Serum Leptin and Ghrelin Levels in Women with ... - CiteSeerX

Original Article

Serum Leptin and Ghrelin Levels in Women with Polycystic Ovary Syndrome: Correlation with Anthropometric, Metabolic, and Endocrine Parameters Shiva Houjeghani, M.Sc.1, Bahram Pourghassem Gargari, Ph.D.2*, Laya Farzadi, M.D.3 6WXGHQWV¶5HVHDUFK&RPPLWWHH)DFXOW\RI+HDOWKDQG1XWULWLRQ7DEUL]8QLYHUVLW\RI0HGLFDO6FLHQFHV7DEUL],UDQ 1XWULWLRQDO5HVHDUFK&HQWHU'HSDUWPHQWRI%LRFKHPLVWU\DQG'LHW7KHUDS\)DFXOW\RI+HDOWKDQG 1XWULWLRQ7DEUL]8QLYHUVLW\RI0HGLFDO6FLHQFHV7DEUL],UDQ 'HSDUWPHQWRI2EVWHWULFVDQG*\QHFRORJ\)DFXOW\RI0HGLFLQH7DEUL]8QLYHUVLW\RI0HGLFDO6FLHQFHV7DEUL],UDQ

Abstract

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

5HVXOWV ,Q3&26ZRPHQVHUXPOHYHOVRIOHSWLQLQVXOLQ+20$,5WHVWRVWHURQH/+ DQG/+)6+ZHUHVLJQL¿FDQWO\KLJKHUZKLOH6+%*ZDVORZHUWKDQLQKHDOWK\ZRPHQ *KUHOLQDQG)6+ZHUHVLPLODULQERWKJURXSV6HUXPOHYHOVRIOHSWLQFRUUHODWHGZLWK%0, U  S  ZDLVW WR KLS UDWLR :+5  U  S  LQVXOLQ OHYHOV U  S DQG+20$,5U S ZKLOHJKUHOLQOHYHOVKDGDQLQYHUVHDVVRFLDWLRQZLWKWHVWRVWHURQHU S   &RQFOXVLRQ 7KH UHVXOWV VKRZHG LQFUHDVHG OHSWLQ OHYHOV ZKLOH JKUHOLQ UHPDLQHG XQFKDQJHGLQ3&26SDWLHQWV,Q3&26SDWLHQWVOHSWLQSRVLWLYHO\FRUUHODWHGZLWK%0, :+5LQVXOLQDQGLQVXOLQUHVLVWDQFHZKLOHJKUHOLQZDVRQO\DVVRFLDWHGZLWKVHUXP WHVWRVWHURQHOHYHOV Keywords:3RO\F\VWLF2YDU\6\QGURPH/HSWLQ*KUHOLQ,QVXOLQ Citation: Houjeghani S, Pourghassem Gargari B, Farzadi L. Serum leptin and ghrelin levels in women with polycystic ovary syndrome: correlation with anthropometric, metabolic, and endocrine parameters. Int J Fertil Steril. 2012; 6(2): 117-126.

Introduction 3RO\F\VWLF RYDU\ V\QGURPH 3&26  DIIHFWV DSSUR[LPDWHO\±RIZRPHQRIUHSURGXFWLYHDJH DQG LV FKDUDFWHUL]HG E\ RYDULDQ G\VIXQFWLRQ KLUsutism, hyperandrogenism, insulin resistance, and REHVLW\ 7KHHWLRORJ\RI3&26LVPXOWLIDFWRULDO LQFOXGLQJ ERWK JHQHWLF DQG HQYLURQPHQWDO LVVXHV Received: 26 Sep 2011, Accepted: 4 Jan 2012 * Corresponding Address: P.O.Box: 5166614711, Nutritional Research Center, Department of Biochemistry and Diet Therapy, Faculty of Health and Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran Email: [email protected]

$OWKRXJK K\SHUDQGURJHQLVP RYDULDQ G\VIXQFtion, abnormalities in the hypothalamic-pituitary D[LVDQGH[FHVVLQVXOLQDFWLYLW\DUHNQRZQWREH responsible for pathogenesis of the syndrome, the H[DFWHWLRORJ\KDV\HWWREHGLVFRYHUHG  2EHVLW\ LV D YHU\ FRPPRQ FOLQLFDO IHDWXUH LQ ZRPHQDIIHFWHGE\3&260RUHWKDQRI

Royan Institute International Journal of Fertility and Sterility Vol 6, No 2, Jul-Sep 2012, Pages: 117-126

117

Houjeghani et al.

