Lecture #:3

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Modlcol Commit

The Uniwttltv of,_."

Endocrine system

Subject :Adrenal glan<J' Doctor : Salim Khresha #.3

Done By: Slides

Date : 1 7/3/2013

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Aldoslorono

Anterior pllullary

ACIII

Cortisol

FIUUI\E 41·3 Tho rn~llllntlon uC corLi!;ol sccrotionlly Lho laypothalamic·pituitary•auronol axis. A vnrloly ol Inputs lo'tho hypolhalnmus F>limulnlo corlicolropin-roloasing hormone (CRH) secro• lion, and In turn ndronucorlicolrupin (A C'J'Jl) nnd corll!lol Hocrotiort'Cortisol oxorts nogalivo tootll>nck nt both tho hypothnlnmlc nnd tho pilu itnr'y lovuls. ALJH, Aulidiuretic hormone; LJHEA·

I , I • ,. ! .. ' . ~ .

·.' ... ! \ .,

\" s. dehydroepiamlroste10ne sul!ato. 1 .

1- ACT\-\ is ali C\nieriar pHuiiary polypcpiidQ hormon·e:· ·.- .. : ~- ·- · .. ··1:

z- R"9Ulaitl~h~ 'rowth at~cl s•crttion ofthe adrellal.cc:.rt~x.:· .. · .·.·,::J '3" lts most 11'11porlant tar,tt 9land hormone i~ cor!Tlt, , .·· .. .-:. ,n 4- teius A CTH synthesis and stcf'ttion beginjuU b• or~ ...... ..

the dtv-elopment of' ih.adttnb{ c~r~ex.. .·· S"-1he re~u!aticn of A CTH s~crt:t.ion is a1non9 -the m()si

comptex. of ~It th~ pituitaflJ h crmcpc.s. _.·.i

G- A lt/lo1<9 h the 11'1 tc han ""'5 .ra, ••c ~ .fb rm • F c:onlrot are. not complc1el y · ...... ·, ; .. ::/,>j clu,.., the CRH i.s ihe imp orla11t w•<licrtor. A J) ~ al3CJ txhiblis :· .· .. _:.·.~.:._·.;_.··;_._:_ ... '·.··_:_.-~_:_:~.:;,· . .::,!

cortico'U'opil1-r4.L••sin~ a~tiuify ...... .

·A C1!-l sectetion rt!spoJ'\ds most striki119ly to st:-esJ.f~~-~;::;_',·.':'·_~_.:;\-(.V:;~ riimuli

1 a ff.spon5e ~hat is crifical to su,vi~a~;_; ~ ..... _ ........ ·.::::···:,.-_~

;E><1Yaad.r~naL actions of A CTH: lipolvsis ~ciMSH I... Ike~~

'.

{

lnlocllon Acotylcholino ,

1 Stress I TAroum1a , y-Aminobulyrole

nos! 10110 Anxlotyfr Sorotonin L------' Surgory 1Deprenlon Norepinephrine (a)

Hypoglycemia l !

Endorph_in _____ __,

Slup/wake~

.d ). Hypothalamus Fee lng~

Androslonedlone DHEA·S

Aldosl"rone

Anterior pllultary

ACTH

Nourolrommitlors

c/o~~

~-

Carl hoi

.,

FIUUr\E 41·3 Tho re~rulntion or cortisol sccrolion by lho hypothalamic·pituitary·ndrennl axis. A vntloty or Inputs to tho hypothalnmus r;thnulnto corllcoltopln-roloaslng hormone (CJIH) secro· lion, om\ In turn ndrollocotllcoltopln (1\G'/"11) nntl corllnol nocrollort""Cortlsol oxerts 11egnllvo reotlbnclt at both tho hypothnlntnlc nutlllro pituiLnr'y lovul[l./\DH, AnlitHurelic hormone: VHEA· S, dehydroepiaudrosterone sutrate.

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F i g. 1 2 . 1 5 T lw a n a c o n1 i c l o c a c i o n o f c h c a d r c IL \. ~ ,:; l a n d s an cl c h t:

organization of their blood supply. Nort rhac che:- ;ucerial supply IS

via n1any sn1all arteries which origi nace from chc: ::orta. The venous drainage is via a largt cc:ncral vein chac c:n1pcic:s i:-:co the inferior

vena cava.

