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Dexamethasone Dexamethasone:a fluorinated steroid analogue (glucocorticoid).
A dexamethasone suppression test (DST) is carried out on autistic children to investigate the function of the hypothalamo-pituitary adrenal axis (HPA-axis) (Hoshino, 1984). A high rate of nonsuppression after dexamethasone has been found (Cook 1990;von Frenckel, 1987; Richdale, Dexamethasone acts here as TRH analogue. G q/11: Dexamethasone increases G alpha q-11 expression (Mitchell, 1997) Research has suggested that there may be dysfunction in the control of the hypothalamic-pituitary-adrenal axis in autistic (Richdale, 1992), as well as ADHD children (Kaneko et al, 1993). Both an abnormal cortisol circadian rhythm and failure to suppress cortisol secretion in response to dexamethasone have been reported in autistic children. The tendency towards cortisol hypersecretion may indicate an "environmental stress response" in this group (Richdale, 1992). Dexamethasone increases G alpha q-11 expression and hormone-stimulated phospholipase C activity in rat osteosarcoma (UMR106) cells (Mitchell, 1997; Cheung, 2002). It has been shown that fluoride causes osteosarcomas and Gq/11 is the biochemical reason behind it. Of course osteosarcomas are closely related to TSH, for the same reason - activation of Gq/11. The TSH receptor which activates Gq/11 is highly expressed in those same osteosarcoma cells (Inoue et al, 1998). It has been shown that retinoic acids and T3 act synergistically with dexamethasone (Nogami, 2000). This is interesting especially as it relates to the research done by Mary Megson and Vitamin A. This has also been shown to occur in fetal rat pituitary gland in culture (Nogami et al, 2000). There are over 700 studies documenting effects of dexamethasone on thyroid hormone function. DEXAMETHASONE & THYROID(700 references) Others have shown that the effects of such drugs as dexamethasone are not due to a release of thyroid hormones from the thyroid itself, but is likewise related to a release of thyroxine from cellular pools such as A blunted TSH response is seen after administration of dexamethasone. Glucocorticoid treatment has shown identical blunted TSH response to TRH as are seen in autism (Coiro et al, 2000). After dexamethasone administration in healthy subjects there is significant decrease in the levels of TSH, T3, and Free T3 (Kjellman et al, 1993). Other animal and human studies have shown that dexamethasone increases the production of rT3 (Messer et al,1995; Maes et al, 1990), clearly a sign that thyroid conversion is inhibited in peripheral tissue, not the thyroid gland itself. Dexamethasone increased IGF-I secretion and decreased IGF-I binding (Nougues et al, 1993). Fluoride also increases IGF-1 levels, and may mimic the action of IGF-1. Dexamethasone had a pronounced suppressive effect on basal TSH and FT3 levels. It had a significant stimulating effect on rT3 levels (Maes et al, 1990). In 1993, while studying the neurotoxicity associated with the treatment of childhood leukemia, Mullenix et al demonstrated that dexamethasone disrupted behavior in rats to a greater degree than its non-fluorinated counterpart prednisone (Mullenix et al, 1994). [See also: Waber et al, 2000] ================== Baus E, Van Laethem F, Andris F, Rolin S, Urbain J, Leo O - “Dexamethasone increases intracellular cyclic AMP Cheung R, Mitchell J - “Mechanisms of regulation of G(11)alpha protein by dexamethasone in osteoblastic UMR 106-01 cells”Am J Physiol Endocrinol Metab 2002 Jan;282(1):E24-30 (2002) Coiro V, Volpi R, Cataldo S, Capretti L, Caffarri G, Pilla S, Chiodera P - "Dopaminergic and cholinergic involvement in the inhibitory effect of dexamethasone on the TSH response to TRH" Investig Med 48(2):133-6 (2000) Cook EH - "Autism: review of neurochemical investigation" Synapse 6:292-308 (1990) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=1700486&form=6&db=m&Dopt=r Cook EH, Leventhal