Hypothyroidism advances mammary involution in lactating rats through inhibition of PRL signaling and induction of LIF/STAT3 mRNAs

CARON, R.W.; CAMPO VERDE ARBOCCO, F.; HAPON, M.B.; SASSO, C.V.; JAHN, G.A.

Mendoza

Congreso; XXXIV Reunión Científica anual de la Sociedad de Biología de Cuyo; 2016

Sociedad de Biología de Cuyo

Hypothyroidism 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 involved in the impact of hypothyroidism 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 day 21 of lactation. 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 paralleled the increase 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 the turnover of this protein is altered. 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