**5. Conclusions**

Our results supported the hypothesis that *CRY1* and *CRY2*, being AngII-regulated genes, and showing a differential expression in APAs when compared with the adjacent adrenal cortex, might be involved in adrenal cell function, and in the regulation of aldosterone production. However, silencing *CRY1* and *CRY2* expression in HAC15 adrenocortical cells resulted only in a modest upregulation of the *HSD3B2* gene, which was not consistent with the experimental observations in the *Cry*-null animal model. Species differences should be considered when studying the role of these genes in adrenal function, and further exploration in this research area is warranted to elucidate the complex role of the circadian clock in adrenal aldosterone production.

#### **Supplementary Materials:** Supplementary materials can be found at http://www.mdpi.com/1422-0067/19/6/ 1675/s1.

**Author Contributions:** M.T., C.M. and S.M. performed the in-vitro experiments (cell culture, gene expression studies and sequencing, silencing studies) and wrote the manuscript; I.C. performed the histopathological analyses and the immunohistochemistry; F.V. (Francesca Veneziano) performed the immunohistochemistry; F.V. (Franco Veglio) critically revised the manuscript; S.M. and P.M. conceived the design of the study, wrote part of the manuscript and critically revised it.

**Funding:** This research was funded by MIUR Ricerca locale ex-60% 2015.

**Conflicts of Interest:** The authors declare no conflict of interest.