BL - "The serotonin system in autism" Curr Opin Pediatr 8(4):348-54 (1996) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=9053096&form=6&db=m&Dopt=r Cook EH Jr, Arora RC, Anderson GM, Berry-Kravis EM, Yan SY, Yeoh HC, Sklena PJ, Charak DA, Leventhal BL - "Platelet serotonin studies in hyperserotonemic relatives of Hoshino Y, Ohno Y, Murata S, Yokoyama F, Kaneko M, Kumashiro H - "Dexamethasone suppression test in autistic children" Folia Psychiatr Neurol Jpn 38(4):445-9 (1984) Inoue M, Tawata M, Yokomori N, Endo T, Onaya T - "Expression of thyrotropin receptor on clonal osteoblast-like rat osteosarcoma cells" Thyroid 8(11):1059-64 (1998) Kaneko M, Hoshino Y, Hashimoto S, Okano T, Kumashiro H - "Hypothalamic-pituitary-adrenal axis function in children with attention-deficit hyperactivity disorder" J Autism Dev Disord 23(1):59-65(1993) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=8463202&form=6&db=m&Dopt=r
Kjellman BF, Thorell LH, Orhagen T, d'Elia G, Kagedal B - "The hypothalamic-pituitary-thyroid axis in depressive patients and healthy subjects in relation to the hypothalamic-pituitary-adrenal axis" Psychiatry Res 47(1):7-21 (1993) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=8516419&form=6&db=m&Dopt=r Reinhardt W, Sauter V, Jockenhovel F, Kummer G, Uppenkamp M, Witzke O, Philipp T, Reinwein D, Mann K - “Unique alterations of thyroid function parameters after i.v. administration of alkylating drugs (cyclophosphamide and ifosfamide)" Exp Clin Endocrinol Diabetes 107(3):177-82 (1999) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=10376442&form=6&db=m&Dopt=r Richdale AL, Prior MR - "Urinary cortisol circadian rhythm in a group of high-functioning children with autism" J Autism Dev Disord 22(3):433-47 (1992) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=1400105&form=6&db=m&Dopt=r Maes M, Vandewoude M, Schotte C, Martin M, Blockx P - "Suppressive effects of dexamethasone on hypothalamic-pituitary-thyroid axis function in depressed patients" J Affect Disord 20(1):55-61 (1990) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=2147190&form=6&db=m&Dopt=r Messer NT, Ganjam VK, Nachreiner RF, Krause GF - "Effect of dexamethasone administration on serum thyroid hormone concentrations in clinically normal horses"J Am Vet Med Assoc 206(1):63-6 (1995) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=7744665&form=6&db=m&Dopt=r Mitchell J, Bansal A - "Dexamethasone increases G alpha q-11 expression and hormone-stimulated phospholipase C activity in UMR-106-01 cells" Am J Physiol 273(3 Pt 1):E528-35 (1997) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=9316442&form=6&db=m&Dopt=r Mullenix PJ, Kernan WJ, Schunior A, Howes A, Waber DP, Sallan SE, Tarbell NJ - ”Interactions of steroid, methotrezate and radiation determine neurotoxicity in an animal model to study therapy for childhood leukemia” Pediatr Res (35):171-178 (1994). Nogami H, Matsubara M, Harigaya T, Katayama M, Kawamura K - "Retinoic acids and thyroid hormone act synergistically with dexamethasone to increase growth hormone-releasing hormone receptor messenger ribonucleic acid expression" Endocrinology 141(12):4396-401 (2000) Nougues J, Reyne Y, Barenton B, Chery T, Garandel V, Soriano J - " Differentiation of adipocyte precursors in a serum-free medium is influenced by glucocorticoids and endogenously produced insulin-like growth factor-I" Int J Obes Relat Metab Disord 17(3):159-67(1993) von Frenckell R - "What do you say, agnostic?" Acta Psychiatr Belg 87(1):85-91 (1987) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=3604725&form=6&db=m&Dopt=r Waber DP, Carpentieri SC, Klar N, Silverman LB, Schwenn M, Hurwitz CA, Mullenix PJ, Tarbell NJ, Sallan SE - “Cognitive sequelae in children treated for acute Yeung MY, Smyth JP - Hormonal factors in the morbidities associated with extreme prematurity and the potential benefits of hormonal supplement” Biol Neonate 81(1):1-15 (2002)
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