Testosterone Could Induce Cardiac Hypertrophy in Ovariectomized SHR Through the Activation of the Mtorc2/Atg9a

Objective: The estrogen level of postmenopausal women decreased sharply, while the androgen level did not decrease significantly, which was characterized by the inversion of estrogen / androgen ratio. Therefore, it could be observed that relative excess androgen in the circulation of postmenopausal women, which may be one of the reasons for the increase of cardiovascular disease in postmenopausal women. In this study, the model of postmenopausal hypertension was established by bilateral ovariectomy in spontaneously hypertensive rats (SHR), and the specific mechanism of testosterone-induced myocardial hypertrophy in ovariectomized SHR was explored. Design and method: 24 SHR were randomly divided into four groups: WKY group (n=6), sham operation group (Sham group, n=6), bilateral ovariectomized group (OVX group, n=6) and testosterone propionate intervention group (OVX+T group, 6mg/kg/Weekly, im for 4 weeks, n=6). Western Blot was used to detect the protein expression of B-MHC, ANP, Androgen receptor, Akt, p-Akt, mTORC2 and its subunits Rictor. Moreover, the expression of autophagy-related proteins LC3 was observed. Results: 1. Testosterone-induced cardiac hypertrophy in ovariectomized SHR: the expression of B-MHC and ANP was significantly increased in both the OVX and OVX+T groups when compared to the WKY and Sham groups. Additionally, the expression of androgen receptors was markedly upregulated in both the OVX and OVX+T groups. These findings strongly suggest that testosterone primarily induces myocardial hypertrophy in SHR after ovariectomy through androgen receptors. 2. Testosterone activation of mTORC2 expression in myocardial tissue: Testosterone exhibited a notable capacity to activate mTORC2 expression and the p-Rictor subunit in the OVX+T group. 3. Testosterone inhibit cardiomyocyte autophagy: A conspicuous reduction in the expression of LC3II was observed in the OVX+T group when compared to the OVX groups. This reduction indicates that testosterone may effectively inhibit cardiomyocyte autophagy under the experimental conditions. Conclusions: In bilateral ovariectomized SHR, testosterone could inhibit cardiac autophagy by activating the expression of mTORC2, which, in turn, leads to cardiac hypertrophy.