Antiadipogenic Effects of the Mineralocorticoid Receptor Antagonist Drospirenone: Potential Implications for the Treatment of Metabolic Syndrome

Abstract

fatty acids and minimal obesity, absent GH activation leads to steatosis because phosphorylated STAT5 prevents hepatic steatosis. These results raise the possibility of low-dose GH treatment for nonalcoholic fatty liver disease. Endocrinology, published November 17, 2010, 10.1210/en. 2010 The Somatotrope as a Metabolic Sensor: Deletion of Leptin Receptors Causes Obesity Gwen V. Childs, Noor Akhter, Anessa Haney, Mohsin Syed, Angela Odle, Michael Cozart, Zachary Brodrick, Dana Gaddy, Larry J. Suva, Nisreen Akel, Christopher Crane, Helen Benes, Amanda Charlesworth, Raul Luque, Streamson Chua, and Rhonda D. Kineman Leptin, the product of the Lep gene, reports levels of adiposity to the hypothalamus and other regulatory cells, including pituitary somatotropes, which secrete GH. Leptin deficiency is associated with a decline in somatotrope numbers and function, suggesting that leptin may be important in their maintenance. This hypothesis was tested in a new animal model in which exon 17 of the leptin receptor (Lepr) was selectively deleted in somatotropes by Cre-loxP technology. Organ genotyping confirmed the recombination of the floxed LepR allele only in the pituitary. Deletion mutant mice showed a 72% reduction in pituitary cells bearing leptin receptor (LEPR)-b, a 43% reduction in LEPR proteins and a 60% reduction in percentages of immunopositive GH cells, which correlated with reduced serum GH. In mutants, LEPR expression by other pituitary cells was like that of normal animals. Leptin stimulated phosphorylated Signal transducer and activator of transcription 3 expression in somatotropes from normal animals but not from mutants. Pituitary weights, cell numbers, IGF-I, and the timing of puberty were not different from control values. Growth curves were normal during the first 3 months. Deletion mutant mice became approximately 30-46% heavier than controls with age, which was attributed to an increase in fat mass, with no significant effects on lean mass. Serum leptin levels were either normal in younger animals or reflected the level of obesity in older animals. The specific ablation of the Lepr exon 17 gene in somatotropes resulted in GH deficiency with a consequential reduction in lipolytic activity normally maintained by GH and increased adiposity. Endocrinology, published November 17, 2010, 10.1210/en. 2010 During pregnancy, trophoblasts grow to adapt the feto-maternal unit to fetal requirements. Aldosterone and cortisol levels increase, the latter being inactivated by a healthy placenta. By contrast, preeclamptic placental growth is reduced while aldosterone levels are low and placental cortisol tissue levels are high due to improper deactivation. Aldosterone acts as a growth factor in many tissues, whereas cortisol inhibits growth. We hypothesized that in preeclampsia low aldosterone and enhanced cortisol availability might mutually affect placental growth and function. Proliferation of cultured human trophoblasts was time-and dose-dependently increased with aldosterone (P Ͻ 0.04 to P Ͻ 0.0001) and inhibit...

Adipocytes Produce Aldosterone Through Calcineurin-Dependent Signaling Pathways

“…Of importance, this locally produced aldosterone might have an autocrine (patho)physiological role by influencing, among other processes, adipocyte differentiation. 16,17,19,26 Our findings demonstrate that the selective CYP11B2 inhibitor FAD286 prevented adipocyte differentiation, triacylglycerol accumulation, and expression of adipocyte differentiation markers peroxisome proliferator-activated receptor-␥ and aP2. In support of these data, MR-gene knockout adipocytes fail to accumulate lipids.…”

“…[16][17][18] Experimental and clinical studies demonstrated positive outcomes of MR blockade in obesity/diabetes mellitus-related cardiovascular and kidney disease. [19][20][21] We previously reported the presence of aldosterone in conditioned culture medium (CCM) from the 3T3-L1 adipocyte cell line.…”

Adipocyte-Specific Mineralocorticoid Receptor Overexpression in Mice Is Associated With Metabolic Syndrome and Vascular Dysfunction: Role of Redox-Sensitive PKG-1 and Rho Kinase

“…There is increased expression and activation of MR in adipose tissue in experimental and human obesity, diabetes, and cardiovascular diseases (6,14,15,32). 2.…”

Overcome Barriers in Prescription of Hormonal Contraception (Clinical Lecture)

“…Дроспиренон объединяет в себе эффекты эндогенного прогестерона (антигонадотропный и антиандрогенный) со свойствами антиминералокортикоидов, которые клинически выража-ются в уменьшении задержки жидкости и натрия в орга-низме, что способствует дополнительному снижению массы тела [10][11][12][13][14][15]. Кроме того, режим приема КОК 24/4 в сравнении с режимом 21/7 достоверно уменьшает дли-тельность и обильность планового кровотечения отмены [16], а также высокоэффективен в купировании симпто-мов при тяжелом предменструальном синдроме [13,17].…”