Thecal cell sensitivity to luteinizing hormone and insulin in polycystic ovarian syndrome

被引:66
作者
Cadagan, David [1 ]
Khan, Raheela [1 ]
Amer, Saad [1 ]
机构
[1] Univ Nottingham, Derby Hosp, Sch Grad Entry Med, Nottingham DE22 3DT, England
关键词
17; alpha-Hydroxylase; Androgen; Insulin; Luteinizing hormone; Theca; GROWTH-FACTOR-I; RIBONUCLEIC-ACID EXPRESSION; SIGNAL-TRANSDUCTION; ANDROGEN PRODUCTION; INTERSTITIAL CELLS; RECEPTOR; WOMEN; RESISTANCE; BIOSYNTHESIS; TESTOSTERONE;
D O I
10.1016/j.repbio.2015.12.006
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
This study examined whether a defect of steroid synthesis in ovarian theca cells may lead to the development of PCOS, through contributions to excess androgen secretion. Polycystic ovarian syndrome (PCOS) is one of the leading causes of infertility worldwide affecting around 1 in 10 of women of a reproductive age. One of the fundamental abnormalities in this syndrome is the presence of hormonal irregularities, including hyperandrogenemia, hyperinsulinemia and hypersecretion of luteinizing hormone (LH). Studies suggest that insulin treatment increases progesterone and androstenedione secretion in PCOS theca cells when compared to insulin treated normal theca cells. Furthermore the augmented effects of LH and insulin have been seen to increase ovarian androgen synthesis in non-PCOS theca cultures whilst also increasing the expression of steroidogenic enzymes specific to the PI3-K pathway. Our examination of primary thecal cultures showed an increase in both the expression of the steroidogenic enzyme CYP17 and androgen secretion in PCOS theca cells under basal conditions, when compared to non-PCOS cells. This was increased significantly under treatments of LH and insulin combined. Our results support the previous reported hypothesis that a dysfunction may exist within the PI3-K pathway. Specifically, that sensitivity exists to physiological symptoms including hyperinsulinemia and hyper secretion of LH found in PCOS through co-stimulation. The impact of these findings may allow the development of a therapeutic target in PCOS. (C) 2016 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Sp. z o.o. All rights reserved.
引用
收藏
页码:53 / 60
页数:8
相关论文
共 32 条
[1]   Developmental origin of polycystic ovary syndrome - a hypothesis [J].
Abbott, DH ;
Dumesic, DA ;
Franks, S .
JOURNAL OF ENDOCRINOLOGY, 2002, 174 (01) :1-5
[2]  
ADASHI EY, 1994, FERTIL STERIL, V62, P20
[3]   Commentary: Polycystic ovary syndrome: A syndrome of ovarian hypersensitivity to insulin? [J].
Baillargeon, JP ;
Nestler, JE .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2006, 91 (01) :22-24
[4]   HYPERSECRETION OF LUTEINIZING-HORMONE AND THE POLYCYSTIC-OVARY-SYNDROME [J].
BALEN, AH .
HUMAN REPRODUCTION, 1993, 8 :123-128
[5]  
BARBIERI RL, 1984, OBSTET GYNECOL, V64, P73
[6]   Selective insulin resistance in the polycystic ovary syndrome [J].
Book, CB ;
Dunaif, A .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1999, 84 (09) :3110-3116
[7]   CELLULAR MECHANISMS OF INSULIN RESISTANCE IN POLYCYSTIC OVARIAN SYNDROME [J].
CIARALDI, TP ;
ELROEIY, A ;
MADAR, Z ;
REICHART, D ;
OLEFSKY, JM ;
YEN, SSC .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1992, 75 (02) :577-583
[8]   EVIDENCE FOR DISTINCTIVE AND INTRINSIC DEFECTS IN INSULIN ACTION IN POLYCYSTIC-OVARY-SYNDROME [J].
DUNAIF, A ;
SEGAL, KR ;
SHELLEY, DR ;
GREEN, G ;
DOBRJANSKY, A ;
LICHOLAI, T .
DIABETES, 1992, 41 (10) :1257-1266
[9]   THE OVARIAN ANDROGEN PRODUCING CELLS - A REVIEW OF STRUCTURE-FUNCTION RELATIONSHIPS [J].
ERICKSON, GF ;
MAGOFFIN, DA ;
DYER, CA ;
HOFEDITZ, C .
ENDOCRINE REVIEWS, 1985, 6 (03) :371-399
[10]   MEDICAL PROGRESS - POLYCYSTIC-OVARY-SYNDROME [J].
FRANKS, S .
NEW ENGLAND JOURNAL OF MEDICINE, 1995, 333 (13) :853-861