3&26ZRPHQDUHREHVH $GLSRVLW\LVREVHUYHG LQ 3&26 SDWLHQWV DQG SOD\V DQ LPSRUWDQW UROH LQ their metabolic phenotype through the producWLRQ RI YDULRXV DGLSRF\WHGHULYHG F\WRNLQHV DQG SURWHLQVNQRZQDVDGLSRNLHQV &HQWUDOREHVLW\ has a close relationship with the altered secretion of some adipocytokines like leptin. Production of DGLSRF\WRNLQHVDIIHFWVLQVXOLQVHQVLWLYLW\DQGLVD SUHGLFWRURIPHWDEROLFV\QGURPH  Leptin, the product of the ob REHVH  JHQH LV D VLQJOHFKDLQ  N'D SURWHLQ FRQVLVWLQJ RI  amino acid residues. Leptin is produced mainly in DGLSRVHWLVVXHDQGLVLQYROYHGLQWKHUHJXODWLRQRI energy homeostasis, reproduction, insulin action, and lipid metabolism. The relationship between OHSWLQ DQG UHSURGXFWLYH IXQFWLRQ LV FRPSOH[ DQG QRWFRPSOHWHO\XQGHUVWRRG  Leptin is a key hormone in energy homeostasis DQGQHXURHQGRFULQHIXQFWLRQDQGKDVDSHUPLVVLYH UROHLQWKHSDWKRJHQHVLVRIUHSURGXFWLYHG\VIXQFWLRQ   5HFHQW VWXGLHV VXJJHVW WKDW VRPH KRUPRQHVPD\PHGLDWHVRPHRIWKHDGYHUVHHIIHFWVRI REHVLW\RQRYDULDQIXQFWLRQLQ3&26 6WXGLHVRQWKHOHSWLQLQ3&26KDYHFRQÀLFWLQJUHVXOWV VRPH VKRZ LQFUHDVHG OHYHOV RI OHSWLQ   ZKLOH RWKHUVVKRZQRGLIIHUHQFHLQOHSWLQLQ3&26FRPSDUHGWRKHDOWK\VXEMHFWV  *KUHOLQ DQ HQGRJHQRXV OLJDQG IRU WKH JURZWK KRUPRQHVHFUHWDJRJXHUHFHSWRULVV\QWKHVL]HGSULQcipally in the stomach. It stimulates food intake and transduces signals to hypothalamic regulatory nuclei that control energy homeostasis and are linked to the control of key aspects of reproduction function. The SHSWLGHFRQVLVWVRIDPLQRDFLGV 6WXGLHVRQ WKH JKUHOLQ OHYHOV LQ 3&26 DUH FRQÀLFWLQJ 2ULR HW DO   KDYH VKRZQ QR GLIIHUHQFH LQ JKUHOLQ OHYHOV DPRQJ3&26DQGKHDOWK\FRQWUROV+RZHYHU:DVNR HW DO   QRWHG KLJK JKUHOLQ OHYHOV ZKLOH 0LWNRY HWDO DQG.DPDOHWDO VKRZHGORZOHYHOV RIJKUHOLQLQ3&26SDWLHQWVFRPSDUHGWRWKHFRQWURO JURXS *OLQWERUJ HW DO   KDYH IRXQG WKDW JKUHOLQ OHYHOVGHFUHDVHGLQKLUVXWH3&26SDWLHQWV 7KHUHLVHYLGHQFHRIOHSWLQDQGJKUHOLQRSHUDWLQJ as endocrine-paracrine mediators, establishing a link between energy homeostasis and reproduction  7KHPDMRUVLWHRIWKHVHQRYHOPHGLDWRUVRIWKH DSSHWLWHLVWKHFHQWUDOQHUYRXVV\VWHP&16 HVSHcially the hypothalamus and pituitary, where they DIIHFW JRQDGRWURSLQUHOHDVLQJ KRUPRQH *Q5+  IJFS, Vol 6, No 2, Jul-Sep 2012

118

SXOVDWLOLW\ IROOLFOH VWLPXODWLQJ KRUPRQH )6+  DQGOXWHLQL]LQJKRUPRQH/+ SURGXFWLRQDQGVHFUHWLRQ  &RQWUDGLFWRU\UHVXOWVLQVWXGLHVLQYHVWLJDWLQJVHUXP leptin and ghrelin encouraged us to carry out the current research. We further assessed the association beWZHHQ /+ )6+ WHVWRVWHURQH VH[ KRUPRQHELQGLQJ JOREXOLQ6+%* ERG\PDVVLQGH[%0, ZDLVWWR KLSUDWLR:+5 DQGLQVXOLQUHVLVWDQFHZLWKWKHWZR DERYHPHQWLRQHGKRUPRQHV

Materials and Methods The present case-control study was conducted on 3&26SDWLHQWVDQGKHDOWK\SDWLHQWVPDWFKHG IRU DJH %0, DQG :+5 WKDW ZHUH UHIHUUHG WR $O]DKUD+RVSLWDOLQ7DEUL],UDQ6DPSOLQJODVWHG IURP1RYHPEHUWR)HEUXDU\7KHVWXG\ SURWRFROZDVDSSURYHGE\WKH(WKLFV&RPPLWWHHRI WKH7DEUL]8QLYHUVLW\RI0HGLFDO6FLHQFHV After being informed of the purpose and proceGXUHVRIWKHVWXG\DOOVXEMHFWVVLJQHGDQLQIRUPHG FRQVHQW IRUP7KH GLDJQRVLV RI 3&26 ZDV PDGH E\DJ\QHFRORJLVWXVLQJ5RWWHUGDPFULWHULDZKLFK LQFOXGHV FOLQLFDO DQGRU ELRFKHPLFDO VLJQV RI K\perandrogenism (increased serum total testosWHURQH RU IUHH DQGURJHQ LQGH[  ROLJRPHQRUUKRHD VL[RUIHZHUPHQVHVSHU\HDU RUDPHQRUUKRHDQR PHQVHVLQWKHODVWVL[PRQWKV DQGSRO\F\VWLFRYDULHVE\XOWUDVRQRJUDSKLFH[DPLQDWLRQ   0HGLFDO KLVWRU\ SK\VLFDO DQG SHOYLF H[DPLQDWLRQ and complete blood tests were used to determine the healthy status of women in the control group. ExcluVLRQFULWHULDIRUDOOVXEMHFWVLQFOXGHGSUHJQDQF\K\SRthyroidism, hyperprolactinemia, Cushing’s syndrome, FRQJHQLWDO DGUHQDO K\SHUSODVLD FXUUHQW RU SUHYLRXV ZLWKLQWKHODVWWKUHHPRQWKV XVHRIRUDOFRQWUDFHSWLYHV JOXFRFRUWLFRLGV DQWLDQGURJHQV RYXODWLRQ LQduction agents, antidiabetic and anti-obesity drugs, or other hormonal drugs. None of the patients were affected by any neoplastic, metabolic, or other concurrent medical illness. Weight and height were measXUHGWRFDOFXODWHWKH%0,%RG\KHLJKWZDVPHDVXUHG WRWKHQHDUHVWFPZLWKWKHVXEMHFWVWDQGLQJZLWKRXW shoes. Body weight in light indoor clothing was measXUHGWRWKHQHDUHVWNJ7KH%0,ZDVFDOFXODWHG XVLQJWKHVWDQGDUGIRUPXODRIZHLJKWNJ KHLJKWP2  :DLVWDQGKLSFLUFXPIHUHQFHVDWWKHOHYHORIWKHKLS ERQH DQWHULRU VXSHULRU LOLDF VSLQHV  ZHUH DOVR PHDVXUHGLQWKHVWDQGLQJSRVLWLRQWRFDOFXODWHWKH:+5

