Maternal 3,3'-Diiodothyronine Sulfate Formation from Guinea Pig Placenta Perfused with 3,3',5-Triodothyronine
UMass Chan AffiliationsDepartment of Medicine, Division of Endocrinology and Metabolism
sulfation of thyroid hormone
Endocrinology, Diabetes, and Metabolism
Hormones, Hormone Substitutes, and Hormone Antagonists
Reproductive and Urinary Physiology
MetadataShow full item record
AbstractOBJECTIVE: Serum 3, 3',5-triiodothyronine (T3) remains low in near-term fetus to prevent the growing fetus from undue exposure to its active catabolic effect in mammals. The present study was undertaken to gain insight in the role of placenta in T3 metabolism, fetal to maternal transfer of T3, and its metabolites by in situ placenta perfusion with outer-ring labeled [(125)I]-T3 in pregnant guinea pig, a species showing increased sulfated 3, 3'-diiodothyronine (T2S) levels in maternal serum in late pregnancy (term = 65 days), similarly to humans in pregnancy. MATERIALS AND METHODS: One-pass placenta perfusions performed on pregnant guinea pigs were studied between 58 - 65 days of gestation. In two separate experiments, the umbilical artery of the guinea pig placenta was perfused in situ at 37 degrees C with outer-ring labeled [(125)I]-T3. Maternal sera and umbilical effluents were obtained for analysis at the end of a 60-minute perfusion, when the steady-state levels of radioactivity were reached in the placenta effluent after 30-minute. RESULTS: Sulfated [(125)I]-T2S was readily detected in the maternal serum as the major metabolite of T3 following the perfusion of placenta with [(125)I]-T3, suggesting that placental inner-ring deiodinase and sulfotransferase may play an important role in fetal T3 homeostasis and in the fetal to maternal transfer of sulfated iodothyronine metabolites. CONCLUSIONS: The expression of type 3 deiodinase (D3) and thyroid hormone sulfotransferase activity in placenta may play an important role to protect developing organs against undue exposure to active thyroid hormone in late gestation in the fetus. The combined activities of D3 and sulfotransferase promoted a placental transfer of T2S into maternal circulation. The maternal circulation of T2S is fetal T3 in origin and its role as a fetal thyroid function biomarker deserves further evaluations and studies.
Wu SY, Emerson CH, Tjioe E, Chen DB. Maternal 3,3'-Diiodothyronine Sulfate Formation from Guinea Pig Placenta Perfused with 3,3',5-Triodothyronine. Endocrinol Disord. 2021 Sep;5(7):01-6. doi: 10.31579/2640-1045/101. Epub 2021 Oct 25. PMID: 35098142; PMCID: PMC8797160. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/42692
RightsCopyright: © 2021 Sing-yung Wu, This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Showing items related by title, author, creator and subject.
CIS/SOCS Proteins in Growth Hormone Action: A DissertationDu, Ling (2000-10-01)CIS/SOCS (cytokine-inducible SH2 protein/suppressor of cytokine signaling) are a family of proteins that are thought to act as negative regulators of signaling by erythropoetin, interleukin-6 and other cytokines whose receptors are related to the growth hormone receptor (GHR), and like growth hormone (GH), signal through the JAK/STAT pathway. We examined the possibility that CIS/SOCS proteins may also be involved in GH signaling, in particular, in termination of the transient insulin-like effects of GH. mRNAs for CIS, SOCS3, and to a lesser extent SOCS1 were detectable by Northern blot analysis of rat adipocyte total RNA, and the expression of CIS and SOCS3 was markedly increased 30 min after incubation with 500 ng/ml hGH. Both CIS and SOCS3 were detected in adipocyte extracts by immunoprecipitation and immunoblotting with their corresponding antisera. GH stimulated the tyrosine phosphorylation of a 120 kDa protein (p120) that was co-precipitated from adipocyte extracts along with αCIS and detected in Western blots with phospho-tyrosine antibodies. However, no tyrosine phosphorylated proteins in these cell extracts were immunoprecipitated with antibodies to CIS3/SOCS3. p120 was later identified as the GHR based on the observations that two GHR antibodies recognized p120 in scale-up experiments and that p120 and the GHR share several characteristics, including their molecular weights, tyrosine phosphorylation upon GH stimulation, interaction with CIS, similar extent of glycosylation as judged by electrophoretic mobility shift after Endo F digestion, comparable mobility shifts upon thrombin digestion, and N-terminal histidine-tagging. The findings, however, do not rule out the possibility that there might be other tyrosine phosphorylated 120 kDa protein(s) that interact with CIS and contribute to the p120 signal, as well as the GHR. Further studies of the association of CIS with the GHR revealed that CIS might selectively interact with multiply tyrosine phosphorylated forms of the GHR, and these tyrosines are likely located near the carboxyl end of the GHR. Overexpression of CIS partially inhibited GH-induced STAT5 phosphorylation in CHO cells. Studies in freshly isolated and GH-deprived (sensitive) adipocytes revealed that the abundance of CIS does not correlate with the termination of the insulin-like effects of GH or the emergence of refractoriness. Neither the association of CIS with the GHR nor the tyrosine phosphorylation status of the GHR, JAK2 and STAT5 appear responsible for refractoriness in adipocytes. These data imply that some negative regulators other than CIS might contribute to the termination of GH-induced insulin-like effects in adipocytes.
