Hyperthyroidism modulates hypotalamic Tyrosine Hydroxilase activity and PRL signaling during late pregnancy and early lactacion in rats

PENNACCHIO GISELA E; ACOSTA CRISTIAN; SELTZER ALICIA M; SOAJE MARTA; JAHN GRACIELA A; VALDEZ SUSANA R

San Diego

Congreso; 2016 Annual Meeting for Society of Neuroscience; 2016

Society for Neuroscience

<!-- /* Font Definitions */@font-face{font-family:Calibri;panose-1:2 15 5 2 2 2 4 3 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:3 0 0 0 1 0;} /* Style Definitions */p.MsoNormal, li.MsoNormal, div.MsoNormal{mso-style-parent:"";margin-top:0cm;margin-right:0cm;margin-bottom:8.0pt;margin-left:0cm;line-height:107%;mso-pagination:widow-orphan;font-size:11.0pt;font-family:"Times New Roman";mso-ascii-font-family:Calibri;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;mso-hansi-font-family:Calibri;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-ansi-language:ES-AR;mso-fareast-language:EN-US;}@page Section1{size:612.0pt 792.0pt;margin:70.85pt 3.0cm 70.85pt 3.0cm;mso-header-margin:36.0pt;mso-footer-margin:36.0pt;mso-paper-source:0;}div.Section1{page:Section1;}--><!-- /* Font Definitions */@font-face{font-family:Cambria;panose-1:2 4 5 3 5 4 6 3 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:3 0 0 0 1 0;} /* Style Definitions */p.MsoNormal, li.MsoNormal, div.MsoNormal{mso-style-parent:"";margin:0cm;margin-bottom:.0001pt;mso-pagination:widow-orphan;font-size:12.0pt;font-family:"Times New Roman";mso-ascii-font-family:Cambria;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Cambria;mso-fareast-theme-font:minor-latin;mso-hansi-font-family:Cambria;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-fareast-language:EN-US;}@page Section1{size:595.0pt 842.0pt;margin:70.85pt 3.0cm 70.85pt 3.0cm;mso-header-margin:35.4pt;mso-footer-margin:35.4pt;mso-paper-source:0;}div.Section1{page:Section1;}-->Thyroid disorders compromisefertility in women of reproductive age and cause pregnancy disorders andlactation failure. Prolactin (PRL) is essential for female reproduction. Themain regulator of PRL secretion is dopamine, produced by the dopaminergicneurons located in the medial basal hypothalamus (MBH). To explore ifhyperthyroidism affects PRL secretion through alterations of the hypothalamicdopaminergic systems, we studied the effect of T4 treatment on hypothalamicexpression of Tyrosine hydroxylase (TOH, the rate-limiting enzyme for dopamine synthesis),PRL receptor (PRLR), members of the PRL signaling pathway (STAT, SOCS, CIS), inMBH during late pregnancy and early lactation. We also studied this neuronsexpress thyroid receptors by immunofluorescence (IF). Wistar control (Co:vehicletreated) and hyperthyroid (HyperT: T4 sc, 250 μg/kg/day) rats were mated8 days after the start of treatment and sacrificed at days 19 (G19), 20 (G20),21 (G21) of pregnancy and day 2 of Lactation. Total RNAs were extracted fromMBH and the mRNA expression was measured using real time PCR. In control rats,the mRNA expression of PRLR long, STAT5b, SOCS3, SOCS1 and CIS showed similarpatterns of variations between late pregnancy and early lactation. HyperT ratsshowed a similar pattern but PRLR and SOCS3 mRNAs. STAT5 protein varied in parallelwith changes in PRLR mRNA in both groups; the protein level decreased from G19to G20 and remained low thereafterin controls while in the HyperT group values were significantly higher thancontrols in G19 and L2. CIS protein levels increased in controls at G20 andfell afterwards to levels similar to G19, while in the HyperT group CIS wassignificantly higher at G19 compared with controls and declined afterwards tovalues similar to controls. In controls,TOH mRNA and protein values diminishedfrom G19 to G21 and remained low on L2. In HyperT rats TOH mRNA was similaar tocontrols on G19 and G20 but significantly higher on G21 and L2. HyperT decreasedsignificantly TOH protein at G19 and G20. In control rats, p- TOH declinedslowly from G20 to L2. HyperT increased significantly p-TOH on G19 and L2 comparedwith the controls. IF showed that TOH+ neurons also express TRβ, suggesting a possibledirect action of THs on these neurons. Conclusion: the activity of hypothalamicneurons that regulate PRL secretion is affected by the HyperT, resulting inincreased PRL signaling and TOH activation on G19 and L2. This pattern can becorrelated with the advancement in the antepartum PRL peak followed by impairedPRL secretion during lactation previously observed in HyperT rats, thatcompromises the hyperprolactinemia necessary for a successful lactation.