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4 3 4 ,,, ! R I L .... 1 9 8 0 VOL. 2 N O . a

~ ~ 'i ̧¸̧ ~ , , i~ !, ~ i~ , !~ C O N T R A C E ,,rI'tON

e:t~11y ted o t ~ t . The telence~h wa~ had ov~r d tho Y!~d.~a .... over c tax r~movod hy curL! the

~ t rhi~~ c ~ssr~ o(~ ~ach ~ihls re The clnc a,,c g s was ~OP a ~ d fro~ the c s c

juct behind thc m y T~ was then o~ by ~ o ~ g ~ mcai£ e d g e the

C ~r~ ~ le ~lY 2 tbo S fac a,

f rent parts of the br n, weighing ~0- rag, ware h ogvnlzod in a g/nan h ~:unlzor with 6.0 c o~o -math

c ' , "o ~ a c h h e n a , e (2:1) uc ~or~Iz~ to e moth of F ~Icb c .(6), ' , t war ~hz~cn periodic ly for ~ he re tamp, ~d filtered through sln Cared gin ~ z tel ( G - I ~ ) . The roroldu9, thus obt~aed~ wa~ ~: z~ b enlzed Wlth 2.0 e}~ 0£ -mOt~ d itored.

u n V c of c h ~xtr t w ~ ~0.0 wl e orO - th . Let a U e ~ -llp~d sUbrt as Wor~ redo d r r t l lPldC by U~I ~/~th Of C norm s l n e . E h test tube war ~h c a g lY r t h 1 d ~ ~d at N in a ref~gerator overnight f c iota sap a of the o I rs. The J u tl of l rs of C h t e s t ~ c wn~ m~rkcd d upper layer w~ d1~c~r d. Th~ ~ layer collected I~ rLo|)pered tec~ tabu d s~ored at ~°C unL~ fin use. ~0 t~ct tU ~ yore dried d ~hc v o of ~h~ 1 er i y of o h ~t b~ wa~ measured. ~ r ~ ~ ed the u r ~ a L l o n of tot llpid~, phospholiPlds~ chol teroi~ ee

C ~ ~ fn%ty a id:, d . terlfled fa~y lds. To~ llpids were colori- metric ly determlne~ by t method I o~ d t ~e (7) CholerterOl td pho~phollpids were ~'t ~ted car tO the me~hod of oar . (S) d M ino it1 ( 9 ) , rosPeCtlvely, ee fatty

l(l.n ~ero an ysed aCco ~0 t~e me&h ~ . . . . . Oa of Mo.~in~cr (~0) d csteri ed try Ids wore err ated th~ math Stern SbuP 0 ( I I ).

da a w e c c y= d using St udenC, s Cos t . gnl t di ~~es betwc mo . . . . ~ of d c o n t ~ ~ g C ~IC~ ated .... d p V ~ U e S re obt ne

R ULTS

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% ) F(~<,wl~l~ t|~.I¢)O-d~,y ~t~i[~it~Lratlo~ of ~,t~,roid co~ltrac,)DLIvo t r~ ttxtl r: t ie,,..~l IX re(fro '" !&'~tl ~'~C~U~L C ~l~tI~|~: wer~ observed tb~,~t nftor tho 60-dt~ treatmont i!, all. tI~,) r,~l:iOI~='of tbo br ~| .]XCept t|~O YEd old llUClO~. In t|~u ]~ter~ mol'o !~f~tif'Ic:tr, t C|t~tlt~eS woro dl.~cornl 0 ~tfter~O <l~>-S ,s c |)arid tb 90, <|,~ys. Sl|~,l.i ~'.[c:~nt "d,~cr(,m~,,~,t in tbo cot,t(,nt ~f t O ~ ].IPld~ woro Sot Ont',lo IF, hlp{~ ~|~tlS (P L_O.05) n~%(l midlln~) nucloi of t|~ai~nus, l'ho:'f)iloil~I~id~ woro ~].[:~,[f;iCn y dop].otod in tb¢~ ttypotl~.amus (P .'°_0o0~) hiPi~ ),tlS fund In.i{L11no nuc]@i of tbo L|*~e ~US ( P ~_0. O0 | ) fO]~OWit*F~'60- ttnd 90-~y ,te ninlstr~ttlon ~ of

The y~d old nucleu~ Pl v n ~ig~l~c t r e in rood ~tin~: the hyl,otb~ Ic-pltult 'y is and cot, trollir~F.- ovt~nt!ott. In tbls n.~c, .... "leun, h onor. woro moro o octlve nft~r 60 d~-s d vlgtllflc~u~y decreased levels of tot i lpids, pho~pholipids [utd slg¢,Iflc~t~tiy !no ared iovelr oE o~torlfi~d try Ids woro obsorvod in tbls p~riod. IntorBstint~ly, t|~ero was no clKItlficant ch~ngo in t h e lipid moiotles of this nucloun f i.owlng 90 d s of ~torold tr~i%tm~nt.