l__, __ _

~~

~------ ----··-----·------·

Ti\BLE 1!1-2 Major Adrenocortical Abnormalities

ABNORfttAUII' CONDl'TION CAUSE SYMPTOI\tS -----···· ---------------------------------·-----·

£,;cess aldosterone

E.:r::cr.ss corli!wl

r:: . .xcess llllrlrogr.n

JJt'licil'nl cln·tisol turrln/tlosfl'r .. •n··

JJI'ficicn/ coT'lisol

Conn's .;yndrome (primary hypera!dosteronism)

Second<J.ry hyperaldosterClnism

Cu~hirrg's syndrome

1\dren· gcnit.ll syndrnnrc

;\ddi::, n's di';•:;l.<;r' (prirn;11y <ldr•·r" r:nrtic;d insr rfficicncy)

~;,_.,:,lll'lary ~rlrcnor:urtical

iw.u ffl,~ienc:;

Hypersecreting tumor of zona glomerulosa

Inappropriately high activity of renin-angiotensin system

bces.s CRH and/or ACfH caused by hypothalmic or vnterior pituitary disease; ~:y~,e~e~r~ti_n~ tl!f!lOr of inne. layers r,f adrenal cortex; AOII-secreting tumorinlu1~

Lxk of emyme in cortisol

pathway

Dcstructioro or idiopilthic iltrophy of adrrn;JI con ex

Insufficient /\Cil! caus(~d by hypolh<J.lamic or anterior piluitar:-· fai.ure

Hy-pernatremia; hypokalemia; h)-pertension

Glucose excess; protein shonage; abnormal fat distribution

h)oppropri<~te

mil$culinization in all but adult males

Related to corti.snl deficiency: poor r~pons~ to strcs.<;; hypoglycemia; li!ck or penni.ssiveness for many metabolic iiCtivities

Related to aldosterone deficiency: hyperkalemia; h'f-ponatremia; hypotension (if severe enough. fatal)

-, I

?··---

Adrenal androgens (DHEA ·and androstenedi­one). DHEA ·and androstenedione are andro­genic steroi9s produced by the :ion~ reticularis. These compounds have only \Veak androgenic acti~_ity, but i~ the testes, th~y are· converted to testosterone, a more potent androgen. The precursors .for .the adrenal. androgens are 17-hydro~yp:egnenolone and 17-hyc~ro:xyprogester­one, which are converted to androgens by re­moval of the C20,21 side chi:ti#.rn· ~ales, adrenal androgens are. of little sig0·if1can,ce; the testes prodLJ.ce th~ir ovvn te~tosterone from· choles-

.· terol ~nd do not.require thE. adre~1al precursors · .-: _ --~- .:·._ ~- ~--~. In females, ho~.vever, the adre-

__ nal cortex is the major source of androgenic compoun9s. ·

Actions of Adrenal Androgens

. Females: presenc<; of pubic C\n:i : ~ . · ~Il~ary hair; libido _ -: W~alcs: same as tes-tosterone

.· .

~ .. ;:,..~·.;:-:_:·-':,; .... ~.~ ·~ ...... -~-~ .. ~~ ". ,: .::: ~~:,; ;. 0::,~1- i:;~;:;~\flf;{~::

• ~ • J -.. · ~ ~ ..

:'·

Angiotensin 11 ,.;~~~'; ' .· ..

-· ·.\·•,<, :t,. :. Androgens

' .• ~ ··.-. r.

· Mlneraloi::orticoids Glucocortlcolds ·

RE 9-21. Biosynthetic pathways for glucocorticoids, mineralocorticolds, and androgens in the adrenal cortex. ACT~' adreno- J ·Jtropic hormone.

Actions of Adrenal Androgens

Females: presence of pubic and ~"'<ll~ary hair; libl¢~

Males: same as testosterone

iO

;o

HO

HO

o?

Cholesterol

Prognonolono

CH3 I c=o

CH3 I c=o

17 cr. -Hydroxypregnenolone

0

De hydroepiand ros terone

FIGURE 5

.,..

)--

26

27

0

HO

Progostorono

CH3 I c=o

CH3 I c=o ---OH

17 cr.-Hydroxyprogesterone

0

Androstenedione

Estrone

0

Testosterone

HO

Estradiol

Biosynthetic pathway for androgens and estrogens. In the adrenal, the sequence docs not usually proceed all the way to testosterone and the estrogens, which arc the gonadal hor­mones. Because the cells of the zona glomcrulosa lack 17o.-hydroxylasc, these reactions can occur only in the inner zones.