Leptin and Ghrelin in Women with PCOS

The analyses were carried out during the early IROOLFXODU SKDVH GD\V   LQ ZRPHQ ZKR KDG menstrual cycles, and in any phase of the cycle in 3&26SDWLHQWV%DVDOEORRGVDPSOHVZHUHREWDLQHG WR HYDOXDWH VHUXP OHSWLQ JKUHOLQ /+ )6+ WRWDO WHVWRVWHURQH 6+%* IDVWLQJ LQVXOLQ DQG JOXFRVH OHYHOV$OOEORRGVDPSOHVIRUHDFKVXEMHFWZHUHDVsayed in duplicate and immediately centrifuged. 7KHVHUXPZDVVWRUHGDWÛ&XQWLODQDO\VLV In each woman, the estimate of insulin resistance by homeostasis model assessment of insulin resistDQFH+20$,5 ZDVFDOFXODWHGZLWKWKHIROORZLQJIRUPXODIDVWLQJVHUXPLQVXOLQP8O îIDVWLQJ SODVPDJOXFRVHPJGO   $OO EORRG VDPSOHV ZHUH REWDLQHG EHWZHHQ  DPDQGDPDIWHUDQRYHUQLJKWIDVW7KHVHUXP OHSWLQ OHYHO ZDV PHDVXUHG XVLQJ D +XPDQ /HSWLQ (/,6$.LW%LR9HQGRU*PE+,P1HXHQKHLPHU)HOG '+HLGHOEHUJ*HUPDQ\ ZKLFKKDGDQ LQWUDDVVD\ DQG LQWHUDVVD\ FRHI¿FLHQW RI YDULDWLRQ DQGUHVSHFWLYHO\DQGVHQVLWLYLW\ RIQJPO,QDOOVXEMHFWVSODVPDLPPXQRUHDFWLYH JKUHOLQ OHYHOVZHUHPHDVXUHGXVLQJDFRPPHUFLDOO\ DYDLODEOH5,$WKDWXVHV,ODEHOHGELRDFWLYHJKUHlin as a tracer and a rabbit polyclonal antibody raised against full-length octanoylated human ghrelin (Phoe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ll parameters studied or calculated showed norPDOGLVWULEXWLRQVZKLFKZHUHFRQ¿UPHGE\WKHRQH VDPSOH .ROPRJRURY6PLUQRII WHVW 5HVXOWV ZHUH H[SUHVVHGDVPHDQ“VWDQGDUGGHYLDWLRQ6' &RPparisons between the two groups were made using an

independent samples t test. Pearson correlation analyVHVZHUHSHUIRUPHGWRGH¿QHFRUUHODWLRQVEHWZHHQSDUDPHWHUVSZDVUHJDUGHGDVVWDWLVWLFDOO\VLJQL¿FDQW$OODQDO\VHVZHUHUXQXVLQJWKH6366YHUVLRQ 6366&KLFDJR,/ 

Results 7KHUH ZHUH  ZRPHQ ZHUH LQ WKH 3&26 JURXS DQGLQWKHFRQWUROJURXS7KHDQWKURSRPHWULFDQG laboratory data of the groups are presented in table 1. )LJXUHVKRZVPHDQVHUXPOHYHOVRIJKUHOLQ'DWD FRQ¿UPHG WKDW WKH VXEMHFWV LQ WKH KHDOWK\ FRQWURO JURXSPDWFKHGVXEMHFWVLQWKH3&26JURXSLQWHUPV RIDJH%0,DQG:+57DEOH  Table 1: Anthropometric, metabolic, and hormonal characteristics of patients and controls 3&26Q 

&RQWUROQ 

$JH<

“

“

:HLJKW.J

“

“

+HLJKWFP

“

“

%0,.JP

“

“

:DLVWFP

“

“

+LSFP

“

“

:+5

“

“

/HSWLQQJPO

“

“

*KUHOLQSPROO

“

“

,QVXOLQPXO

“

“

*OXFRVHPJGO

“

“

+20$,5

“

“

7RWDOWHVWRVWHURQH QJPO

“

“

6+%*QJPO

“

“

/+P,8PO

“

“

)6+P,8PO

“

“

'DWD  SUHVHQWHG DV PHDQV “ 6' %0, ERG\ PDVV LQGH[ )6+IROOLFOHVWLPXODWLQJKRUPRQH+20$,5KRPHRVWDVLVPRGHODVVHVVPHQWRILQVXOLQUHVLVWDQFH/+OXWHLQL]LQJ KRUPRQH 3&26 SRO\F\VWLF RYDU\ V\QGURPH 6+%* VH[ KRUPRQHELQGLQJJOREXOLQDQG:+5ZDLVWWRKLSUDWLR  S

S 119

Houjeghani et al.

