Altered Neuroendocrine Regulation of Luteinizing Hormone Secretion in Postmenopausal Women with Parkinson’s Disease

Abstract

The secretion of gonadotropins and the role exerted by the endogenous opioid system on luteinizing hormone (LH) secretion were investigated in 6 postmenopausal women affected by idiopathic Parkinson’s disease (PD) as well as in 6 age- and weight-matched normal postmenopausal women as controls. The mean plasma follicle-stimulating hormone (FSH) and LH levels were evaluated both under basal conditions and after 20 days of conjugated estrogen administration (1.25 mg/day). At the same time, the activity of the endogenous opioid system was evaluated, as well as the LH response to the 4-hour infusion of the opioid antagonist naloxone (1.6 mg i.v. bolus followed by 1.6 mg/h). Both before and during estrogen administration, plasma FSH levels were similar in the two groups of subjects, whereas plasma LH levels were significantly lower (p < 0.01) in parkinsonian than in control women. In each subject estrogen administration significantly blunted (p < 0.01) plasma FSH levels. Plasma LH levels were reduced only in controls (p < 0.05), but not in women with PD. In each subject, before estrogen administration, the plasma LH levels did not vary during naloxone infusion. In control women after 20 days of estrogen administration, the plasma LH levels significantly increased during naloxone infusion (p < 0.01). By contrast, in women with PD, conjugated estrogens failed to restore the LH response to naloxone. The present results suggest that the neurotransmitter mechanisms, which regulate LH secretion, are altered, and, in particular, the activity of the endogenous opioid system is deficient in women with PD.

The endocrine dyscrasia that accompanies menopause and andropause induces aberrant cell cycle signaling that triggers re-entry of post-mitotic neurons into the cell cycle, neurodysfunction, neurodegeneration and cognitive disease

“…Although plasma FSH was unchanged between PD and controls, plasma LH levels are significantly lower in Parkinsonian than in control women (Bonuccelli, et al 1990; Cagnacci et al 1991). While estrogens significantly blunted plasma FSH levels, plasma LH levels were reduced only in controls, but not in women with PD.…”

“…Differences in the neuroendocrine regulation of LH secretion in post-menopausal women with PD has been reported (Cagnacci, et al 1991). Although plasma FSH was unchanged between PD and controls, plasma LH levels are significantly lower in Parkinsonian than in control women (Bonuccelli, et al 1990; Cagnacci et al 1991).…”

“…While estrogens significantly blunted plasma FSH levels, plasma LH levels were reduced only in controls, but not in women with PD. In women with PD, estrogens also failed to restore the LH response to naloxone, suggesting reduced endogenous opioid control of the HPG axis in PD (Cagnacci et al 1991). Other hypophyseal hormones and gonadal steroids are unchanged, suggesting a selective alteration of hypothalamic dopaminergic mechanisms which regulate LH secretion (Bonuccelli et al 1990).…”

Environmental toxicant exposure and Parkinson’s disease: LRRK2 and inflammatory processes

“…While the view of PD as a complex genetic disease has gained traction in review literature many researchers are still using cell culture or animal models based solely on one factor [37,[165][166][167][168][169]. Several researchers have begun to explore the disease process using a combination of genetic factors and environmental toxicants [48,50,[170][171][172][173][174], however, there has yet to be wide uptake of these combinatorial studies as evidenced by the large number of studies, especially in non-human primates, utilizing 6-OHDA and MPTP [166,168,169,175,176]. Rising genetic evidence has demonstrated that many PD genes have low penetrance increasing with age suggesting that PD is both progressive and that PD pathology may be triggered by environmental exposures in vulnerable individuals.…”