Insulin and insulin-like growth factor stimulation of vascular endothelial growth factor production by luteinized granulosa cells: comparison between polycystic ovarian syndrome (PCOS) and non-PCOS women.
BACKGROUND
Vascular endothelial growth factor A (VEGF-A) is a potent cytokine that promotes angiogenesis and vascular permeability. After controlled ovarian stimulation (COS) for in vitro fertilization (IVF), excessive VEGF-A production can occur, particularly in women with polycystic ovarian syndrome (PCOS); however, it is unclear whether the regulation of VEGF-A production is different between PCOS and non-PCOS women.


OBJECTIVE
The aim of this study was to determine whether there were differences in the dose- and time-dependent effects of insulin and IGFs on VEGF-A production by luteinized granulosa cells (LGCs) from women with and without PCOS.


METHODS
A prospective comparative experimental study was conducted at an institutional practice.


METHODS
Patients included six PCOS and six non-PCOS women undergoing COS and IVF.


METHODS
Interventions included COS for IVF.


METHODS
VEGF-A levels in culture media were collected daily for 3 d from LGCs after incubation with variable doses of insulin, IGF-I, and IGF-II in the presence and absence of LH.


RESULTS
In both study groups, exposure to LH alone did not alter VEGF-A levels. However, insulin or IGF increased VEGF-A levels within 1 d and appeared to synergize with LH at 3 d. VEGF-A production by non-PCOS LGCs was more sensitive to IGF exposure, whereas PCOS cells were more sensitive to insulin. Although an increase in DNA content (P < 0.05) was noted in cultures of PCOS cells, progesterone levels were lower compared with non-PCOS LGCs.


CONCLUSIONS
Insulin and IGFs promote VEGF-A production in LGCs, but the response patterns are different when cells from PCOS and non-PCOS women are compared.
Stanek
Meghan B
MB
Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, Oregon 97239, USA.
Borman
Sherri M
SM
Molskness
Theodore A
TA
Larson
Janine M
JM
Stouffer
Richard L
RL
Patton
Phillip E
PE
D000328:Adult; D002478:Cells, Cultured; D003470:Culture Media / Q000494:pharmacology; D005260:Female; D005307:Fertilization in Vitro; D006107:Granulosa Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000378:metabolism / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000378:metabolism / Q000494:pharmacology; D034461:Luteinization; D007986:Luteinizing Hormone / Q000494:pharmacology; D010062:Ovulation Induction; D011085:Polycystic Ovary Syndrome / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D003470:Culture Media; D007004:Hypoglycemic Agents; D007328:Insulin; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D007986:Luteinizing Hormone