Albumin, which binds calcium, may

alter circulating calcium levels

PARATHYROID HORMONE (PTH)


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PARATHYROID HORMONE (PTH)

Parathyroid hormone (molecular weight

9,500) is synthesized and secreted by

chief cells of the parathyroid in

response to systemic Ca2+ levels


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PTH Is Secreted as an 84-Amino-Acid Peptide

The immediate precursor of PTH is proPTH,

which differs from the native 84-amino-acid

hormone by having a highly basic hexapeptide

amino terminal extension


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The primary gene product and the immediateprecursor for proPTH is the 115-amino-acidpreproPTH

This differs from proPTH by having an additional 25-amino-acid amino terminal extension that ishydrophobic

PTH 134 has full biologic activity, and the region2534 is primarily responsible for receptor binding.


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Structure of bovine preproparathyroid hormone. Arrows indicate sites cleaved by

processing enzymes in the parathyroid gland (15) and in the liver after secretion of the

hormone (45).


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Parathyroid hormone also exists in

storage vesicles

As much as 8090% of the proPTHsynthesized is degraded before it enters

this final storage compartment, especially

when Ca2+ levels are high in the

parathyroid cell

PTH


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PTH

An acute decrease of calcium results inmarked increase of PTH mRNA

The role of PTH is to regulate Ca2+

concentration in extracellular fluids PTH acts by binding to cAMP-coupled

plasma membrane receptors

The body response to PTH is complexbut is aimed in all tissues at increasingCa2+ levels in extracellular fluids


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PTH induces the dissolution of bone by

stimulating osteoclast activity, which leads

to elevated plasma Ca2+ and phosphate

In the kidney, PTH reduces renal Ca2+

clearance by stimulating its reabsorption

At the same time, PTH reduces the

reabsorption of phosphate and therebyincreases its excretion in the kidneys


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PTH acts on the liver, kidney, and

intestine to stimulate the production of

the steroid hormone 1,25-

dihydroxycholecalciferol (calcitriol) or

Vitamin D, which is responsible for Ca2+

absorption in the intestine


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Hyperparathyroidism is usually due to cancer

causing high ionized calcium and low serum

phosphate levels.

Secondary hyperparathyroidism may be seenin patients with progressive renal failure due

to inefficient calcium absorption caused by

decreased activity of vitamin D which is not

activated by the kidney

1,25 -DIHYDROXYCHOLECALCIFEROL

(VITAMIN D)


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(VITAMIN D)

The only hormone that can promote the

translocation of calcium against the

concentration gradient which exists

across the intestinal cell membrane

Deficiency causes Rickets in children

and osteomalacia in adults, both due to

deficient bone mineralization


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Vitamin D is normally found in persons

exposed to sufficient sunlight

1,25 -DIHYDROXYCHOLECALCIFEROL ORCALCITRIOL [1,25(OH)2-D3], is the most

potent naturally occurring metabolite of

vitamin D

(calcidiol)
http://en.wikipedia.org/wiki/Calcidiolhttp://en.wikipedia.org/wiki/Calcidiol


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In the skin, Vitamin D is produced from 7-

dehydrocholesterol during the photolysis reaction

(calcidiol)
http://en.wikipedia.org/wiki/Calcidiolhttp://en.wikipedia.org/wiki/Calcidiol


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In the liver, Vitamin D-binding protein binds Vit D3 from theskin or intestine where it undergoes hydroxylation in the

endoplasmic reticulum (by 25-hydroxylase). This reaction

requires Mg NADPH and oxygen


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In the mitochondria of the renal proximal convoluted tubule,25-mono-hydroxy D3 from the liver is converted to its activeform by hydroxylation at position C1 (by 1 -hydroxylase)


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NADPH, Mg2+, molecular oxygen, and at

least three enzymes are needed for the

activation of Vitamin D in the kidney:

(1) a flavoprotein, renal ferredoxin reductase

(2) an iron sulfur protein, renal ferredoxin

(3) cytochrome P450


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Calcitonin (CT)


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Ca c to (C )

32-amino acid peptide secreted byparafollicular C cells of the thyroidgland

Employed therapeutically to relieve thesymptoms of osteoporosis

formed by proteolytic cleavage of a

larger prepropeptide which is theproduct of the CALC1 gene

CT


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Calcitonin has the counter effects of

parathyroid hormone but most

evidence indicates that calcitonin is of

very little physiological importance to

humans. Rather, calcium and

phosphate homeostasis is primarily

under the control of PTH.


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CT has been shown to reduce the

synthesis of osteoporin (Opn), a

protein made by osteoclasts and

responsible for attaching osteoclasts

to bone

ACTIONS OF CT


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Calcitonin reduces blood calcium levels in

three ways:

Decreasing calcium absorption by the

intestines

Decreasing osteoclast activity in bones

Decreasing calcium and phosphate

reabsorption by the kidney tubules


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CT is a satiety hormone

It Inhibits food intake in rats and monkeys

It may have CNS action involving theregulation of feeding and appetite


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Like the PTH receptor, the receptor of

calcitonin is a serpentine G protein-

coupled receptor with seven membrane

spanning regions which is coupled by Gs

to adenylyl cyclase and thereby to the

generation of cAMP in target cells.

hypothalamic pituitary thyroid calcium 1-13

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