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

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...

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Main Authors: Cadagan, David, Khan, Raheela, Amer, Saad A.
Format: Article
Published: Elsevier 2016
Subjects:
Online Access:https://eprints.nottingham.ac.uk/44223/
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author Cadagan, David
Khan, Raheela
Amer, Saad A.
author_facet Cadagan, David
Khan, Raheela
Amer, Saad A.
author_sort Cadagan, David
building Nottingham Research Data Repository
collection Online Access
description 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.
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spelling nottingham-442232020-05-04T17:39:20Z https://eprints.nottingham.ac.uk/44223/ Thecal cell sensitivity to luteinizing hormone and insulin in polycystic ovarian syndrome Cadagan, David Khan, Raheela Amer, Saad A. 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. Elsevier 2016-03-31 Article PeerReviewed Cadagan, David, Khan, Raheela and Amer, Saad A. (2016) Thecal cell sensitivity to luteinizing hormone and insulin in polycystic ovarian syndrome. Reproductive Biology, 16 (1). pp. 53-60. ISSN 2300-732X 17α-Hydroxylase Androgen Insulin Luteinizing hormone Theca https://doi.org/10.1016/j.repbio.2015.12.006 doi:10.1016/j.repbio.2015.12.006 doi:10.1016/j.repbio.2015.12.006
spellingShingle 17α-Hydroxylase
Androgen
Insulin
Luteinizing hormone
Theca
Cadagan, David
Khan, Raheela
Amer, Saad A.
Thecal cell sensitivity to luteinizing hormone and insulin in polycystic ovarian syndrome
title Thecal cell sensitivity to luteinizing hormone and insulin in polycystic ovarian syndrome
title_full Thecal cell sensitivity to luteinizing hormone and insulin in polycystic ovarian syndrome
title_fullStr Thecal cell sensitivity to luteinizing hormone and insulin in polycystic ovarian syndrome
title_full_unstemmed Thecal cell sensitivity to luteinizing hormone and insulin in polycystic ovarian syndrome
title_short Thecal cell sensitivity to luteinizing hormone and insulin in polycystic ovarian syndrome
title_sort thecal cell sensitivity to luteinizing hormone and insulin in polycystic ovarian syndrome
topic 17α-Hydroxylase
Androgen
Insulin
Luteinizing hormone
Theca
url https://eprints.nottingham.ac.uk/44223/
https://eprints.nottingham.ac.uk/44223/
https://eprints.nottingham.ac.uk/44223/