Researcher Database

（Last updated : 2020-09-29 17:36:04）

HATTORI Naoki

Department / Course College of Pharmaceutical Sciences Department of Pharmacy

Title / Position Professor

Other Affiliations
1.	Graduate School of Pharmacy
2.	Research Organization of Open Innovation & Collaboration Research Center for Medical and Long-Term Care Management
3.	Research Organization of Science and Technology Research Center for Drug Discovery and Development Scieces
4.	Research Organization of Science and Technology The Institute of Science and Engineering

Academic background
1.		│ Kyoto University Ph.D. in Medical Science
2.	～1983/03	Faculty of Medicine │ Kyoto University │ Graduated
3.	～1990/03	Doctorial Course │ Internal Medicine │ Graduate School, Division of Medicine │ Kyoto University │ Completed

Research activities
1.		The Endocrine Society (USA)
2.		The Japan Diabetes Society
3.		The Japanese Society of Internal Medicine
4.		The Japan Endocrine Society
5.		The Pharmaceutical Society of Japan
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Qualification and license
1.	1983	Medical Doctor's degree

Subject of research
1.	Reassessment of the results of hormone assays in patients with autoantibodies against them
2.	Basic and clinical study about a new cause of hyperprolactinaemia: Macroprolactinaemia because of anti-prolactin autoantibodies
3.	Clinical and biochemical evaluation of macro TSH
4.	Establishment of ultra-sensitive enzyme immunoassays for hormones: application for the study about the regulation of hormone secretion in the immune and nervous systems

Research summary
Reassessment of the results of hormone assays in patients with autoantibodies against them As it became evident that immune, nervous and endocrine systems are closely related to one another after being traditionally considered independent of one another, there came a new area called Immunoneuroendocrinology. These systems share the same ligand and receptor, and affect one another. This researcher has been engaged in study of Immunoneuroendocrinology and identified as follows: (1) Conducting basic and clinical consideration of "macroprolactinemia caused by PRL autoantibody" that is a new cause of hyperprolactinemia (prolactin is abbreviated as PRL): PRL is peptide with molecular weight of 23kDa, secreted from anterior pituitary. In terms of physiology, it increases during pregnancy and helps facilitate growth of lacteal glands, and producing and secreting milk. In terms of disease, PRL production pituitary adenoma or a drug causes hyperprolactinemia, resulting in irregular period or milk leakages. The newly identified macroprolactinemia has the characteristics as follows: 1. Macroprolactinemia is mainly a PRL and PRL autoantibody complex. 2. This occurs very often - one out of 30 general able-bodied adults. 3. Lower clearance due to heavy molecular weight accumulates PRL in the blood, showing hyperprolactinemia. 4. In spite of being hyperprolactinemia, macroprolactinemia does not show clinical symptoms such as missing periods or milk leakages. This is simply because IgG associated PRL is biologically inactive, and free PRL value in the blood is normal. Note that dissociating from IgG will become as biologically active as before association. 5. Because epitope (the area where antibody recognizes and associates) contains PRL receptor associated area, it will competitively prevent signal transduction (Jak2-Stat5). The possible causes of antigenicity acquisition include differences of phosphorylation. 6. Immunizing a rat against rat PRL produces autoantibody and reproduces pathological model similar to macroprolactinemia. From the above findings, we suggest a clinical message that, when we conduct a diagnosis of a patient with hyperprolactinemia, it is important to exclude macroprolactinemia before carrying out diagnosis or treatment. This message is being gradually accepted. (2) Establishing high sensitive assay system of hormone and clarifying mechanism to secrete or adjust hormone in immunity or neurons: This researcher has established the super high sensitivity enzyme immunoassay (EIA), that is almost 1000 times as sensitive as the traditional measuring method, in human growth hormone (GH) and PRL systems, and has applied in basic and clinical ways. Urinary GH measurement using GH super high sensitivity EIA allows you to noninvasively know GH secretion dynamics, and is clinically applied to conduct diagnosis of GH secretion insufficiency or follow up acromegaly. For the first time, we reported, using this measurement system, that human lymphocyte produces and secretes GH and that secretion is adjusted differently from master gland. (3) Clarifying roles, in terms of physiology and disease, of endocrine system hormone and its molecular fragment peptide in the immune and nervous systems (Locating involvement in autoimmune diseases or Alzheimer's disease, and medications): Using cultured rat hippocampal neurons, this researcher has identified neurons toxicity mechanism by pathological physiological concentration amyloidβprotein (Aβ). (4) Optimizing medication: Reassessing clinical examination of those who are hormone autoantibody positive: It has been reported that autoantibody also exists in thyroid-stimulating, follicle-stimulating, luteinizing and other hormones. The existence of this autoantibody may impact clinical examination, resulting in an excessive hormone replacement therapy. This researcher is making efforts to establish assay system of this hormone autoantibody and to conduct survey.

