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Presence of estrogen and progesterone receptors in proliferating and involuting infantile hemangiomas

  • Author Footnotes
    1 Adam Johnson and Haihong Zhang contributed equally to this work.
    Adam Johnson
    Footnotes
    1 Adam Johnson and Haihong Zhang contributed equally to this work.
    Affiliations
    Department of Otolaryngology-Head and Neck Surgery, Director of Velopharyngeal Dysfunction, Arkansas Children's Research Institute, University of Arkansas for Medical Sciences, Little Rock, AR, United States
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  • Author Footnotes
    1 Adam Johnson and Haihong Zhang contributed equally to this work.
    Haihong Zhang
    Footnotes
    1 Adam Johnson and Haihong Zhang contributed equally to this work.
    Affiliations
    Department of Otolaryngology-Head and Neck Surgery, Arkansas Children's Research Institute, University of Arkansas for Medical Sciences, Little Rock, AR, United States
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  • Santiago R. Gonzalez
    Correspondence
    Corresponding author.
    Affiliations
    Resident Physician, Division of Plastic and Reconstructive Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
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  • Madison Lee
    Affiliations
    Department of Otolaryngology-Head and Neck Surgery, Arkansas Children's Research Institute, University of Arkansas for Medical Sciences, Little Rock, AR, United States
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  • Ting Wei
    Affiliations
    Department of Otolaryngology-Head and Neck Surgery, Arkansas Children's Research Institute, University of Arkansas for Medical Sciences, Little Rock, AR, United States
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  • Gresham Richter
    Affiliations
    Pediatric Otolaryngology, Department of Otolaryngology-Head and Neck Surgery, University of Arkansas for Medical Sciences, Little Rock, AR, United States
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  • Author Footnotes
    1 Adam Johnson and Haihong Zhang contributed equally to this work.
Published:April 19, 2021DOI:https://doi.org/10.1016/j.bjps.2021.03.100

      Summary

      Background

      Studies in the literature have demonstrated the presence of sex hormone receptors in infantile hemangiomas (IHs), but further investigation is needed to determine the role of these receptors in their proliferation and involution. To date, there are no studies in the literature that aimed to quantitatively examine the expression of sex hormone receptors throughout the different phases of hemangioma development.

      Objective

      The objective of our study was to quantitatively evaluate the expression of estrogen (ER) and progesterone (PR) receptors in the proliferative and involuting phases of IHs through the use of real-time polymerase chain reaction (RT-PCR).

      Methods

      Twenty IHs (10 proliferating and 10 involuting) were harvested and prepared for molecular investigation. ER receptor alpha (ERα) and beta (ERβ) and the PR expression were examined by RT-PCR and western blot.

      Results

      RT-PCR analysis demonstrated that mRNA expression of ERα, ERβ, and PR was significantly lower in proliferating versus involuting IH. Western blot analysis revealed increased protein expression of ERα in involuting hemangiomas as compared to proliferating ones.

      Conclusions

      Our study demonstrates the variable expression of ER and PR receptors in proliferating and involuting hemangiomas. Further studies are needed to determine the exact role of these hormone receptors in the growth and involution of IHs.

