HYPOTHYROIDISM DECRESES JAK/STAT SIGNALING PATHWAY IN LACTATING RAT MAMMARY GLAND THROUGH LACTION

CAMPO VERDE ARBOCCO F; PERSIA ANDRES; HAPON M. BELÉN; G A JAHN

Mendoza

Congreso; Sociedad de Biologia de Cuyo 2016; 2016

Sociedad de Biologia de Cuyo

HYPOTHYROIDISM ADVANCES MAMMARY INVOLUTION IN LACTATING RATS THROUGH INHIBITION OF PRL SIGNALING AND INDUCTION OF LIF/STAT3 mRNAS.Campo Verde Arbocco Fiorella, Sasso V Corina, Caron W Ruben, Hapon María Belén, Jahn GracielaHypothyroidism has deleterious effects on lactation, litter growth and survival, hindering suckling-induced hormone release and causing milk stasis that leads to premature mammary involution. To determine the mechanism of hypothyroidism involved on the impact on late lactation, we analyzed the effect of hypothyroidism on mammary expression of members of JAK/STAT/SOCS signaling pathway, hormonal receptors and markers of involution (such as stat3 and lif) on lactation day 21. We analyzed stat3, socs3 and lif mRNA level by Real Time PCR, STAT5a/b, and isoforms of estrogen and progesterone receptors protein levels by western blot and serum estradiol level by radioimmunoassay. HypoT increased SOCS3, STAT3 and LIF mRNAs, suggesting a decrease in PRL signaling and induction of involution markers. Furthermore, progesterone receptor isoform A and estrogen receptor alpha protein level were increased coupled with an increased in estradiol serum level, indicating that mammary gland display post lactational intracellular response to hormonal environment of involution. Also, hypothyroidism increased the STAT5a/b protein level, showing that alters the turnover of this protein. These results show that the mechanism by which hypothyroidism induce premature mammary involution, involve the inhibition of prolactin signaling along with the activation of the LIF-STAT3 pathway and the inactivation of the main lactation transcription factor STAT5a/b and result in hormonal and intracellular changes that leads to premature involution.