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

Parkinson's disease (PD) is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. Dopamine precursor L-dopa is used as the first-line treatment for PD. Evidence suggests neuroprotective effects of estrogens in PD. Since both E2 and L-dopa act as regulators of prolactin secretion from the pituitary gland, we investigated their effect on the expression of prolactin (PRL) in prolactinomas that developed in ovariectomized hemiparkinsonian rats treated with 17b-estradiol (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. ELISA and immunohistochemistry were used to assess the serum concentrations of PRL and E2 and expression of PRL and SytIV in the tissue of adenohypophysis, respectively. We found that high levels of serum 17b-estradiol 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.

Release mode of large and small dense-core vesicles specified by different synaptotagmin isoforms in PC12 cells

Many cells release multiple substances in different proportions according to the specific character of a stimulus. PC12 cells, a model neuroendocrine cell line, express multiple isoforms of the exocytotic Ca2+ sensor synaptotagmin. We show that these isoforms sort to populations of dense-core vesicles that differ in size. These synaptotagmins differ in their Ca2+ sensitivities, their preference for full fusion or kiss-and-run, and their sensitivity to inhibition by synaptotagmin IV. In PC12 cells, vesicles that harbor these different synaptotagmin isoforms can be preferentially triggered to fuse by different forms of stimulation. The mode of fusion is specified by the synaptotagmin isoform activated, and because kiss-and-run exocytosis can filter small molecules through a size-limiting fusion pore, the activation of isoforms that favor kiss-and-run will select smaller molecules over larger molecules packaged in the same vesicle. Thus synaptotagmin isoforms can provide multiple levels of control in the release of different molecules from the same cell.