%LYDULDWHFRUUHODWLRQV7DEOHDQG)LJ UHYHDOHG WKDWVHUXPOHYHOVRIOHSWLQLQ3&26ZRPHQVLJQL¿FDQWO\FRUUHODWHGZLWK%0,U S  :+5 U  S   LQVXOLQ OHYHOV U  S   DQG+20$,5U S  

Leptin (ng/ml)

A

A PCOS

Ghrelin (pmol/l)

non PCOS

BMI (kg/m2)

B

PCOS

Leptin (ng/ml)

non PCOS

BMI (kg/m2)

PCOS non PCOS

HOMA-IR

Ghrelin (pmol/l)

B

C

PCOS

Leptin (ng/ml)

non PCOS

HOMA-IR

C non PCOS

Total testosterone (kg/m2)

Fig 1: (A) Correlation between serum leptin levels and BMI 3&26U S&RQWUROVU S % +20$,5 3&26 U  S &RQWUROV U  S  &  7RWDO WHVWRVWHURQH 3&26 U  S! &RQWUROV U  S! 

,Q WKH 3&26 JURXS VHUXP OHYHOV RI OHSWLQ LQVXOLQ +20$,5 WHVWRVWHURQH /+ DQG /+ )6+ZHUHVLJQLILFDQWO\KLJKHUWKDQLQWKHFRQWURO JURXS 6+%* FRQFHQWUDWLRQ ZDV IRXQG WR EHORZHULQWKH3&26JURXS$VIRUJKUHOLQDQG )6+ QR VLJQLILFDQW GLIIHUHQFH ZDV GHWHFWHG LQ either group. IJFS, Vol 6, No 2, Jul-Sep 2012

120

Ghrelin (pmol/l)

PCOS

PCOS non PCOS

Total testosterone (ng/ml)

Fig 2: (A) Correlation between serum Ghrelin levels and %0, 3&26 U  S! &RQWUROV U  S!  % +20$,53&26U S!&RQWUROVU  S!  &  7RWDO WHVWRVWHURQH 3&26 U  S &RQWUROVU S! 

Leptin and Ghrelin in Women with PCOS

Table 2: Pearson correlation tests of clinical, metabolic, and hormonal parameters with leptin and ghrelin in the study groups 3&26Q  /HSWLQ

&RQWUROQ 

*KUHOLQ

/HSWLQ

*KUHOLQ

:HLJKW.J









%0,.JP









:DLVWFP









:+5









,QVXOLQPXO









+20$,5









/+P,8PO









)6+P,8PO









/+)6+









7RWDO WHVWRVWHURQHQJPO









6+%*QJPO









)6+)ROOLFOHVWLPXODWLQJKRUPRQH+20$,5+RPHRVWDVLVPRGHODVVHVVPHQWRILQVXOLQUHVLVWDQFH /+/XWHLQL]LQJKRUPRQH6+%*6H[KRUPRQHELQGLQJJOREXOLQDQG:+5:DLVWWRKLSUDWLR  S

S

S

7KHUHZDVQRVLJQL¿FDQWFRUUHODWLRQRIJKUHOLQWR ZHLJKW%0,:+5LQVXOLQ+20$,5)6+DQG /+LQERWKJURXSV$VLJQL¿FDQWLQYHUVHDVVRFLDtion was found between ghrelin and testosterone OHYHOVLQERWKWKH3&26U S  DQGWKH FRQWUROJURXSU S  )LJ 7HVWRVWHURQHOHYHOVWHQGHGWRFRUUHODWHSRVLWLYHO\ZLWK%0, U S  DQGZDLVWFLUFXPIHUHQFHU  S  LQ3&26ZRPHQ ,QVXOLQOHYHOVVLJQL¿FDQWO\FRUUHODWHGZLWK%0, DQGZDLVWFLUFXPIHUHQFHLQERWKWKH3&26JURXS DQGWKHFRQWUROJURXS%0,U S  DQG ZDLVW FLUFXPIHUHQFH ZHUH DOVR SRVLWLYHO\ DVVRFLDWHGZLWK+20$,5U S  

pituitary axis by stimulating estrogen secretion. 7KH QHJDWLYH LPSDFW RI OHSWLQ LQ FRQGLWLRQV OLNH K\SHUOHSWLQHPLDLVWKHLQKLELWLRQRIWKHRYDULDQUHVSRQVHWRJRQDGRWURSKLQVWLPXODWLRQ  6WXGLHV RI OHSWLQ OHYHOV LQ 3&26 ZRPHQ KDYH \LHOGHGFRQÀLFWLQJUHVXOWV6LPLODUWRWKH¿QGLQJV RI0LWNRYHWDO DQG3HKOLYDQRYHWDO ZH VKRZHGDQLQFUHDVHGOHYHORIOHSWLQLQ3&26SDWLHQWV2WKHUDXWKRUVKDYHIDLOHGWRVKRZDQ\GLIIHUHQFHDPRQJ3&26DQGKHDOWK\ZRPHQ  It can be said that differences in age, anthropometULFLQGLFHVRIJURXSVRUWKHVHYHULW\RIWKHGLVHDVH FDQDFFRXQWIRUWKHVHGLYHUJHQWUHVXOWV

