Effects of L-dopa on expression of prolactin and synaptotagmin IV in 17-estradiol-induced prolactinomas of ovariectomized hemiparkinsonian rats

Maja Zorovic,Kaja Kolmančič,Marko Živin

doi:10.17305/bjbms.2021.5491

Maja Zorovic, Kaja Kolmančič + Show 1 more

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https://doi.org/10.17305/bjbms.2021.5491

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Abstract

ABSTRACTParkinson’s disease (PD) is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. Dopamine precursor levodopa (L-dopa) is used as the first-line treatment for PD. Evidence suggests neuroprotective effects of estrogens in PD. Since both 17b-estradiol (E2) and L-dopa act as regulators of prolactin (PRL) secretion from the pituitary gland, we investigated their effect on the expression of PRL in prolactinomas that developed in ovariectomized hemiparkinsonian rats treated with E2. We also investigated the effect of E2 and L-dopa on the expression of synaptotagmin IV (Syt IV), an immediate early gene whose product is abundant in the pituitary gland and was found to be highly co-expressed with PRL in lactotrophs (>90%). The hemiparkinsonian rat model was obtained by unilateral lesioning of dopaminergic nigrostriatal neurons. Rats received silastic tubing implants with E2 and were treated with L-dopa. Enzyme-linked immunosorbent assay and immunohistochemistry were used to assess the serum concentrations of PRL and E2 and expression of PRL and Syt IV in the tissue of adenohypophysis, respectively. We found that high levels of serum E2 were associated with the upregulation of Syt IV and PRL in PRL-ir cells, while treatment with L-dopa decreased the size of prolactinomas and downregulated Syt IV but had no effect on PRL expression or serum concentrations.

Highlights

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms and a second most common neurodegenerative disorder after Alzheimer’s disease [1]
In accordance with studies described in the literature [21,22], we found that in all E2-treated animals, higher than physiological serum levels of E2 resulted in pituitary hyperplasia
The extent of dopaminergic lesions did not differ between the 6-OHDA groups E2 and E2 + L-dopa (89.2 ± 6.84% and 87.4 ± 5.84%, respectively)

Summary

Introduction

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms and a second most common neurodegenerative disorder after Alzheimer’s disease [1]. The major pathologic feature of PD is a progressive loss of dopamine-producing neurons of the substantia nigra (SN), resulting in a reduction of the dopamine content in the target field of these neurons, the striatum [2]. Dopamine precursor levodopa (L-dopa) is the most common first-line treatment for motor symptoms of PD. Increasing evidence suggests that estrogens may protect motor neurons and reduce the motor symptoms of PD [3]. Submitted: 15 January 2021/Accepted: 24 March 2021

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