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.
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