Findings from current research show that women ZLWK3&26KDGKLJKHUOHYHOVRILQVXOLQ+20$ ,5WHVWRVWHURQH/+DQG/+)6+DQGORZHUFRQFHQWUDWLRQVRI6+%*

$FRUUHODWLRQEHWZHHQVHUXPOHSWLQDQG%0,KDV EHHQVKRZQLQ3&26ZRPHQ 2XU¿QGLQJVFRQ¿UPWKHUHVXOWRISUHYLRXVVWXGLHVVKRZLQJ D VLJQL¿FDQW FRUUHODWLRQ EHWZHHQ %0, DQG waist circumference with leptin. This further supports the importance of abdominal fat mass in the secretion of leptin.

+LJKHU OHSWLQ OHYHOV PD\ KDYH D UROH LQ WKH SDWKRSK\VLRORJ\ RI 3&26 /HSWLQ KDV D GXDO HIIHFWRQUHSURGXFWLRQ7KHSRVLWLYHHIIHFWRIOHSWLQ is its role as a trigger of puberty on hypothalamic-

6+%* LV D JO\FRSURWHLQ SURGXFHG LQ WKH OLYHU acting as a carrier for different sexual steroid horPRQHV,WVKRZVDKLJKHUDI¿QLW\IRUWHVWRVWHURQH   7KH FRQFHQWUDWLRQ RI 6+%* LV VWLPXODWHG

Discussion

121

Houjeghani et al.

by cortisol, estrogens, and growth hormone and decreased by androgens, insulin and prolactin   /RZHU 6+%* OHYHOV FDXVHG E\ K\SHULQsulinemia may be responsible for the increased ELRDYDLODELOLW\RIVH[KRUPRQHVLQWDUJHWWLVVXHV  7KLVPD\LQWXUQOHDGWRWKHGHYHORSPHQW of abdominal obesity. Insulin resistance and subsequent hyperinsulinePLDDUHIRXQGLQRI3&26SDWLHQWV+LJK LQVXOLQOHYHOVDUHDVVRFLDWHGZLWKK\SHUDQGURJHQLVPDQGDQRYXODWLRQ ,WKDVEHHQSURYHQ WKDW LQVXOLQ LV DEOH WR VWLPXODWH RYDULDQ VWHURLGRJHQHVLV DQGLQFUHDVHRYDU\/+UHFHSWRUVDQG WKHVHQVLWLYLW\RISLWXLWDU\JRQDGRWURSHVWR*Q5+ DFWLRQ  The steady-state basal serum glucose and insulin concentrations are determined by their interaction in a feedback loop. A computer model is used to predict the homeostatic concentrations that result IURP YDU\LQJ GHJUHHV RI LQVXOLQ UHVLVWDQFH DQG ȕFHOO GH¿FLHQF\ &RPSDULVRQ RI D SDWLHQW¶V IDVWLQJ OHYHOV ZLWK WKH PRGHO¶V SUHGLFWLRQV SURYLGHV D TXDQWLWDWLYH DVVHVVPHQW RI WKH FRQWULEXWLRQV RI GH¿FLHQW ȕFHOO IXQFWLRQ DQG LQVXOLQ UHVLVWDQFH WR the fasting hyperglycemia (homeostasis model asVHVVPHQW +20$    ,Q RXU VWXG\ ZH DSSOLHG WKH+20$LQGH[WRHYDOXDWHWKHVWDWXVRILQVXOLQ resistance in the two study groups. ,Q WKH SUHVHQW VWXG\ WKH 3&26 JURXS VKRZHG KLJKHU LQVXOLQ OHYHOV +20$,5 HOHYDWHG WHVWRVWHURQH DQG GHFUHDVHG 6+%* OHYHOV WKDQ WKH healthy controls. 3HULSKHUDOKHSDWLFDQGVNHOHWDOPXVFOH LQVXOLQ VHQVLWLYLW\ DQG SDQFUHDWLF ȕFHOO IXQFWLRQ LV LPSURYHGYLDOHSWLQDFWLRQLQWKHVHVLWHV ,QVXOLQ stimulates both leptin biosynthesis and secretion from adipose tissue, creating an endocrine adipoinsular feedback loop called the "adipo-insular D[LV 2QWKHRWKHUKDQGLQFOLQLFDOLQWHUYHQtional studies, postprandial and short term hyperinsulinemia using euglycemic-hyperinsulinemia FODPS VWXGLHV KDYH EHHQ XQDEOH WR VKRZ DQ LQFUHDVHLQOHSWLQVHFUHWLRQ  &XUUHQWUHVHDUFKKDVUHYHDOHGWKDWLQWKH3&26 DQGFRQWUROJURXSOHSWLQZDVSRVLWLYHO\FRUUHODWHG ZLWK LQVXOLQ OHYHOV DQG +20$,5 7KHUH LV HYLGHQFHRIOHSWLQDELOLW\LQVWLPXODWLQJ*Q5+IURP WKH K\SRWKDODPXV DQG /+)6+ UHOHDVH IURP WKH

