Relationship between the expression of HSD3B2, SRD5A2 and androgen receptor in hypospadias patients

Abstract

Testosterone is converted into dihydrotestosterone (DHT) by steroid-5-alpha-reductase. DHT induces the development of the external genitalia, both through the effect on the androgen receptor (AR) steroid-5-alpha-reductase type 2 (SRD5A2) and Hydroxy-delta-5-steroid dehydrogenase,3 beta- and steroid delta-isomerase 2 (HSD3B2) influenced testosterone production. The gene encoding SRD5A2 is particularly interesting because this enzyme is expressed during male genital development around the ventral part of the remodelling urethra and it converts testosterone to the more potent androgen DHT, which induces formation of the external genitalia. The clinical presentation of HSD3B2 deficiency is heterogeneous and may range from salt-losing congenital hyperplasia to premature pubarche, mild hyperandrogenism and the possibility of abnormalities in male genital development, such as hypospadias. From September 2017 – December 2018, we reviewed 80 patients, comprising 70 patients who underwent repair of hypospadias (46 proximal hypospadias (group 1) and 24 distal hypospadias (group 2)) without DSD, and 10 patients with no known anomaly who underwent circumcision (group 3), prospectively. We used periurethral dartos obtained during surgery. The expression of SRD5A2, HSD3B2 and AR was investigated by quantitative real time polymerase chain reaction (qRT-PCR). Median age was 5 years. The median of SRD5A2 was 22,68 (8,57-34,29) and mean of HSD3B2 and AR were 17,14 (2,12 ± 29,85) and 6,96 (1,62±13,92). We found a statistically significant difference between the expression of SRD5A2, HSD3B2 and AR in group 1 vs 3 and group 2 vs 3 but no difference in group 1 vs 2. We found positive correlation between SRD5A2 and HSD3B2 in hypospadias (r=0.38; p=0.001) but no correlation between both of them with androgen receptor. The correlation between SRD5A2 and HSD3B2 might influence the testosterone production but had no effect in androgen receptor.