USSI

trot~ens d progost~Jrgn~s e kn n to c ate to n si£nlflc t extent the centr nervou~ ry~tem d their cor~aentr~

glonv of t h o centr nervous ryntem h a v e b~on ~61e6ted for th~j -~v uatlon of tbo effects of o~tro~;on d Progesterone.

In the prevent s tu~. tot liplds were fo d to be docr~ja~ed in 1 the br n reglon.~- ~following the a inlstratloa, of the r tero±d contr eptive, date, no report of ~ho effect of steroid contra- coptlvo on the tot~ li~idz of dlscrote area~ of the br n i ava able. H ever, w-~ter . (13) have reported a ~ decreare in p l a s m a tot lipldn in m e rats after istratlon of e~tra benzoate, roca~ds the roglon~ phosphollplds concontrati most Inve.~tlgat s b e observed ~ elevation of ibs level In ~he

4 3 8 A P R I L 1 9 8 0 VOL. 21 NO. 4

CONTRACE ION

forum. O~y Aftorgood and Alfin-~ator (I|+) have reported a consistently docroared ~,ort~ phospb t p l d love! avon when they a Inistered doses

.~ ov d E (0.052 m E / d a y / 20 t c lli~hcr than Lho physlol ic doses o £ ' i ra~). C~zr ~tudles .~oem to f I in llno th thl~ fln ng slnce slgnlfl- cat~LlY decreased 2 0 V O ~ Of pbo~phollPlds In hypoth~ us~ hlppoc pus, m~dlln¢, nucl~31 d g ~ = clng I, bare ~oen cotls!ctontly observed.

No gener~ roe nt 9 n g fferent investigators ~oems to exist on the effect of steroid contraeoptlves on ch ester level. On the one hand, yd (15)noted diminution of plasma cb eatOrgl level i n m e rats C011 In6 t h o nt~inlntratlon of a v~le~y of estr ann d Brady

~. (16) reported depletion of plasma ch ester in the h fern o ~~ or contraccptlves, the oth0r hand, Debrsberg et • (17)

hgve observed that plasma cholestor love! r ned c d. Ad - ti0nnlly, Aure . (~8) d L son-Cohn • (19) have sh n that plarmn C h e~ter el was elevated after ini~tratl of or contr eptives. In ~enera/_, increase of bypath ic cholester was nee p i~d by d~pletlon ~ of cholesterol levels in pp pus, ygd aid nucleus, ml Ino nuc2el of th d g us clt~ i. 8 e of these effects m~ght have b e o t l dUO tO the c ntlon of estrogen in these br n reSion~ nnd Cormntlon of estr e C motabolltos which m i g h t not o y feet choloster iovo~s one but so th~ other lipid contents of the br n

L er level~ of plasma eo f~ty acids in women t~Ing antiovulatory ugs were ~0 reported by L sson-Cohn . . . ,~. (19). e decrement

in the ].oval of free fatty ida in t V lees regions of the br n f nd in the prep:oat stu~ thus supports the e~lier finding. The f~l of the level of free f~tty acids c be expl~ned in the light of the reported increase In ins in d lag contr eptlve tree nt (20). This reduces tbo concontPntlon of free fatty ids (21). t h e ore, lovelacf oster~fi~ fatty holds wore =o £o d to be decre ed .~n hypoLb r~mus, ~llppc~~pus, ~ ine n~lel of th s d g us clng i

tar l.m. a it~tration of sterold contraceptive.

It is well known ( ) that distinct region flare es c in the 21pAd content d t no-vet in cell types ~nd v ious P a t s and ce.ters O f the m~mm~ian br ; ei, g., m y e ~ n n t "white matter" (high in lipid) d yellnated "gr~ matter" (i lipid). Gonor~ly t the changer ~ in the c o o ration of fferent br~n llpl wore statlstle~lY more slgnlflc t tar 90 S Of i.m. in]ec~i of t steroi~ con~r op~ive. This may be expl ed on t b i~ of prc~ a y grQnter c ~atlon of os~rog@~ d pr esterone in tNese br~n regions ~ter 90 d g, reported by e liar I estig s (~, ~2). t, the old nucleus showed m de orlon of the

iiid level after 60 d ~ of the contr~~pt~e ~ s tratlon, .......... ~Is

the Inhibltory effect of steroid contr eptive thereon might h e ro~ ted the m suppression of its tivl tar 60 d s. intercstibngl~~the re~ponso of g cln i, which is f tlonally known to e h t onlst of d ~ is ~,ist the opposite.

