Corticotropin-releasing hormone reduces basal estradiol production in zebrafish follicular cells

Corticotropin-releasing hormone (CRH) plays a key regulatory role in coordinating the regulation of endocrine, autonomic nervous, immune, and reproductive systems. Two CRH (CRH alpha and CRH beta) and their receptors (CRHR1 and CRHR2) had been identified in zebrafish. However, their functions remained uncovered in the ovary of zebrafish. Therefore, this study aimed to determine whether CRH acts directly on the ovary to regulate steroidogenesis in cultured zebrafish follicular cells. Firstly, CRH and its receptors are expressed in the zebrafish ovary. The expression profile of CRH beta fluctuated during ovarian development in zebrafish, and the highest CRHa mRNA levels were observed at the mature follicle. The highest CRHR1 and CRHR2 mRNA levels existed in midvitellogenic (MV) and early vitellogenic (EV) stages, respectively. In primary cultured zebrafish follicular cells, both of the CRHa and CRH beta inhibited expression of hsd17b3 mRNA levels and decreased content of estradiol (E2) in the medium. Furthermore, CRH activated p38 MAPK and p38 MAPK inhibitor SB203580 attenuated the phosphorylation of p38 MAPK induced by CRHa. Simultaneously, SB203580 changed the effect of CRH on cyp19a1a expression but not hsd17b1 and hsd17b3. SB203580 alone or combined with CRH inhibited the E2 content. Finally, the CRHR inhibitor alpha-helical 9-41 also blocked the phosphorylation of p38 MAPK induced by CRHa but did not change the inhibitory effect of CRH on the mRNA expression of the steroidogenic gene and the content of E2 in the culture medium. Taken together, our findings suggest that the anti-steroidogenic effects of CRH may be mediated partly through activation of the p38 MAPK signaling pathway.

Automated summary

The study showed that CRH is expressed in the zebrafish ovary and can partly inhibit steroidogenesis by activating the p38 MAPK signaling pathway, resulting in reduced estradiol synthesis.