LH-Receptor Gene Expression in Human Granulosa and Cumulus Cells from Antral and Preovulatory Follicles

Context: Human granulosa cells (GC) acquire LH receptor (LHR) expression during the follicular phase of the menstrual cycle. Currently, the precise follicular stage is unknown, and specific roles of LH in the follicular development are not fully understood. Objective: Our objective was to measure LHR gene expression on GC and cumulus cells (CC) from normal human follicles with diameters form 3-20 mm. Design, Setting, and Patients: At a university hospital, GC, CC, and the corresponding follicular fluid (FF) were collected from patients undergoing fertility preservation by having one ovary frozen and patients undergoing infertility treatment. Interventions: Cells and fluids were isolated from surgically excised ovaries or from aspirated preovulatory follicles. Main Outcome Measures: We evaluated gene expression of LHR, FSHR, androgen receptor (AR), aromatase (CYP19a1), and AMHR2 normalized to the GAPDH expression and associated with FF levels of anti-Mullerian hormone, inhibin-B, and steroids. Results: LHR expression was maximal in GC from preovulatory follicles before ovulation induction. A majority of 150 antral follicles (3-10 mm in diameter) showed LHR expression at approximately 10% of the maximum, and LHR expression showed significant associations with FSHR, AR, CYP19a1, and AMHR2 and with FF estradiol and progesterone. Levels of FSHR continued to decline in GC as the follicular diameter increased. Conclusions: The LHR gene is expressed in GC of human antral follicles throughout the follicular phase and is significantly associated with expression of the CYP19a1 gene and with the corresponding FF concentrations of estradiol and progesterone. LH appears to affect human follicular development during most the follicular phase in normal women. (J Clin Endocrinol Metab 97: E1524-E1531, 2012)