APRIL 1 9 8 0 VOL. 21 NO. 4 4 3 9

CONTRACI:~PTION

CbanKoz in th.j lipld ,2o:,t~¢~L d lipid c Ponl~1on must b. du.~ to c|~tn{~os lit Pato~ of anab~i~m I enteb Ism, or bo~h. Tho.o pr O~~S a~ cont~o!/~d by t|10 tlVl~ioS Of ~,pF ~ia~O Z 0~. E~r]lO~ ~h zo.rd . llnd }! ~J~d ~o~. (~+~25) have ~%~Ke~ted tha~

l'ed @d lipop~t~n IlPa~:@ .c~Ivl~y m~ bo a f to= col%tribu~i tO tho incre.cod plasma llpid. ~ po=siUi]ltytthat the2 br~]n llplds mi£ht be mobilized eor~]~~ w~ll with i b~ repo~t~d £nere~=o in 5ho lovol o£ ~oPt~ 21pld. (18, |9). ~|mr stu os On t ~Otlv~ty Of ~IPld syr, t h~:Izlng and do~:ra n~ enz us la &h,j various leZlonv oF tho brain loll I contr O p ~ v ~ a I s tra- tlon w£11 onabl, a Z)o~ter under~ dl this c plox pr 1 .

ACK~; EH

~ j ~ l n v ~ t I E a t l o n wa~ 8upp '~od by ~he I n Cou o~ M~dia R e s e a r c h d U n l v e r ~ l ~ F G~ ~s C s ~ i o n No. ~ / 7 8 / (S~II), New lhl. ~ e n~.Lth~~ wleh to th ProF. ~ ~ta Mo~In, }load of the ~partment of Ob, totrlc~ d Gynaec o . J. N. Modlc Coll~g,~~A.M.U., ~i~ b I r provl ~ In¥~un o fncilltlen for thln work.

0 APRIL 1980 VOL. 21 NO. 4

C O N T R A C E ION

R

2~

3~

0

6~

7~

1

0

10.

11.

12.

13.

Ve~ney, HoP. ~d ~ R. = Inve~tlgatlon of relation between use of or~ nontr optlve~ d thr be bollc seases, it Hod J 2= 199, 1968.

V o ~ o ~ M.P. d ll t R. = Z n v e ~ , t l g a t ! o f r e l a t i o n between use of era/ oontracePtlves d thr be b Ic dlaeanec. A rthor r~port. Brlt Med J 2t 691, 1969.

I ~ W. tt.W. d Vesseyp H.P.~ lnvestlgntl s o£ death [rm b i s = p monary ooron y d cerebr thrombosis d w en

o r cb d be i e . i t H o d J 2~ 193, 1968.

V dot Steeg, H.J. d Pro , JoC. t The elf t of or e tra- ceptlve set llpoprote~nS d sk id tb kness y w ~n. Contr eptlo~ 16 z 29, 19~7.

Hc en~ B.~. d Pie , D.W. = e%OP in~~enci sex he one , by rat br n regions. ~. ec~s 0£ neonat trea ent s

h hysoct y d c petl steroid on e~%r t e . R e s 21t iz 1970.

chy J.j c ~ l.t L?@st M.. Heath~ 3. A. and Le ~ FoN.~ Proparat~~ of 1~pld excr ts fr bP tissue, j Ch 191= 833, i9 .~ t .

We , ~D. d Pr~ce~ C.P. t C atlon o£ se tot 11 d. Cil ca C ta 38= 3 9 , 19P2.

~oor, W.R~, Pelk ~ K.F. d en~ D.M.| te nr~tlon of fatty a c i d s d c h ~ e s t o r b l ~ sm 1 o C Of b l o o d p l a s m ~ J Chore ~2= 191, 19 .

M~~ne%t£__G.V . = Chr a t raph£~ seP~atXon identification ~ d ' 2 ~n y~S . ~ phosphate . J Lipid Res ~ 3, 196 .

