Abstract
The hypothalamic–pituitary–adrenocortical (HPA) system in drug abusers may be affected due to disorders of the hypothalamic dopaminergic system. The present study investigated alterations in the adenohypophysis of middle-aged drug abusers (40–60 years of age), using clusterin-containing mixed cell-follicles as the indicator, in which clusterin (apolipoprotein J) is a multifunctional glycoprotein related to neurodegeneration. The paraffin-embedded adenohypophyses of methamphetamine and psychotropic drug abusers (n = 76) were compared with those of non-abusers (n = 82). The number of follicles was larger in drug abusers independent of the immediate cause of death, although the size was not significantly different. When cell types forming the follicles were immunohistochemically examined, drug abusers showed an increase of prolactin (PRL) cells and gonadotroph cells and a reciprocal decrease of growth hormone cells, suggesting hypofunction of dopaminergic neurons in the hypothalamus, while there was no change in the adrenocorticotropic hormone and thyroid-stimulating hormone cells. These increases of the clusterin-containing follicles and PRL cells in the follicles may be related to the dysfunction of dopaminergic neurons in the hypothalamus of chronic drug abusers and may be useful for investigating drug abuse in forensic casework.
Similar content being viewed by others
References
Nishida N, Ikeda N, Kudo K et al (2003) Sudden unexpected death of a methamphetamine abuser with cardiopulmonary abnormalities: a case report. Med Sci Law 43:267–271
Patel MM, Belson MG, Wright D et al (2005) Methylenedioxymethamphetamine (ecstasy)-related myocardial hypertrophy: an autopsy study. Resuscitation 66:197–202
Moriya F, Hashimoto Y (2002) A case of fatal hemorrhage in the cerebral ventricles following intravenous use of methamphetamine. Forensic Sci Int 129:104–109
Sen T, Abdulsalam CA, Pal S (2002) Effect of amitriptyline on gastric ulceration. Fundam Clin Pharmacol 16:311–315
Carroll BJ (2004) Untreated depression and hippocampal volume loss. Am J Psychiatry 161:1309–1310
Strupp M, Hamann GF, Brandt T (2000) Combined amphetamine and cocaine abuse caused mesencephalic ischemia in a 16-year-old boy—due to vasospasm? Eur Neurol 43:181–182
De Letter EA, Espeel MF, Craeymeersch ME et al (2003) Immunohistochemical demonstration of the amphetamine derivatives 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) in human post-mortem brain tissues and the pituitary gland. Int J Legal Med 117:2–9
Sillaber I, Montkowski A, Landgraf R et al (1988) Enhanced morphine-induced behavioural effects and dopamine release in the nucleus accumbens in a transgenic mouse model of impaired glucocorticoid (type II) receptor function: influence of long-term treatment with the antidepressant moclobemide. Neuroscience 85:415–425
Steckler T, Holsboer F (1999) Enhanced conditioned approach responses in transgenic mice with impaired glucocorticoid receptor function. Behav Brain Res 102:151–163
Dinan TG (1996) Noradrenergic and serotonergic abnormalities in depression: stress-induced dysfunction? J Clin Psychiatry 57:14–17
Plotsky PM, Owens MJ, Nemeroff CB (1998) Psychoneuroendocrinology of depression. Hypothalamic–pituitary–adrenal axis. Psychiatr Clin North Am 21:293–307
Piazza PV, Le Moal ML (1996) Pathophysiological basis of vulnerability to drug abuse: role of an interaction between stress, glucocorticoids, and dopaminergic neurons. Annu Rev Pharmacol Toxicol 36:359–378
Schatzberg AF, Rothschild AJ, Langlais PJ et al (1985) A corticosteroid/dopamine hypothesis for psychotic depression and related states. J Psychiatr Res 19:57–64
Holtzman DM (2004) in vivo effects of Apo E and clusterin on amyloid-beta metabolism and neuropathology. J Mol Neurosci 23:247–254
Choi-Miura NH, Ihara Y, Fukuchi K et al (1992) SP-40,40 is a constituent of Alzheimer’s amyloid. Acta Neuropathol (Berl) 83:260–264
Pumarola M, Vidal E, Trens JM (2005) Neuronal intranuclear inclusion disease in a horse. Acta Neuropathol (Berl) 110:191–195
Freixes M, Puig B, Rodriguez A et al (2004) Clusterin solubility and aggregation in Creutzfeldt–Jakob disease. Acta Neuropathol (Berl) 108:295–301
Imhof A, Charnay Y, Vallet PG (2006) Sustained astrocytic clusterin expression improves remodeling after brain ischemia. Neurobiol Dis 22:274–283
Lidstrom AM, Bogdanovic N, Hesse C et al (1998) Clusterin (apolipoprotein J) protein levels are increased in hippocampus and in frontal cortex in Alzheimer’s disease. Exp Neurol 154:511–521
Zwain I, Amato P (2000) Clusterin protects granulosa cells from apoptotic cell death during follicular atresia. Exp Cell Res 257:101–110
Ishikawa T, Miyaishi S, Tachibana T et al (2003) Role of adenohypophyseal mixed cell-follicles in age estimation. Acta Med Okayama 57:83–89