IJFS, Vol 6, No 2, Jul-Sep 2012

122

SLWXLWDU\    5HFRPELQDQW KXPDQ OHSWLQ treatment in patients with hypothalamic amenorUKHD KDV EHHQ UHSRUWHG WR LQFUHDVH WKH PHDQ /+ OHYHOVDQG/+SXOVHIUHTXHQF\ZLWKLQWZRZHHNV RIUHFHLYLQJWUHDWPHQW  6WXGLHV LQ ZKLFK  KRXU /+ SXOVHV ZHUH REVHUYHG LQ 3&26 SDWLHQWV   VKRZHG DQ LQYHUVH UHODWLRQVKLSEHWZHHQOHSWLQDQGKRXUPHDQ/+ OHYHOV7KHORVVRIELKRUPRQDOV\QFKURQ\EHWZHHQ OHSWLQDQG/+UHOHDVHZDVUHSRUWHGE\9HOGKXLVHW DO $SRVLWLYHDVVRFLDWLRQEHWZHHQOHSWLQDQG VHUXP/+OHYHOVZDVGHPRQVWUDWHGE\$WDPHUHW DO ,QDJUHHPHQWZLWK0HQGRQoDHWDO ZH GLGQRWREVHUYHDUHODWLRQEHWZHHQOHSWLQDQG/+ LQHLWKHUWKH3&26RUFRQWUROJURXS  6WXGLHV LQYHVWLJDWLQJ WKH DVVRFLDWLRQ RI OHSWLQ ZLWK /+ WKDW PHDVXUHG  KRXUV /+ DQG OHSWLQ SXOVHVSURYLGHDPRUHSUHFLVHVHQVLWLYHDQGREMHFWLYHLQGH[RIDOWHUDWLRQVLQELKRUPRQDOOLQNDJH than studies using a single measurement of serum concentration of these two hormones, as used in RXUVWXG\+RZHYHUWKHLQYROYHPHQWRIOHSWLQLQ PRGXODWLQJ/+DQG)6+YLDLWVSXOVDWLOHVHFUHWRU\ characteristics has yet to be elucidated in either KHDOWK\RU3&26VXEMHFWV ,W KDV EHHQ VKRZQ WKDW PRVW REHVH LQGLYLGXDOVQHHGKLJKHUGRVHVRIJRQDGRWURSLQVIRURYDU\ hyper-stimulation, despite comparable absorption RI JRQDGRWURSLQV IURP VXEFXWDQHRXV WLVVXH   7KHUHDUHDOVRUHSRUWVRIOHSWLQKDYLQJDQLQKLELWRU\HIIHFWRQWKHV\QHUJLFDFWLRQRI)6+DQGLQVXlin-like growth factor I on granulosa cell estradiol SURGXFWLRQ  +RZHYHU VLPLODU WR 5RXUX HW DO   RXU UHsearch did not show a relationship between leptin DQG VHUXP )6+ OHYHOV 7KH ODFN RI D VLJQL¿FDQW relationship may be explained in this way: leptin UHGXFHV)6+IXQFWLRQQRWVROHO\E\UHGXFLQJ)6+ VHUXP OHYHOV VRPH RWKHU PHFKDQLVPV VXFK DV D GHFUHDVHRI)6+UHFHSWRUVLQJUDQXORVDFHOOVPLJKW EHLPSOLFDWHG(IIHFWVRIOHSWLQRQ)6+OHYHODUH more noticeable when it is exogenously administered and in vitro studies may also demonstrate a PRUHFOHDUSHUVSHFWLYHRIDSUREDEOHDVVRFLDWLRQ In hypogonadal men, testosterone supplementaWLRQKDVEHHQVKRZQWRQRUPDOL]HHOHYDWHGOHSWLQ concentrations without any changes in body fat or %0, 6LJQL¿FDQWFRUUHODWLRQVEHWZHHQOHSWLQ

