AUTHOR=Shu Tingting , Shu Yuqin , Gao Yanping , Jin Xia , He Jiangyan , Zhai Gang , Yin Zhan 

TITLE=Depletion of Tissue-Specific Ion Transporters Causes Differential Expression of PRL Targets in Response to Increased Levels of Endogenous PRL

JOURNAL=Frontiers in Endocrinology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2018.00683

DOI=10.3389/fendo.2018.00683

ISSN=1664-2392

ABSTRACT=<p>Prolactin (PRL) has been considered a key regulator of ion uptake in zebrafish. The genes <italic>slc12a10.2</italic> and <italic>slc12a3</italic>, which are Na<sup>+</sup> and chloride Cl<sup>−</sup> co-transporters, have been reported to be regulated by PRL in freshwater fish. The integrative network of PRL signaling dissected from the knockout of tissue-specific downstream PRL ion transporters remains poor. In the present study, zebrafish models with increased endogenous levels of PRL were generated through the knockout of <italic>slc12a10.2</italic> or <italic>slc12a3</italic>, and the developmental consequences were analyzed. The increased levels of pituitary PRL were observed in both <italic>slc12a10.2</italic>- and <italic>slc12a3</italic>-deficient fish. Unlike the <italic>slc12a3</italic>-deficient fish, which could survive to adulthood, the <italic>slc12a10.2</italic>-deficient fish began to die at 9 days post-fertilization (dpf) and did not survive beyond 17 dpf. This survival defect is a result of defective Cl<sup>−</sup> uptake in this mutant, indicating that Slc12a10.2 plays an essential role in Cl<sup>−</sup> uptake. Intriguingly, compared to the levels in control fish, no significant differences in the levels of Na<sup>+</sup> in the body were observed in <italic>slc12a10.2</italic>- or <italic>slc12a3</italic>-deficient zebrafish. The upregulations of the PRL downstream transporters, <italic>slc9a3.2, slc12a10.2</italic>, and <italic>atp1a1a.5</italic> were observed in <italic>slc12a3</italic>-deficient fish in both the gills/skin and the pronephric duct. However, this type of response was not observed in the pronephric duct of <italic>slc12a10.2</italic>-deficient fish, except under Na<sup>+</sup>-deprived conditions. Our results show that PRL is susceptible to deficiencies in downstream ion transporters. Moreover, both the gills/skin and pronephric duct show differential expression of downstream PRL targets in response to increased levels of pituitary PRL caused by the depletion of tissue-specific ion transporters.</p>