OH

OH

Renal interstitial.

fluid

' I

I !Nucleus i

: l

Principal cells

I - I -~

\

mANA i i I I Proteins(& @ " 1

Tubular lumen

I @J~§V ___ -+-~ ~Nac

:ff~ { I' Na+ ~ 1+

I • 4( Of\\Na+

II.. Mitochondrial Amiloride enzymes

\, ________ _

Figure 77-4 Aldosterone-responsive epithelial cell signaling p 3th­WJ'j':). ENaC, epithelial sodium channel proteins; MR, miner·alo­corticoid receptor. Activation of the MR by aldosterone can be an i:Jgonized with spironolactone. Amiloride is a drug that can be used to block ENaC.

'

The most important stimuli for aldosterone are (1) increased extracellular potassium concentration and (2) increased angiotensin II levels, which typically occur in conditions associated with sodium and volume depletion or low blood pressure. The increased secretion of aldoster­one associated with these conditions causes renal sodium and water retention, helping to increase extracellular fluid volume and restore blood pressure toward normal.

In the absence of aldosterone, as occurs with adrenal destruction or malfunction (Addison's disease), there is marked loss of sodium from the body and accumulation of potassium. Conversely, excess aldosterone secretion, as occurs in patients with adrenal tuinors (Conn's syndrome), is associated with sodium retention and decreased plasma potassium concentration due, in part, to excessive potas­sium secretion by the kidneys. Although day-to-day reg­ulation of sodium balance can be maintained as long as minimal levels of aldosterone are present, the inability to appropriately adjust aldosterone secretion greatly impairs the regulation of renal potassium excretion and potas­sium concentration of the body fluids. Thus, aldosterone is even more important as a regulator of potassium con­centration than it is for sodium concentration.

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Figure 26.7 Relation of a nephron's structure to its three basic functions: glomerular filtration, tubular reabsorption, and tubulm· secretion. Excreted substances remain in the urine and subsequently leave the body. Fur any subs Lance S. excretion rate of S = filtration rate of S - reabsorption rate of S + secretion rate or S.

~ Glomerular filtration occurs in the renal corpuscle; tubular reabsorption and tubular secretion occur all along the renal tubule and collecting duct.

Afferent !Ill

arteriole

Efferent "' arteriole

Renal corpuscle Renal tubule and collecting duct

Peritubular capillaries

;~ 0 Tubular reabsorption from fluid into blood

{) Tubular secretion from blood into fluid

Unne (contains cxcrctccl ::;ubstances)

Blood (contains reabsorbed substances)

Reabsorption. Angiotensin II is perhaps the body's most powerful sodium-retaining hormone. As discussed in Chapter 19, angiotensin II formation increases in circum­stances associated with low blood pressure and/or low extracellular fluid volume, such as during hemorrhage or loss of salt and water from the body fluids by excessive sweating or severe diarrhea. The increased formation of angiotensin II helps to return blood pressure and extra­cellular volume toward normal by increasing sodium and water reabsorption from the renal tubules through three main effects:

1. Angiotensin II stimulates aldosterone secretion, \Vhich in turn increases sodium reabsorption.

2. Angiotensin II constricts the efferent arterioles, which has two effects on peritubular capillary dynamics that increase sodium and water reabsorption. First, effer­ent arteriolar constriction reduces peritubular capil­lary hydrostatic pressure, which increases net tubular reabsorption, especially from the proximal tubules. Second, efferent arteriolar constriction, by reducing renal blood flow, raises filtration fraction in the glo­merulus and increases the concentration of proteins and the colloid osmotic pressure in the peritubular capillaries; this increases the reabsorptive force at the peritubular capillaries and raises tubular reabsorption of sodium and water.

3. Angiotensin II directly stimulates sodium reabsorp­tion in the proximal tubules, the loops of Henle, tlze dis­tal tubules, and the collecting tubules. One of the direct effects of angiotensin II is to stimulate the sodium­potassium ATPase pump on the tubular epithelial cell basolateral membrane. A second effect is to stimulate sodium-hydrogen exchange in the luminal membrane, especially in the proximal tubule. A third effect of angio­tensin II is to stimulate sodium-bicarbonate co-transport in the basolateral membrai1e (Figure 27-17).

Thus, angiotensin II stimulates sodium transport across both the luminal and the basolateral surfaces of the epithelial cell membrane in most renal tubular segments. These multiple actions of angiotensin II cause marked sodium and \Vater retention by the kidneys vvhen angio­tensin li levels are incre;J.sed and play a critical role in permitting the body to adapt to wide variations in sodium intake without large changes in extracellular fluid volume and blood pressure.

