title: Thecal cell sensitivity to luteinizing hormone and insulin in polycystic ovarian syndrome.
abstract: 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.
authors.affiliation: School of Graduate Entry Medicine, Derby Hospital, Nottingham University, DE22 3DT, United Kingdom. Electronic address: davecadagan@hotmail.com.
authors.forename: David
authors.initials: D
authors.lastname: Cadagan
authors.affiliation: School of Graduate Entry Medicine, Derby Hospital, Nottingham University, DE22 3DT, United Kingdom.
authors.forename: Raheela
authors.initials: R
authors.lastname: Khan
authors.affiliation: School of Graduate Entry Medicine, Derby Hospital, Nottingham University, DE22 3DT, United Kingdom.
authors.forename: Saad
authors.initials: S
authors.lastname: Amer
mesh_terms: D000328:Adult; D000735:Androstenedione / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000378:metabolism*; D008875:Middle Aged; D011085:Polycystic Ovary Syndrome / Q000378:metabolism*; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism; D013799:Theca Cells / Q000187:drug effects* / Q000502:physiology; D055815:Young Adult
chemical_list: D007328:Insulin; D000735:Androstenedione; D007986:Luteinizing Hormone; D013254:Steroid 17-alpha-Hydroxylase
keywords: 17α-Hydroxylase; Androgen; Insulin; Luteinizing hormone; Theca