Present specialized field
Medical pharmacy, General Pharmacology, Laboratory medicine, Neurology, Endocrinology, Collagen Disease/Allergy/Infectious Disease Medicine (Keyword：Growth hormone/ prolactin/ macroprolactin/ hyperprolactinaemia/ enzyme immunoassay/ amyloid beta/ chloride ATPase/ immunology/ neurology/ endocrinology/Thyroid stimulating hormone/ Macrothyrotropinemia)

Books
1.	2011	Autoimmunity in the pituitary gland and pituitary hormones Advances in Medicine and Biology (Leon V Berhardt ed.) │ ,pp.33-74 (Co-authored)
2.	2008	Macroprolactinemia: A New Cause of Hyperprolactinemia Due to Anti-Prolactin (PRL) Autoantibodies. New Research on Autoantibodies (Claude T. Petrelli ed.) │ ,pp.13-59 (Co-authored)
3.	1991	Molecular and Clinical Advances in Pituitary Disorders. (S.Melmed, R.J.Robbins ed.) (Ultrasensitive assays in evaluation of growth hormone disorders) │ ,pp.261-271 (Co-authored)
4.	1988	Advances in Pituitary Adenoma Research (A.M. Landalt, P.U. Heitz, J. Zapf, J. Girard, E. Del Pozo ed.)(Prolactinoma treatment with long-acting bromocriptine) │ ,pp.317-320 (Co-authored)
5.	1988	Basic and Clinical Aspects of Growth Hormone. (B.B. Bercu ed.) (Acromegaly) │ ,pp.95-103 (Co-authored)
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Papers
1.	2020/09	Re‐evaluation of serum leptin and adiponectin concentrations normalized by body fat mass in patients with rheumatoid arthritis │ Scientific Reports │ (Co-authored)
2.	2019/10	Procedures for the diagnosis of macro-follicle stimulating hormone (FSH) in a patient with high serum FSH concentrations │ Clinical Chemistry and Laboratory Medicine │ 58 (2),pp.e40-e43 (Co-authored)
3.	2018/10	Current Thyrotropin Immunoassays Recognize Macro-Thyrotropin Leading to Hyperthyrotropinemia in Females of Reproductive Age. │ Thyroid │ 28 (10),pp.1252-1260 (Co-authored)
4.	2017/02	Anti-TSH autoantibodies in patients with macro-TSH and long-term changes in macro-TSH and serum TSH levels │ Thyroid │ 27 (2),pp.138-146 (Co-authored)
5.	2016	A possible cause of the variable detectability of macroprolactin by different immunoassay systems │ Clinical Chemistry and Laboratory Medicine │ 54,pp.603-608 (Co-authored)
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Academic conference presentation
1.	2019/03/24	A Case with Elevated Serum Follicle-Stimulating-Hormone (FSH) Concentrations Due to Macro-FSH. (The 101st Annual Meeting of the American Endocrine Society)
2.	2018/10/05	Methodologies for the Diagnosis of Macro-TSH and the Prevalence in Females of Reproductive Age (88th Annual Meeting of American Thyroid Association)
3.	2018/03/17	Establishment of in vitro system to identify suitable insulin analogues in patients with type 2 diabetes having anti-insulin antibodies (The 100th Annual Meeting of the American Endocrine Society)
4.	2017/10/21	Macro TSH in fertile women: the nature and effects on commercial TSH assay platforms (87th Annual Meeting of the American Thyroid Association)
5.	2016/04/02	Variable detectability of macro TSH in different immunoassay systems (The 98th Annual Meeting of the American Endocrine Society)
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Teaching achievements

●Other Special Instructions about Teaching Activities

1.	2015/07	Lecture and Practice of physical assessment to UCLA college students