Renal interstitial

fluid

Tubular cells

:aNa+ ®

Hco;

Tubular lumen

Figure 27-17 Direct effects of angiotensin II (Ang II) to increase proximal tubular sodium reabsorption. Ang II stimulates sodium sodium-hydrogen exchange (NHE) on the luminal membrane and the sodium-potassium ATPase transporter as well as sodium-bicarbonate co-transport on the basolateral membrane. These same effects of Ang II likely occur in several other parts of the renal tubule, including the loop of Henle, distal tubule, and collecting tubule.

FIGURE 33.8 The formation of angiotensins I, II, and Ill from angiotensinogen.

~Renin

Angiotensinogen

His~ ~R Angiotensin I

~Converting enzyme

Ex9 Angiotensin II

~Aminopeptidase

@ lie His~ Angiotensin Ill

• Angiotensin Ill is as potent a stimulator of aldosterone secre­tion as angiotensin II.

®. SALIVARY (No,J.

·T\ GLANDS t K i -...

RENAL TUBULES (~a;

r1 l_/ J.

INTrSTINES~~at /(('·

l2J (No.l­SWEAT GLANDS l tc 't

@ ACTH

t:.P, t:,V, t:.(No}, t:.(K) ~

"'-......__ ".'I/ l ALDO~>TERONE ~ _ - @j

~' J

I

BETA-ADRE:NERGIC l\ STIMULATION

~~ JGA OF KfONEY

~ ADiiENAL (ll(No)J,

CORTEX (O(KJ f fij;

~ ANGIOTENS.N :'7

,..

' !SHORT FE£0BACK lOOP) I 1

RENIN t RENIN SUBSTRATE ---t ANGIOTENSIN I (0£CAPEPiiOE l (LIVER)

T ESTROGENIC

AGENTS

IF£EDBACK LOO?)

L~~~) ({'

ANGIOTENSIN I! !OCTAPEPTIDE l

l" VASOCONSTRICTION

_ _____,, ·._

(HEPTAPE?TIQ_,

I AMINOPEPTIDASE

L__ . FIGURE 5-18: The physiologic factors controlling aldosterone secretion rate (C.E. = enzyme) .

...... ~.

converting

·.

668

•' .:

··" Em.locriue System c/· ..

Homorrhooo Uprlghl posluro

Sodium doprlvallon

j} t Exlrocellulor lluid

volume

Polossium load

+-t' t Plasma polonium

~

Aldosterone

-+-t+ Angiotensin II

~~tro.­L:j~W~

Angiolonaln I

Angioleminogon

Convorling enzymo

~ ~

.•;

FIGUnE 11-0 'l'l1e IP.~Julnliou of aldosterone secretion. Activation of the renin-angiotensin sys· lP.II\ I~· IC'R!HJ.tsr. to hypuvolo1uin is ·.:.IJ !JICd:..J!,,:,lilllt stimulus to aldostorono production. Elova· tion of plnsuw polnssiulll is lhu uthor lllojor sLilllulus. . . ,.

'•: --· .. -........ , .. ·· .. .-·~J /~>· !' .. 1

·,.

\ \

.J

..... .:.-

TABLE 5-3: Physiologic Actions of Glucocorticoid Hormones

1. Carbohydrate ,\tfetabolisrn: stimulates gluconeogenesis; increases glycogen content in liver_ and glucose concentrations in blood: may also decrcas1: peripli.cral utilization of glucose. -

,)

2. Protein Metabolism: induces marked losses of nitrogen in urine as protein is catabolized to .<-X-'(

form glucose.

3. Fat Metabolism: increases total body fat at the expense of protein; leads to centripetal redistribution of fat.

4. Water Metabolism: enhances water diuresis by preserving the rate of glomr;::-u]ar filtration.

5. Hematologic Effects: decreases lymphocytes, basophils, and eosinophils; increases neutrophils; total white blood cell count rises slightly: red blood cell count rises.

6. Central Nervous System Effects: may control threshold for electrical excita.nility of the brain; psychiatric disturbances are common with both lack and excess of cortisol.

7. Gascrointescinal EjJects: production of gastric acid increases and pepsin decreases; the tendency for peptic ulcer formation increases \'l.'ith increasing concentration of cortisol in plasma.

B. Bone Metabolism: high levels inhibit formation of protein matrix of bone; this may lead to demineralization of the bone and osteoporosis.

9. Cardiovascular System: m_ai11tains sensitivity to pressor effects of catecholc.:.nbes.

10. Mesenchymal System: alters connecli\•e tissue response to injury, namely, decreased hyperemia .. exu"datiot?-, and cellular infiltration. This·illustrates the antiinflammatory action of glucocorticoid hormones.

11. Immunologic 'Effect5: high concentrations of glucocorticoids in blood lyse fixed plasma cells and lymphocytes, thereby decreasing antibody production .

