Cabergoline Suppresses FSH-Induced Differentiation and Steroidogenesis in Primary Cultured Rat Granulosa Cells.

PURPOSE: Cabergoline, a dopamine D2 receptor agonist widely used to prevent ovarian hyperstimulation syndrome (OHSS), has unclear effects on granulosa cells during the follicular phase. This study aimed to investigate how cabergoline affects follicle-stimulating hormone (FSH)-induced cell differentiation and steroidogenesis.

METHODS

Primary granulosa cells were isolated from immature female rats pretreated with diethylstilbestrol (DES) and cultured under four conditions: control, cabergoline alone, FSH alone, and FSH combined with cabergoline. mRNA expression of Lhcgr, Cyp19a1, and related genes was quantified by real-time PCR, and luteinizing hormone (LH) receptor binding, estradiol (E2) and progesterone (P4) secretion, and cyclic adenosine monophosphate (cAMP) production were evaluated. Dopamine D2 receptor expression was analyzed by Western blotting.

RESULTS

Cabergoline significantly suppressed FSH-induced mRNA expression of Lhcgr, Cyp19a1, Cyp11a1, and Hsd3b1; hCG binding; E2 and P4 secretion; and cAMP accumulation. Most inhibitory effects were dose dependent, although cAMP suppression did not exhibit clear concentration dependency. Dopamine D2 receptor expression was detectable, although at low levels.

CONCLUSIONS

Cabergoline suppresses FSH-induced granulosa cell differentiation and steroidogenesis, at least partly through attenuation of FSH-induced cAMP signaling. Although dopamine D2 receptor signaling may contribute to the inhibitory effects of cabergoline, the downstream molecular mechanisms remain unclear, warranting further investigation.