In the liver, the sterol response element binding protein (SREBP) and the SREBP cleavage-activated protein (SCAP) complex upregulates cholesterol biosynthesis by gene induction of de novo cholesterol synthetic enzymes (Hmgcr, Cyp51, and Dhcr7). Insulin induced gene 1 (INSIG1) negatively regulates cholesterol biosynthesis by the inhibition of de novo cholesterol biosynthetic gene expression. In the ovary, cholesterol is de novo synthesized; however, the roles of SREBP and its regulators (SCAP and INSIG1) are not well understood. In this study, when immature mice were treated with gonadotropins (eCG followed by hCG), eCG induced and hCG maintained the expression of SREBP-1a, -2, and SCAP granulosa cells, whereas INSIG1 expression was dramatically downregulated after hCG injection. Downregulation of INSIG1 led to generate the SREBPs active form and translocate the SREBPs active form to nuclei. Inhibition of generation of the SREBPs active form by fatostatin or Scap siRNA in both in vivo and in vitro significantly decreased the expressions of de novo cholesterol biosynthetic enzymes, cholesterol accumulation, and progesterone (P4) production compared to control group. Fatostatin treatment inhibited the ovulation and increased the formation of abnormal corpus luteum which trapped the matured oocyte in the corpus luteum, however, the phenomenon was abolished by P4 administration. The results showed that decreasing INSIG1 level after hCG stimulation activated SREBP-induced de novo cholesterol biosynthesis in granulosa cells of preovulatory follicles, which is essential for P4 production and the rupture of matured oocyte during ovulation process.

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ObjectiveMountain districts normally have tougher geographic conditions than plain districts, which might worsen heart failure (HF) conditions in patients. Also, those places frequently are associated with social problems of ageing, underpopulation and fewer medical services, which might cause delay in detection of disease progression and require more admissions. We investigated the association of residence altitude with readmission in patients with HF.MethodsWe followed 452 patients with HF to determine all-cause readmissions over a median of 1.1 years. The altitude of patient residences, population, proportion of the elderly and number of hospitals or clinics in a minor administrative district (Cho-Aza district) located at the residences were examined using data from the 2010 census and Google Maps.ResultsAll-cause readmissions were observed in 269 (60%) patients. The altitude of ≥200  m was significantly associated with readmissions (HR, 1.49; 95 % CI 1.12 to 1.96; p=0.006) after adjustment for physical and haemodynamic parameters, left ventricular ejection fraction, brain natriuretic peptide and components of the established score for predicting readmission for HF. Altitude was significantly associated with ageing, underpopulation, fewer hospitals or clinics and lower temperature (all p<0.01), with an increased tendency for readmission during the winter season; however, it was not associated with patient clinical parameters.ConclusionsHigh altitude residence may be an important predictor for readmission in patients with HF. This relationship may be confounded by unfavourable sociogeographic conditions at higher altitudes.

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