. .... ··--.····--·- . -· .. --·--- ------~----~ ~

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.. ;:._~ ..:.:-. .:". -·· :· · .. ---~:~-::~··· • ~-:-;··= .. -. · ... ,.

~ . .. - .. ; ·:=:~w?~ __ .. _. .. - ... :~---·-~-=~·---·.· : . . . 7- .

.._ Role of the fetal cortex. In vitro studies of primate adrenals and estimation of steroids in umbilical venous blood showed that th·e fetal adrenal is capable of steroid production at an early stage of gestation!Giucocorticoids_ in !he _fetus are involved in a number of important processes:

I Production of surfactant from type II cells of the alveoli of the lung-a lack of which leads to the respiratory distress syndrome in newborn infants. 2 Development of hypothalamic function and of the thyroid-

. . . p1tu1tary axis. 3 The sequential changes of placental structure and in the ionic composition of amniotic and allantoic fluids during develop­ment. 4 They are most important in the initiation of the endocrine changes of the fetus and mother ~rhich are responsible for par­turition. 5 The development of hepatic enzymes, including those in­volved in gluconeogenesis. 6 Induction of thymic involution.

--"'==========="'""'="·,.,..,...··..,..·· -----:?· . --·· -·- -·-- --· --

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TABLE 9-ll. Actions of Adrenocortical Steroids

Actions o~ Glucocorticoids

Increase gluconeogenesis Increase proteolysis (catabolic) Increase lipolysis · Decrease glucose utilization Decrease insulin sensitivity Anti-inflammatory Immunosuppression Maintain vascular

responsiveness to catecholamines

Inhibit bone form~i;•m lncrt:ase (jFf< Decrease RE;"vi sle<.!p

Actions of Mineralocorticoids

Increase Na • reabsorption Increase K• secretion Increase H• secretion

Actions of Adrenal Androgens I

Females: presence of pubic and a.xillary hair; libido

Males: same as testosterone

'---.

(

'l

_/ .; .,

.:J ·II ·.·· ._-.!

----l

Stress response -increased vascular lono

Fat cells­Increased lipolysis

--t-------j Cortisol

Increased mobilization of

glycerol and fatty acids

~---:>

-----1

Liver Increased

gluconeogenesis, · glycogenesis,

glycogen storage, and enzym.e activity

(e.g. glucose ... 6-phosphate)

Fig. 12.18 The princip:tl

physiological anions of chc

gkcoconicoi<.l hormone,

cor~ isol.

Immunosuppressive and

anli-innamm<Jlory actions

Skeletal muscle

and other tissues

Increased mobilization

of amino acids

1 Some Effects of Glucocorticoids l £E¥1MitH§f'IWtM 'fi'W4Hdf¥M421 9%i'h851 t AI"' C&H¥ tU¢' It 41" fi >«>Nth I!*I{PQIIS ijitWfd*¥11tiM!iftl4ji\ZWtzt:ttri

Tissue

Central nervous system

Cardiovascular : system

Gastroin tcs tina! tract

Liver Lungs

P~tuitary'

IGdney

Done

Muscle

I';'

!Jnn1une systczn (sec .text)

'I i't:, ',

Connective . tissue .

Effects ;.'".: ·. 1:, • .• ·, ,; ''"·.··I

Taste, hcari ng, and smell T in acuity .'\vith .. adrcn:d cortic:-~1 in.sufTicicncy :-~nd lin

Cushing's di.o;c~lsc . 1 Corticotropin-n·lc:a~ing honnonc (sc..·c tcxt) l AD H Sl"C n:cion Maintain 5c:n.sitivity co c..·pincphrinc and

norc:pi n<.·ph ri n c:

T Sensitivity co v:-~soconscrictor :tgcnt'i M:-~intain n1i<.:roc.:irculation . •,: :' ,- .· : T G:-~stric acid sc:crc:tion :r: . .. ·.·. :. , .. ,. 1 G:-~scric n1ucos3l cell prolifc:racio.n : · T Gluconcogcnc:sis 1 . . :~ •• ,

1 M:-~turation and surf.1cc:-~nt p~o~uctiori during, r 1 d 1 · · ' · ·, !.· 1cta c:vc: opn1en t . · ::. ·. . . .... . : . . ..

l ACTI-I secretion (acute) 'and 's}rnthcSis · : · · ... ~.' • !\ ~ ' r . , •• \ ·• • I \ If ~ I

(chrontc) · . · · .. · ···· .. · .... I· • •i I

T GFR ~ .. ·. ·.'r , , . , 1 I •' : , .· ·• : i;: ,:· ......