Leptin and Ghrelin in Women with PCOS

DQGVHUXPWHVWRVWHURQHKDYHQRWEHHQIRXQGLQDOO VWXGLHV+RZHYHUDQLQYHUVHDVVRFLDWLRQKDVEHHQ reported in both untreated and testosterone-treated K\SRJRQDGDO PHQ   6LPLODU WR +DIIQHU HW DO we did not detect a correlation between leptin and WHVWRVWHURQH :HEHOLHYHOHSWLQPD\PRGXODWH WHVWRVWHURQHOHYHOVLQ3&26WKURXJKLWVHIIHFWRQ LQVXOLQ FRQFHQWUDWLRQV 6LQFH K\SHULQVXOLQHPLD LVDVVRFLDWHGZLWKKLJKOHSWLQFRQFHQWUDWLRQV  and the role of insulin in regulating a key step of DQGURJHQ IRUPDWLRQ UHJXODWLRQ RI 3F HQ]\PH    LW LV SUREDEOH WKDW OHSWLQ DIIHFWV DQGURJHQ OHYHOV YLD LWV LPSDFW RQ LQVXOLQ VHFUHWLRQ instead of a direct alteration of serum testosterone. /RZHUOHYHOVRI6+%*SUREDEO\PLUURUDKLJKHU WHVWRVWHURQH WR HVWURJHQ UDWLR   6RPH VWXGLHV KDYH VKRZQ WKDW 6+%* OHYHOV PD\ KDYH DQ HIIHFWRQDOWHUHGOHSWLQOHYHOVE\ZHLJKWORVVZKLFK PD\EHGXHWRLPSURYHPHQWVLQOHSWLQVHQVLWLYLW\ LQWKHVHVXEMHFWV /HSWLQFRQFHQWUDWLRQPLJKW LQGLUHFWO\KDYHDUHODWLRQVKLSZLWK6+%*OHYHOVLQ 3&26 VXEMHFWV LQ RXU VWXG\ 3&26 SDWLHQWV ZLWK KLJKHU OHSWLQ OHYHOV FRPSDUHG WR KHDOWK\ ZRPHQ KDYH ORZHU 6+%* FRQFHQWUDWLRQV 2XU ¿QGLQJV VXSSRUWWKH¿QGLQJVIURPRWKHUVWXGLHVWKDWIRXQG QR FRUUHODWLRQ EHWZHHQ OHSWLQ DQG 6+%* OHYHOV LQ ZRPHQ ZLWK KLUVXWLVP   DQG VXEMHFWV ZLWK 3&26  ,QRXUVWXG\JKUHOLQOHYHOVGLGQRWVKRZDVLJQL¿FDQWGLIIHUHQFHEHWZHHQWKHWZRJURXSV,QWKH OLWHUDWXUHREHVH3&26FRPSDUHGWRREHVHKHDOWK\ VXEMHFWV KDYH EHHQ IRXQG WR KDYH ORZHU JKUHOLQ OHYHOV EXW ZKHQ OHDQ DQG REHVH 3&26 JURXSV ZHUH WDNHQ DV D ZKROH DQG FRPSDUHG WR %0, PDWFKHG FRQWUROV JKUHOLQ OHYHOV ZHUH IRXQG WR EH VLPLODU EHWZHHQ ERWK JURXSV   2ULR HW DO  DQG'DJKHVWDQLHWDO VKRZHGVLPLODUUHVXOWV,QVWXGLHVFRQGXFWHGE\0LWNRYHWDO  *OLQWERUJHWDO DQG.DPDOHWDO VHUXP ghrelin concentration was reported to be lower in WKH3&26JURXSWKDQLQKHDOWK\FRQWUROV'HVSLWH WKHVH UHVXOWV:DVNR HW DO   KDYH UHSRUWHG HOHYDWHGOHYHOVRISODVPDJKUHOLQLQ3&26SDWLHQWV compared to healthy controls. This discrepancy of results may be explained by confounding factors, such as body weight, fat mass, age, hormonal staWXVDQGVHYHULW\RIGLVHDVH 6LPLODU WR WKH ¿QGLQJV RI RXU VWXG\ 6FKRÀ HW DO   VKRZHG WKDW JKUHOLQ OHYHO GLG QRW FRUUH-

late ZLWK %0, 2Q WKH RWKHU KDQG 'DJKHVWDQL HW DO VKRZHG D VLJQL¿FDQW LQYHUVH UHODWLRQVKLS EHWZHHQ JKUHOLQ DQG %0, LQ ERWK 3&26 DQG KHDOWK\VXEMHFWV,WPXVWEHVDLGWKDW:+5ZDV VLJQL¿FDQWO\GLIIHUHQWEHWZHHQWKHWZRJURXSVLQ WKH'DJKHVWDQLHWDO VWXG\ It has been shown that ghrelin administration to healthy humans at pharmacological doses reduces LQVXOLQVHFUHWLRQ DQGFRQYHUVHO\LQVXOLQDGministration at high doses is capable of reducing JKUHOLQ VHFUHWLRQ   2XU UHVXOWV KDYH VKRZQ WKDWGHVSLWHGLIIHUHQFHVLQFLUFXODWLQJLQVXOLQOHYHOVWKHUHZDVQRWDVLJQL¿FDQWFRUUHODWLRQEHWZHHQ LQVXOLQOHYHOVDQG+20$,5ZLWKIDVWLQJJKUHOLQ FRQFHQWUDWLRQV 7KH UHDVRQ ZK\ RXU UHVXOWV KDYH not shown this relation might be that insulin or ghrelin are able to affect each other when they are administered at pharmacological doses. ,QKXPDQVWKHVSHFL¿FHIIHFWVRIJKUHOLQRQ/+ VHFUHWLRQ KDYH QRW EHHQ LQGLFDWHG ,W LV IHDVLEOH WKDWPRUHFRPSUHKHQVLYHDQDO\VHVLQYROYLQJSUHFLVHDVVHVVPHQWRI/+SXOVDWLOLW\DIWHUJKUHOLQDGPLQLVWUDWLRQPLJKWUHYHDODVXEWOHUHJXODWRU\UROH of ghrelin in the control of gonadotropin secretion LQKXPDQV:HKDYHIRXQGQRFRUUHODWLRQEHWZHHQ JKUHOLQOHYHOVDQGVHUXP/+)6+RU/+)6+UDWLRLQ3&26DQGFRQWUROJURXSV7KHVH¿QGLQJGR not support the idea that ghrelin might alter gonDGRWURSLQOHYHOV The ghrelin receptor is found not only in the &16EXWDOVRLQWKHRYDULDQWLVVXHVVXJJHVWLQJ D SRVVLEOH UHSURGXFWLYH IXQFWLRQ   0RUHRYHUWKHFDSDELOLW\RIJKUHOLQWRDOWHUVWLPXODWHG testosterone secretion in vitro has been docuPHQWHG   8VLQJ ELYDULDWH FRUUHODWLRQV ZH IRXQGDVLJQLILFDQWLQYHUVHDVVRFLDWLRQEHWZHHQ total testosterone and ghrelin in both study JURXSV ,Q SUHYLRXV VWXGLHV WKHUH ZHUH UHSRUWV RIQRVLJQLILFDQWDVVRFLDWLRQ DQGDQLQYHUVH DVVRFLDWLRQ EHWZHHQVHUXPOHYHOVRIJKUHlin and testosterone. In the current research, we further examined WKH DVVRFLDWLRQ RI WHVWRVWHURQH ZLWK %0, DQG ZDLVWFLUFXPIHUHQFH$VWKH%0,DQGZDLVWFLUcumference increased, the serum testosterone OHYHOV VKRZHG D VLJQLILFDQW HOHYDWLRQ 7KHVH ILQGLQJVKDYHGHPRQVWUDWHGWKDWWKHLQFUHDVHRI body weight and fat tissue is associated with ab-

