Corticotrophin-Releasing-Hormone (CRH) modulates ovarian steroid biosynthesis in human primary granulosa cells

Introduction: Corticotrophin-Releasing-Hormone (CRH) is majorly involved in the body's stress response and regulates ovarian steroid biosynthesis by blocking GnRH release via a negative feedback loop. In addition, CRH has been highlighted to modulate ovarian response in a more direct way – most presumably via CRH-receptors (CRHRs) expressed in ovarian granulosa cells. We recently demonstrated CRHR1 to be present in human ovarian follicles. Since functional data are missing so far, the current study aimed to elucidate whether CRH is able to directly act on ovarian granulosa cells.

Materials: Human primary granulosa cells isolated from follicle aspirates as well as the human granulosa cell line HGL5 were used.

Methods: Cell cultures were tested for expression of CRHR1 and CRHR2. Estradiol-/progesterone synthesis as well as expression of 184 transcripts was analysed in cultures treated with CRH vs. carrier solution.

Results: Both CRHR isoforms were abundantly expressed. Out of 184 transcripts nine were found to be down-regulated by CRH treatment while three mRNAs were upregulated. Cultures incubated with CRH produced significantly less estradiol (0.64-fold, p = 0.028) and progesterone (0.66-fold, p = 0.028). This effect was not due to reduced cell viability or increased apoptosis in CRH treated samples.

Conclusion: Our data show that CRH regulates gene expression as well as estradiol and progesterone synthesis of cultured human granulosa cells. CRH may diretly influence granulosa cells thereby transmitting stress signals to the ovary.