Endocrine Abstracts

About 50% of women have nausea and vomiting during pregnancy. In about 35% of women who have these symptoms, nausea and vomiting are clinically significant, worsening their living conditions and consisting in a case of gender gap. The severe form, hyperemesis gravidarum, ranges from 0.3 to 1.0% of cases and is characterized by persistent vomiting, gestational thyrotoxicosis, weight loss of more than 5%, ketonuria, hypokalemia and dehydration, although the pathophysiological mechanism is unknown. Some studies found that increasing human chorionic gonadotropin (hCG) levels overlap the fall of thyroid stimulating hormone (TSH) levels, the increase of thyroid hormone (T3 and T4) levels, and the appearance of hyperemesis gravidarum. Thus, it was hypothesized that hCG binds to TSH receptor (TSHR), perturbing thyroid functions and triggering hyperemesis gravidarum. The aim of this study is to characterize hCG-TSHR cross-interactions in vitro, finding a rationale to support the clinical hints. Mechanistic experiments evaluating TSHR-dependent cell signaling pathways were performed in COS7 cell line. Cells were transfected with TSHR-coding plasmid and treated with pM-nM hCG doses before Gs and Gq protein-mediated pathway analysis. Intracellular levels of cyclic adenosine monophosphate (cAMP) and calcium ions (Ca²⁺) increase were measured by bioluminescence resonance energy transfer (BRET), while inositol monophosphate (IP1) was evaluated by homogeneous time resolved fluorescence (HTRF). Results were compared by Kruskall-Wallis test (n=5; P<0.05) and corrected by Dunn’s post-hoc test. Results demonstrated that 50 nM hCG activates the TSHR/Gαq pathway, resulting in intracellular IP1 and Ca²⁺ increase, while no cAMP activation occurred. Results were compared to those obtained from transfected cells treated with the vehicle, in the absence of hCG, which did not result in any Ca²⁺/IP1 increase. These data support the clinical relationship between hCG and thyroid functions in hyperemesis gravidarum.