Important Role of the GLP-1 Axis for Glucose Homeostasis after Bariatric SurgeryLarraufie, Pierre; Roberts, Geoffrey P.; McGavigan, Anne K.; Kay, Richard G.; Li, Joyce H.; Leiter, Andrew B.; Melvin, Audrey; Biggs, Emma K.; Ravn, Peter; Davy, Kathleen; et al. (2019-02-05)Bariatric surgery is widely used to treat obesity and improves type 2 diabetes beyond expectations from the degree of weight loss. Elevated post-prandial concentrations of glucagon-like peptide 1 (GLP-1), peptide YY (PYY), and insulin are widely reported, but the importance of GLP-1 in post-bariatric physiology remains debated. Here, we show that GLP-1 is a major driver of insulin secretion after bariatric surgery, as demonstrated by blocking GLP-1 receptors (GLP1Rs) post-gastrectomy in lean humans using Exendin-9 or in mice using an anti-GLP1R antibody. Transcriptomics and peptidomics analyses revealed that human and mouse enteroendocrine cells were unaltered post-surgery; instead, we found that elevated plasma GLP-1 and PYY correlated with increased nutrient delivery to the distal gut in mice. We conclude that increased GLP-1 secretion after bariatric surgery arises from rapid nutrient delivery to the distal gut and is a key driver of enhanced insulin secretion.
Associations of HDL metrics with coronary artery calcium score and density among women traversing menopauseEl Khoudary, Samar R.; Nasr, Alexis; Matthews, Karen A.; Orchard, Trevor J.; Brooks, Maria M.; Billheimer, Jeffrey; McConnell, Dan; Janssen, Imke; Everson-Rose, Susan A.; Crawford, Sybil L.; et al. (2021-07-22)The cardioprotective association of high-density lipoprotein cholesterol (HDL-C) may vary by menopause stage or estradiol level. We tested whether associations of comprehensive HDL metrics (HDL subclasses, phospholipid and triglyceride content, and HDL cholesterol efflux capacity [HDL-CEC]) with coronary artery calcium (CAC) score and density vary by menopause stage or estradiol level in women transitioning through menopause. Participants (N = 294; mean age [SD]: 51.3 [2.9]) had data on HDL metrics and CAC measures at one or two time points during the menopause transition. Generalized estimating equations were used for analyses. Effect modifications by menopause stage or estradiol level were tested in multivariable models. In adjusted models, menopause stage modified the associations of specific HDL metrics with CAC measures. Higher small HDL particles (HDL-P) concentrations (p-interaction = 0.008) and smaller HDL size (p-interaction = 0.02) were associated with greater odds of CAC presence in late perimenopause than in pre/early perimenopause stage. Women in the highest estradiol tertile, but not the lower tertiles, showed a protective association of small HDL-P with CAC presence (p-interaction = 0.007). Lower large HDL-P concentrations (p-interaction = 0.03) and smaller HDL size (p-interaction = 0.03) were associated with lower CAC density in late perimenopause than in postmenopause stage. Associations of HDL phospholipid and triglyceride content and HDL-CEC with CAC measures did not vary by menopause stage or estradiol level. We concluded that HDL subclasses may impact the likelihood of CAC presence and the stability of coronary plaque differently over the menopause transition. Endogenous estradiol levels may contribute to this observation.