Olatunji Lawrence A, Usman Taofeek O, Akinade Aminat I, Adeyanju Oluwaseun A, Kim InKyeom, Soladoye Ayodele O
a Department of Physiology, Cardiovascular Research Laboratory , College of Health Sciences, University of Ilorin , Ilorin , Nigeria.
b Department of Physiology, Cardiovascular Unit, College of Health sciences , Osun State University , Osogbo , Nigeria.
Arch Physiol Biochem. 2017 Dec;123(5):286-292. doi: 10.1080/13813455.2017.1320681. Epub 2017 May 8.
Elevated gestational circulating testosterone has been associated with pathological pregnancies that increase the risk of development of cardiometabolic disorder in later life.
We hypothesised that gestational testosterone exposure, in late pregnancy, causes glucose deregulation and atherogenic dyslipidaemia that would be accompanied by high plasminogen activator inhibitor-1 (PAI-1). The study also hypothesise that low-dose spironolactone treatment would ameliorate these effects.
Pregnant Wistar rats received vehicle, testosterone (0.5 mg/kg; sc), spironolactone (0.5 mg/kg, po) or testosterone and spironolactone daily between gestational days 15 and 19.
Gestational testosterone exposure led to increased HOMA-IR, circulating insulin, testosterone, 1-h post-load glucose, atherogenic dyslipidaemia, PLR, PAI-1 and MDA. However, all these effects, except that of circulating testosterone, were ameliorated by spironolactone.
These results demonstrate that low-dose spironolactone ameliorates glucose deregulation and atherogenic dyslipidaemia during elevated gestational testosterone exposure, at least in part, by suppressing elevated PAI-1.