123

Houjeghani et al.

normalities in sex steroid balance. 6RPH OLPLWDWLRQV RI WKH SUHVHQW VWXG\ ZHUH WKHUHODWLYHO\ORZVDPSOHVL]HQDUURZUDQJHRI %0, DQG WKH PHDVXULQJ RI OHSWLQ DQG JKUHOLQ RQO\ LQ D IDVWLQJ VWDWH 0DWFKLQJ VXEMHFWV IRU DJHDQGDQWKURSRPHWULFLQGLFHVKDYHEHHQFRQVLGHUHG DV VWUHQJWKV RI RXU VWXG\ +RZHYHU WR UHDFK D EHWWHU XQGHUVWDQGLQJ RI 3&26 SDWKRphysiology, more studies are warranted in which 3&26SDWLHQWVDUHJURXSHGEDVHGRQWKHLU%0, LQVXOLQ DQG DQGURJHQ OHYHOV SUHVHQFH RI FOLQLFDO IHDWXUHV RI K\SHUDQGURJHQLVP DQG VHYHULW\RISRO\F\VWLFRYDULHV*KUHOLQDQGOHSWLQRU other hormones should be precisely measured in both fasting and postprandial states in relation to endocrine parameters.

   







Conclusion 7KH ILQGLQJV RI WKLV VWXG\ KDYH VXJJHVWHG WKDWLQGLFHVRIDGLSRVLW\%0,DQG:+5 DUH UHVSRQVLEOH IRU HOHYDWHG OHSWLQ LQVXOLQ UHVLVWDQFHDQGWHVWRVWHURQHOHYHOVLQ3&26SDWLHQWV The role of leptin and ghrelin in the pathogenHVLV RI 3&26 PD\ RFFXU E\ ZD\V RWKHU WKDQ the simple concentration of these hormones in circulation, particularly as leptin inserts its endocrine effects mostly through modulating LQVXOLQOHYHOV

11.







Acknowledgments This article was written based on the dataset RI DQ 06 WKHVLV UHJLVWHUHG DW WKH 7DEUL] 8QLYHUVLW\RI0HGLFDO6FLHQFHVDQGZDVFDUULHGRXW ZLWKILQDQFLDOVXSSRUWIURPWKH1XWULWLRQDO5HVHDUFK&HQWHUDQG9LFH&KDQFHOORUIRU5HVHDUFK DW 7DEUL] 8QLYHUVLW\ RI 0HGLFDO 6FLHQFHV 7DEUL],UDQ We thank all of the patients and healthy blood GRQRUVIRUSURYLGLQJEORRGVDPSOHVDQGDOOWKRVH who assisted us in this research. There is no conÀLFWRILQWHUHVW

1.

1RUPDQ 5- 'HZDLOO\ ' /HJUR 56 +LFNH\ 7( 3RO\F\VWLF RYDU\V\QGURPH/DQFHW 



'DVJXSWD65HGG\%03UHVHQWVWDWXVRIXQGHUVWDQGLQJ RQ WKH JHQHWLF HWLRORJ\ RI SRO\F\VWLF RYDU\ V\QGURPH 3RVWJUDG0HG  3DVTXDOL5&DVLPLUUL)7KHLPSDFWRIREHVLW\RQK\SHUDQGURJHQLVPDQGSRO\F\VWLFRYDU\V\QGURPHLQSUHPHQR-

IJFS, Vol 6, No 2, Jul-Sep 2012





 

References





124

  

SDXVDOZRPHQ&OLQ(QGRFULQRO (Oxf)  $KLPD 56 )OLHU -6$GLSRVH WLVVXH DV DQ HQGRFULQH RUJDQ7UHQGV(QGRFULQRO0HWDE  )DVVKDXHU 0 3DVFKNH 5 5HJXODWLRQ RI DGLSRF\WRNLQHV DQG LQVXOLQ UHVLVWDQFH 'LDEHWRORJLD    0DUJHWLF6*D]]ROD&3HJJ**+LOO5$/HSWLQDUHYLHZ RILWVSHULSKHUDODFWLRQVDQGLQWHUDFWLRQV,QW-2EHV5HODW 0HWDE'LVRUG  6DOHKSRXU67DKHU]DGHK%URXMHQL31HLVDQL6DPDQL( /HSWLQJKUHOLQDGLSRQHFWLQKRPRF\VWHLQHDQGLQVXOLQUHVLVWDQFHUHODWHGWRSRO\F\VWLFRYDU\V\QGURPH,QW-)HUWLO 6WHULO  /D]RYLF * 5DGLYRMHYLF 8 0LOLFHYLF 6 6SUHPRYLF 6 ,QÀXHQFHRIDGLSRVLW\RQOHSWLQ/+DQGDQGURJHQOHYHOVLQ OHDQ RYHUZHLJKW DQG REHVH 3&26 SDWLHQWV ,QW - )HUWLO :RPHQV0HG  $WDPHU$'HPLU%%D\KDQ*$WDPHU