. •·

Nc:edcd to t·xcrc:tc: dilute: unnc ··1' :.-

T I~csorption ·· · .. :.:.c. 1 Form:ttion · ·: · .. ·:,;·._....... . . : 1 Fatit,ruc (probJbly sccondJry

1 to· carJ.i.ovJscular

actions) T Protein C;!t.lbolisrn 1 Glucost: oxicbcion

r 11 s ul in '\l.ll' it i \'it y Protl·in syntiH:~i'

..

l 1 1 l

Ma\s of thynnt~ and lymph noc.l<.·s Blood conceJltr.Hions of c:o!\inophil.s, ·and lyn1phocytl'S

basophib,

l Ccllubr inununity l Activity of fibroblasts l Colbgc:n synthL·sis

• I I • ,I\. _I .:_

I·. . : ', ,_:(:.:·- ·• . . , 1 ::. • • ~ . . ' • • •

''• . ,> r j .•

1-' ;,

' .··!.,I

ADI-I, nntidiurctic hormone; ACri-r, ildrenocorticotropic hormone;· GFf{, glomerular fil tr(l tion r11 tc. . :

I

----:-;--· -·-"4·---------~·--·--·· ·---------- ···-· ... - . ... . . ·---.. ·-·· -·--······ r ·-- ----------~--------: . ~~~::~::i~:i:r: potent, accounts for about 95 ;c;;cc;.;.:·~f a~-\' .

, i 'glucocorticoid activity) . : .~rr·,:,.•:: ::;',;;;:.;.:.~._".I: ,• r: : : ':'; ·: • 1 • Corticosterone (provides about 4 per cent of. total•·glucocorti-. ·:. ·, \' ;.~,:>~J.~ .·. coid activity.· but much less potent ·than cortisol)::;.::_'';'.:\\·.;:i:~>:: '·<·. · · ·.· .~:·! I ••• :.

1• L .. • Cortisone _.(synthetic,· almost as ·potent. as' cor:tiso~) :.:

1

'/;:\.'\~t.;f;;,;:;:: :.:1,· · ... :_·,. ·:; ~':~'·<.::1 1: •; Prcdniso: 1C (synthetic, _four ti mcs as ·:po~cnt ·as·c<?r:t,isc_J):;~:;:: .. :.\··~· >.:· : ii .. · :\:·: .:: .. ;. !-" • .. Methyl prednisone (synthetic. live times ~l.s potcnt!:u~.;.c9rtisol) .. ·· ·.-:.,;

: .. : :. j\_:_3~x.~~11ctbasonc · (synt~1ctic,. 30 tir~es·as .rot~nt ~:f;!·~~~'~·~:~;~,~-;·:':;.:.-~·~y:~;:\ !

·t-·

l I I.

.. . . .. . . .. . ... . . . .. . .

\ I --

~~te

CH3

I C=O ~0--<

?- cxr' , > I j - ~

1-':0 ~ C ... V:~s~-=0

Andr~::::.-"'-".:~e

y

..\C!re~ai ~en.s . ; teS"tcSieiooe · ·. :~ ·-~~tra)e-~:'"~·-·

· :~ estra.::fd-17 .B .. ·- -. ~- ~ -: · .. ,/· .:~- :

~

HO

Pregneno:One

'f

Dehydroepiandrcsle'VI'le

0

-~X.?r~~e--;.:;. (cor:tisol} -.·;"

CH20H

I C=O

,.

1

CH3 I

c==o

CH20H

I C==O·

11-Deoxycor:ic:oster.:.r.e

...

;..;.~""'fi·~:.---·-

Corticos!erone :c-1 .. :.:-::•-:-:-e-..:·-::· ·:

CHpH I C==O

~

0

j)8#(~~:,] ......

Fig. 12..17 Th<" princip:ll steps in rhe synthesis o( rhe adrenal steroid hormor.es (rom cholesrtrol. Con:isol is rhe princip-.!.1 glc.:w:on:!coid

2.0d Jldosttrone is rhe princip:U mintr.docorricoid. _ .___)

_.:;:.\:-;f.::·,~· -· _,

y-;,~tii' , : -'

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'I ' • o ; : •; ~ ;' I

:~.

., :

···'

.. -. (. : \

I '. ', ~

·.' '-+-- ':I 0· ... ..

