Comparative effect of 5α‐dihydrotestosterone (DHT) and 17β‐estradiol (E2) on norepinephrine (NE)‐induced hypertrophy in neonatal rat ventricular myocytes (NRVM)

Abstract

Cardiac hypertrophy increases after menopause. As a result the potential role of E2 has been examined while the role of DHT is understudied. We compared the effect of DHT to E2 on markers of NE‐elicited hypertrophy in NRVM including: 1) cell surface area (CSA), 2) myofibrillar organization by actin staining, 3) fetal gene expression by real‐time RT‐PCR and 4) ERK activation (ERK∼P/ERK‐total) by Western blot. NRVMs were exposed to NE (1μM), E2 (10nM), DHT (100nM), E2+NE, or DHT+NE in phenol‐free DMEM for 48 hrs (n=3). Compared to control, NE nearly doubled CSA and greatly increased actin fiber alignment and organization. E2 decreased and DHT increased CSA but both induced myofibrillar disorganization. E2 and DHT reduced NE‐elicited augmentation of CSA and myofibrillar organization. CSA was greater in DHT than E2‐exposed cells regardless of NE treatment. E2 alone did not alter fetal gene expression whereas DHT increased α‐myosin heavy chain (MHC) and sarcoplasmic reticular calcium ATPase. NE increased expression of β‐MHC, skeletal actin, ANP and BNP, but neither E2 nor DHT altered the NE response. ERK∼P to total ERK ratio was not altered by any treatment. In conclusion, similar to E2, DHT reduces hypertrophy but not gene expression or ERK activation after 48 hrs of NE exposure. Supported by NR009014 & HL62426