HYPOTHYROIDISM ADVANCES MAMMARY INVOLUTION IN LACTATING 2 RATS THROUGH INHIBITION OF PRL SIGNALING AND INDUCTION OF 3 LIF/STAT3 mRNAs

FIORELLA CAMPO VERDE ARBOCCÓ; CORINA V. SASSO; ESTEBAN A. ACTIS; RUBÉN W. CARÓN; MARÍA BELÉN HAPON; GRACIELA A. JAHN

MOLECULAR AND CELLULAR ENDOCRINOLOGY.

ELSEVIER IRELAND LTD

Lugar: Amsterdam; Año: 2016

0303-7207

Thyroid diseases have deleterious effects on lactation, litter growth and survival, and hinderthe suckling-induced hormone release, leading in the case of hyperthyroidism, to prematuremammary involution. To determine the effects of hypothyroidism (HypoT) on latelactation, we analyzed the effect of chronic 6-propyl-2-thiouracil (PTU)-induced HypoT onmammary histology and the expression of members of the JAK/STAT/SOCS signalingpathway, milk proteins, prolactin (PRLR), estrogen (ER), progesterone (PR) and thyroidhormone (TR) receptors, markers of involution (such as stat3, lif, bcl2, BAX and PARP) onlactation (L) day 21. HypoT mothers showed increased histological markers of involutioncompared with control rats, such as adipose/epithelial ratio, inactive alveoli, picnotic nucleiand numerous detached apoptotic cells within the alveolar lumina. We also found decreasedPRLR, β-casein and α-lactoalbumin mRNAs, but increased SOCS1, SOCS3, STAT3 andLIF mRNAs, suggesting a decrease in PRL signaling and induction of involution markers.Furthermore, Caspase-3 and 8 and PARP labeled cells and the expression of structuralproteins such as β-Actin, α-Tubulin and Lamin B were increased, indicating the activationof apoptotic pathways and tissue remodelation. HypoT also increased PRA (mRNA andprotein) and erβ and decreased erαmRNAs, and increased strongly TRα1, TRβ1, PRA andERα protein levels. These results show that lactating HypoT rats have premature mammaryinvolution, most probably induced by the inhibition of prolactin signaling along with theactivation of the LIF-STAT3 pathway.