I:.,,

c ... ·;.-, .. ·-- :;

...... .... _._ .. :\, :-·

·';'.·

_.··.

ro E_ V'l

ro - \I"\ .. , O..-o ·-0 N ~ . - (],)

~ +-''. • V'l

1.r) 0 .• """ u-....., ·-

-·-·-··-------0 '---·~ ----

-0 V1 ,....... ·- ~ t:: 0

....._, u

--

0 N

0 m

01 c ·--o c ·-..0

I

-o ·-0 \-Q.)

+-' V"'

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-~ co u ......... c ·-Q.)

+-' 0 \-

0..

. -----··-----···

...

c ·-E ::J

.0 --<I:

\

20

16

12

Cortisol (mg/dl)

8

4

0 12 4

Midnight

~------------------AwakP. I

8 12 Noon

Time elapsed (hr)

4 8

50

25 ACTH (pg/ml)

0 12

Midnight

FIGURE 49-5. Rhythm of ACTH and cortisol. The conicotrophs release ACTH in a circadian rhythm, grcJtcr in the cJrl}" m,,rnm~ lwurs and less late in the afternoon and early eYening. Superimposed on the circadian rhythm is the effect on the conicNrophs of d:c pulsJtile secretion of CRH br the hrpothabmus. Thus, ACTH levels exhibit both circadian and pulsatile bcha\·ior. ~otice that. .;::\ .. '~::;h bL>th ACTH and conisol are secreted cpisodic:llly, the duration of the ACTH bursts is briefer. renecting the slwncr h;1lf-lifc ,1f .\CHi ::·, [11.1<-m:l

ACTH, adrenocorticotropic hormone; CRH, conicotropin-releJsing hormone. (Data from Wilson JD et a!: Wil!iJms Tcxtb,,,,~ ,,f L.:nd,)Lr\­nology. Philadelphia, WB Saunders, 1998.)

-

.' I

>­u c Q) ...... 0 a. Q)

> ·;::: ro Q)

0:

>-ro -o ......... 0 E --....

c 0

·;::: ::J .0 ·c ....... c 0 u Q)

> ....... ro Q)

a:

COHTISOL

1.0 r-

0.5 -

·- --·--··-·--·-·---- -----·----····

ALDOSTERONE

(n) Glucocorticoid activity

o~----~--~----L---~----

1.0

0.1

0.01-

(b) Mineralocorticoid activity

.___CI __ ----·---

100 r--

10 -1 ~

0.1 -

10T 50

I I

(c) Secretion rate

(d) Glucocorticoid contribution

100L 50 I ..__-".._ _ _...\ · ·l.._ __ (e-)-Mineralocorticoid _ . . contribution

Fig. 3·5 A con1parison of cortisol and of aldosterone. Glucocorticoid activity was n1easurcd as ability to increase glycogen in the liver: cortisol is very potent in this assay. Mineralocorticoid effects were measured in tern1s of the ability to reduce the ratio of the excretion of sodium to the excretion of potassium in urine; aldosterone is much more potent. However, since the rate or secretion of cortisol is much higher, it can have signi~canttnineralocnnic,)id ciTcus (sec d and c).

· .. ''

. ·,·

\ ~

\ I I \ r

I '

Cortex Medulla

Zonil t;lo111erulosa (11ineralocorticoids)

'"

-ZlH~<l raso:.·fculatn (Glucocort1co1tls and

1\ntlrogcns)

Hcliculc:~ris (Glucocorticoids c:~nd

Androgens)

( Cil tecllo 1 ar.Ji nes)

l'l(;\JHE !i-1: Crw;s t:oc:linll lh1 n11gh lhr! ndrlltlld, iii1L~Irnllng ll10 runJor auuJivlsluns nnJ colllnyors 11:1 woll n~ ll11dr horrno:\1\l pi!HIIit:l:-:. ( t\dopfr:d jHJCII: I lorn lllld Corr11uck, 1070.)

'.I

\

0

,--.. '\

)

\_ FIGURE 41-1

Cross section through adrenoi eland ...,

.~····

Cortex 80%

.. Medulla~,

20% L J...~~::u

Zones

Capsule

... .·

--·------

Main secretory product

Glomerulose- Aldosterone

!2%

Fasciculata -Cortisol

G~%

Reticularis -- Androgens :1..3%

Medulla ___ Epinephrine Norepinephrine

v

Schematic representation of the adrenal gland and its main secretory products. '

c-c-~:;cc_-;;; ':CC --- --;-· --~:--~-c~c-~.~~~r ~- ''/; -- ·i}R, ' -,:·•-:;~ -.-<' ~r-0 ,·7~: i}~~lr~b!~;~fji.~

C<Jpsule

Smooth ondopl<~smic roliculum

r~~~~~~~~~; ~ ~ ~ ~ ~~-~~-:~:: : '·'· . -'-'---..:.J •'

Cod.ox ...... ,,...:::---....__, go%

M ed.ulto. 20o/o

Zonn fa::.cicul<:~l<J

6)%

..........................................

