EFFECT OF MILD HYPERTHYROIDISM ON HYPOTHALAMIC PROLACTIN SIGNALING PATHWAY IN EARLY LACTATION

NEIRA FLAVIA J; PENNACCHIO GISELA E; SOAJE MARTA; MACKERN OBERTI, JUAN PABLO; JAHN GRACIELA A; VALDEZ SUSANA R

Mar del Plata

Congreso; LXIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; 2018

SAIC-SAFE-SAB

During late pregnancy thehypothalamic neuroendocrine control of PRL secretion adapts, decreasingdopaminergic tone, to promote adequate lactation. Previously we described thatsevere hyperthyroidism elevates dopaminergic tone, blunting suckling-inducedprolactin (PRL) release that results in early litter death. In this work, westudied the effects of mild hyperthyroidism, which also reduces PRL secretionbut allows the maintenance of lactation and litter survival, on hypothalamicregulation of PRL secretion using a dose of T4 (0.1mg/ml/kg/day, s.c.) on latepregnancy (day 19, G19) and early lactation (L2). Hypothalamic mRNA ofhyperthyroid (HyperT) and control (Co) rats was obtained and the expression ofreceptors (R) of thyroid hormone (TRα1, TRβ1, TRβ2), progesterone (PR, PRB), estrogen (ERα, ERβ) and prolactin (PRLRLong isoform) and members of the PRL signaling pathway (STAT5b, SOCS1 andSOCS3) was determined by RT-qPCR. TRβ2 expression decreased on L2 compared to G19in Co and HyperT (P<0.001). PRB showed lower expression on L2 respect to G19(P<0.0001 in HyperT and P<0.05 in Co). Also, the HyperT PRB expressionwas increased with respect to Co on G19 (P<0.05). PRLR expression in theHyperT group was increased on L2 compared with G19 (P<0.01), while Coremained unchanged. Furthermore, PRLR expression was increased in HyperTcompared with Co rats on L2 (P<0.05). HyperT also decreased the expressionof CIS on L2 with respect to G19 (P<0.01), whereas the expression in Co wasstable. HyperT increased CIS expression on G19 compared to Co (P<0.05) anddecreased SOCS1 expression on L2 compared with G19 (P<0.01) while there wereno differences in Co. Thus, mild HyperT increased PRLR and decreased SOCS1 andCIS expression on L2, maintaining an increased hypothalamic dopaminergic tone thatis responsible for the impaired suckling-induced PRL secretion observed inHyperT mothers. &amp;amp;lt;!-- /* Font Definitions */@font-face{font-family:"Cambria Math";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:-536870145 1107305727 0 0 415 0;}@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:-536870145 1073786111 1 0 415 0;}@font-face{font-family:"Arial Unicode MS";panose-1:2 11 6 4 2 2 2 2 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:-134238209 -371195905 63 0 4129279 0;} /* Style Definitions */p.MsoNormal, li.MsoNormal, div.MsoNormal{mso-style-unhide:no;mso-style-parent:"";margin:0cm;margin-bottom:.0001pt;mso-pagination:widow-orphan;font-size:12.0pt;font-family:"Times New Roman";mso-fareast-font-family:"Arial Unicode MS";border:none;mso-ansi-language:EN-US;mso-fareast-language:EN-US;}p.Body, li.Body, div.Body{mso-style-name:Body;mso-style-unhide:no;mso-style-parent:"";margin-top:0cm;margin-right:0cm;margin-bottom:10.0pt;margin-left:0cm;line-height:115%;mso-pagination:widow-orphan;font-size:11.0pt;font-family:Calibri;mso-fareast-font-family:Calibri;mso-bidi-font-family:Calibri;color:black;border:none;text-underline:black;}.MsoChpDefault{mso-style-type:export-only;mso-default-props:yes;font-size:10.0pt;mso-ansi-font-size:10.0pt;mso-bidi-font-size:10.0pt;mso-fareast-font-family:"Arial Unicode MS";border:none;}.MsoPapDefault{mso-style-type:export-only;}@page WordSection1{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.WordSection1{page:WordSection1;}--&amp;amp;gt;