Yüksek ET-1 İfadesinin Meme Bezi Fizyolojisi Üzerine Etkileri

Abstract

Objective: Alongside its role as a potent vasoconstrictor in the cardiovascular system, endothelin-1 (ET-1) is involved in numerous physiological processes. Its expression is thought to be an important function for both breastfeeding and newborns since it occurs especially during pregnancy and lactation. In this study, we projected the effects of ET-1 on mammary gland physiology employing ET-1 transgenic mice. Materials and Methods: In this study, we compared the mammary glands of ET-1 transgenic mice with the control mice in different physiological states (adolescence, pregnant, lactation and involution). Parallel sections were prepared from mammary glands and microscopic examinations were performed with hematoxylin and eosin (HE)-staining. Western blot techniques were used in the analysis of signal proteins that have important functions in mammary gland development and the metabolism (STAT5, AKT, STAT3). Genes known to play a key function in metabolic activities (WAP, beta casein, GLUT-1, SRBF-1 Claudin 8, IL-6, LIF) were analyzed employing real-time PCR techniques. Results: It was determined that ET-1 transgenic mice developed pathological conditions such as secretory damage, lactational failure and early involution, respectively. Our western blot studies showed that STAT5 activation was not affected by this process in the transgenic group, but a decrease in AKT protein level was detected. We detected STAT3 activation seen in the involution process in transgenic mice only on the 3rd day of lactation. In addition, we found that WAP was suppressed due to high ET-1 expression and that LIF protein expression increased significantly, by real-time PCR analysis. Conclusion: ET-1 expression is thought to be an important function for both lactation and newborns, especially during pregnancy and lactation. In this study, it was found that when ET-1 expression increases, it causes lactation failure in the mammary gland and directly affects the synthesis of genes known to be important in mammary physiology. Hereby, it was determined that the regulation of ET-1 plays a critical role in the development and secretory function of the mammary gland.