Zona 2 3"/o reticularis

(b) lipid droplets Mitochondria

MccJuii<J

l_: _____________ _ Stomgc gr<Jnulcs

(a)

·-

Fig. 12.16 (a) A diagrammacic rc:prc:scncacion of a scccion through chc: corccx and mc.:dulla of the: adrenal gland. Note the tllrc:r..: /.()11L'S or the adrenal corc<:x, dK' cc.:lls or which secrete steroid hor­

mones. (b) The appearance of

steroid-secretin~ celts. (c) A !>i ngk cacc.:chobnl i m:-sc:crcc ing chromaffin cell.

The adrenal cortex .. ---

There arc three morphologically distincc zones of cells within

the: adrenal cortex (fig. 12.16). The:sc: arc the ouccr zona glomcm­

loSrt (occupying arouncl l 0 per ccnc of the: acln.:nal cortex), the zona fascimlcttct (around 75 per cc:nt), and che ZOIIcl retiml(rris,

which lies closest co the aclrenal mc:clulla~fhc zona rcticularis

docs not diffc:n;:ntiate fully unci l be:cwee:n G ant! S yc:ars of age:. In

the aclulc gland, the: cells of the: glomcrulosa concinually migrate

down through the zona fasciculaca to che zona rcticularis,

changing their sc:crc:tory pactc:rn as chc:y go. Th<: purpose of chis

migration is not ckar.

,· I : . ·=..:.· ··... :·. _·:·;

" X; '_,.c:~:o:j::i~~---~:!},~dr_eria~.:Gl?-nds ~:~\<:--/: ··- . ·;:· ·.:: ~L:'i~: ---~:~r e~-~1 'iii~d~_-i s: ~act e'; ~l()~--{~:i~;1~· s~ i~6~·.: ~r i;;;~-~:~·T?c:7~-~-~-

. the adrenal' cortex and adrena~ 'med!-.!lla, ,,·hich' ~~~~e:s._--~~--'

- ' '

_ ,~-- ~~eir his tolo·g~~al ~ stru~ ~ ur_~ 1 :.: ... ~1?-~-~~-~?Y; .·devel?:p~~n~:: --~-!!-~ -~

. _;iuncti-ons. ·1'f~ iotiJ 't(/~;l) 0,. 0- / o; 9 ; -

* The adrenal cortex is essential to life, b.ecause it:.

a), ,7 •

Controls Na, k and H2o metab6lism.

.

b)f .r Control~·6arbohydrate, f~t and'ptn. metaboli~m and ' . -

mobil:lsatiori. for _energy._,-... : --~·-_: '• - - -_. _·.--_-.:~-~,:'·_:·_ ·- -----· ·.(\- ;~-;ti~lp-~tes ~~ -r~s~~n~:;·~---;~- ~~-;~:~-~s of -~arid~~ k{nds. ~-- .... __ ..... ·/t~--- .. -.-- _ .. -: ·---·--.,.- . _ _ __ ___ . ___ : : _ ~- . ::·.~:.:.~:. · -- -.--.!·::-;~ :_;_ ·.:,_.E::i<;-~_-..:.: ... :_·. '"'~ __ -;~::-·-::-.-. :, ___ ::-:.,;_.:.jt-~~-.:::~~:~:-__ "-- ------- ----- - ----

___........ ·-------\ 1_ ... -- -

·• -··· .

~ £---------

Cc:cifrriScil- I

A!JREilAI.·

ACTIVE PROTEIN KINl.SE

+ ~ I SPE:!Flt

PROt ElM

rD .·.: :·: ·._:·<<.:·' • · •. : . .i.. ·~: ~. :.

!he Mo6t lrnpofto.nt o~

~\\ "'~ A c TH- 5t;li1U.L~ tL(·' I Sterc For Gntrolk~ Ad''-~

IMlO(t)c.a.\ I

!

I ~(.h· vo..t,·on I . i De.s rn.o la..s~

~e..cre t ,·a~' 1::

(')r !he.. ~ l\ ~-'! )·~-:

t ... r'· \ r"' ; v v n , c; \ rt, i_, "~

lnit,·~1 Gnvers1·on () f [ Ckles (era/ tf> fr5n~"'' 1'' !

i

fig 16-10.-Simplifled scheme of stimulation of cortisol synthesis and s~ by ;n!. Note i:mportRnce of mitochondrion.