Hypothyroidism decreses JAK/STAT signaling pathway in lactating rat mammary gland through lactation.

PERSIA FA; CAMPO VERDE ARBOCCO F; JAHN GA; HAPON MB

Mendoza

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

Sociedad de Biología de Cuyo

Thyroid hormones (TH) are essential for prolactin actions in the mammary gland. Exposure to excessive or insufficient quantities of THs during lactation diminish milk production and quality, and advances mammary involution. To continue investigating the mechanism through which hypothyroidism (hypoT) alters mammary function, we studied its effect on day 2, 7 and 14 of lactation (L2, L7 and L14) on expression and activation of main members of prolactin signaling pathway in the rat mammary gland. We analyzed by western blot, protein expression of prolactin receptor (PRLR), STAT5a/b, phospho-STAT5a/b (P-STAT5), SOCS3, and CIS protein. The patterns of PRLR and STAT5a/b proteins expression decreased gradually through lactation with a significant difference between L2 and L14. HypoT significantly decreased the RPRL protein level in the three days and STAT5a/b protein level in L2 and L7, abolishing the gradual decrease of control group. The P-STAT5a/b protein level increased through lactation in controls but hypoT decreased them significantly in L7 and L14.SOCS3 and CIS protein levels remained constant between L2 and L14 in the controls, but hypoT significantly diminished the protein levels of both in L2 and of CIS in L7.The present results demonstrate that hypoT has a negative effect on the PRL signaling pathway, evidenced by a reduction of the mammary contents of PRLR and STAT5a/b and particularly of p-STAT5thatis the main transcription factor of lactating mammary gland. However, the decrease in the inhibitor proteins levels could be a compensatory cell response to the PRL signaling deficit. According to the evolutive importance of lactation it is probable that mammary cells are able to deploy compensatory responses to hormonal deficits in an attempt to keep milk production, although it is important to note that in any case, this mechanism could not be maintained up to L14. These results can explain the lactation deficit and advanced mammary involution previously described by us, as well as provide a mechanistic explanation of clinical observations, which show that hypothyroid mothers with inadequate TH supplementation have deficient lactation.