Hausmann R, Biermann T, Wiest I et al (2004) Neuronal apoptosis following human brain injury. Int J Legal Med 118:32–36
Feldmann RE Jr, Mattern R (2006) The human brain and its neural stem cells postmortem: from dead brains to live therapy. Int J Legal Med 120:201–211
Ishikawa T, Zhu BL, Li DR et al (2006) Age-dependent increase of clusterin in the human pituitary gland. Leg Med (Tokyo) 8:28–33
Inoue K, Couch EF, Takano K et al (1999) The structure and function of folliculo-stellate cells in the anterior pituitary gland. Arch Histol Cytol 62:208–211
Shirasawa N, Yoshimura F (1982) Immunohistochemical and electron microscopical studies of mitotic adenohypophysial cells in different ages of rats. Anat Embryol (Berl) 165:51–61
Ishikawa H, Nogami H, Shirasawa N (1983) Novel clonal strains from adult rat anterior pituitary producing S-100 protein. Nature 303:711–713
Shirasawa N, Kihara H, Yamaguchi S et al (1983) Pituitary folliculo-stellate cells immunostained with S-100 protein antiserum in postnatal, castrated and thyroidectomized rats. Cell Tissue Res 231:235–249
Yoshimura F, Ishikawa H (1967) A histometrical procedure to estimate the number of cells in the adenohypophysis. Endocrinol Jpn 14:118–133
Ogawa S, Ishibashi Y, Sakamoto Y et al (1997) The glycoproteins that occur in the colloid of senescent porcine pituitary glands are clusterin and glycosylated albumin fragments. Biochem Biophys Res Commun 234:712–718
Perez-Carceles MD, Noguera J, Jimenez JL et al (2004) Diagnostic efficacy of biochemical markers in diagnosis post-mortem of ischaemic heart disease. Forensic Sci Int 142:1–7
Quan L, Ishikawa T, Michiue T et al (2005) Ubiquitin-immunoreactive structures in the midbrain of methamphetamine abusers. Leg Med (Tokyo) 7:144–150
Stumm G, Schlegel J, Schafer T et al (1999) Amphetamine induce apoptosis and regulation of bcl-x splice variants in neocortical neurons. FASEB J 13:1065–1072
Xu W, Zhu JP, Angulo JA (2005) Induction of striatal pre- and postsynaptic damage by methamphetamine requires the dopamine receptors. Synapse 58:110–121
Chadwick IS, Curry PD, Linsley A et al (1991) Ecstasy, 3-4 methylenedioxymethamphetamine(MDMA), a fatality associated with coagulopathy and hyperthermia. J R Soc Med 84:371
Mirecki A, Fitzmaurice P, Ang L et al (2004) Brain antioxidant system in human methamphetamine users. J Neurochem 89:1396–1408
O’Connor KA, Ginsberg AB, Maksimova E et al (2004) Stress-induced sensitization of the hypothalamic–pituitary adrenal axis is associated with alterations of hypothalamic and pituitary gene expression. Neuroendocrinology 80:252–263
Jayanthi LD, Ramamoorthy S (2005) Regulation of monoamine transporters: influence of psychostimulants and therapeutic antidepressants. AAPS J 7:728–738
Rong Xu, Albert FP, Yanyan W (2002) The effects of dopamine and D2 receptor antagonists on pituitary hormone secretion are intact in mice lacking dopamine D2L receptor. Brain Res 939:95–99
de Silva HV, Stuart WD, Park YB et al (1990) Purification and characterization of apolipoprotein J. J Biol Chem 265:14292–14297
Ordonez C, Navarro A, Perez C et al (2006) Apolipoprotein D expression in substantia nigra of Parkinson disease. Histol Histopathol 21:361–366
Veronesi B, Makwana O, Pooler M et al (2005) Effects of subchoronic exposures to concentrated ambient particles. VII. Degeneration of dopaminergic neurons in Apo E−/−mice. Inhal Toxicol 17:235–241
Tsai SC, Chiao YC, Lu CC (1996) Inhibition by amphetamine of testosterone secretion through a mechanism involving an increase of cyclic AMP production in rat testes. Br J Pharmacol 118:984–988
Becker AL, Epperson CN (2006) Female puberty: clinical implications for the use of prolactin-modulating psychotropics. Child Adolesc Psychiatr Clin N Am 15:207–220
Molitch ME (2005) Medication-induced hyperprolactinemia. Mayo Clin Proc 80:1050–1057
Takanashi R, Ishikawa H (1984) Increase acidophils of the hypophysis in liver cirrhosis. Acta Pathol Jpn 34:67–75
Acknowledgements
The authors are deeply grateful to Dr. T. Takata at Ehime Prefectural University of Health Sciences for advice regarding this study. This study was supported in part by a Fund for Medical Research from Osaka City University Medical Research Foundation, Japan and a grant for 21st Century Program “Base to Overcome Fatigue” supported by MEXT (Ministry of Education, Culture, Sports, Science and Technology).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ishikawa, T., Zhu, BL., Miyaishi, S. et al. Increase in clusterin-containing follicles in the adenohypophysis of drug abusers. Int J Legal Med 121, 395–402 (2007). https://doi.org/10.1007/s00414-006-0138-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00414-006-0138-2