Analysis of the mammary gland specific effect of endothelin-1 in transgenic mice [article]

Nadir Gül, Humboldt-Universität Zu Berlin, Humboldt-Universität Zu Berlin
Endothelin-1 (ET-1) is a potent vasoactive peptide having wide physiological effects on vascular homeostasis and on a variety of pathophysiological processes unrelated to cardiovascular system. It has been noted that ET-1 is expressed in mammary glands during pregnancy and lactation periods. Furthermore, ET-1 is secreted into milk, suggesting additional physiological roles in the lactating mother and in the suckling neonate. Hence, the present study was proposed to elucidate the possible
more » ... the possible functional roles of ET-1 in mammary gland development employing ET-1 transgenic mice. ET-1 transgenic mice had been generated by using a human genomic ET-1 construct containing 5´ and 3´ regulatory sequences. This transgenic construction strategy grants to analyse the specific functions of ET-1 in normal mammary gland physiology. The transgene expression was found in mammary gland during pregnancy and lactation. ET-1 transgenic mice exhibited a lactational incompetence with reduced weight gain and increased mortality of their newborns, as a result of a secretory defect. In virtue of this defect, ET-1 transgenic mammary glands histologically revealed a reduced ductal outgrowth, collapsed alveoli with a reduced expansion capacity, increased adipocyte accumulation, and persistence of cystoplasmic lipid droplets (CLDs) during lactation. In addition, the expression of the milk protein, WAP, was found to be constantly suppressed in ET-1 mammary glands although the activity of STAT5, which is known to be a regulator of the expression of milk proteins and alveolar expansion, was found to be normal. Furthermore, as a consequence of the secretory defect, ET-1 transgenic mammary glands exhibited focal precocious involution during early stages of lactation along with an increased activity of STAT3. Consistently, the known activator of STAT3, LIF, was strongly upregulated during lactation and pregnancy. Besides the secretory defect of ET-1 transgenic mammary glands, histological analysis revealed a local lactational hyperplasia during the mid [...]
doi:10.18452/16338 fatcat:y63nl6dsvbex5bqrvpkk6lth6y