Prolactin receptor in pituitary, white and brown adipose tissue, and liver in mice with global or lactotrope specific deletion of the dopamine type 2 receptor

LOPEZ VICCHI, FELICITAS; DE WINNE, CATALINA; BECU-VILLALOBOS, DAMASIA; ORNSTEIN, ANA MARIA

Congreso; Growth Hormone/Prolactin Family in Biology and Disease; 2019

Prolactin is a pituitary hormone whose functions are critical for pregnancy and lactation, during which it acts on different tissues such as adipose tissue, liver, pancreas and brain in order to meet the energy requirements of the mother and offspring. Prolactin may act on both white (WAT) and brown adipose tissue (BAT). In WAT it modulates adipogenesis and in both BAT and WAT it regulates adipocyte differentiation.Dopamine may also regulate adipose tissue function by sympathetic neuro-adipose connections, either indirectly by brain activation of D2R and food intake, or by a direct proinflammatory actions on adipocytes. Besides, it might be involved in BAT thermogenesis. Both Drd2-/- and lacDrd2KO female have chronic hyperprolactinemia, but only lacDrd2KO are obese and have increased adipogenesis. Therefore, in order to uncover potential actions of D2Rs on different adipose tissues and understand the phenotypes observed in these hyperprolactinemic mouse models, we studied Prlr mRNA expression in BAT and in gonadal WAT in females of both animal models.Using RTqPCR the expression of Prlr and Cis mRNA levels (one of the main suppressors of Prlr pathway, together with the SOCS family) was assessed in adipose tissue of 10 months old female mice. In addition the expression of the thermogenic gene Ucp1 was measured. Its presence in WAT might be considered as a sign of ?beiging?. In gonadal WAT of Drd2-/- mice increased mRNA levels of Cis and Ucp1 were found, while in lacDrd2KO mice these transcripts unchanged. For Prlr mRNA no changes were found. In the case of BAT for both mouse models Prlr mRNA levels seemed to increase, although significant differences were only found Drd2-/-mice. Moreover, Cis mRNA was increased in lacDrd2KO but and decreased in Drd2-/-. On the other hand Ucp1 levels decreased in lacDrd2KO, indicating impaired thermogenesis, while they increased in the Drd2-/- model. In the liver Prlr mRNA levels increased in both models. Together, these data indicate that lower BAT Ucp1 expression in lacDrd2KO mice may contribute to weight gain due to decreased thermogenesis, an effect which was absent when D2Rs were ablated globally. We also analyzed the expression of Prlr and Cis mRNA levels in the pituitary gland. It has been suggested that prolactin exerts an autocrine negative feedback in the pituitary. An increase in Prlr mRNA was detected in lacDrd2KO and in Drd2-/- , while no differences were detected for Cis mRNA. Finally, to further evaluate the prolactin autocrine actions in vivo in the pituitary gland and using the Cre/loxP technology we developed knockout mice with a specific deletion of Prlr in lactotropes (lacPrlrKO). Decreased expression of pituitary Prlr was validated by decreased Prlr mRNA, and prolactin induced phosphorylation of STAT5. At 5 months of age there was no difference in body weight, but lacPrlrKO mice presented lower levels of glucose in a GTT analysis.