Effects of gonadotropin inducible ovarian transcription factor 1 in the paraventricular nucleus on fluid intake after dehydration of ovariectomized female rats.

In order to maintain body fluid balance after dehydration, hypothalamic neurons of the paraventricular nucleus (PVN) are activated to promote secretion of vasopressin (AVP) and oxytocin (OXT) from the neurohypophysis, and to modulate the behavioural allostatic responses of thirst and salt appetite. Gonadotropin inducible transcription factor (GIOT1) is a Krüppel-type zinc finger protein induced by gonadotropins and oestradiol (E2). This transcription factor is expressed in the hypothalamus, specifically in the PVN where expression of Giot1 mRNA increases following hydromineral challenges such as water deprivation or salt loading, although its physiological role is not clear. We hypothesize that GIOT1 has a central role in the integrated homeostatic and allostatic responses to disturbances in hydromineral balance, especially in the presence of female gonadal hormones. Female rats with intact ovaries or ovariectomized rats were subjected to specific microinjection of a lentiviral vector mediating Giot1 knockdown in the PVN. Three weeks after injection, rats were subjected to 48 h water deprivation, and thereafter water and salt intake were evaluated. Giot1 knockdown in PVN reduced water and saline intake as well as AVP and OXT secretion. Furthermore, Giot1 knockdown had profound effects on gene expression in the PVN, reducing the abundance of transcripts encoded by the Avp, Oxt, Nr4a1 and Crh genes. In conclusion, the present study shows for the first time that GIOT1 in the PVN regulates both transcription and fluid intake, although any connection to ovarian hormones remains to be established.