Mo~InEer~ F, i Phot o t C adaptatlon o£ le's mlerodet~ atlon of ~ree ~at~y Ids. ~r Id ~eS 6~ 15~, ~ ~ 5 .

Stern, I . d Ire B. = A rapid d s ple method f dete tlon of est,rlfied fa[~ ids d for to~ ~ty acids ~n o J Ch Path 6= 158, 1953.

Wade, G.N., I , C.F. d der, H.H.# t e of 1, progesterone in ov leot izod r s~ 5 nea piEs and h stets= Correlatlon tb specles re es in bob lot resp s eness.

n Res 61: 3 ~ , 1973.

Fewster~ M.E.~ P~r e, R.~ d ner~ D.A, : ct of estra benzoate on l~pld metab ism in the rat. d rln z ~ 3 ~ 1 ~ 7 o

A£tergo , L, d ~£ - a%er~ R . B . z tber st~adles e of ors o£ ~O atory l~pid met Ism in the rat. J pid Res 12t 305, 1971.

APRIL 1 9 8 0 VOL. 21 NO. 4 441

C O N T R A C E + I O N

~ 0 ¸

! 8 .

2 7 .

22+

2 3 .

d, ~ + 5 + t ~ l d r £ n ~ r i n l i p i d m t + L ~ b o ~ i ~ m . t ~ + l +

~ d o r a L i P r

Be y++ ~+ H~++da~+ A , ~ . t ~+ii+++mon+ h . t b o r g + A. d V ~ r Q t , O. + ~++++ +o+££o¢Pt, o £ .... ~ + o+ +a+~ .... inh++ib+/L+oP+ on+ ~ho l l + P l d m+e+++ab+~1 .

tn H+o+~ + and+ 1+? t ~0 i+, ++966+ +

+dr ~+r~+n ++t+~+ +~ t h o++ ~ r o g o n +~ +,+ +:+,+++++++ +on +++ ++++++++++++ + ++m++,++:++++++oP+~iveo ++ O b a t +GXn+o+c+~ 31+ i 8 6 , 1+,~8.

A u r o + 1 1 + ........ C r o r p K . 6 |+|y+bo+ G+. : So+r . ! ip!+++!+ i l p o p + r o t e l n a d +£ng+ ~: f o r m a+ t N i g+ LP m +ore o £ + +oP ~ c +on :t: P o p +i++ e+ L +++ ++ , .~ ++, .+

+8 ~ o n - C o + h n + ++ + + +++++ r ........ ...... + +++ ...... .... +++l+int_R, an++d V to+t++ 0.++ Et+ ¢ t + o £ +¢+ b tno+d a n d I d .... ++o n o r + c t r ++pt£+v+++ on+ ~lam+m+a i p l + i+n+C++~U + £ n + d p + b o + s p h ~ + i P i d + + , + ++m d+++ r + ++63 |+ ? i ? + + 9 7 0 ,

+

+~T~ ~ a c Y + W, ~ t +A r m v £ + o v o £ + a r b o l t y d r + a t + ¢ ram+ t n + b ~ i + m . . . . . d + L ~ O r ~ c o a t r Op++++ivm++++++:. a += t + 1++0~1 8 +96+9 ++ ++ . . . . . + +++++ . . . . + + + ++ ++ + ~ + + +

+ E . L . + + - L . d Q+ V . P + : ~ o r ±n i n o n Of £atty iris ~~ t!~UO 1 9 1 1

. . d Ka k t a + t H, u r h l c ~ c h g e ~ i n c p o d ! t 1 m o t a b £~m . . . . d no o t . r ~ £ n t b o h br n th O. I n t g e u r o b l o r A g i n g + J .M+ d K . R . + ) P l o n N O V r R d London+ le)75+ ~ i ~ .

y t h e = + Z . R . t n Hoch i d Beh o . 2rid ¢ t E o n . a e k v o i l t n ¢ l Pu + ~ £ d t g h , 1 9 7 6 .

d, W+ R. + , M. d = d o , J , D. ~ E. L+ t St On moth 0£ £ ed vels i n d Od b y o r a l ~ t D a c o p t i .. ~ g,l j Meal 2 8 0 | t~y + 1<;69,

o d R o+ R.: a o~ivones~ d 11p rotoin 11P a~ o ~ £ t y C ~ r S ..... d 1 .... ~ U b j ee t s t i ~ c on t COp~iweS. 3 S t G>neQ t 628, 9,

2 A P R I L I 9 8 0 V O L 2 1 N O o , 4