THYROID DISORDERS INFLUENCE THYROID RECEPTOR COMODULATORS GENE EXPRESSION IN RAT HYPOTHALAMUS DURING LATE PREGNANCY: A TRANSITION PERIOD INTO LACTATION

PENNACCHIO GISELA E; AYALA CAROLINA; SOAJE MARTA; JAHN GRACIELA A; VALDEZ, SUSANA R

Mendoza

Congreso; XXXI Reunión Anual de la Sociedad de Biología de Cuyo; 2013

Sociedad de Biología de Cuyo

Thyroid disorders compromise fertility in women and cause pregnancy disorders and lactation failure. Previously we have shown that these pathologies alter thyroid hormones receptors (TR) expression at hypothalamus level. TR transcriptional activity is regulated by modulators with emerging roles in homeostasis. In this work we explore the repressors (NCoR), activators (CoA) of TR and the iodothyronine deiodinasa II (DIO2) that converts locally T4 to T3. To study the effects of hyperthyroidism and hypothyroidism on the regulation of TR pathways we determined the effects of thyroid status in the expression of modulators of TR activity in neuroendocrine dopaminergic neurons in medial basal hypothalamus (MBH) during late pregnancy (a transition period into lactation) and early lactation. Wistar control (Co: vehicle-treated) hypothyroid (HypoT: 0.1 g/L PTU in drinking water), hyperthyroid (HyperT: T4, 250 µg/kg/day. sc) rats were mated 8 days after the start of treatment and sacrificed at days 19 (G19), 20 (G20), 21 (G21) of pregnancy and 2 day of lactation (L2). The MBH expression of modulators was measure using real time RT-PCR. Two way ANOVA analyse were performed. HypoT CoA1 and CoA2 expression were decreased at G19 and increased at G21 (p<0.05 vs G19 and L2 HypoT). NCoR2 was decreased on G19 HypoT and increased on G20 (p<0.05 vs HypoT G19, G21 and L2). Also at G19 HypoT rats showed lower levels of NCoR compared to Co and HyperT (p<0.05). DIO2 showed low expression in G19 and augmented on G21 (p<0.05 vs HypoT G19 and G20) and DIO2 expression at G19 was lower than Co and HyperT (p<0.001). These results indicate that TR co-regulators expression was differentially affected by hypothyroidism in HMB at late pregnancy. Hypothyroidsm increased coactivators and DIO2 expression and decreased NCoR2 at G21 problably contribuiting to the homeostasis of brain thyroid status.