      Keywords

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      References

        • Phillips J.D.
        • Zhang H.
        • Wei T.
        • Richter G.T.
        Expression of β-adrenergic receptor subtypes in proliferative, involuted, and propranolol-responsive infantile hemangiomas.
        JAMA Facial Plast Surg. 2017; 19: 102https://doi.org/10.1001/jamafacial.2016.1188
        • Munden A.
        • Butschek R.
        • Tom W.L.
        • et al.
        Prospective study of infantile haemangiomas: incidence, clinical characteristics and association with placental anomalies.
        Br J Dermatol. 2014; 170: 907-913https://doi.org/10.1111/bjd.12804
        • Itinteang T.
        • Tan S.T.
        • Guthrie S.
        • et al.
        A placental chorionic villous mesenchymal core cellular origin for infantile haemangioma.
        J Clin Pathol. 2011; 64: 870-874https://doi.org/10.1136/jclinpath-2011-200191
        • Auger N.
        • Fraser W.D.
        • Arbour L.
        • Healy-Profitós J.
        • Drolet B.A.
        Pre-eclampsia and risk of infantile haemangioma.
        Br J Dermatol. 2017; 176: 371-377https://doi.org/10.1111/bjd.14958
        • Holmes L.B.
        Chorionic villus sampling and hemangiomas.
        J Craniofac Surg. 2009; 20: 675-677https://doi.org/10.1097/SCS.0b013e318193d61a
        • Kilcline C.
        • Frieden I.J.
        Infantile hemangiomas: how common are they? A systematic review of the medical literature.
        Pediatr Dermatol. 2008; 25: 168-173https://doi.org/10.1111/j.1525-1470.2008.00626.x
        • Huoh K.C.
        • Rosbe K.W.
        Infantile hemangiomas of the head and neck.
        Pediatr Clin North Am. 2013; 60: 937-949https://doi.org/10.1016/j.pcl.2013.04.003
        • Wong A.
        • Hardy K.L.
        • Kitajewski A.M.
        • Shawber C.J.
        • Kitajewski J.K.
        • Wu J.K.
        Propranolol accelerates adipogenesis in hemangioma stem cells and causes apoptosis of hemangioma endothelial cells.
        Plast Reconstr Surg. 2012; 130: 1012-1021https://doi.org/10.1097/PRS.0b013e318267d3db
        • North P.E.
        • Waner M.
        • Mizeracki A.
        • et al.
        A unique microvascular phenotype shared by juvenile hemangiomas and human placenta.
        Arch Dermatol. 2001; 137: 559-570
        • Paterni I.
        • Granchi C.
        • Katzenellenbogen J.A.
        • Minutolo F.
        Estrogen receptors alpha (ERα) and beta (ERβ): subtype-selective ligands and clinical potential.
        Steroids. 2014; 0: 13-29https://doi.org/10.1016/j.steroids.2014.06.012
        • Dahlman-Wright K.
        • Cavailles V.
        • Fuqua S.A.
        • et al.
        International Union of Pharmacology. LXIV. Estrogen receptors.
        Pharmacol Rev. 2006; 58: 773-781https://doi.org/10.1124/pr.58.4.8
        • Heldring N.
        • Pike A.
        • Andersson S.
        • et al.
        Estrogen receptors: How do they signal and what are their targets.
        Physiol Rev. 2007; 87: 905-931https://doi.org/10.1152/physrev.00026.2006
        • Chen C.
        • Opazo J.C.
        • Erez O.
        • et al.
        The human progesterone receptor shows evidence of adaptive evolution associated with its ability to act as a transcription factor.
        Mol Phylogenet Evol. 2008; 47: 637-649https://doi.org/10.1016/j.ympev.2007.12.026
        • Elmlinger M.W.
        • Kühnel W.
        • Ranke M.B.
        Reference ranges for serum concentrations of lutropin (LH), follitropin (FSH), estradiol (E2), prolactin, progesterone, sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), cortisol and ferritin in neonates, children and young adults.
        Clin Chem Lab Med. 2002; 40https://doi.org/10.1515/cclm.2002.202
        • Lui W.
        • Zhang S.
        • Hu T.
        • Wei F.
        • Gao Y.
        • Cheng N.
        Sex hormone receptors of hemangiomas in children.
        Chin Med J (Engl). 1997; 110: 349-351
        • Pedersen S.B.
        • Bruun J.M.
        • Hube F.
        • Kristensen K.
        • Hauner H.
        • Richelsen B.
        Demonstration of estrogen receptor subtypes alpha and beta in human adipose tissue: influences of adipose cell differentiation and fat depot localization.
        Mol Cell Endocrinol. 2001; 182: 27-37
        • Xiao X.
        • Liu J.
        • Sheng M.
        Synergistic effect of estrogen and VEGF on the proliferation of hemangioma vascular endothelial cells.
        J Pediatr Surg. 2004; 39: 1107-1110https://doi.org/10.1016/j.jpedsurg.2004.03.067
        • Sasaki G.H.
        • Pang C.Y.
        • Wittliff J.L.
        Pathogenesis and treatment of infant skin strawberry hemangiomas: Clinical and in vitro studies of hormonal effects.
        Plast Reconstr Surg. 1984; 73: 359-370
        • Hyder S.M.
        • Huang J.C.
        • Nawaz Z.
        • et al.
        Regulation of vascular endothelial growth factor expression by estrogens and progestins.
        Environ Health Perspect. 2000; 108: 785-790
        • Xiao X.
        • Hong L.
        • Sheng M.
        Promoting effect of estrogen on the proliferation of hemangioma vascular endothelial cells in vitro.
        J Pediatr Surg. 1999; 34: 1603-1605
        • Shao R.
        • Egecioglu E.
        • Weijdegård B.
        • et al.
        Dynamic regulation of estrogen receptor-alpha isoform expression in the mouse fallopian tube: Mechanistic insight into estrogen-dependent production and secretion of insulin-like growth factors.
        Am J Physiol Endocrinol Metab. 2007; 293: E1430-E1442https://doi.org/10.1152/ajpendo.00384.2007
        • Mai H.
        • Mai H.
        • Zheng J.
        • Wang Y.
        The potential role of progesterone during pregnancy as an induction of infantile hemangioma.
        Shanghai Kou Qiang Yi Xue Shanghai J Stomatol. 2011; 20: 669-672
        • Chen X.D.
        • Ma G.
        • Chen H.
        • Ye X.X.
        • Jin Y.B.
        • Lin X.X.
        Maternal and perinatal risk factors for infantile hemangioma: A case-control study.
        Pediatr Dermatol. 2013; 30: 457-461https://doi.org/10.1111/pde.12042