Cross-talk between Follicle stimulating hormone receptor (FSHR), and Luteinizing hormone receptor (LHR) involving Insulin receptor substrates (IRS-1 and IRS-2)

Follicle stimulating hormone (FSH) and luteinizing hormones (LH), the gonadotropins are the regulators of follicle growth, ovulation, and oocyte maturation. An imbalance in their levels or activity is known to cause subfertility or infertility, especially in women with polycystic ovary syndrome (PCOS). In many of these women, LH levels are high along with untimely LH receptor (LHR) expression in granulosa cells in the follicular phase of menstrual cycles. Here, we demonstrate that high LHR activity due to high LH stimulate abnormal cAMP levels. The interaction between FSHR and IRS proteins (IRS-1 or IRS-2) is altered due to high LH/LHR expression/activity. This study demonstrates novel therapeutic targets in women with PCOS. The inhibition of high LHR activity with antagonistic peptides or LHR specific nanobodies would pave a way towards management of hormonal imbalance in women with PCOS.